Preliminary evaluation of the impact of a Web-based HIV testing programme in Abruzzo Region on the prevention of late HIV presentation and associated mortality.

PubMed

Polilli, Ennio; Sozio, Federica; Di Stefano, Paola; Clerico, Luigi; Di Iorio, Giancarlo; Parruti, Giustino

2018-04-01

This study aimed to analyze the efficacy of a Web-based testing programme in terms of the prevention of late HIV presentation. The clinical characteristics of patients diagnosed with HIV via the Web-based testing programme were compared to those of patients diagnosed in parallel via standard diagnostic care procedures. This study included the clinical and demographic data of newly diagnosed HIV patients enrolled at the study clinic between February 2014 and June 2017. These patients were diagnosed either via standard diagnostic procedures or as a result of the Web-based testing programme. Eighty-eight new cases of HIV were consecutively enrolled; their mean age was 39.1±13.0 years. Fifty-nine patients (67%) were diagnosed through standard diagnostic procedures and 29 (33%) patients came from the Web-based testing programme. Late presentation (62% vs. 34%, p=0.01) and AIDS-defining conditions at presentation (13 vs. 1, p=0.02) were significantly more frequent in the standard care group than in the Web-based group; four of 13 patients with AIDS diagnosed under standard diagnostic procedures died, versus none in the Web-based testing group (p<0.001). Web-based recruitment for voluntary and free HIV testing helped to diagnose patients with less advanced HIV disease and no risk of death, from all at-risk groups, in comparison with standard care testing. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pre-examination factors affecting molecular diagnostic test results and interpretation: A case-based approach.

PubMed

Payne, Deborah A; Baluchova, Katarina; Peoc'h, Katell H; van Schaik, Ron H N; Chan, K C Allen; Maekawa, Masato; Mamotte, Cyril; Russomando, Graciela; Rousseau, François; Ahmad-Nejad, Parviz

2017-04-01

Multiple organizations produce guidance documents that provide opportunities to harmonize quality practices for diagnostic testing. The International Organization for Standardization ISO 15189 standard addresses requirements for quality in management and technical aspects of the clinical laboratory. One technical aspect addresses the complexities of the pre-examination phase prior to diagnostic testing. The Committee for Molecular Diagnostics of the International Federation for Clinical Chemistry and Laboratory Medicine (also known as, IFCC C-MD) conducted a survey of international molecular laboratories and determined ISO 15189 to be the most referenced guidance document. In this review, the IFCC C-MD provides case-based examples illustrating the value of select pre-examination processes as these processes relate to molecular diagnostic testing. Case-based examples in infectious disease, oncology, inherited disease and pharmacogenomics address the utility of: 1) providing information to patients and users, 2) designing requisition forms, 3) obtaining informed consent and 4) maintaining sample integrity prior to testing. The pre-examination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. The clinical vignettes presented in this paper illustrate the value of applying select ISO 15189 recommendations for general laboratory to the more specialized area of Molecular Diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

Cost Implications of Value-Based Pricing for Companion Diagnostic Tests in Precision Medicine.

PubMed

Zaric, Gregory S

2016-07-01

Many interpretations of personalized medicine, also referred to as precision medicine, include discussions of companion diagnostic tests that allow drugs to be targeted to those individuals who are most likely to benefit or that allow treatment to be designed in a way such that individuals who are unlikely to benefit do not receive treatment. Many authors have commented on the clinical and competitive implications of companion diagnostics, but there has been relatively little formal analysis of the cost implications of companion diagnostics, although cost reduction is often cited as a significant benefit of precision medicine. We investigate the potential impact on costs of precision medicine implemented through the use of companion diagnostics. We develop a framework in which the costs of companion diagnostic tests are determined by considerations of profit maximization and cost effectiveness. We analyze four scenarios that are defined by the incremental cost-effectiveness ratio of the new drug in the absence of a companion diagnostic test. We find that, in most scenarios, precision medicine strategies based on companion diagnostics should be expected to lead to increases in costs in the short term and that costs would fall only in a limited number of situations.

Development of diagnostic test instruments to reveal level student conception in kinematic and dynamics

NASA Astrophysics Data System (ADS)

Handhika, J.; Cari, C.; Suparmi, A.; Sunarno, W.; Purwandari, P.

2018-03-01

The purpose of this research was to develop a diagnostic test instrument to reveal students' conceptions in kinematics and dynamics. The diagnostic test was developed based on the content indicator the concept of (1) displacement and distance, (2) instantaneous and average velocity, (3) zero and constant acceleration, (4) gravitational acceleration (5) Newton's first Law, (6) and Newton's third Law. The diagnostic test development model includes: Diagnostic test requirement analysis, formulating test-making objectives, developing tests, checking the validity of the content and the performance of reliability, and application of tests. The Content Validation Index (CVI) results in the category are highly relevant, with a value of 0.85. Three questions get negative Content Validation Ratio CVR) (-0.6), after revised distractors and clarify visual presentation; the CVR become 1 (highly relevant). This test was applied, obtained 16 valid test items, with Cronbach Alpha value of 0.80. It can conclude that diagnostic test can be used to reveal the level of students conception in kinematics and dynamics.

Likelihood-Based Clustering of Meta-Analytic SROC Curves

ERIC Educational Resources Information Center

Holling, Heinz; Bohning, Walailuck; Bohning, Dankmar

2012-01-01

Meta-analysis of diagnostic studies experience the common problem that different studies might not be comparable since they have been using a different cut-off value for the continuous or ordered categorical diagnostic test value defining different regions for which the diagnostic test is defined to be positive. Hence specificities and…

New and improved tuberculosis diagnostics: evidence, policy, practice, and impact.

PubMed

Pai, Madhukar; Minion, Jessica; Steingart, Karen; Ramsay, Andrew

2010-05-01

The aim is to summarize the evidence base for tuberculosis (TB) diagnostics, review recent policies on TB diagnostics, and discuss issues such as how evidence is translated into policy, limitations of the existing evidence base, and challenges involved in translating policies into impact. Case detection continues to be a major obstacle to global TB control. Fortunately, due to an unprecedented level of interest, funding, and activity, the new diagnostics pipeline for TB has rapidly expanded. There have been several new policies and guidelines on TB diagnostics. However, there are major gaps in the existing pipeline (e.g. lack of a point-of-care test) and the evidence base is predominantly made up of research studies of test accuracy. With the availability of new diagnostics and supporting policies, the next major step is translation of policy into practice. The impact of new tests will depend largely on the extent of their introduction and acceptance into the global public sector. This will itself depend in part on policy decisions by international technical agencies and national TB programs. With the engagement of all key stakeholders, we will need to translate evidence-based policies into epidemiological and public health impact.

Modeling companion diagnostics in economic evaluations of targeted oncology therapies: systematic review and methodological checklist.

PubMed

Doble, Brett; Tan, Marcus; Harris, Anthony; Lorgelly, Paula

2015-02-01

The successful use of a targeted therapy is intrinsically linked to the ability of a companion diagnostic to correctly identify patients most likely to benefit from treatment. The aim of this study was to review the characteristics of companion diagnostics that are of importance for inclusion in an economic evaluation. Approaches for including these characteristics in model-based economic evaluations are compared with the intent to describe best practice methods. Five databases and government agency websites were searched to identify model-based economic evaluations comparing a companion diagnostic and subsequent treatment strategy to another alternative treatment strategy with model parameters for the sensitivity and specificity of the companion diagnostic (primary synthesis). Economic evaluations that limited model parameters for the companion diagnostic to only its cost were also identified (secondary synthesis). Quality was assessed using the Quality of Health Economic Studies instrument. 30 studies were included in the review (primary synthesis n = 12; secondary synthesis n = 18). Incremental cost-effectiveness ratios may be lower when the only parameter for the companion diagnostic included in a model is the cost of testing. Incorporating the test's accuracy in addition to its cost may be a more appropriate methodological approach. Altering the prevalence of the genetic biomarker, specific population tested, type of test, test accuracy and timing/sequence of multiple tests can all impact overall model results. The impact of altering a test's threshold for positivity is unknown as it was not addressed in any of the included studies. Additional quality criteria as outlined in our methodological checklist should be considered due to the shortcomings of standard quality assessment tools in differentiating studies that incorporate important test-related characteristics and those that do not. There is a need to refine methods for incorporating the characteristics of companion diagnostics into model-based economic evaluations to ensure consistent and transparent reimbursement decisions are made.

Defining the Needs for Next Generation Assays for Tuberculosis

PubMed Central

Denkinger, Claudia M.; Kik, Sandra V.; Cirillo, Daniela Maria; Casenghi, Martina; Shinnick, Thomas; Weyer, Karin; Gilpin, Chris; Boehme, Catharina C.; Schito, Marco; Kimerling, Michael; Pai, Madhukar

2015-01-01

To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. PMID:25765104

A computational framework for converting textual clinical diagnostic criteria into the quality data model.

PubMed

Hong, Na; Li, Dingcheng; Yu, Yue; Xiu, Qiongying; Liu, Hongfang; Jiang, Guoqian

2016-10-01

Constructing standard and computable clinical diagnostic criteria is an important but challenging research field in the clinical informatics community. The Quality Data Model (QDM) is emerging as a promising information model for standardizing clinical diagnostic criteria. To develop and evaluate automated methods for converting textual clinical diagnostic criteria in a structured format using QDM. We used a clinical Natural Language Processing (NLP) tool known as cTAKES to detect sentences and annotate events in diagnostic criteria. We developed a rule-based approach for assigning the QDM datatype(s) to an individual criterion, whereas we invoked a machine learning algorithm based on the Conditional Random Fields (CRFs) for annotating attributes belonging to each particular QDM datatype. We manually developed an annotated corpus as the gold standard and used standard measures (precision, recall and f-measure) for the performance evaluation. We harvested 267 individual criteria with the datatypes of Symptom and Laboratory Test from 63 textual diagnostic criteria. We manually annotated attributes and values in 142 individual Laboratory Test criteria. The average performance of our rule-based approach was 0.84 of precision, 0.86 of recall, and 0.85 of f-measure; the performance of CRFs-based classification was 0.95 of precision, 0.88 of recall and 0.91 of f-measure. We also implemented a web-based tool that automatically translates textual Laboratory Test criteria into the QDM XML template format. The results indicated that our approaches leveraging cTAKES and CRFs are effective in facilitating diagnostic criteria annotation and classification. Our NLP-based computational framework is a feasible and useful solution in developing diagnostic criteria representation and computerization. Copyright © 2016 Elsevier Inc. All rights reserved.

Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force.

PubMed

Cox, Linda; Williams, Brock; Sicherer, Scott; Oppenheimer, John; Sher, Larry; Hamilton, Robert; Golden, David

2008-12-01

The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.

[Diagnostic test scale SI5: Assessment of sacroiliac joint dysfunction].

PubMed

Acevedo González, Juan C; Quintero Oliveros, Silvia

2015-01-01

Sacroiliac joint dysfunction is a known cause of low back pain. We think that a diagnostic score scale (SI5) may be performed to assess diagnostic utility of clinical signs of sacroiliac joint dysfunction. The primary aim of the present study was to conduct the pilot study of our new diagnostic score scale, the SI5, for sacroiliac joint syndrome. We reviewed the literature on clinical characteristics, diagnostic tests and imaging most commonly used in diagnosing sacroiliac joint dysfunction. Our group evaluated the diagnostic utility of these aspects and we used those considered most representative to develop the SI5 diagnostic scale. The SI5 scale was applied to 22 patients with low back pain; afterwards, the standard test for diagnosing this pathology (selective blockage of the SI joint) was also performed on these patients. The sensitivity and specificity for each sign were also assessed and the diagnostic scale called SI5 was then proposed, based on these data. The most sensitive clinical tests for diagnosing SI joint dysfunction were 2 patient-reported clinical characteristics, the Laguerre Test, sacroiliac rocking test and Yeomans test (greater than 80% sensitivity). The tests with greatest diagnostic specificity (>80%) were the Lewitt test, Piedallu test and Gillet test. The proposed SI5 test score scale showed sensitivity of 73% and specificity of 71%. Sacroiliac joint syndrome has been shown to produce low back pain frequently; however, the diagnostic value of examination tests for sacroiliac joint pain has been questioned by other authors. The pilot study on the SI5 diagnostic score scale showed good sensitivity and specificity. However, the process of statistical validation of the SI5 needs to be continued. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Bootstrap-based procedures for inference in nonparametric receiver-operating characteristic curve regression analysis.

PubMed

Rodríguez-Álvarez, María Xosé; Roca-Pardiñas, Javier; Cadarso-Suárez, Carmen; Tahoces, Pablo G

2018-03-01

Prior to using a diagnostic test in a routine clinical setting, the rigorous evaluation of its diagnostic accuracy is essential. The receiver-operating characteristic curve is the measure of accuracy most widely used for continuous diagnostic tests. However, the possible impact of extra information about the patient (or even the environment) on diagnostic accuracy also needs to be assessed. In this paper, we focus on an estimator for the covariate-specific receiver-operating characteristic curve based on direct regression modelling and nonparametric smoothing techniques. This approach defines the class of generalised additive models for the receiver-operating characteristic curve. The main aim of the paper is to offer new inferential procedures for testing the effect of covariates on the conditional receiver-operating characteristic curve within the above-mentioned class. Specifically, two different bootstrap-based tests are suggested to check (a) the possible effect of continuous covariates on the receiver-operating characteristic curve and (b) the presence of factor-by-curve interaction terms. The validity of the proposed bootstrap-based procedures is supported by simulations. To facilitate the application of these new procedures in practice, an R-package, known as npROCRegression, is provided and briefly described. Finally, data derived from a computer-aided diagnostic system for the automatic detection of tumour masses in breast cancer is analysed.

Accuracy of AccessBio Immunoglobulin M and Total Antibody Rapid Immunochromatographic Assays for the Diagnosis of Acute Scrub Typhus Infection

DTIC Science & Technology

2010-02-01

archived samples, we assessed the diagnostic capacity of a rapid immunochromatographic test (ICT) for the detection of Orientia tsutsugamushi IgM and...illness in the Asia-Pacific region. As very few health facilities have accessible accurate diagnostic tests , the diagnosis of scrub fever must be based...develop- ment of rapid , diagnostic tests by the use of immunochromato- graphic test (ICf) technologies has provided a mechanism for point-of-care

Noncontact techniques for diesel engine diagnostics using exhaust waveform analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gore, D.A.; Cooke, G.J.

1987-01-01

RCA Corporation's continuing efforts to develop noncontact test techniques for diesel engines have led to recent advancements in deep engine diagnostics. The U.S. Army Tank-Automotive Command (TACOM) has been working with RCA for the development of new noncontact sensors and test techniques which use these sensors in conjunction with their family of Simplified Test Equipment (STE) to perform vehicle diagnostics. The STE systems are microprocessor-based maintenance tools that assist the Army mechanic in diagnosing malfunctions in both tactical and combat vehicles. The test systems support the mechanic by providing the sophisticated signal processing capabilities necessary for a wide range ofmore » diagnostic testing including exhaust waveform analysis.« less

Evaluation of Raman spectroscopy in comparison to commonly performed dengue diagnostic tests

NASA Astrophysics Data System (ADS)

Khan, Saranjam; Ullah, Rahat; Khurram, Muhammad; Ali, Hina; Mahmood, Arshad; Khan, Ajmal; Ahmed, Mushtaq

2016-09-01

This study demonstrates the evaluation of Raman spectroscopy as a rapid diagnostic test in comparison to commonly performed tests for an accurate detection of dengue fever in human blood sera. Blood samples of 104 suspected dengue patients collected from Holy Family Hospital, Rawalpindi, Pakistan, have been used in this study. Out of 104 samples, 52 (50%) were positive based on immunoglobulin G (IgG), whereas 54 (52%) were positive based on immunoglobulin M (IgM) antibody tests. For the determination of the diagnostic capabilities of Raman spectroscopy, accuracy, sensitivity, specificity and false positive rate have been calculated in comparison to normally performed IgM and IgG captured enzyme-linked immunosorbent assay tests. Accuracy, precision, specificity, and sensitivity for Raman spectroscopy in comparison to IgM were found to be 66%, 70%, 72%, and 61%, whereas based on IgG they were 47%, 46%, 52%, and 43%, respectively.

Web-Based Two-Tier Diagnostic Test and Remedial Learning Experiment

ERIC Educational Resources Information Center

Lai, Ah-Fur; Chen, Deng-Jyi

2010-01-01

Offering a series of diagnosis and individual remedial learning activities for a general class by means of web and multimedia technology can overcome the dilemma of conventional diagnosis and remedial instruction. The study proposes a three-layer conceptual framework and adopts a two-tier diagnostic test theory to develop a web-based two-tier…

Molecular malaria diagnostics: A systematic review and meta-analysis.

PubMed

Roth, Johanna M; Korevaar, Daniël A; Leeflang, Mariska M G; Mens, Pètra F

2016-01-01

Accurate diagnosis of malaria is essential for identification and subsequent treatment of the disease. Currently, microscopy and rapid diagnostic tests are the most commonly used diagnostics, next to treatment based on clinical signs only. These tests are easy to deploy, but have a relatively high detection limit. With declining prevalence in many areas, there is an increasing need for more sensitive diagnostics. Molecular tools may be a suitable alternative, although costs and technical requirements currently hamper their implementation in resource limited settings. A range of (near) point-of-care diagnostics is therefore under development, including simplifications in sample preparation, amplification and/or read-out of the test. Accuracy data, in combination with technical characteristics, are essential in determining which molecular test, if any, would be the most promising to be deployed. This review presents a comprehensive overview of the currently available molecular malaria diagnostics, ranging from well-known tests to platforms in early stages of evaluation, and systematically evaluates their published accuracy. No important difference in accuracy was found between the most commonly used PCR-based assays (conventional, nested and real-time PCR), with most of them having high sensitivity and specificity, implying that there are no reasons other than practical ones to choose one technique over the other. Loop-mediated isothermal amplification and other (novel) diagnostics appear to be highly accurate as well, with some offering potential to be used in resource-limited settings.

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological review of health technology assessments.

PubMed

Shinkins, Bethany; Yang, Yaling; Abel, Lucy; Fanshawe, Thomas R

2017-04-14

Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests.

Rapid diagnostic tests to improve treatment of malaria and other febrile illnesses: patient randomised effectiveness trial in primary care clinics in Afghanistan

PubMed Central

Mikhail, Amy; Mayan, Ismail; Cundill, Bonnie; Anwar, Mohammed; Bakhtash, Sayed Habib; Mohammed, Nader; Rahman, Habib; Zekria, Rohullah; Whitty, Christopher J M; Rowland, Mark

2014-01-01

Objective To assess the impact of rapid diagnostic tests on the diagnostic accuracy and treatment of malaria and non-severe fever in an Asian setting. Design Patient randomised trial in primary level clinics. Setting Two areas of Afghanistan where Plasmodium vivax and Plasmodium falciparum are endemic; one area with moderate transmission (eastern region) and one with low transmission (northern region). Participants 5794 patients of all ages with suspected malaria enrolled by 80 clinicians in 22 clinics. Interventions Malaria rapid diagnostic tests were compared with clinical diagnosis where no parasite diagnostic test was available, longer established field microscopy, and recently introduced microscopy. Main outcome measures Proportion of patients appropriately treated with an antimalarial, defined as patients with P vivax who received chloroquine, patients with P falciparum who received artemisinin based combination therapy, and patients with no malaria parasites who did not receive an antimalarial. Secondary outcomes included diagnostic test accuracy and the proportion of patients negative for malaria who received antibiotics and antimalarials. Results In the low transmission area, comparing rapid diagnostic tests with clinical diagnosis, 65% (212/325) versus 12% (40/321) of febrile patients were appropriately treated for malaria (adjusted odds ratio 92.7, 95% confidence interval 12.4 to 694.1, P<0.001). The proportion of patients who were negative for malaria and received an antibiotic was 57% (185/325) in the rapid diagnostic test arm compared with 14% (46/321) in the clinical diagnosis arm (16.9, 3.8 to 75.4, P<0.001). In the comparison of rapid diagnostic test with microscopy in the moderate transmission area, 83.6% (1696/2028) versus 76.3% (1512/1983) of patients were appropriately treated for malaria (1.70, 1.30 to 2.23, P<0.001). A higher proportion of P falciparum cases received appropriate treatment with artemisinin based combination therapy when malaria was diagnosed by rapid diagnostic test (82%, 58/71 v 32%, 24/76; 9.2, 3.88 to 21.66, P<0.001). Conclusions In South and central Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance. PMID:24948695

A Research Agenda for Malaria Eradication: Diagnoses and Diagnostics

PubMed Central

2011-01-01

Many of malaria's signs and symptoms are indistinguishable from those of other febrile diseases. Detection of the presence of Plasmodium parasites is essential, therefore, to guide case management. Improved diagnostic tools are required to enable targeted treatment of infected individuals. In addition, field-ready diagnostic tools for mass screening and surveillance that can detect asymptomatic infections of very low parasite densities are needed to monitor transmission reduction and ensure elimination. Antibody-based tests for infection and novel methods based on biomarkers need further development and validation, as do methods for the detection and treatment of Plasmodium vivax. Current rapid diagnostic tests targeting P. vivax are generally less effective than those targeting Plasmodium falciparum. Moreover, because current drugs for radical cure may cause serious side effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, more information is needed on the distribution of G6PD-deficiency variants as well as tests to identify at-risk individuals. Finally, in an environment of very low or absent malaria transmission, sustaining interest in elimination and maintaining resources will become increasingly important. Thus, research is required into the context in which malaria diagnostic tests are used, into diagnostics for other febrile diseases, and into the integration of these tests into health systems. PMID:21311583

A hybrid model for combining case-control and cohort studies in systematic reviews of diagnostic tests

PubMed Central

Chen, Yong; Liu, Yulun; Ning, Jing; Cormier, Janice; Chu, Haitao

2014-01-01

Systematic reviews of diagnostic tests often involve a mixture of case-control and cohort studies. The standard methods for evaluating diagnostic accuracy only focus on sensitivity and specificity and ignore the information on disease prevalence contained in cohort studies. Consequently, such methods cannot provide estimates of measures related to disease prevalence, such as population averaged or overall positive and negative predictive values, which reflect the clinical utility of a diagnostic test. In this paper, we propose a hybrid approach that jointly models the disease prevalence along with the diagnostic test sensitivity and specificity in cohort studies, and the sensitivity and specificity in case-control studies. In order to overcome the potential computational difficulties in the standard full likelihood inference of the proposed hybrid model, we propose an alternative inference procedure based on the composite likelihood. Such composite likelihood based inference does not suffer computational problems and maintains high relative efficiency. In addition, it is more robust to model mis-specifications compared to the standard full likelihood inference. We apply our approach to a review of the performance of contemporary diagnostic imaging modalities for detecting metastases in patients with melanoma. PMID:25897179

Temporal Trends in the Utilization of Noninvasive Diagnostic Tests for Coronary Artery Disease in Ontario Between 2008 and 2014: A Population-Based Study.

PubMed

Roifman, Idan; Wijeysundera, Harindra C; Austin, Peter C; Maclagan, Laura C; Rezai, Mohammad R; Wright, Graham A; Tu, Jack V

2017-02-01

The proliferation of cardiac diagnostic tests over the past few decades has received substantial attention from policymakers. However, contemporary population-based temporal trends of the utilization of noninvasive cardiac diagnostic tests for coronary artery disease are not known. Our objective was to examine the temporal trends in the utilization of coronary computed tomography angiography (CCTA), myocardial perfusion imaging (MPI), exercise stress testing (GXT), and stress echocardiography between 2008 and 2014. We performed a population-based repeated cross-sectional study of the adult population of Ontario between January 1, 2008 and December 31, 2014. Annual utilization rates of noninvasive cardiac diagnostic tests were computed. For each cardiac testing modality, a negative binomial regression model was used to assess temporal changes in test utilization. GXT and MPI collectively accounted for 88% of all cardiac noninvasive diagnostic tests throughout our study period. Age- and sex-standardized rates of GXT declined from 26.7/1000 adult population to 21.6/1000 adult population (mean annual reduction of 3.4%; P < 0.001). MPI rates declined from 21.1/1000 adult population to 19.5/1000 adult population (mean annual reduction of 1.3%; P < 0.001). Although utilization rates for both CCTA and stress echocardiography increased over time, the combined rate of all available tests decreased from 50.8/1000 adult population to 49.1/1000 adult population (mean annual reduction of 1.1%; P < 0.001). In conclusion, utilization rates for the most prevalent noninvasive cardiac diagnostic tests-GXT and MPI-declined over our study period. Furthermore, the overall test utilization rate also declined over time. We believe our findings are encouraging from a health policy perspective. Nonetheless, rising utilization rates for CCTA and stress echocardiography will need to be monitored in the future. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

[Evidence-based cardiology: practical applications from epidemiology. III. Diagnostic capacity of a clinical test].

PubMed

Rodríguez-Escudero, Juan Pablo; López-Jiménez, Francisco; Trejo-Gutiérrez, Jorge F

2011-01-01

This article reviews different characteristics of validity in a clinical diagnostic test. In particular, we emphasize the likelihood ratio as an instrument that facilitates the use of epidemiologic concepts in clinical diagnosis.

Get the Diagnosis: an evidence-based medicine collaborative Wiki for diagnostic test accuracy.

PubMed

Hammer, Mark M; Kohlberg, Gavriel D

2017-04-01

Despite widespread calls for its use, there are challenges to the implementation of evidence-based medicine (EBM) in clinical practice. In response to the challenges of finding timely, pertinent information on diagnostic test accuracy, we developed an online, crowd-sourced Wiki on diagnostic test accuracy called Get the Diagnosis (GTD, http://www.getthediagnosis.org). Since its launch in November 2008 till October 2015, GTD has accumulated information on 300 diagnoses, with 1617 total diagnostic entries. There are a total of 1097 unique diagnostic tests with a mean of 5.4 tests (range 0-38) per diagnosis. 73% of entries (1182 of 1617) have an associated sensitivity and specificity and 89% of entries (1432 of 1617) have associated peer-reviewed literature citations. Altogether, GTD contains 474 unique literature citations. For a sample of three diagnoses, the search precision (percentage of relevant results in the first 30 entries) in GTD was 100% as compared with a range of 13.3%-63.3% for PubMed and between 6.7% and 76.7% for Google Scholar. GTD offers a fast, precise and efficient way to look up diagnostic test accuracy. On three selected examples, GTD had a greater precision rate compared with PubMed and Google Scholar in identifying diagnostic test information. GTD is a free resource that complements other currently available resources. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Nonparametric predictive inference for combining diagnostic tests with parametric copula

NASA Astrophysics Data System (ADS)

Muhammad, Noryanti; Coolen, F. P. A.; Coolen-Maturi, T.

2017-09-01

Measuring the accuracy of diagnostic tests is crucial in many application areas including medicine and health care. The Receiver Operating Characteristic (ROC) curve is a popular statistical tool for describing the performance of diagnostic tests. The area under the ROC curve (AUC) is often used as a measure of the overall performance of the diagnostic test. In this paper, we interest in developing strategies for combining test results in order to increase the diagnostic accuracy. We introduce nonparametric predictive inference (NPI) for combining two diagnostic test results with considering dependence structure using parametric copula. NPI is a frequentist statistical framework for inference on a future observation based on past data observations. NPI uses lower and upper probabilities to quantify uncertainty and is based on only a few modelling assumptions. While copula is a well-known statistical concept for modelling dependence of random variables. A copula is a joint distribution function whose marginals are all uniformly distributed and it can be used to model the dependence separately from the marginal distributions. In this research, we estimate the copula density using a parametric method which is maximum likelihood estimator (MLE). We investigate the performance of this proposed method via data sets from the literature and discuss results to show how our method performs for different family of copulas. Finally, we briefly outline related challenges and opportunities for future research.

Development of an antigen-based rapid diagnostic test for the identification of blowfly (Calliphoridae) species of forensic significance.

PubMed

McDonagh, Laura; Thornton, Chris; Wallman, James F; Stevens, Jamie R

2009-06-01

In this study we examine the limitations of currently used sequence-based approaches to blowfly (Calliphoridae) identification and evaluate the utility of an immunological approach to discriminate between blowfly species of forensic importance. By investigating antigenic similarity and dissimilarity between the first instar larval stages of four forensically important blowfly species, we have been able to identify immunoreactive proteins of potential use in the development of species-specific immuno-diagnostic tests. Here we outline our protein-based approach to species determination, and describe how it may be adapted to develop rapid diagnostic assays for the 'on-site' identification of blowfly species.

Testing Expert-Based versus Student-Based Cognitive Models for a Grade 3 Diagnostic Mathematics Assessment

ERIC Educational Resources Information Center

Roduta Roberts, Mary; Alves, Cecilia B.; Chu, Man-Wai; Thompson, Margaret; Bahry, Louise M.; Gotzmann, Andrea

2014-01-01

The purpose of this study was to evaluate the adequacy of three cognitive models, one developed by content experts and two generated from student verbal reports for explaining examinee performance on a grade 3 diagnostic mathematics test. For this study, the items were developed to directly measure the attributes in the cognitive model. The…

An electronic thesaurus of Evidence Based Laboratory Medicine hematological and biochemical diagnostic tests.

PubMed

Dorizzi, R M; Maconi, M; Giavarina, D; Loza, G; Aman, M; Moreira, J; Bisoffi, Z; Gennuso, C

2009-10-01

The adoption of Evidence Based Laboratory Medicine (EBLM) has been hampered until today by the lack of effective tools. The SIMeL EBLM e-Thesaurus (on-line Repertoire of the diagnostic effectiveness of the laboratory, radiology and cardiology test) provides a useful support to clinical laboratory professionals and to clinicians for the interpretation of the diagnostic tests. The e-Thesaurus is an application developed using Microsoft Active Server Pages technology and carried out with Web Server Microsoft Internet Information Server and is available at the SIMeL website using a browser running JavaScript scripts (Internet Explorer is recommended). It contains a database (in Italian, English and Spanish) of the sensitivity and specificity (including the 95% confidence interval), the positive and negative likelihood ratios, the Diagnostic Odds Ratio and the Number Needed to Diagnose of more than 2000 diagnostic (most laboratory but also cardiology and radiology) tests. The e-Thesaurus improves the previous SIMeL paper and CD Thesaurus; its main features are a three languages search and a continuous and an easy updating capability.

Turning the Page: Advancing Paper-Based Microfluidics for Broad Diagnostic Application.

PubMed

Gong, Max M; Sinton, David

2017-06-28

Infectious diseases are a major global health issue. Diagnosis is a critical first step in effectively managing their spread. Paper-based microfluidic diagnostics first emerged in 2007 as a low-cost alternative to conventional laboratory testing, with the goal of improving accessibility to medical diagnostics in developing countries. In this review, we examine the advances in paper-based microfluidic diagnostics for medical diagnosis in the context of global health from 2007 to 2016. The theory of fluid transport in paper is first presented. The next section examines the strategies that have been employed to control fluid and analyte transport in paper-based assays. Tasks such as mixing, timing, and sequential fluid delivery have been achieved in paper and have enabled analytical capabilities comparable to those of conventional laboratory methods. The following section examines paper-based sample processing and analysis. The most impactful advancement here has been the translation of nucleic acid analysis to a paper-based format. Smartphone-based analysis is another exciting development with potential for wide dissemination. The last core section of the review highlights emerging health applications, such as male fertility testing and wearable diagnostics. We conclude the review with the future outlook, remaining challenges, and emerging opportunities.

A Model-Based Expert System for Space Power Distribution Diagnostics

NASA Technical Reports Server (NTRS)

Quinn, Todd M.; Schlegelmilch, Richard F.

1994-01-01

When engineers diagnose system failures, they often use models to confirm system operation. This concept has produced a class of advanced expert systems that perform model-based diagnosis. A model-based diagnostic expert system for the Space Station Freedom electrical power distribution test bed is currently being developed at the NASA Lewis Research Center. The objective of this expert system is to autonomously detect and isolate electrical fault conditions. Marple, a software package developed at TRW, provides a model-based environment utilizing constraint suspension. Originally, constraint suspension techniques were developed for digital systems. However, Marple provides the mechanisms for applying this approach to analog systems such as the test bed, as well. The expert system was developed using Marple and Lucid Common Lisp running on a Sun Sparc-2 workstation. The Marple modeling environment has proved to be a useful tool for investigating the various aspects of model-based diagnostics. This report describes work completed to date and lessons learned while employing model-based diagnostics using constraint suspension within an analog system.

How does study quality affect the results of a diagnostic meta-analysis?

PubMed Central

Westwood, Marie E; Whiting, Penny F; Kleijnen, Jos

2005-01-01

Background The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited. PMID:15943861

Economic evaluation of test-and-treat and empirical treatment strategies in the eradication of Helicobacter pylori infection; A Markov model in an Iranian adult population.

PubMed

Mazdaki, Alireza; Ghiasvand, Hesam; Sarabi Asiabar, Ali; Naghdi, Seyran; Aryankhesal, Aidin

2016-01-01

Helicobacter pylori may cause many gastrointestinal problems in developing countries such as Iran. We aimed to analyze the cost- effectiveness and cost- utility of the test-and-treat and empirical treatment strategies in managing Helicobacter pylori infection. This was a Markov based economic evaluation. Effectiveness was defined as the symptoms free numbers and QALYs in 100,000 hypothetical adults. The sensitivity analysis was based on Monte Carlo approach. In the test- and- treat strategy, if the serology is the first diagnostic test vs. histology, the cost per symptoms free number would be 291,736.1 Rials while the cost per QALYs would be 339,226.1 Rials. The cost per symptoms free number and cost per QALYs when the 13 C-UBT was used as the first diagnostic test vs. serology was 1,283,200 and 1,492,103 Rials, respectively. In the empirical strategy, if histology is used as the first diagnostic test vs. 13 CUBT, the cost per symptoms free numbers and cost per QALYs would be 793,234 and 955,698 Rials, respectively. If serology were used as the first diagnostic test vs. histology, the cost per symptoms free and QALYs would be 793,234 and 368941 Rials, respectively. There was no significant and considerable dominancy between the alternatives and the diagnostic tests.

Defining the needs for next generation assays for tuberculosis.

PubMed

Denkinger, Claudia M; Kik, Sandra V; Cirillo, Daniela Maria; Casenghi, Martina; Shinnick, Thomas; Weyer, Karin; Gilpin, Chris; Boehme, Catharina C; Schito, Marco; Kimerling, Michael; Pai, Madhukar

2015-04-01

To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Empirical likelihood-based confidence intervals for the sensitivity of a continuous-scale diagnostic test at a fixed level of specificity.

PubMed

Gengsheng Qin; Davis, Angela E; Jing, Bing-Yi

2011-06-01

For a continuous-scale diagnostic test, it is often of interest to find the range of the sensitivity of the test at the cut-off that yields a desired specificity. In this article, we first define a profile empirical likelihood ratio for the sensitivity of a continuous-scale diagnostic test and show that its limiting distribution is a scaled chi-square distribution. We then propose two new empirical likelihood-based confidence intervals for the sensitivity of the test at a fixed level of specificity by using the scaled chi-square distribution. Simulation studies are conducted to compare the finite sample performance of the newly proposed intervals with the existing intervals for the sensitivity in terms of coverage probability. A real example is used to illustrate the application of the recommended methods.

Nested-PCR and a new ELISA-based NovaLisa test kit for malaria diagnosis in an endemic area of Thailand.

PubMed

Thongdee, Pimwan; Chaijaroenkul, Wanna; Kuesap, Jiraporn; Na-Bangchang, Kesara

2014-08-01

Microscopy is considered as the gold standard for malaria diagnosis although its wide application is limited by the requirement of highly experienced microscopists. PCR and serological tests provide efficient diagnostic performance and have been applied for malaria diagnosis and research. The aim of this study was to investigate the diagnostic performance of nested PCR and a recently developed an ELISA-based new rapid diagnosis test (RDT), NovaLisa test kit, for diagnosis of malaria infection, using microscopic method as the gold standard. The performance of nested-PCR as a malaria diagnostic tool is excellent with respect to its high accuracy, sensitivity, specificity, and ability to discriminate Plasmodium species. The sensitivity and specificity of nested-PCR compared with the microscopic method for detection of Plasmodium falciparum, Plasmodium vivax, and P. falciparum/P. vivax mixed infection were 71.4 vs 100%, 100 vs 98.7%, and 100 vs 95.0%, respectively. The sensitivity and specificity of the ELISA-based NovaLisa test kit compared with the microscopic method for detection of Plasmodium genus were 89.0 vs 91.6%, respectively. NovaLisa test kit provided comparable diagnostic performance. Its relatively low cost, simplicity, and rapidity enables large scale field application.

Combining computer adaptive testing technology with cognitively diagnostic assessment.

PubMed

McGlohen, Meghan; Chang, Hua-Hua

2008-08-01

A major advantage of computerized adaptive testing (CAT) is that it allows the test to home in on an examinee's ability level in an interactive manner. The aim of the new area of cognitive diagnosis is to provide information about specific content areas in which an examinee needs help. The goal of this study was to combine the benefit of specific feedback from cognitively diagnostic assessment with the advantages of CAT. In this study, three approaches to combining these were investigated: (1) item selection based on the traditional ability level estimate (theta), (2) item selection based on the attribute mastery feedback provided by cognitively diagnostic assessment (alpha), and (3) item selection based on both the traditional ability level estimate (theta) and the attribute mastery feedback provided by cognitively diagnostic assessment (alpha). The results from these three approaches were compared for theta estimation accuracy, attribute mastery estimation accuracy, and item exposure control. The theta- and alpha-based condition outperformed the alpha-based condition regarding theta estimation, attribute mastery pattern estimation, and item exposure control. Both the theta-based condition and the theta- and alpha-based condition performed similarly with regard to theta estimation, attribute mastery estimation, and item exposure control, but the theta- and alpha-based condition has an additional advantage in that it uses the shadow test method, which allows the administrator to incorporate additional constraints in the item selection process, such as content balancing, item type constraints, and so forth, and also to select items on the basis of both the current theta and alpha estimates, which can be built on top of existing 3PL testing programs.

Potential for palivizumab interference with commercially available antibody-antigen based respiratory syncytial virus diagnostic assays.

PubMed

Deming, Damon J; Patel, Nita; McCarthy, Michael P; Mishra, Lalji; Shapiro, Alan M; Suzich, JoAnn A

2013-10-01

Palivizumab is a monoclonal antibody indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus infection in infants. The potential for palivizumab to interfere with commercially available respiratory syncytial virus diagnostic tests was demonstrated. Negative test results in palivizumab-treated subjects should be interpreted with caution and confirmed by a nucleic acid amplification-based assay.

Rapid diagnostic tests for malaria at sites of varying transmission intensity in Uganda.

PubMed

Hopkins, Heidi; Bebell, Lisa; Kambale, Wilson; Dokomajilar, Christian; Rosenthal, Philip J; Dorsey, Grant

2008-02-15

In Africa, fever is often treated presumptively as malaria, resulting in misdiagnosis and the overuse of antimalarial drugs. Rapid diagnostic tests (RDTs) for malaria may allow improved fever management. We compared RDTs based on histidine-rich protein 2 (HRP2) and RDTs based on Plasmodium lactate dehydrogenase (pLDH) with expert microscopy and PCR-corrected microscopy for 7000 patients at sites of varying malaria transmission intensity across Uganda. When all sites were considered, the sensitivity of the HRP2-based test was 97% when compared with microscopy and 98% when corrected by PCR; the sensitivity of the pLDH-based test was 88% when compared with microscopy and 77% when corrected by PCR. The specificity of the HRP2-based test was 71% when compared with microscopy and 88% when corrected by PCR; the specificity of the pLDH-based test was 92% when compared with microscopy and >98% when corrected by PCR. Based on Plasmodium falciparum PCR-corrected microscopy, the positive predictive value (PPV) of the HRP2-based test was high (93%) at all but the site with the lowest transmission rate; the pLDH-based test and expert microscopy offered excellent PPVs (98%) for all sites. The negative predictive value (NPV) of the HRP2-based test was consistently high (>97%); in contrast, the NPV for the pLDH-based test dropped significantly (from 98% to 66%) as transmission intensity increased, and the NPV for expert microscopy decreased significantly (99% to 54%) because of increasing failure to detect subpatent parasitemia. Based on the high PPV and NPV, HRP2-based RDTs are likely to be the best diagnostic choice for areas with medium-to-high malaria transmission rates in Africa.

Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders

PubMed Central

Pfundt, Rolph; del Rosario, Marisol; Vissers, Lisenka E.L.M.; Kwint, Michael P.; Janssen, Irene M.; de Leeuw, Nicole; Yntema, Helger G.; Nelen, Marcel R.; Lugtenberg, Dorien; Kamsteeg, Erik-Jan; Wieskamp, Nienke; Stegmann, Alexander P.A.; Stevens, Servi J.C.; Rodenburg, Richard J.T.; Simons, Annet; Mensenkamp, Arjen R.; Rinne, Tuula; Gilissen, Christian; Scheffer, Hans; Veltman, Joris A.; Hehir-Kwa, Jayne Y.

2017-01-01

Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10–20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test. Methods: We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting. Results: In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to –5.8% per disorder). Conclusions: This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics. Genet Med advance online publication 27 October 2016 PMID:28574513

Diagnosis and therapy with CRISPR advanced CRISPR based tools for point of care diagnostics and early therapies.

PubMed

Uppada, Vanita; Gokara, Mahesh; Rasineni, Girish Kumar

2018-05-20

Molecular diagnostics is of critical importance to public health worldwide. It facilitates not only detection and characterization of diseases, but also monitors drug responses, assists in the identification of genetic modifiers and disease susceptibility. Based upon DNA variation, a wide range of molecular-based tests are available to assess/diagnose diseases. The CRISPR-Cas9 system has recently emerged as a versatile tool for biological and medical research. In this system, a single guide RNA (sgRNA) directs the endonuclease Cas9 to a targeted DNA sequence for site-specific manipulation. As designing CRISPR-guided nucleases can be done easily and relatively fast, the CRISPR/Cas9 system has evolved as widely used DNA editing tool. This technique led to a large number of gene editing studies in variety of organisms. CRISPR/Cas9-mediated diagnosis and therapy has picked up pace due to specificity and accuracy of CRISPR. The aim is not only to identify specific pathogens, especially virus but also to repair disease-causing alleles by changing the DNA sequence at the exact location on the chromosome. At present, PCR-based molecular diagnostic testing predominates; however, alternative technologies aimed at reducing genome complexity without PCR are anticipated to gain momentum in the coming years. Furthermore, development of integrated chip devices should allow point-of-care testing and facilitate genetic readouts from single cells and molecules. Together with molecular based therapy CRISPR based diagnostic testing will be a revolution in modern health care settings. In this review, we emphasize on current developing diagnostic techniques based upon CRISPR Cas approach along with short insights on its therapeutic usage. Copyright © 2018 Elsevier B.V. All rights reserved.

Voxel-Based Morphometry for Separation of Schizophrenia From Other Types of Psychosis in First-Episode Psychosis: Diagnostic Test Review.

PubMed

Palaniyappan, Lena; Maayan, Nicola; Bergman, Hanna; Davenport, Clare; Adams, Clive E; Soares-Weiser, Karla

2016-03-01

Subtle but widespread deficit in the cortical and subcortical grey matter is a consistent neuroimaging observation in schizophrenia. Several studies have used voxel based morphometry (VBM) to investigate the nature of this structural deficit. We conducted a diagnostic test review to explore the diagnostic potential of VBM in differentiating schizophrenia from other types of first-episode psychoses. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Comparison of the Mathematical Performance of Mature Students and Traditional Students over a 10-Year Period

ERIC Educational Resources Information Center

Faulkner, Fiona; Fitzmaurice, Olivia; Hannigan, Ailish

2016-01-01

Every student who enrols in a degree programme involving service mathematics in the University of Limerick in Ireland is given a mathematics diagnostic test. The diagnostic test was developed due to mathematics lecturers' anxiety regarding students' mathematical competency levels. Students receive the 40 question paper-based test in their first…

Crack identification for reinforced concrete using PZT based smart rebar active sensing diagnostic network

NASA Astrophysics Data System (ADS)

Song, N. N.; Wu, F.

2016-04-01

An active sensing diagnostic system using PZT based smart rebar for SHM of RC structure has been currently under investigation. Previous test results showed that the system could detect the de-bond of concrete from reinforcement, and the diagnostic signals were increased exponentially with the de-bonding size. Previous study also showed that the smart rebar could function well like regular reinforcement to undertake tension stresses. In this study, a smart rebar network has been used to detect the crack damage of concrete based on guided waves. Experimental test has been carried out for the study. In the test, concrete beams with 2 reinforcements have been built. 8 sets of PZT elements were mounted onto the reinforcement bars in an optimized way to form an active sensing diagnostic system. A 90 kHz 5-cycle Hanning-windowed tone burst was used as input. Multiple cracks have been generated on the concrete structures. Through the guided bulk waves propagating in the structures from actuators and sensors mounted from different bars, crack damage could be detected clearly. Cases for both single and multiple cracks were tested. Different crack depths from the surface and different crack numbers have been studied. Test result shows that the amplitude of sensor output signals is deceased linearly with a propagating crack, and is decreased exponentially with increased crack numbers. From the study, the active sensing diagnostic system using PZT based smart rebar network shows a promising way to provide concrete crack damage information through the "talk" among sensors.

Evidence-Based Point-of-Care Diagnostics: Current Status and Emerging Technologies

NASA Astrophysics Data System (ADS)

Chan, Cangel Pui Yee; Mak, Wing Cheung; Cheung, Kwan Yee; Sin, King Keung; Yu, Cheuk Man; Rainer, Timothy H.; Renneberg, Reinhard

2013-06-01

Point-of-care (POC) diagnostics brings tests nearer to the site of patient care. The turnaround time is short, and minimal manual interference enables quick clinical management decisions. Growth in POC diagnostics is being continuously fueled by the global burden of cardiovascular and infectious diseases. Early diagnosis and rapid initiation of treatment are crucial in the management of such patients. This review provides the rationale for the use of POC tests in acute coronary syndrome, heart failure, human immunodeficiency virus, and tuberculosis. We also consider emerging technologies that are based on advanced nanomaterials and microfluidics, improved assay sensitivity, miniaturization in device design, reduced costs, and high-throughput multiplex detection, all of which may shape the future development of POC diagnostics.

Using a web-based application to define the accuracy of diagnostic tests when the gold standard is imperfect.

PubMed

Lim, Cherry; Wannapinij, Prapass; White, Lisa; Day, Nicholas P J; Cooper, Ben S; Peacock, Sharon J; Limmathurotsakul, Direk

2013-01-01

Estimates of the sensitivity and specificity for new diagnostic tests based on evaluation against a known gold standard are imprecise when the accuracy of the gold standard is imperfect. Bayesian latent class models (LCMs) can be helpful under these circumstances, but the necessary analysis requires expertise in computational programming. Here, we describe open-access web-based applications that allow non-experts to apply Bayesian LCMs to their own data sets via a user-friendly interface. Applications for Bayesian LCMs were constructed on a web server using R and WinBUGS programs. The models provided (http://mice.tropmedres.ac) include two Bayesian LCMs: the two-tests in two-population model (Hui and Walter model) and the three-tests in one-population model (Walter and Irwig model). Both models are available with simplified and advanced interfaces. In the former, all settings for Bayesian statistics are fixed as defaults. Users input their data set into a table provided on the webpage. Disease prevalence and accuracy of diagnostic tests are then estimated using the Bayesian LCM, and provided on the web page within a few minutes. With the advanced interfaces, experienced researchers can modify all settings in the models as needed. These settings include correlation among diagnostic test results and prior distributions for all unknown parameters. The web pages provide worked examples with both models using the original data sets presented by Hui and Walter in 1980, and by Walter and Irwig in 1988. We also illustrate the utility of the advanced interface using the Walter and Irwig model on a data set from a recent melioidosis study. The results obtained from the web-based applications were comparable to those published previously. The newly developed web-based applications are open-access and provide an important new resource for researchers worldwide to evaluate new diagnostic tests.

Application of Immunohistochemistry and Molecular Diagnostics to Clinically Relevant Problems in Endometrial Cancer Bojana Djordjevic, Shannon Westin, Russell R. Broaddus

PubMed Central

Djordjevic, Bojana; Westin, Shannon; Broaddus, Russell R.

2012-01-01

Synopsis A number of different clinical scenarios are presented in which lab-based analyses beyond the usual diagnosis based on light microscopic examination of H&E stained slides – immunohistochemistry and PCR-based assays such as sequencing, mutation testing, microsatellite instability analysis, and determination of MLH1 methylation - are most helpful for guiding diagnosis and treatment of endometrial cancer. The central goal of this information is to provide a practical guide of key current and emerging issues in diagnostic endometrial cancer pathology that require the use of ancillary laboratory techniques, such as immunohistochemistry and molecular testing. The authors present the common diagnostic problems in endometrial carcinoma pathology, types of endometrial carcinoma, description of tissue testing and markers, pathological features, and targeted therapy. PMID:23687522

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting.

PubMed

Werner, Simone; Krause, Friedemann; Rolny, Vinzent; Strobl, Matthias; Morgenstern, David; Datz, Christian; Chen, Hongda; Brenner, Hermann

2016-04-01

In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population. We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results. AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68-0.87] and 0.56 (95% CI, 0.53-0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings. Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer. ©2015 American Association for Cancer Research.

Promoting the hydrostatic conceptual change test (HCCT) with four-tier diagnostic test item

NASA Astrophysics Data System (ADS)

Purwanto, M. G.; Nurliani, R.; Kaniawati, I.; Samsudin, A.

2018-05-01

Hydrostatic Conceptual Change Test (HCCT) is a diagnostic test instrument to identify students’ conception on Hydrostatic field. It is very important to support the learning process in the classroom. Based on that point of view, the researcher decided to develop HCCT instrument test into four-tier test diagnostic items. The resolve of this research is planned as the first step of four-tier test-formatted HCCT development as one of investigative test instrument on Hydrostatic. The research method used the 4D model which has four comprehensive steps: 1) defining, 2) designing, 3) developing and 4) disseminating. The instrument developed has been tried to 30 students in one of senior high schools. The data showed that four-tier- test-formatted HCCT is able to identify student’s conception level of Hydrostatic. In conclusion, the development of four-tier test-formatted HCCT is one of potential diagnostic test instrument that able to classify the category of students who misconception, no understanding, understanding, partial understanding and no codeable about concept of Hydrostatic.

A Meta-Analysis of Typhoid Diagnostic Accuracy Studies: A Recommendation to Adopt a Standardized Composite Reference

PubMed Central

Storey, Helen L.; Huang, Ying; Crudder, Chris; Golden, Allison; de los Santos, Tala; Hawkins, Kenneth

2015-01-01

Novel typhoid diagnostics currently under development have the potential to improve clinical care, surveillance, and the disease burden estimates that support vaccine introduction. Blood culture is most often used as the reference method to evaluate the accuracy of new typhoid tests; however, it is recognized to be an imperfect gold standard. If no single gold standard test exists, use of a composite reference standard (CRS) can improve estimation of diagnostic accuracy. Numerous studies have used a CRS to evaluate new typhoid diagnostics; however, there is no consensus on an appropriate CRS. In order to evaluate existing tests for use as a reference test or inclusion in a CRS, we performed a systematic review of the typhoid literature to include all index/reference test combinations observed. We described the landscape of comparisons performed, showed results of a meta-analysis on the accuracy of the more common combinations, and evaluated sources of variability based on study quality. This wide-ranging meta-analysis suggests that no single test has sufficiently good performance but some existing diagnostics may be useful as part of a CRS. Additionally, based on findings from the meta-analysis and a constructed numerical example demonstrating the use of CRS, we proposed necessary criteria and potential components of a typhoid CRS to guide future recommendations. Agreement and adoption by all investigators of a standardized CRS is requisite, and would improve comparison of new diagnostics across independent studies, leading to the identification of a better reference test and improved confidence in prevalence estimates. PMID:26566275

Recent advances in tuberculosis diagnostics in resource-limited settings.

PubMed

Seki, Mitsuko; Kim, Chang-Ki; Hayakawa, Satoshi; Mitarai, Satoshi

2018-04-19

Smear-negative and drug-resistant cases of tuberculosis (TB) disease necessitate the development of new diagnostic methods, especially in resource-limited settings. To improve the current TB situations, sensitive and specific TB point-of-care tests (POCTs) should be developed. This review addresses the current status of TB, novel diagnostic methodologies for TB, and the impact of those new diagnostics on TB control in such situations. Moreover, the perspective of TB management based on laboratory examinations is described. Smear microscopy with sputum samples is the only laboratory examination available in many resource-limited settings and is still used globally. Several nucleic acid amplification tests (NATs) have been developed. The World Health Organization (WHO) endorsed novel diagnostics based on NATs and updated their definition of a bacteriologically confirmed case requiring the biological specimen to be positive by smear microscopy, culture, or the WHO-recommended rapid diagnostic protocols. The use of new diagnostics increased the number of bacteriologically confirmed TB cases. Novel diagnostics are now available, but their sensitivity is still lower than that of conventional liquid culture method. To address the increasing incidence of TB, more resources including novel diagnostics as POCTs with higher sensitivity must be allocated to healthcare systems.

A stochastic model to determine the economic value of changing diagnostic test characteristics for identification of cattle for treatment of bovine respiratory disease.

PubMed

Theurer, M E; White, B J; Larson, R L; Schroeder, T C

2015-03-01

Bovine respiratory disease is an economically important syndrome in the beef industry, and diagnostic accuracy is important for optimal disease management. The objective of this study was to determine whether improving diagnostic sensitivity or specificity was of greater economic value at varied levels of respiratory disease prevalence by using Monte Carlo simulation. Existing literature was used to populate model distributions of published sensitivity, specificity, and performance (ADG, carcass weight, yield grade, quality grade, and mortality risk) differences among calves based on clinical respiratory disease status. Data from multiple cattle feeding operations were used to generate true ranges of respiratory disease prevalence and associated mortality. Input variables were combined into a single model that calculated estimated net returns for animals by diagnostic category (true positive, false positive, false negative, and true negative) based on the prevalence, sensitivity, and specificity for each iteration. Net returns for each diagnostic category were multiplied by the proportion of animals in each diagnostic category to determine group profitability. Apparent prevalence was categorized into low (<15%) and high (≥15%) groups. For both apparent prevalence categories, increasing specificity created more rapid, positive change in net returns than increasing sensitivity. Improvement of diagnostic specificity, perhaps through a confirmatory test interpreted in series or pen-level diagnostics, can increase diagnostic value more than improving sensitivity. Mortality risk was the primary driver for net returns. The results from this study are important for determining future research priorities to analyze diagnostic techniques for bovine respiratory disease and provide a novel way for modeling diagnostic tests.

Gearbox Tooth Cut Fault Diagnostics Using Acoustic Emission and Vibration Sensors — A Comparative Study

PubMed Central

Qu, Yongzhi; He, David; Yoon, Jae; Van Hecke, Brandon; Bechhoefer, Eric; Zhu, Junda

2014-01-01

In recent years, acoustic emission (AE) sensors and AE-based techniques have been developed and tested for gearbox fault diagnosis. In general, AE-based techniques require much higher sampling rates than vibration analysis-based techniques for gearbox fault diagnosis. Therefore, it is questionable whether an AE-based technique would give a better or at least the same performance as the vibration analysis-based techniques using the same sampling rate. To answer the question, this paper presents a comparative study for gearbox tooth damage level diagnostics using AE and vibration measurements, the first known attempt to compare the gearbox fault diagnostic performance of AE- and vibration analysis-based approaches using the same sampling rate. Partial tooth cut faults are seeded in a gearbox test rig and experimentally tested in a laboratory. Results have shown that the AE-based approach has the potential to differentiate gear tooth damage levels in comparison with the vibration-based approach. While vibration signals are easily affected by mechanical resonance, the AE signals show more stable performance. PMID:24424467

Model-Based Diagnosis in a Power Distribution Test-Bed

NASA Technical Reports Server (NTRS)

Scarl, E.; McCall, K.

1998-01-01

The Rodon model-based diagnosis shell was applied to a breadboard test-bed, modeling an automated power distribution system. The constraint-based modeling paradigm and diagnostic algorithm were found to adequately represent the selected set of test scenarios.

Development and Evaluation of the Diagnostic Power for a Computer-Based Two-Tier Assessment

ERIC Educational Resources Information Center

Lin, Jing-Wen

2016-01-01

This study adopted a quasi-experimental design with follow-up interview to develop a computer-based two-tier assessment (CBA) regarding the science topic of electric circuits and to evaluate the diagnostic power of the assessment. Three assessment formats (i.e., paper-and-pencil, static computer-based, and dynamic computer-based tests) using…

Built-In Diagnostics (BID) Of Equipment/Systems

NASA Technical Reports Server (NTRS)

Granieri, Michael N.; Giordano, John P.; Nolan, Mary E.

1995-01-01

Diagnostician(TM)-on-Chip (DOC) technology identifies faults and commands systems reconfiguration. Smart microcontrollers operating in conjunction with other system-control circuits, command self-correcting system/equipment actions in real time. DOC microcontroller generates commands for associated built-in test equipment to stimulate unit of equipment diagnosed, collects and processes response data obtained by built-in test equipment, and performs diagnostic reasoning on response data, using diagnostic knowledge base derived from design data.

Current ante-mortem techniques for diagnosis of bovine tuberculosis.

PubMed

Bezos, Javier; Casal, Carmen; Romero, Beatriz; Schroeder, Bjoern; Hardegger, Roland; Raeber, Alex J; López, Lissette; Rueda, Paloma; Domínguez, Lucas

2014-10-01

Bovine tuberculosis (TB), mainly caused by Mycobacterium bovis, is a zoonotic disease with implications for Public Health and having an economic impact due to decreased production and limitations to the trade. Bovine TB is subjected to official eradication campaigns mainly based on a test and slaughter policy using diagnostic assays based on the cell-mediated immune response as the intradermal tuberculin test and the gamma-interferon (IFN-γ) assay. Moreover, several diagnostic assays based on the detection of specific antibodies (Abs) have been developed in the last few years with the aim of complementing the current diagnostic techniques in the near future. This review provides an overview of the current ante-mortem diagnostic tools for diagnosis of bovine TB regarding historical background, methodologies and sensitivity (Se) and specificity (Sp) obtained in previous studies under different epidemiological situations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunochromatographic diagnostic test analysis using Google Glass.

PubMed

Feng, Steve; Caire, Romain; Cortazar, Bingen; Turan, Mehmet; Wong, Andrew; Ozcan, Aydogan

2014-03-25

We demonstrate a Google Glass-based rapid diagnostic test (RDT) reader platform capable of qualitative and quantitative measurements of various lateral flow immunochromatographic assays and similar biomedical diagnostics tests. Using a custom-written Glass application and without any external hardware attachments, one or more RDTs labeled with Quick Response (QR) code identifiers are simultaneously imaged using the built-in camera of the Google Glass that is based on a hands-free and voice-controlled interface and digitally transmitted to a server for digital processing. The acquired JPEG images are automatically processed to locate all the RDTs and, for each RDT, to produce a quantitative diagnostic result, which is returned to the Google Glass (i.e., the user) and also stored on a central server along with the RDT image, QR code, and other related information (e.g., demographic data). The same server also provides a dynamic spatiotemporal map and real-time statistics for uploaded RDT results accessible through Internet browsers. We tested this Google Glass-based diagnostic platform using qualitative (i.e., yes/no) human immunodeficiency virus (HIV) and quantitative prostate-specific antigen (PSA) tests. For the quantitative RDTs, we measured activated tests at various concentrations ranging from 0 to 200 ng/mL for free and total PSA. This wearable RDT reader platform running on Google Glass combines a hands-free sensing and image capture interface with powerful servers running our custom image processing codes, and it can be quite useful for real-time spatiotemporal tracking of various diseases and personal medical conditions, providing a valuable tool for epidemiology and mobile health.

Immunochromatographic Diagnostic Test Analysis Using Google Glass

PubMed Central

2014-01-01

We demonstrate a Google Glass-based rapid diagnostic test (RDT) reader platform capable of qualitative and quantitative measurements of various lateral flow immunochromatographic assays and similar biomedical diagnostics tests. Using a custom-written Glass application and without any external hardware attachments, one or more RDTs labeled with Quick Response (QR) code identifiers are simultaneously imaged using the built-in camera of the Google Glass that is based on a hands-free and voice-controlled interface and digitally transmitted to a server for digital processing. The acquired JPEG images are automatically processed to locate all the RDTs and, for each RDT, to produce a quantitative diagnostic result, which is returned to the Google Glass (i.e., the user) and also stored on a central server along with the RDT image, QR code, and other related information (e.g., demographic data). The same server also provides a dynamic spatiotemporal map and real-time statistics for uploaded RDT results accessible through Internet browsers. We tested this Google Glass-based diagnostic platform using qualitative (i.e., yes/no) human immunodeficiency virus (HIV) and quantitative prostate-specific antigen (PSA) tests. For the quantitative RDTs, we measured activated tests at various concentrations ranging from 0 to 200 ng/mL for free and total PSA. This wearable RDT reader platform running on Google Glass combines a hands-free sensing and image capture interface with powerful servers running our custom image processing codes, and it can be quite useful for real-time spatiotemporal tracking of various diseases and personal medical conditions, providing a valuable tool for epidemiology and mobile health. PMID:24571349

Affirm VPIII microbial identification test can be used to detect gardnerella vaginalis, Candida albicans and trichomonas vaginalis microbial infections in Korean women.

PubMed

Byun, Seung Won; Park, Yeon Joon; Hur, Soo Young

2016-04-01

The aim of this study was to compare Affirm VPIII Microbial Identification Test results for Korean women to those obtained for Gardnerella vaginalis through Nugent score, Candida albicans based on vaginal culture and Trichomonas vaginalis based on wet smear diagnostic standards. Study participants included 195 women with symptomatic or asymptomatic vulvovaginitis under hospital obstetric or gynecologic care. A definite diagnosis was made based on Nugent score for Gardnerella, vaginal culture for Candida and wet prep for Trichomonas vaginalis. Affirm VPIII Microbial Identification Test results were then compared to diagnostic standard results. Of the 195 participants, 152 were symptomatic, while 43 were asymptomatic. Final diagnosis revealed 68 (37.87%) cases of Gardnerella, 29 (14.87%) cases of Candida, one (0.51%) case of Trichomonas, and 10 (5.10%) cases of mixed infections. The detection rates achieved by each detection method (Affirm assay vs diagnostic standard) for Gardnerella and Candida were not significantly different (33.33% vs 34.8% for Gardnerella, 13.33% vs 14.87% for Candida, respectively). The sensitivity and specificity of the Affirm test for Gardnerella compared to the diagnostic standard were 75.0% and 88.98%, respectively. For Candida, the sensitivity and specificity of the Affirm test compared to the diagnostic standard were 82.76% and 98.80%, respectively. The number of Trichomonas cases was too small (1 case) to be statistically analyzed. The Affirm test is a quick tool that can help physicians diagnose and treat patients with infectious vaginitis at the point of care. © 2016 Japan Society of Obstetrics and Gynecology.

Diagnostic accuracy of tests to detect Hepatitis C antibody: a meta-analysis and review of the literature.

PubMed

Tang, Weiming; Chen, Wen; Amini, Ali; Boeras, Debi; Falconer, Jane; Kelly, Helen; Peeling, Rosanna; Varsaneux, Olivia; Tucker, Joseph D; Easterbrook, Philippa

2017-11-01

Although direct-acting antivirals can achieve sustained virological response rates greater than 90% in Hepatitis C Virus (HCV) infected persons, at present the majority of HCV-infected individuals remain undiagnosed and therefore untreated. While there are a wide range of HCV serological tests available, there is a lack of formal assessment of their diagnostic performance. We undertook a systematic review and meta-analysis to evaluate he diagnostic accuracy of available rapid diagnostic tests (RDT) and laboratory based EIA assays in detecting antibodies to HCV. We used the PRISMA checklist and Cochrane guidance to develop our search protocol. The search strategy was registered in PROSPERO (CRD42015023567). The search focused on hepatitis C, diagnostic tests, and diagnostic accuracy within eight databases (MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, SCOPUS, Literatura Latino-Americana e do Caribe em Ciências da Saúde and WHO Global Index Medicus. Studies were included if they evaluated an assay to determine the sensitivity and specificity of HCV antibody (HCV Ab) in humans. Two reviewers independently extracted data and performed a quality assessment of the studies using the QUADAS tool. We pooled test estimates using the DerSimonian-Laird method, by using the software R and RevMan. 5.3. A total of 52 studies were identified that included 52,673 unique test measurements. Based on five studies, the pooled sensitivity and specificity of HCV Ab rapid diagnostic tests (RDTs) were 98% (95% CI 98-100%) and 100% (95% CI 100-100%) compared to an enzyme immunoassay (EIA) reference standard. High HCV Ab RDTs sensitivity and specificity were observed across screening populations (general population, high risk populations, and hospital patients) using different reference standards (EIA, nucleic acid testing, immunoblot). There were insufficient studies to undertake subanalyses based on HIV co-infection. Oral HCV Ab RDTs also had excellent sensitivity and specificity compared to blood reference tests, respectively at 94% (95% CI 93-96%) and 100% (95% CI 100-100%). Among studies that assessed individual oral RDTs, the eight studies revealed that OraQuick ADVANCE® had a slightly higher sensitivity (98%, 95% CI 97-98%) compared to the other oral brands (pooled sensitivity: 88%, 95% CI 84-92%). RDTs, including oral tests, have excellent sensitivity and specificity compared to laboratory-based methods for HCV antibody detection across a wide range of settings. Oral HCV Ab RDTs had good sensitivity and specificity compared to blood reference standards.

The impact of commercial rapid respiratory virus diagnostic tests on patient outcomes and health system utilization.

PubMed

Ko, Fiona; Drews, Steven J

2017-10-01

Acute respiratory tract infections due to influenza A/B and respiratory syncytial virus (RSV) are major causes of morbidity and mortality globally. Rapid tests for detection of these pathogens include antigen detection point of care tests (POC) and newer easy to use molecular tests. From experience, these assays improve both laboratory workflow and assay interpretation issues. However, the question of the benefits of using rapid test technology compared to routine laboratory testing for respiratory viral pathogens is still often asked. Areas covered: Specifically, this review aims to; 1) identify clinical/patient indicators that can be measured prior to and following the implementation of rapid diagnostic test for influenza and RSV, 2) provide multiple perspectives on the extent of impact of a rapid diagnostic test, including direct and indirect outcomes, and 3) identify the technological advancements in the development of rapid testing, demonstrating a timeline that transitions from antigen-based assays to molecular assays. Expert commentary: Key benefits to the use of either antigen-based or molecular rapid tests for patient care, patient flow within institutions, as well as laboratory utilization are identified. Due to improved test characteristics, the authors feel that rapid molecular tests have greater benefits than antigen-based detection methods.

A fast Monte Carlo EM algorithm for estimation in latent class model analysis with an application to assess diagnostic accuracy for cervical neoplasia in women with AGC

PubMed Central

Kang, Le; Carter, Randy; Darcy, Kathleen; Kauderer, James; Liao, Shu-Yuan

2013-01-01

In this article we use a latent class model (LCM) with prevalence modeled as a function of covariates to assess diagnostic test accuracy in situations where the true disease status is not observed, but observations on three or more conditionally independent diagnostic tests are available. A fast Monte Carlo EM (MCEM) algorithm with binary (disease) diagnostic data is implemented to estimate parameters of interest; namely, sensitivity, specificity, and prevalence of the disease as a function of covariates. To obtain standard errors for confidence interval construction of estimated parameters, the missing information principle is applied to adjust information matrix estimates. We compare the adjusted information matrix based standard error estimates with the bootstrap standard error estimates both obtained using the fast MCEM algorithm through an extensive Monte Carlo study. Simulation demonstrates that the adjusted information matrix approach estimates the standard error similarly with the bootstrap methods under certain scenarios. The bootstrap percentile intervals have satisfactory coverage probabilities. We then apply the LCM analysis to a real data set of 122 subjects from a Gynecologic Oncology Group (GOG) study of significant cervical lesion (S-CL) diagnosis in women with atypical glandular cells of undetermined significance (AGC) to compare the diagnostic accuracy of a histology-based evaluation, a CA-IX biomarker-based test and a human papillomavirus (HPV) DNA test. PMID:24163493

Assessing Clinical Reasoning (ASCLIRE): Instrument Development and Validation

ERIC Educational Resources Information Center

Kunina-Habenicht, Olga; Hautz, Wolf E.; Knigge, Michel; Spies, Claudia; Ahlers, Olaf

2015-01-01

Clinical reasoning is an essential competency in medical education. This study aimed at developing and validating a test to assess diagnostic accuracy, collected information, and diagnostic decision time in clinical reasoning. A norm-referenced computer-based test for the assessment of clinical reasoning (ASCLIRE) was developed, integrating the…

Verifying Diagnostic Software

NASA Technical Reports Server (NTRS)

Lindsey, Tony; Pecheur, Charles

2004-01-01

Livingstone PathFinder (LPF) is a simulation-based computer program for verifying autonomous diagnostic software. LPF is designed especially to be applied to NASA s Livingstone computer program, which implements a qualitative-model-based algorithm that diagnoses faults in a complex automated system (e.g., an exploratory robot, spacecraft, or aircraft). LPF forms a software test bed containing a Livingstone diagnosis engine, embedded in a simulated operating environment consisting of a simulator of the system to be diagnosed by Livingstone and a driver program that issues commands and faults according to a nondeterministic scenario provided by the user. LPF runs the test bed through all executions allowed by the scenario, checking for various selectable error conditions after each step. All components of the test bed are instrumented, so that execution can be single-stepped both backward and forward. The architecture of LPF is modular and includes generic interfaces to facilitate substitution of alternative versions of its different parts. Altogether, LPF provides a flexible, extensible framework for simulation-based analysis of diagnostic software; these characteristics also render it amenable to application to diagnostic programs other than Livingstone.

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

PubMed Central

2013-01-01

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology. PMID:24090398

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.

PubMed

Canonica, Giorgio Walter; Ansotegui, Ignacio J; Pawankar, Ruby; Schmid-Grendelmeier, Peter; van Hage, Marianne; Baena-Cagnani, Carlos E; Melioli, Giovanni; Nunes, Carlos; Passalacqua, Giovanni; Rosenwasser, Lanny; Sampson, Hugh; Sastre, Joaquin; Bousquet, Jean; Zuberbier, Torsten

2013-10-03

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.

Systematic reviews of diagnostic tests in endocrinology: an audit of methods, reporting, and performance.

PubMed

Spencer-Bonilla, Gabriela; Singh Ospina, Naykky; Rodriguez-Gutierrez, Rene; Brito, Juan P; Iñiguez-Ariza, Nicole; Tamhane, Shrikant; Erwin, Patricia J; Murad, M Hassan; Montori, Victor M

2017-07-01

Systematic reviews provide clinicians and policymakers estimates of diagnostic test accuracy and their usefulness in clinical practice. We identified all available systematic reviews of diagnosis in endocrinology, summarized the diagnostic accuracy of the tests included, and assessed the credibility and clinical usefulness of the methods and reporting. We searched Ovid MEDLINE, EMBASE, and Cochrane CENTRAL from inception to December 2015 for systematic reviews and meta-analyses reporting accuracy measures of diagnostic tests in endocrinology. Experienced reviewers independently screened for eligible studies and collected data. We summarized the results, methods, and reporting of the reviews. We performed subgroup analyses to categorize diagnostic tests as most useful based on their accuracy. We identified 84 systematic reviews; half of the tests included were classified as helpful when positive, one-fourth as helpful when negative. Most authors adequately reported how studies were identified and selected and how their trustworthiness (risk of bias) was judged. Only one in three reviews, however, reported an overall judgment about trustworthiness and one in five reported using adequate meta-analytic methods. One in four reported contacting authors for further information and about half included only patients with diagnostic uncertainty. Up to half of the diagnostic endocrine tests in which the likelihood ratio was calculated or provided are likely to be helpful in practice when positive as are one-quarter when negative. Most diagnostic systematic reviews in endocrine lack methodological rigor, protection against bias, and offer limited credibility. Substantial efforts, therefore, seem necessary to improve the quality of diagnostic systematic reviews in endocrinology.

A fault injection experiment using the AIRLAB Diagnostic Emulation Facility

NASA Technical Reports Server (NTRS)

Baker, Robert; Mangum, Scott; Scheper, Charlotte

1988-01-01

The preparation for, conduct of, and results of a simulation based fault injection experiment conducted using the AIRLAB Diagnostic Emulation facilities is described. An objective of this experiment was to determine the effectiveness of the diagnostic self-test sequences used to uncover latent faults in a logic network providing the key fault tolerance features for a flight control computer. Another objective was to develop methods, tools, and techniques for conducting the experiment. More than 1600 faults were injected into a logic gate level model of the Data Communicator/Interstage (C/I). For each fault injected, diagnostic self-test sequences consisting of over 300 test vectors were supplied to the C/I model as inputs. For each test vector within a test sequence, the outputs from the C/I model were compared to the outputs of a fault free C/I. If the outputs differed, the fault was considered detectable for the given test vector. These results were then analyzed to determine the effectiveness of some test sequences. The results established coverage of selt-test diagnostics, identified areas in the C/I logic where the tests did not locate faults, and suggest fault latency reduction opportunities.

Combined evaluation of commonly used techniques, including PCR, for diagnosis of mouse fur mites.

PubMed

Karlsson, Eleanor M; Pearson, Laura M; Kuzma, Kristen M; Burkholder, Tanya H

2014-01-01

Our study evaluated and compared the false-negative rates (FNR) of a wide array of fur-mite diagnostic tests, including 2 postmortem tests (pelt exam and sticky paper) and 3 antemortem tests (adhesive tape, fur pluck, and PCR). Past publications examining fur-mite diagnostic techniques primarily used paired comparisons, evaluating tests by their level of agreement with only one other test. However, different combinations or pairs of diagnostics are used in the different studies, making the results of these comparisons difficult to interpret across all available diagnostics. In the current study, mice from a conventionally maintained colony endemic for Myobia musculi were identified as positive based on at least one positive diagnostic test. From this pool of positive animals, the FNR of all tests were quantified. The PCR assay and the pelt exam performed the best, with 0% and 2% FNR respectively, whereas tape, fur-pluck, and sticky-paper tests showed 24%, 26%, and 36% FNR, respectively. Our study shows that for mice in a colony naturally infested with Myobia musculi, PCR testing can be used for reliable antemortem detection, and pelt exam performed by experienced examiners is reliable for postmortem detection.

Use of a pLDH-based dipstick in the diagnostic and therapeutic follow-up of malaria patients in Mali

PubMed Central

2011-01-01

Background Malaria is a major public health problem in Mali and diagnosis is typically based on microscopy. Microscopy requires a well trained technician, a reliable power source, a functioning microscope and adequate supplies. The scarcity of resources of community health centres (CHC) does not allow for such a significant investment in only one aspect of malaria control. In this context, Rapid Diagnostic Tests (RDTs) may improve case management particularly in remote areas. Methods This multicentre study included 725 patients simultaneously screened with OptiMal-IT test and thick smears for malaria parasite detection. While evaluating the therapeutic efficacy of choroquine in 2 study sites, we compared the diagnostic values of thick smear microscopy to OptiMal-IT test applying the WHO 14 days follow-up scheme using samples collected from 344 patients. Results The sensitivity and the specificity of OptiMal-IT compared to thick smear was 97.2% and 95.4%, whereas the positive and negative predictive values were 96.7 and 96.1%, respectively. The percent agreement between the two diagnostic tests was 0.93. The two tests were comparable in detecting malaria at day 0, day 3 and day 14. The only difference was observed at day 7 due to high gametocytemia. Subjectively, health care providers found OptiMal-IT easier to use and store under field conditions. Conclusion OptiMal-IT test revealed similar results when compared to microscopy which is considered the gold standard for malaria diagnostics. The test was found to have a short processing time and was easier to use. These advantages may improve malaria case management by providing a diagnostic and drug efficacy follow-up tool to peripheral health centres with limited resources. PMID:22114867

Investigating the Effectiveness of Classroom Diagnostic Tools

ERIC Educational Resources Information Center

Schultz, Robert K.

2012-01-01

The primary purposes of the study are to investigate what teachers experience while using the Classroom Diagnostic Tools (CDT) and to relate those experiences to the rate of growth in students' mathematics achievement. The CDT contains three components: an online computer adaptive diagnostic test, interactive web-based student reports, and…

Examinations of electron temperature calculation methods in Thomson scattering diagnostics.

PubMed

Oh, Seungtae; Lee, Jong Ha; Wi, Hanmin

2012-10-01

Electron temperature from Thomson scattering diagnostic is derived through indirect calculation based on theoretical model. χ-square test is commonly used in the calculation, and the reliability of the calculation method highly depends on the noise level of input signals. In the simulations, noise effects of the χ-square test are examined and scale factor test is proposed as an alternative method.

INNOVATIVE TECHNOLOGY VERIFICATION REPORT "FIELD MEASUREMENT TECHNOLOGIES FOR TOTAL PETROLEUM HYDROCARBONS IN SOIL" STRATEGIC DIAGNOSTICS INC. ENSYS PETRO TEST SYSTEM

EPA Science Inventory

The EnSys Petro Test System developed by Strategic Diagnostics Inc. (SDI), was demonstrated under the U.S. Environmental Protection Agency Superfund Innovative Technology Evaluation Program in June 2000 at the Navy Base Ventura County site in Port Hueneme, California. The...

Assessing value of innovative molecular diagnostic tests in the concept of predictive, preventive, and personalized medicine.

PubMed

Akhmetov, Ildar; Bubnov, Rostyslav V

2015-01-01

Molecular diagnostic tests drive the scientific and technological uplift in the field of predictive, preventive, and personalized medicine offering invaluable clinical and socioeconomic benefits to the key stakeholders. Although the results of diagnostic tests are immensely influential, molecular diagnostic tests (MDx) are still grudgingly reimbursed by payers and amount for less than 5 % of the overall healthcare costs. This paper aims at defining the value of molecular diagnostic test and outlining the most important components of "value" from miscellaneous assessment frameworks, which go beyond accuracy and feasibility and impact the clinical adoption, informing healthcare resource allocation decisions. The authors suggest that the industry should facilitate discussions with various stakeholders throughout the entire assessment process in order to arrive at a consensus about the depth of evidence required for positive marketing authorization or reimbursement decisions. In light of the evolving "value-based healthcare" delivery practices, it is also recommended to account for social and ethical parameters of value, since these are anticipated to become as critical for reimbursement decisions and test acceptance as economic and clinical criteria.

Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

PubMed

Lim, Wei Yin; Goh, Boon Tong; Khor, Sook Mei

2017-08-15

Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (μPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. μPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. μPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Thai Grade 11 Students' Alternative Conceptions for Acid-Base Chemistry

ERIC Educational Resources Information Center

Artdej, Romklao; Ratanaroutai, Thasaneeya; Coll, Richard Kevin; Thongpanchang, Tienthong

2010-01-01

This study involved the development of a two-tier diagnostic instrument to assess Thai high school students' understanding of acid-base chemistry. The acid-base diagnostic test (ABDT) comprising 18 items was administered to 55 Grade 11 students in a science and mathematics programme during the second semester of the 2008 academic year. Analysis of…

Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer?

PubMed

Halliday, C L; Kidd, S E; Sorrell, T C; Chen, S C-A

2015-04-01

Rapid, accurate diagnostic laboratory tests are needed to improve clinical outcomes of invasive fungal disease (IFD). Traditional direct microscopy, culture and histological techniques constitute the 'gold standard' against which newer tests are judged. Molecular diagnostic methods, whether broad-range or fungal-specific, have great potential to enhance sensitivity and speed of IFD diagnosis, but have varying specificities. The use of PCR-based assays, DNA sequencing, and other molecular methods including those incorporating proteomic approaches such as matrix-assisted laser desorption ionisation-time of flight mass spectroscopy (MALDI-TOF MS) have shown promising results. These are used mainly to complement conventional methods since they require standardisation before widespread implementation can be recommended. None are incorporated into diagnostic criteria for defining IFD. Commercial assays may assist standardisation. This review provides an update of molecular-based diagnostic approaches applicable to biological specimens and fungal cultures in microbiology laboratories. We focus on the most common pathogens, Candida and Aspergillus, and the mucormycetes. The position of molecular-based approaches in the detection of azole and echinocandin antifungal resistance is also discussed.

Homogeneity tests of clustered diagnostic markers with applications to the BioCycle Study

PubMed Central

Tang, Liansheng Larry; Liu, Aiyi; Schisterman, Enrique F.; Zhou, Xiao-Hua; Liu, Catherine Chun-ling

2014-01-01

Diagnostic trials often require the use of a homogeneity test among several markers. Such a test may be necessary to determine the power both during the design phase and in the initial analysis stage. However, no formal method is available for the power and sample size calculation when the number of markers is greater than two and marker measurements are clustered in subjects. This article presents two procedures for testing the accuracy among clustered diagnostic markers. The first procedure is a test of homogeneity among continuous markers based on a global null hypothesis of the same accuracy. The result under the alternative provides the explicit distribution for the power and sample size calculation. The second procedure is a simultaneous pairwise comparison test based on weighted areas under the receiver operating characteristic curves. This test is particularly useful if a global difference among markers is found by the homogeneity test. We apply our procedures to the BioCycle Study designed to assess and compare the accuracy of hormone and oxidative stress markers in distinguishing women with ovulatory menstrual cycles from those without. PMID:22733707

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.

PubMed

Vissers, Lisenka E L M; van Nimwegen, Kirsten J M; Schieving, Jolanda H; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A; Willemsen, Michèl A A P

2017-09-01

Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously. Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017.

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

PubMed Central

Vissers, Lisenka E.L.M.; van Nimwegen, Kirsten J.M.; Schieving, Jolanda H.; Kamsteeg, Erik-Jan; Kleefstra, Tjitske; Yntema, Helger G.; Pfundt, Rolph; van der Wilt, Gert Jan; Krabbenborg, Lotte; Brunner, Han G.; van der Burg, Simone; Grutters, Janneke; Veltman, Joris A.; Willemsen, Michèl A.A.P.

2017-01-01

Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation. Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene–based testing) and WES simultaneously. Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted. Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin. Genet Med advance online publication 23 March 2017 PMID:28333917

Diagnostic value of tendon thickness and structure in the sonographic diagnosis of supraspinatus tendinopathy: room for a two-step approach.

PubMed

Arend, Carlos Frederico; Arend, Ana Amalia; da Silva, Tiago Rodrigues

2014-06-01

The aim of our study was to systematically compare different methodologies to establish an evidence-based approach based on tendon thickness and structure for sonographic diagnosis of supraspinatus tendinopathy when compared to MRI. US was obtained from 164 symptomatic patients with supraspinatus tendinopathy detected at MRI and 42 asymptomatic controls with normal MRI. Diagnostic yield was calculated for either maximal supraspinatus tendon thickness (MSTT) and tendon structure as isolated criteria and using different combinations of parallel and sequential testing at US. Chi-squared tests were performed to assess sensitivity, specificity, and accuracy of different diagnostic approaches. Mean MSTT was 6.68 mm in symptomatic patients and 5.61 mm in asymptomatic controls (P<.05). When used as an isolated criterion, MSTT>6.0mm provided best results for accuracy (93.7%) when compared to other measurements of tendon thickness. Also as an isolated criterion, abnormal tendon structure (ATS) yielded 93.2% accuracy for diagnosis. The best overall yield was obtained by both parallel and sequential testing using either MSTT>6.0mm or ATS as diagnostic criteria at no particular order, which provided 99.0% accuracy, 100% sensitivity, and 95.2% specificity. Among these parallel and sequential tests that provided best overall yield, additional analysis revealed that sequential testing first evaluating tendon structure required assessment of 258 criteria (vs. 261 for sequential testing first evaluating tendon thickness and 412 for parallel testing) and demanded a mean of 16.1s to assess diagnostic criteria and reach the diagnosis (vs. 43.3s for sequential testing first evaluating tendon thickness and 47.4s for parallel testing). We found that using either MSTT>6.0mm or ATS as diagnostic criteria for both parallel and sequential testing provides the best overall yield for sonographic diagnosis of supraspinatus tendinopathy when compared to MRI. Among these strategies, a two-step sequential approach first assessing tendon structure was advantageous because it required a lower number of criteria to be assessed and demanded less time to assess diagnostic criteria and reach the diagnosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Technological Innovations for High-Throughput Approaches to In Vitro Allergy Diagnosis.

PubMed

Chapman, Martin D; Wuenschmann, Sabina; King, Eva; Pomés, Anna

2015-07-01

Allergy diagnostics is being transformed by the advent of in vitro IgE testing using purified allergen molecules, combined with multiplex technology and biosensors, to deliver discriminating, sensitive, and high-throughput molecular diagnostics at the point of care. Essential elements of IgE molecular diagnostics are purified natural or recombinant allergens with defined purity and IgE reactivity, planar or bead-based multiplex systems to enable IgE to multiple allergens to be measured simultaneously, and, most recently, nanotechnology-based biosensors that facilitate rapid reaction rates and delivery of test results via mobile devices. Molecular diagnostics relies on measurement of IgE to purified allergens, the "active ingredients" of allergenic extracts. Typically, this involves measuring IgE to multiple allergens which is facilitated by multiplex technology and biosensors. The technology differentiates between clinically significant cross-reactive allergens (which could not be deduced by conventional IgE assays using allergenic extracts) and provides better diagnostic outcomes. Purified allergens are manufactured under good laboratory practice and validated using protein chemistry, mass spectrometry, and IgE antibody binding. Recently, multiple allergens (from dog) were expressed as a single molecule with high diagnostic efficacy. Challenges faced by molecular allergy diagnostic companies include generation of large panels of purified allergens with known diagnostic efficacy, access to flexible and robust array or sensor technology, and, importantly, access to well-defined serum panels form allergic patients for product development and validation. Innovations in IgE molecular diagnostics are rapidly being brought to market and will strengthen allergy testing at the point of care.

Diagnostic performance characteristics of a rapid field test for anthrax in cattle.

PubMed

Muller, Janine; Gwozdz, Jacek; Hodgeman, Rachel; Ainsworth, Catherine; Kluver, Patrick; Czarnecki, Jill; Warner, Simone; Fegan, Mark

2015-07-01

Although diagnosis of anthrax can be made in the field with a peripheral blood smear, and in the laboratory with bacterial culture or molecular based tests, these tests require either considerable experience or specialised equipment. Here we report on the evaluation of the diagnostic sensitivity and specificity of a simple and rapid in-field diagnostic test for anthrax, the anthrax immunochromatographic test (AICT). The AICT detects the protective antigen (PA) component of the anthrax toxin present within the blood of an animal that has died from anthrax. The test provides a result in 15min and offers the advantage of avoiding the necessity for on-site necropsy and subsequent occupational risks and environmental contamination. The specificity of the test was determined by testing samples taken from 622 animals, not infected with Bacillus anthracis. Diagnostic sensitivity was estimated on samples taken from 58 animals, naturally infected with B. anthracis collected over a 10-year period. All samples used to estimate the diagnostic sensitivity and specificity of the AICT were also tested using the gold standard of bacterial culture. The diagnostic specificity of the test was estimated to be 100% (99.4-100%; 95% CI) and the diagnostic sensitivity was estimated to be 93.1% (83.3-98.1%; 95% CI) (Clopper-Pearson method). Four samples produced false negative AICT results. These were among 9 samples, all of which tested positive for B. anthracis by culture, where there was a time delay between collection and testing of >48h and/or the samples were collected from animals that were >48h post-mortem. A statistically significant difference (P<0.001; Fishers exact test) was found between the ability of the AICT to detect PA in samples from culture positive animals <48h post-mortem, 49 of 49, Se=100% (92.8-100%; 95% CI) compared with samples tested >48h post-mortem 5 of 9 Se=56% (21-86.3%; 95% CI) (Clopper-Pearson method). Based upon these results a post hoc cut-off for use of the AICT of 48h post-mortem was applied, Se=100% (92.8-100%; 95% CI) and Sp=100% (99.4-100%; 95% CI). The high diagnostic sensitivity and specificity and the simplicity of the AICT enables it to be used for active surveillance in areas with a history of anthrax, or used as a preliminary tool in investigating sudden, unexplained death in cattle. Copyright © 2015 Elsevier B.V. All rights reserved.

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia.

PubMed

Lucas, Jane S; Barbato, Angelo; Collins, Samuel A; Goutaki, Myrofora; Behan, Laura; Caudri, Daan; Dell, Sharon; Eber, Ernst; Escudier, Estelle; Hirst, Robert A; Hogg, Claire; Jorissen, Mark; Latzin, Philipp; Legendre, Marie; Leigh, Margaret W; Midulla, Fabio; Nielsen, Kim G; Omran, Heymut; Papon, Jean-Francois; Pohunek, Petr; Redfern, Beatrice; Rigau, David; Rindlisbacher, Bernhard; Santamaria, Francesca; Shoemark, Amelia; Snijders, Deborah; Tonia, Thomy; Titieni, Andrea; Walker, Woolf T; Werner, Claudius; Bush, Andrew; Kuehni, Claudia E

2017-01-01

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia. Copyright ©ERS 2017.

Detection of Mycoplasma hyopneumoniae by polymerase chain reaction in swine presenting respiratory problems

PubMed Central

Yamaguti, M.; Muller, E.E.; Piffer, A.I.; Kich, J.D.; Klein, C.S.; Kuchiishi, S.S.

2008-01-01

Since Mycoplasma hyopneumoniae isolation in appropriate media is a difficult task and impractical for daily routine diagnostics, Nested-PCR (N-PCR) techniques are currently used to improve the direct diagnostic sensitivity of Swine Enzootic Pneumonia. In a first experiment, this paper describes a N-PCR technique optimization based on three variables: different sampling sites, sample transport media, and DNA extraction methods, using eight pigs. Based on the optimization results, a second experiment was conducted for testing validity using 40 animals. In conclusion, the obtained results of the N-PCR optimization and validation allow us to recommend this test as a routine monitoring diagnostic method for Mycoplasma hyopneumoniae infection in swine herds. PMID:24031248

Validation of caffeine dehydrogenase from Pseudomonas sp. strain CBB1 as a suitable enzyme for a rapid caffeine detection and potential diagnostic test.

PubMed

Mohanty, Sujit K; Yu, Chi Li; Gopishetty, Sridhar; Subramanian, Mani

2014-08-06

Excess consumption of caffeine (>400 mg/day/adult) can lead to adverse health effects. Recent introduction of caffeinated products (gums, jelly beans, energy drinks) might lead to excessive consumption, especially among children and nursing mothers, hence attracting the Food and Drug Administration's attention and product withdrawals. An "in-home" test will aid vigilant consumers in detecting caffeine in beverages and milk easily and quickly, thereby restricting its consumption. Known diagnostic methods lack speed and sensitivity. We report a caffeine dehydrogenase (Cdh)-based test which is highly sensitive (1-5 ppm) and detects caffeine in beverages and mother's milk in 1 min. Other components in these complex test samples do not interfere with the detection. Caffeine-dependent reduction of the dye iodonitrotetrazolium chloride results in shades of pink proportional to the levels in test samples. This test also estimates caffeine levels in pharmaceuticals, comparable to high-performance liquid chromatography. The Cdh-based test is the first with the desired attributes of a rapid and robust caffeine diagnostic kit.

A computerized handheld decision-support system to improve pulmonary embolism diagnosis: a randomized trial.

PubMed

Roy, Pierre-Marie; Durieux, Pierre; Gillaizeau, Florence; Legall, Catherine; Armand-Perroux, Aurore; Martino, Ludovic; Hachelaf, Mohamed; Dubart, Alain-Eric; Schmidt, Jeannot; Cristiano, Mirko; Chretien, Jean-Marie; Perrier, Arnaud; Meyer, Guy

2009-11-17

Testing for pulmonary embolism often differs from that recommended by evidence-based guidelines. To assess the effectiveness of a handheld clinical decision-support system to improve the diagnostic work-up of suspected pulmonary embolism among patients in the emergency department. Cluster randomized trial. Assignment was by random-number table, providers were not blinded, and outcome assessment was automated. (ClinicalTrials.gov registration number: NCT00188032). 20 emergency departments in France. 1103 and 1768 consecutive outpatients with suspected pulmonary embolism. After a preintervention period involving 20 centers and 1103 patients, in which providers grew accustomed to inputting clinical data into handheld devices and investigators assessed baseline testing, emergency departments were randomly assigned to activation of a decision-support system on the devices (10 centers, 753 patients) or posters and pocket cards that showed validated diagnostic strategies (10 centers, 1015 patients). Appropriateness of diagnostic work-up, defined as any sequence of tests that yielded a posttest probability less than 5% or greater than 85% (primary outcome) or as strict adherence to guideline recommendations (secondary outcome); number of tests per patient (secondary outcome). The proportion of patients who received appropriate diagnostic work-ups was greater during the trial than in the preintervention period in both groups, but the increase was greater in the computer-based guidelines group (adjusted mean difference in increase, 19.3 percentage points favoring computer-based guidelines [95% CI, 2.9 to 35.6 percentage points]; P = 0.023). Among patients with appropriate work-ups, those in the computer-based guidelines group received slightly fewer tests than did patients in the paper guidelines group (mean tests per patient, 1.76 [SD, 0.98] vs. 2.25 [SD, 1.04]; P < 0.001). The study was not designed to show a difference in the clinical outcomes of patients during follow-up. A handheld decision-support system improved diagnostic decision making for patients with suspected pulmonary embolism in the emergency department.

A Needs-Based Approach to the Development of a Diagnostic College English Speaking Test

ERIC Educational Resources Information Center

Zhao, Zhongbao

2014-01-01

This paper investigated the current situation of oral English teaching, learning, and assessment at the tertiary level in China through needs analysis and explored the implications for the development of a diagnostic speaking test. Through random sampling, the researcher administered both a student questionnaire and a teacher questionnaire to over…

Assessing the Success of a Discipline-Based Communication Skills Development and Enhancement Program in a Graduate Accounting Course

ERIC Educational Resources Information Center

Barratt, Catherine; Hanlon, Dean; Rankin, Michaela

2011-01-01

In this paper we present results of the impact diagnostic testing and associated context-specific workshops have on students' written communication skills in a graduate-level accounting course. We find that students who undertook diagnostic testing performed better in their first semester accounting subject. This improvement is positively…

A Diagnostic-Remediation Teaching System for Enhancing Elementary Students' Science Listening Comprehension

ERIC Educational Resources Information Center

Lin, Sheau-Wen; Liu, Yu

2017-01-01

The purpose of this study was to explore elementary students' listening comprehension changes using a Web-based teaching system that can diagnose and remediate students' science listening comprehension problems during scientific inquiry. The 3-component system consisted of a 9-item science listening comprehension test, a 37-item diagnostic test,…

Rapid clinical diagnosis of Legionnaires' disease during the "herald wave" of the swine influenza (H1N1) pandemic: the Legionnaires' disease triad.

PubMed

Cunha, Burke A; Mickail, Nardeen; Syed, Uzma; Strollo, Stephanie; Laguerre, Marianne

2010-01-01

In adults hospitalized with atypical community-acquired pneumonia (CAP), Legionnaires' disease is not uncommon. Legionnaire's disease can be differentiated from typical CAPs and from other atypical CAPs based on its characteristic pattern of extrapulmonary organ involvement. The first clinically useful diagnostic weighted point score system for the clinical diagnosis of Legionnaires' disease was developed by the Infectious Disease Division at Winthrop-University Hospital in the 1980s. It has proven to be diagnostically accurate and useful for more than two decades, but was time-consuming. Because Legionella spp. diagnostic tests are time-dependent and problematic, a need was perceived for a rapid, simple way to render a clinical, syndromic diagnosis of Legionnaires' disease pending Legionella test results. During the "herald wave" of the swine influenza (H1N1) pandemic in the New York area, our hospital, like others, was inundated with patients who presented to the Emergency Department with influenza-like illnesses (ILIs) for H1N1 testing/evaluation. Most patients with ILIs did not have swine influenza. Hospitalized patients with ILIs who tested positive with rapid influenza diagnostic tests (RIDTs) were placed on influenza precautions and treated with oseltamivir. Unfortunately, approximately 30% of adult patients admitted with an ILI had negative RIDTs. Because the definitive laboratory diagnosis of H1N1 pneumonia by reverse transcription-polymerase chain reaction(RT-PCR), testing was restricted by health departments, resulted in clinical and infection control dilemmas in determining which RIDT-negative patients did, in fact, have H1N1 pneumonia. Accordingly, a diagnostic weighted point score system was developed for H1N1 pneumonia patients, based on RT-PCR positivity by the Infectious Disease Division at Winthrop-University Hospital. This diagnostic point score system for hospitalized adults with negative RIDTs was time-consuming. As the pandemic progressed, a simplified diagnostic swine influenza (H1N1) triad was developed for the rapid clinical diagnosis of probable H1N1 pneumonia, which also differentiated it from its mimics as well as from bacterial pneumonia, eg, Legionnaires' disease. During the "herald wave" of the H1N1 pandemic, we noticed an unexplained increase in Legionnaires' disease CAPs. Because clinical resources were stressed to the maximum during the pandemic, it was critically important to rapidly identify patients rapidly with Legionnaire's disease who did not require influenza precautions or oseltamivir, but who did require anti-Legionella antimicrobial therapy. Based on the Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for Legionnaires' disease (modified), key indicators were identified and became the basis for the diagnostic Legionnaires' disease triad. The diagnostic Legionnaires' disease triad was used to make a clinical diagnosis of Legionnaires' disease until the results of Legionella diagnostic tests were reported. The diagnostic Legionnaires' disease triad diagnosed Legionnaires' disease in hospitalized adults with CAPs with extrapulmonary findings (atypical CAP) and relative bradycardia, accompanied by any three (ie, a triad) of the following: otherwise unexplained relative lymphopenia, early/mildly elevated serum transaminases (SGOT/SGPT), highly increased ferritin levels (> or =2 x n), or hypophosphatemia. The diagnostic Legionnaires' disease triad provides clinicians with a rapid way to clinically diagnose Legionnaires' disease, pending Legionella test results. The accuracy of the diagnostic Legionnaires' disease triad was confirmed in our 9 cases of Legionnaires' disease by subsequent Legionella diagnostic testing. The diagnostic Legionnaires' disease triad is particularly useful in situations where a rapid clinical syndromic diagnosis is needed, ie, during an H1N1 pandemic. Copyright 2010 Elsevier Inc. All rights reserved.

A readers' guide to the interpretation of diagnostic test properties: clinical example of sepsis.

PubMed

Fischer, Joachim E; Bachmann, Lucas M; Jaeschke, Roman

2003-07-01

One of the most challenging practical and daily problems in intensive care medicine is the interpretation of the results from diagnostic tests. In neonatology and pediatric intensive care the early diagnosis of potentially life-threatening infections is a particularly important issue. A plethora of tests have been suggested to improve diagnostic decision making in the clinical setting of infection which is a clinical example used in this article. Several criteria that are critical to evidence-based appraisal of published data are often not adhered to during the study or in reporting. To enhance the critical appraisal on articles on diagnostic tests we discuss various measures of test accuracy: sensitivity, specificity, receiver operating characteristic curves, positive and negative predictive values, likelihood ratios, pretest probability, posttest probability, and diagnostic odds ratio. We suggest the following minimal requirements for reporting on the diagnostic accuracy of tests: a plot of the raw data, multilevel likelihood ratios, the area under the receiver operating characteristic curve, and the cutoff yielding the highest discriminative ability. For critical appraisal it is mandatory to report confidence intervals for each of these measures. Moreover, to allow comparison to the readers' patient population authors should provide data on study population characteristics, in particular on the spectrum of diseases and illness severity.

Development and validation of an immunoperoxidase antigen detection test for improved diagnosis of rabies in Indonesia.

PubMed

Rahmadane, Ibnu; Certoma, Andrea F; Peck, Grantley R; Fitria, Yul; Payne, Jean; Colling, Axel; Shiell, Brian J; Beddome, Gary; Wilson, Susanne; Yu, Meng; Morrissy, Chris; Michalski, Wojtek P; Bingham, John; Gardner, Ian A; Allen, John D

2017-11-01

Rabies continues to pose a significant threat to human and animal health in regions of Indonesia. Indonesia has an extensive network of veterinary diagnostic laboratories and the 8 National laboratories are equipped to undertake diagnostic testing for rabies using the commercially-procured direct fluorescent antibody test (FAT), which is considered the reference (gold standard) test. However, many of the Indonesian Provincial diagnostic laboratories do not have a fluorescence microscope required to undertake the FAT. Instead, certain Provincial laboratories continue to screen samples using a chemical stain-based test (Seller's stain test, SST). This test has low diagnostic sensitivity, with negative SST-tested samples being forwarded to the nearest National laboratory resulting in significant delays for completion of testing and considerable additional costs. This study sought to develop a cost-effective and diagnostically-accurate immunoperoxidase antigen detection (RIAD) test for rabies that can be readily and quickly performed by the resource-constrained Provincial laboratories. This would reduce the burden on the National laboratories and allow more rapid diagnoses and implementation of post-exposure prophylaxis. The RIAD test was evaluated using brain smears fixed with acetone or formalin and its performance was validated by comparison with established rabies diagnostic tests used in Indonesia, including the SST and FAT. A proficiency testing panel was distributed between Provincial laboratories to assess the reproducibility of the test. The performance of the RIAD test was improved by using acetone fixation of brain smears rather than formalin fixation such that it was of equivalent accuracy to that of the World Organisation for Animal Health (OIE)-recommended FAT, with both tests returning median diagnostic sensitivity and specificity values of 0.989 and 0.993, respectively. The RIAD test and FAT had higher diagnostic sensitivity than the SST (median = 0.562). Proficiency testing using a panel of 6 coded samples distributed to 16 laboratories showed that the RIAD test had good reproducibility with an overall agreement of 97%. This study describes the successful development, characterisation and use of a novel RIAD test and its fitness for purpose as a screening test for use in provincial Indonesian veterinary laboratories.

Automation of diagnostic genetic testing: mutation detection by cyclic minisequencing.

PubMed

Alagrund, Katariina; Orpana, Arto K

2014-01-01

The rising role of nucleic acid testing in clinical decision making is creating a need for efficient and automated diagnostic nucleic acid test platforms. Clinical use of nucleic acid testing sets demands for shorter turnaround times (TATs), lower production costs and robust, reliable methods that can easily adopt new test panels and is able to run rare tests in random access principle. Here we present a novel home-brew laboratory automation platform for diagnostic mutation testing. This platform is based on the cyclic minisequecing (cMS) and two color near-infrared (NIR) detection. Pipetting is automated using Tecan Freedom EVO pipetting robots and all assays are performed in 384-well micro plate format. The automation platform includes a data processing system, controlling all procedures, and automated patient result reporting to the hospital information system. We have found automated cMS a reliable, inexpensive and robust method for nucleic acid testing for a wide variety of diagnostic tests. The platform is currently in clinical use for over 80 mutations or polymorphisms. Additionally to tests performed from blood samples, the system performs also epigenetic test for the methylation of the MGMT gene promoter, and companion diagnostic tests for analysis of KRAS and BRAF gene mutations from formalin fixed and paraffin embedded tumor samples. Automation of genetic test reporting is found reliable and efficient decreasing the work load of academic personnel.

Safety of falciparum malaria diagnostic strategy based on rapid diagnostic tests in returning travellers and migrants: a retrospective study

PubMed Central

2012-01-01

Background Rapid diagnostic tests for malaria (RDTs) allow accurate diagnosis and prompt treatment. Validation of their usefulness in travellers with fever was needed. The safety of a strategy to diagnose falciparum malaria based on RDT followed by immediate or delayed microscopy reading at first attendance was evaluated in one referral hospital in Switzerland. Methods A retrospective study was conducted in the outpatient clinic and emergency ward of University Hospital, covering a period of eight years (1999–2007). The study was conducted in the outpatient clinic and emergency ward of University Hospital. All adults suspected of malaria with a diagnostic test performed were included. RDT and microscopy as immediate tests were performed during working hours, and RDT as immediate test and delayed microscopy reading out of laboratory working hours. The main outcome measure was occurrence of specific complications in RDT negative and RDT positive adults. Results 2,139 patients were recruited. 1987 had both initial RDT and blood smear (BS) result negative. Among those, 2/1987 (0.1%) developed uncomplicated malaria with both RDT and BS positive on day 1 and day 6 respectively. Among the 152 patients initially malaria positive, 137 had both RDT and BS positive, four only BS positive and five only RDT positive (PCR confirmed) (six had only one test performed). None of the four initially RDT negative/BS positive and none of the five initially BS negative/RDT positive developed severe malaria while 6/137 of both RDT and BS positive did so. The use of RDT allowed a reduction of a median of 2.1 hours to get a first malaria test result. Conclusions A malaria diagnostic strategy based on RDTs and a delayed BS is safe in non-immune populations, and shortens the time to first malaria test result. PMID:23158019

Value of physical tests in diagnosing cervical radiculopathy: a systematic review.

PubMed

Thoomes, Erik J; van Geest, Sarita; van der Windt, Danielle A; Falla, Deborah; Verhagen, Arianne P; Koes, Bart W; Thoomes-de Graaf, Marloes; Kuijper, Barbara; Scholten-Peeters, Wendy G M; Vleggeert-Lankamp, Carmen L

2018-01-01

In clinical practice, the diagnosis of cervical radiculopathy is based on information from the patient's history, physical examination, and diagnostic imaging. Various physical tests may be performed, but their diagnostic accuracy is unknown. This study aimed to summarize and update the evidence on diagnostic performance of tests carried out during a physical examination for the diagnosis of cervical radiculopathy. A review of the accuracy of diagnostic tests was carried out. The study sample comprised diagnostic studies comparing results of tests performed during a physical examination in diagnosing cervical radiculopathy with a reference standard of imaging or surgical findings. Sensitivity, specificity, likelihood ratios are presented, together with pooled results for sensitivity and specificity. A literature search up to March 2016 was performed in CENTRAL, PubMed (MEDLINE), Embase, CINAHL, Web of Science, and Google Scholar. The methodological quality of studies was assessed using the QUADAS-2. Five diagnostic accuracy studies were identified. Only Spurling's test was evaluated in more than one study, showing high specificity ranging from 0.89 to 1.00 (95% confidence interval [CI]: 0.59-1.00); sensitivity varied from 0.38 to 0.97 (95% CI: 0.21-0.99). No studies were found that assessed the diagnostic accuracy of widely used neurological tests such as key muscle strength, tendon reflexes, and sensory impairments. There is limited evidence for accuracy of physical examination tests for the diagnosis of cervical radiculopathy. When consistent with patient history, clinicians may use a combination of Spurling's, axial traction, and an Arm Squeeze test to increase the likelihood of a cervical radiculopathy, whereas a combined results of four negative neurodynamics tests and an Arm Squeeze test could be used to rule out the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Expanding syphilis testing: a scoping review of syphilis testing interventions among key populations.

PubMed

Ong, Jason J; Fu, Hongyun; Smith, M Kumi; Tucker, Joseph D

2018-05-01

Syphilis is an important sexually transmitted infection (STI). Despite inexpensive and effective treatment, few key populations receive syphilis testing. Innovative strategies are needed to increase syphilis testing among key populations. Areas covered: This scoping review focused on strategies to increase syphilis testing in key populations (men who have sex with men (MSM), sex workers, people who use drugs, transgender people, and incarcerated individuals). Expert commentary: We identified many promising syphilis testing strategies, particularly among MSM. These innovations are separated into diagnostic, clinic-based, and non-clinic based strategies. In terms of diagnostics, self-testing, dried blood spots, and point-of-care testing can decentralize syphilis testing. Effective syphilis self-testing pilots suggest the need for further attention and research. In terms of clinic-based strategies, modifying default clinical procedures can nudge physicians to more frequently recommend syphilis testing. In terms of non-clinic based strategies, venue-based screening (e.g. in correctional facilities, drug rehabilitation centres) and mobile testing units have been successfully implemented in a variety of settings. Integration of syphilis with HIV testing may facilitate implementation in settings where individuals have increased sexual risk. There is a strong need for further syphilis testing research and programs.

Diagnosing pulmonary embolisms: the clinician's point of view.

PubMed

Carrillo Alcaraz, A; Martínez, A López; Solano, F J Sotos

Pulmonary thromboembolism is common and potentially severe. To ensure the correct approach to the diagnostic workup of pulmonary thromboembolism, it is essential to know the basic concepts governing the use of the different tests available. The diagnostic approach to pulmonary thromboembolism is an example of the application of the conditional probabilities of Bayes' theorem in daily practice. To interpret the available diagnostic tests correctly, it is necessary to analyze different concepts that are fundamental for decision making. Thus, it is necessary to know what the likelihood ratios, 95% confidence intervals, and decision thresholds mean. Whether to determine the D-dimer concentration or to do CT angiography or other imaging tests depends on their capacity to modify the pretest probability of having the disease to a posttest probability that is higher or lower than the thresholds for action. This review aims to clarify the diagnostic sequence of thromboembolic pulmonary disease, analyzing the main diagnostic tools (clinical examination, laboratory tests, and imaging tests), placing special emphasis on the principles that govern evidence-based medicine. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Power calculation for comparing diagnostic accuracies in a multi-reader, multi-test design.

PubMed

Kim, Eunhee; Zhang, Zheng; Wang, Youdan; Zeng, Donglin

2014-12-01

Receiver operating characteristic (ROC) analysis is widely used to evaluate the performance of diagnostic tests with continuous or ordinal responses. A popular study design for assessing the accuracy of diagnostic tests involves multiple readers interpreting multiple diagnostic test results, called the multi-reader, multi-test design. Although several different approaches to analyzing data from this design exist, few methods have discussed the sample size and power issues. In this article, we develop a power formula to compare the correlated areas under the ROC curves (AUC) in a multi-reader, multi-test design. We present a nonparametric approach to estimate and compare the correlated AUCs by extending DeLong et al.'s (1988, Biometrics 44, 837-845) approach. A power formula is derived based on the asymptotic distribution of the nonparametric AUCs. Simulation studies are conducted to demonstrate the performance of the proposed power formula and an example is provided to illustrate the proposed procedure. © 2014, The International Biometric Society.

Costs of novel tuberculosis diagnostics--will countries be able to afford it?

PubMed

Pantoja, Andrea; Kik, Sandra V; Denkinger, Claudia M

2015-04-01

Four priority target product profiles for the development of diagnostic tests for tuberculosis were identified: 1) Rapid sputum-based (RSP), 2) non-sputum Biomarker-based (BMT), 3) triage test followed by confirmatory test (TT), and 4) drug-susceptibility testing (DST). We assessed the cost of the new tests in suitable strategies and of the conventional diagnosis of tuberculosis as per World Health Organization guidelines, in 36 high tuberculosis and MDR burden countries. Costs were then compared to the available funding for tuberculosis at country level. Costs of diagnosing tuberculosis using RSP ranged US$93-187 million/year; if RSP unit cost is of US$2-4 it would be lower/similar cost than conventional strategy with sputum smear microscopy (US$ 119 million/year). Using BMT (with unit cost of US$2-4) would cost US$70-121 million/year and be lower/comparable cost than conventional diagnostics. Using TT with TPP characteristics (unit cost of US$1-2) followed by Xpert would reduce diagnostic costs up to US$36 million/year. Costs of using different novel DST strategies for the diagnosis of drug resistance would be higher compared with conventional diagnosis. Introducing a TT or a biomarker test with optimal characteristics would be affordable from a cost and affordability perspective at the current available funding for tuberculosis. Additional domestic or donor funding would be needed in most countries to achieve affordability for other new diagnostic tests. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Diagnostics of Polymer Composite Materials and Analysis of Their Production Technology by Using the Method of Acoustic Emission

NASA Astrophysics Data System (ADS)

Bashkov, O. V.; Protsenko, A. E.; Bryanskii, A. A.; Romashko, R. V.

2017-09-01

The strength properties of glass-fiber-reinforced plastics produced by vacuum and vacuum autoclave molding techniques are studied. Based on acoustic emission data, a method of diagnostic and prediction of the bearing capacity of polymer composite materials by using data from three-point bending tests is developed. The method is based on evaluating changes in the exponent of a power function relating the total acoustic emission to the test stress.

Precision medicine for cancer with next-generation functional diagnostics.

PubMed

Friedman, Adam A; Letai, Anthony; Fisher, David E; Flaherty, Keith T

2015-12-01

Precision medicine is about matching the right drugs to the right patients. Although this approach is technology agnostic, in cancer there is a tendency to make precision medicine synonymous with genomics. However, genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer genotype. This limitation can be addressed by functional testing of live patient tumour cells exposed to potential therapies. Recently, several 'next-generation' functional diagnostic technologies have been reported, including novel methods for tumour manipulation, molecularly precise assays of tumour responses and device-based in situ approaches; these address the limitations of the older generation of chemosensitivity tests. The promise of these new technologies suggests a future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients.

Costs and clinical outcomes for non-invasive versus invasive diagnostic approaches to patients with suspected in-stent restenosis.

PubMed

Min, James K; Hasegawa, James T; Machacz, Susanne F; O'Day, Ken

2016-02-01

This study compared costs and clinical outcomes of invasive versus non-invasive diagnostic evaluations for patients with suspected in-stent restenosis (ISR) after percutaneous coronary intervention. We developed a decision model to compare 2 year diagnosis-related costs for patients who presented with suspected ISR and were evaluated by: (1) invasive coronary angiography (ICA); (2) non-invasive stress testing strategy of myocardial perfusion imaging (MPI) with referral to ICA based on MPI; (3) coronary CT angiography-based testing strategy with referral to ICA based on CCTA. Costs were modeled from the payer's perspective using 2014 Medicare rates. 56 % of patients underwent follow-up diagnostic testing over 2 years. Compared to ICA, MPI (98.6 %) and CCTA (98.1 %) exhibited lower rates of correct diagnoses. Non-invasive strategies were associated with reduced referrals to ICA and costs compared to an ICA-based strategy, with diagnostic costs lower for CCTA than MPI. Overall 2-year costs were highest for ICA for both metallic as well as BVS stents ($1656 and $1656, respectively) when compared to MPI ($1444 and $1411) and CCTA. CCTA costs differed based upon stent size and type, and were highest for metallic stents >3.0 mm followed by metallic stents <3.0 mm, BVS < 3.0 mm and BVS > 3.0 mm ($1466 vs. $1242 vs. $855 vs. $490, respectively). MPI for suspected ISR results in lower costs and rates of complications than invasive strategies using ICA while maintaining high diagnostic performance. Depending upon stent size and type, CCTA results in lower costs than MPI.

Exploring "DIALANG'S" Diagnostic Feedback in Online L2 Dynamic Assessment

ERIC Educational Resources Information Center

Ebadi, Saman

2016-01-01

Dynamic assessment (DA) as an alternative to psychometric-based testing focuses on the collaborative dialogue between the learners and the mediator to move the learners from their current capabilities. This study represents a web-based qualitative inquiry in online DA which aims at addressing the inadequacy of the diagnostic feedback of the…

Engineering Paper-Based Sensors for Zika Virus

DOE PAGES

Meagher, Robert J.; Negrete, Oscar A.; Van Rompay, Koen K.

2016-05-30

The emergence of Zika virus in Latin America has created an urgent need for new, simple yet sensitive diagnostic tests. We highlight recent work using paper-based sensors coupled with CRISPR/Cas9 to detect Zika RNA, as a new approach to rapid development and deployment of field-ready diagnostics for emerging infectious diseases.

Engineering Paper-Based Sensors for Zika Virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meagher, Robert J.; Negrete, Oscar A.; Van Rompay, Koen K.

The emergence of Zika virus in Latin America has created an urgent need for new, simple yet sensitive diagnostic tests. We highlight recent work using paper-based sensors coupled with CRISPR/Cas9 to detect Zika RNA, as a new approach to rapid development and deployment of field-ready diagnostics for emerging infectious diseases.

A tri-fold hybrid classification approach for diagnostics with unexampled faulty states

NASA Astrophysics Data System (ADS)

Tamilselvan, Prasanna; Wang, Pingfeng

2015-01-01

System health diagnostics provides diversified benefits such as improved safety, improved reliability and reduced costs for the operation and maintenance of engineered systems. Successful health diagnostics requires the knowledge of system failures. However, with an increasing system complexity, it is extraordinarily difficult to have a well-tested system so that all potential faulty states can be realized and studied at product testing stage. Thus, real time health diagnostics requires automatic detection of unexampled system faulty states based upon sensory data to avoid sudden catastrophic system failures. This paper presents a trifold hybrid classification (THC) approach for structural health diagnosis with unexampled health states (UHS), which comprises of preliminary UHS identification using a new thresholded Mahalanobis distance (TMD) classifier, UHS diagnostics using a two-class support vector machine (SVM) classifier, and exampled health states diagnostics using a multi-class SVM classifier. The proposed THC approach, which takes the advantages of both TMD and SVM-based classification techniques, is able to identify and isolate the unexampled faulty states through interactively detecting the deviation of sensory data from the exampled health states and forming new ones autonomously. The proposed THC approach is further extended to a generic framework for health diagnostics problems with unexampled faulty states and demonstrated with health diagnostics case studies for power transformers and rolling bearings.

Molecular Diagnostics in Transfusion Medicine: In Capillary, on a Chip, in Silico, or in Flight?

PubMed Central

Garritsen, Henk S.P.; Xiu-Cheng Fan, Alex; Lenz, Daniela; Hannig, Horst; Yan Zhong, Xiao; Geffers, Robert; Lindenmaier, Werner; Dittmar, Kurt E.J.; Wörmann, Bernhard

2009-01-01

Summary Serology, defined as antibody-based diagnostics, has been regarded as the diagnostic gold standard in transfusion medicine. Nowadays however the impact of molecular diagnostics in transfusion medicine is rapidly growing. Molecular diagnostics can improve tissue typing (HLA typing), increase safety of blood products (NAT testing of infectious diseases), and enable blood group typing in difficult situations (after transfusion of blood products or prenatal non-invasive RhD typing). Most of the molecular testing involves the determination of the presence of single nucleotide polymorphisms (SNPs). Antigens (e.g. blood group antigens) mostly result from single nucleotide differences in critical positions. However, most blood group systems cannot be determined by looking at a single SNP. To identify members of a blood group system a number of critical SNPs have to be taken into account. The platforms which are currently used to perform molecular diagnostics are mostly gel-based, requiring time-consuming multiple manual steps. To implement molecular methods in transfusion medicine in the future the development of higher-throughput SNP genotyping non-gel-based platforms which allow a rapid, cost-effective screening are essential. Because of its potential for automation, high throughput and cost effectiveness the special focus of this paper is a relative new technique: SNP genotyping by MALDI-TOF MS analysis. PMID:21113259

A Self-Diagnostic System for the M6 Accelerometer

NASA Technical Reports Server (NTRS)

Flanagan, Patrick M.; Lekki, John

2001-01-01

The design of a Self-Diagnostic (SD) accelerometer system for the Space Shuttle Main Engine is presented. This retrofit system connects diagnostic electronic hardware and software to the current M6 accelerometer system. This paper discusses the general operation of the M6 accelerometer SD system and procedures for developing and evaluating the SD system. Signal processing techniques using M6 accelerometer diagnostic data are explained. Test results include diagnostic data responding to changing ambient temperature, mounting torque and base mounting impedance.

Microfluidic technology for molecular diagnostics.

PubMed

Robinson, Tom; Dittrich, Petra S

2013-01-01

Molecular diagnostics have helped to improve the lives of millions of patients worldwide by allowing clinicians to diagnose patients earlier as well as providing better ongoing therapies. Point-of-care (POC) testing can bring these laboratory-based techniques to the patient in a home setting or to remote settings in the developing world. However, despite substantial progress in the field, there still remain many challenges. Progress in molecular diagnostics has benefitted greatly from microfluidic technology. This chapter aims to summarise the more recent advances in microfluidic-based molecular diagnostics. Sections include an introduction to microfluidic technology, the challenges of molecular diagnostics, how microfluidic advances are working to solve these issues, some alternative design approaches, and detection within these systems.

Adoption of Rapid Diagnostic Tests for the Diagnosis of Malaria, a Preliminary Analysis of the Global Fund Program Data, 2005 to 2010

PubMed Central

Zhao, Jinkou; Lama, Marcel; Korenromp, Eline; Aylward, Patrick; Shargie, Estifanos; Filler, Scott; Komatsu, Ryuichi; Atun, Rifat

2012-01-01

Introduction The World Health Organization Guidelines for the Treatment of Malaria, in 2006 and 2010, recommend parasitological confirmation of malaria before commencing treatment. Although microscopy has been the mainstay of malaria diagnostics, the magnitude of diagnostic scale up required to follow the Guidelines suggests that rapid diagnostic tests (RDTs) will be a large component. This study analyzes the adoption of rapid diagnostic testing in malaria programs supported by the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund), the leading international funder of malaria control globally. Methods and Findings We analyzed, for the period 2005 to 2010, Global Fund programmatic data for 81 countries on the quantity of RDTs planned; actual quantities of RDTs and artemisinin-based combination treatments (ACTs) procured in 2009 and 2010; RDT-related activities including RDTs distributed, RDTs used, total diagnostic tests including RDTs and microscopy performed, health facilities equipped with RDTs; personnel trained to perform rapid diagnostic malaria test; and grant budgets allocated to malaria diagnosis. In 2010, diagnosis accounted for 5.2% of malaria grant budget. From 2005 to 2010, the procurement plans include148 million RDTs through 96 malaria grants in 81 countries. Around 115 million parasitological tests, including RDTs, had reportedly been performed from 2005 to 2010. Over this period, 123,132 health facilities were equipped with RDTs and 137,140 health personnel had been trained to perform RDT examinations. In 2009 and 2010, 41 million RDTs and 136 million ACTs were purchased. The ratio of procured RDTs to ACTs was 0.26 in 2009 and 0.34 in 2010. Conclusions/significance Global Fund financing has enabled 81 malaria-endemic countries to adopt WHO guidelines by investing in RDTs for malaria diagnosis, thereby helping improve case management of acute febrile illness in children. However, roll-out of parasitological diagnosis lags behind the roll-out of ACT-based treatment, and will require prioritization of investments. PMID:22952703

Multiplex PCR Tests for Detection of Pathogens Associated with Gastroenteritis

PubMed Central

Zhang, Hongwei; Morrison, Scott; Tang, Yi-Wei

2016-01-01

Synopsis A wide range of enteric pathogens can cause infectious gastroenteritis. Conventional diagnostic algorithms including culture, biochemical identification, immunoassay and microscopic examination are time consuming and often lack sensitivity and specificity. Advances in molecular technology have as allowed its use as clinical diagnostic tools. Multiplex PCR based testing has made its way to gastroenterology diagnostic arena in recent years. In this article we present a review of recent laboratory developed multiplex PCR tests and current commercial multiplex gastrointestinal pathogen tests. We will focus on two FDA cleared commercial syndromic multiplex tests: Luminex xTAG GPP and Biofire FimArray GI test. These multiplex tests can detect and identify multiple enteric pathogens in one test and provide results within hours. Multiplex PCR tests have shown superior sensitivity to conventional methods for detection of most pathogens. The high negative predictive value of these multiplex tests has led to the suggestion that they be used as screening tools especially in outbreaks. Although the clinical utility and benefit of multiplex PCR test are to be further investigated, implementing these multiplex PCR tests in gastroenterology diagnostic algorithm has the potential to improve diagnosis of infectious gastroenteritis. PMID:26004652

A specialized isotope mass spectrometer for noninvasive diagnostics of Helicobacter pylori infection in human beings

NASA Astrophysics Data System (ADS)

Blashenkov, N. M.; Sheshenya, E. S.; Solov'ev, S. M.; Sachenko, V. D.; Gall, L. N.; Zarutskii, I. V.; Gall, N. R.

2013-05-01

A specialized isotope mass spectrometer for noninvasive diagnostics of Helicobacter pylori infection in human beings based on the carbon-13 isotope breath test has been designed and constructed. Important stages of the work included (i) calculating a low-aberration mass analyzer, (ii) manufacturing and testing special gas inlet system, and (iii) creating a small-size collector of ions. The proposed instrument ensures 13C/12C isotopic ratio measurement to within 1.7‰ (pro mille) accuracy, which corresponds to requirements for a diagnostic tool. Preliminary medical testing showed that the mass spectrometer is applicable to practical diagnostics. The instrument is also capable of measuring isotopic ratios of other light elements, including N, O, B (for BF2+ ions), Ar, Cl, and S.

Optimal Combinations of Diagnostic Tests Based on AUC.

PubMed

Huang, Xin; Qin, Gengsheng; Fang, Yixin

2011-06-01

When several diagnostic tests are available, one can combine them to achieve better diagnostic accuracy. This article considers the optimal linear combination that maximizes the area under the receiver operating characteristic curve (AUC); the estimates of the combination's coefficients can be obtained via a nonparametric procedure. However, for estimating the AUC associated with the estimated coefficients, the apparent estimation by re-substitution is too optimistic. To adjust for the upward bias, several methods are proposed. Among them the cross-validation approach is especially advocated, and an approximated cross-validation is developed to reduce the computational cost. Furthermore, these proposed methods can be applied for variable selection to select important diagnostic tests. The proposed methods are examined through simulation studies and applications to three real examples. © 2010, The International Biometric Society.

Diffusion of Molecular Diagnostic Lung Cancer Tests: A Survey of German Oncologists

PubMed Central

Steffen, Julius Alexander

2014-01-01

This study was aimed at examining the diffusion of diagnostic lung cancer tests in Germany. It was motivated by the high potential of detecting and targeting oncogenic drivers. Recognizing that the diffusion of diagnostic tests is a conditio sine qua non for the success of personalized lung cancer therapies, this study analyzed the diffusion of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tests in Germany. Qualitative and quantitative research strategies were combined in a mixed-method design. A literature review and subsequent Key Opinion Leader interviews identified a set of qualitative factors driving the diffusion process, which were then translated into an online survey. The survey was conducted among a sample of 961 oncologists (11.34% response rate). The responses were analyzed in a multiple linear regression which identified six statistically significant factors driving the diffusion of molecular diagnostic lung cancer tests: reimbursement, attitude towards R&D, information self-assessment, perceived attitudes of colleagues, age and test-pathway strategies. Besides the important role of adequate reimbursement and relevant guidelines, the results of this study suggest that an increasing usage of test-pathway strategies, especially in an office-based setting, can increase the diffusion of molecular diagnostic lung cancer tests in the future. PMID:25562146

Paper-based sample-to-answer molecular diagnostic platform for point-of-care diagnostics.

PubMed

Choi, Jane Ru; Tang, Ruihua; Wang, ShuQi; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

2015-12-15

Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

Evidence-Based Toxicology.

PubMed

Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century.

A practical, evidence-based, comprehensive (PEC) physical examination for diagnosing pathology of the long head of the biceps.

PubMed

Rosas, Samuel; Krill, Michael K; Amoo-Achampong, Kelms; Kwon, KiHyun; Nwachukwu, Benedict U; McCormick, Frank

2017-08-01

Clinical examination of the shoulder joint has gained attention as clinicians aim to use an evidence-based examination of the biceps tendon, with the desire for a proper diagnosis while minimizing costly imaging procedures. The purpose of this study is to create a decision tree analysis that enables the development of a clinical algorithm for diagnosing long head of biceps (LHB) pathology. A literature review of Level I and II diagnostic studies was conducted to extract characteristics of clinical tests for LHB pathology through a systematic review of PubMed, Medline, Ovid, and Cochrane Review databases. Tests were combined in series and parallel to determine sensitivities and specificities, and positive and negative likelihood ratios were determined for each combination using a subjective pretest probability. The "gold standard" for diagnosis in all included studies was arthroscopy or arthrotomy. The optimal testing modality was use of the uppercut test combined with the tenderness to palpation of the biceps tendon test. This combination achieved a sensitivity of 88.4% when performed in parallel and a specificity of 93.8% when performed in series. These tests used in combination optimize post-test probability accuracy greater than any single individual test. Performing the uppercut test and biceps groove tenderness to palpation test together has the highest sensitivity and specificity of known physical examinations maneuvers to aid in the diagnosis of LHB pathology compared with diagnostic arthroscopy (practical, evidence-based, comprehensive examination). A decision tree analysis aides in the practical, evidence-based, comprehensive examination diagnostic accuracy post-testing based on the ordinal scale pretest probability. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Intelligent Diagnostic Assistant for Complicated Skin Diseases through C5's Algorithm.

PubMed

Jeddi, Fatemeh Rangraz; Arabfard, Masoud; Kermany, Zahra Arab

2017-09-01

Intelligent Diagnostic Assistant can be used for complicated diagnosis of skin diseases, which are among the most common causes of disability. The aim of this study was to design and implement a computerized intelligent diagnostic assistant for complicated skin diseases through C5's Algorithm. An applied-developmental study was done in 2015. Knowledge base was developed based on interviews with dermatologists through questionnaires and checklists. Knowledge representation was obtained from the train data in the database using Excel Microsoft Office. Clementine Software and C5's Algorithms were applied to draw the decision tree. Analysis of test accuracy was performed based on rules extracted using inference chains. The rules extracted from the decision tree were entered into the CLIPS programming environment and the intelligent diagnostic assistant was designed then. The rules were defined using forward chaining inference technique and were entered into Clips programming environment as RULE. The accuracy and error rates obtained in the training phase from the decision tree were 99.56% and 0.44%, respectively. The accuracy of the decision tree was 98% and the error was 2% in the test phase. Intelligent diagnostic assistant can be used as a reliable system with high accuracy, sensitivity, specificity, and agreement.

Propulsion IVHM Technology Experiment

NASA Technical Reports Server (NTRS)

Chicatelli, Amy K.; Maul, William A.; Fulton, Christopher E.

2006-01-01

The Propulsion IVHM Technology Experiment (PITEX) successfully demonstrated real-time fault detection and isolation of a virtual reusable launch vehicle (RLV) main propulsion system (MPS). Specifically, the PITEX research project developed and applied a model-based diagnostic system for the MPS of the X-34 RLV, a space-launch technology demonstrator. The demonstration was simulation-based using detailed models of the propulsion subsystem to generate nominal and failure scenarios during captive carry, which is the most safety-critical portion of the X-34 flight. Since no system-level testing of the X-34 Main Propulsion System (MPS) was performed, these simulated data were used to verify and validate the software system. Advanced diagnostic and signal processing algorithms were developed and tested in real time on flight-like hardware. In an attempt to expose potential performance problems, the PITEX diagnostic system was subjected to numerous realistic effects in the simulated data including noise, sensor resolution, command/valve talkback information, and nominal build variations. In all cases, the PITEX system performed as required. The research demonstrated potential benefits of model-based diagnostics, defined performance metrics required to evaluate the diagnostic system, and studied the impact of real-world challenges encountered when monitoring propulsion subsystems.

Drug-device trials for infectious diseases: CDRH perspective.

PubMed

Meier, Kristen L; Gitterman, Steven

2011-05-01

Assessing the performance of new diagnostic tests for infectious diseases has traditionally focused on comparing the new assay against a reference standard such as culture. In this paper, we suggest that clinical trial designs with both a diagnostic and therapeutic component may be necessary to evaluate the safety and effectiveness of nonmicrobiologically based assays, with a specific emphasis on the test/marker-stratified design. General design challenges for trials of infectious diseases that simultaneously study both diagnostic and therapeutic components (eg, both devices and drugs) are also discussed.

Malaria rapid diagnostic tests in elimination settings—can they find the last parasite?

PubMed Central

McMorrow, M. L.; Aidoo, M.; Kachur, S. P.

2016-01-01

Rapid diagnostic tests (RDTs) for malaria have improved the availability of parasite-based diagnosis throughout the malaria-endemic world. Accurate malaria diagnosis is essential for malaria case management, surveillance, and elimination. RDTs are inexpensive, simple to perform, and provide results in 15–20 min. Despite high sensitivity and specificity for Plasmodium falciparum infections, RDTs have several limitations that may reduce their utility in low-transmission settings: they do not reliably detect low-density parasitaemia (≤200 parasites/μL), many are less sensitive for Plasmodium vivax infections, and their ability to detect Plasmodium ovale and Plasmodium malariae is unknown. Therefore, in elimination settings, alternative tools with higher sensitivity for low-density infections (e.g. nucleic acid-based tests) are required to complement field diagnostics, and new highly sensitive and specific field-appropriate tests must be developed to ensure accurate diagnosis of symptomatic and asymptomatic carriers. As malaria transmission declines, the proportion of low-density infections among symptomatic and asymptomatic persons is likely to increase, which may limit the utility of RDTs. Monitoring malaria in elimination settings will probably depend on the use of more than one diagnostic tool in clinical-care and surveillance activities, and the combination of tools utilized will need to be informed by regular monitoring of test performance through effective quality assurance. PMID:21910780

Developing a new intelligent system for the diagnosis of tuberculous pleural effusion.

PubMed

Li, Chengye; Hou, Lingxian; Sharma, Bishundat Yanesh; Li, Huaizhong; Chen, ChengShui; Li, Yuping; Zhao, Xuehua; Huang, Hui; Cai, Zhennao; Chen, Huiling

2018-01-01

In countries with high prevalence of tuberculosis (TB), clinicians often diagnose tuberculous pleural effusion (TPE) by using diagnostic tests, which have not only poor sensitivity, but poor availability as well. The aim of our study is to develop a new artificial intelligence based diagnostic model that is accurate, fast, non-invasive and cost effective to diagnose TPE. It is expected that a tool derived based on the model be installed on simple computer devices (such as smart phones and tablets) and be used by clinicians widely. For this study, data of 140 patients whose clinical signs, routine blood test results, blood biochemistry markers, pleural fluid cell type and count, and pleural fluid biochemical tests' results were prospectively collected into a database. An Artificial intelligence based diagnostic model, which employs moth flame optimization based support vector machine with feature selection (FS-MFO-SVM), is constructed to predict the diagnosis of TPE. The optimal model results in an average of 95% accuracy (ACC), 0.9564 the area under the receiver operating characteristic curve (AUC), 93.35% sensitivity, and 97.57% specificity for FS-MFO-SVM. The proposed artificial intelligence based diagnostic model is found to be highly reliable for diagnosing TPE based on simple clinical signs, blood samples and pleural effusion samples. Therefore, the proposed model can be widely used in clinical practice and further evaluated for use as a substitute of invasive pleural biopsies. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards improving diagnosis of memory loss in general practice: TIMeLi diagnostic test accuracy study protocol.

PubMed

Creavin, Sam T; Cullum, Sarah J; Haworth, Judy; Wye, Lesley; Bayer, Antony; Fish, Mark; Purdy, Sarah; Ben-Shlomo, Yoav

2016-07-19

People with cognitive problems, and their families, report distress and uncertainty whilst undergoing evaluation for dementia and perceive that traditional diagnostic evaluation in secondary care is insufficiently patient centred. The James Lind Alliance has prioritised research to investigate the role of primary care in supporting a more effective diagnostic pathway, and the topic is also of interest to health commissioners. However, there are very few studies that investigate the accuracy of diagnostic tests for dementia in primary care. We will conduct a prospective diagnostic test accuracy study to evaluate the accuracy of a range of simple tests for diagnosing all-cause-dementia in symptomatic people aged over 70 years who have consulted with their general practitioner (GP). We will invite eligible people to attend a research clinic where they will undergo a range of index tests that a GP could perform in the surgery and also be assessed by a specialist in memory disorders at the same appointment. Participating GPs will request neuroimaging and blood tests and otherwise manage patients in line with their usual clinical practice. The reference standard will be the consensus judgement of three experts (neurologist, psychiatrist and geriatrician) based on information from the specialist assessment, GP records and investigations, but not including items in the index test battery. The target condition will be all-cause dementia but we will also investigate diagnostic accuracy for sub-types where possible. We will use qualitative interviews with patients and focus groups with clinicians to help us understand the acceptability and feasibility of diagnosing dementia in primary care using the tests that we are investigating. Our results will help clinicians decide on which tests to perform in someone where there is concern about possible dementia and inform commissioning of diagnostic pathways.

Automatic brain caudate nuclei segmentation and classification in diagnostic of Attention-Deficit/Hyperactivity Disorder.

PubMed

Igual, Laura; Soliva, Joan Carles; Escalera, Sergio; Gimeno, Roger; Vilarroya, Oscar; Radeva, Petia

2012-12-01

We present a fully automatic diagnostic imaging test for Attention-Deficit/Hyperactivity Disorder diagnosis assistance based on previously found evidences of caudate nucleus volumetric abnormalities. The proposed method consists of different steps: a new automatic method for external and internal segmentation of caudate based on Machine Learning methodologies; the definition of a set of new volume relation features, 3D Dissociated Dipoles, used for caudate representation and classification. We separately validate the contributions using real data from a pediatric population and show precise internal caudate segmentation and discrimination power of the diagnostic test, showing significant performance improvements in comparison to other state-of-the-art methods. Copyright © 2012 Elsevier Ltd. All rights reserved.

A review of current and future molecular diagnostic tests for use in the microbiology laboratory.

PubMed

Jannes, Geert; De Vos, Daniel

2006-01-01

Nucleic acid-based diagnostics gradually are replacing or complementing culture-based, biochemical, and immunological assays in routine microbiology laboratories. Similar to conventional tests, the first-generation deoxyribonucleic acid assays determined only a single analyte. Recent improvements in detection technologies have paved the way for the development of multiparameter assays using macroarrays or micro-arrays, while the introduction of closed-tube real-time polymerase chain reaction systems has resulted in the development of rapid microbial diagnostics with a reduced contamination risk. The use of these new molecular technologies is not restricted to detection and identification of microbial pathogens but also can be used for genotyping, allowing one to determine antibiotic resistance or to perform microbial fingerprinting.

Appropriate use of screening and diagnostic tests to foster high-value, cost-conscious care.

PubMed

Qaseem, Amir; Alguire, Patrick; Dallas, Paul; Feinberg, Lawrence E; Fitzgerald, Faith T; Horwitch, Carrie; Humphrey, Linda; LeBlond, Richard; Moyer, Darilyn; Wiese, Jeffrey G; Weinberger, Steven

2012-01-17

Unsustainable rising health care costs in the United States have made reducing costs while maintaining high-quality health care a national priority. The overuse of some screening and diagnostic tests is an important component of unnecessary health care costs. More judicious use of such tests will improve quality and reflect responsible awareness of costs. Efforts to control expenditures should focus not only on benefits, harms, and costs but on the value of diagnostic tests-meaning an assessment of whether a test provides health benefits that are worth its costs or harms. To begin to identify ways that practicing clinicians can contribute to the delivery of high-value, cost-conscious health care, the American College of Physicians convened a workgroup of physicians to identify, using a consensus-based process, common clinical situations in which screening and diagnostic tests are used in ways that do not reflect high-value care. The intent of this exercise is to promote thoughtful discussions about these tests and other health care interventions to promote high-value, cost-conscious care.

Diagnostic Approach to Acute Diarrheal Illness in a Military Population on Training Exercises in Thailand, a Region of Campylobacter Hyperendemicity▿

PubMed Central

Tribble, David R.; Baqar, Shahida; Pang, Lorrin W.; Mason, Carl; Houng, Huo-Shu H.; Pitarangsi, Chittima; Lebron, Carlos; Armstrong, Adam; Sethabutr, Orntipa; Sanders, John W.

2008-01-01

High rates of Campylobacter fluoroquinolone resistance highlight the need to evaluate diagnostic strategies that can be used to assist with clinical management. Diagnostic tests were evaluated with U.S. soldiers presenting with acute diarrhea during deployment in Thailand. The results of bedside and field laboratory diagnostic tests were compared to stool microbiology findings for 182 enrolled patients. Campylobacter jejuni was isolated from 62% of the cases. Clinical and laboratory findings at the time of presentation were evaluated to determine their impact on the posttest probability, defined as the likelihood of a diagnosis of Campylobacter infection. Clinical findings, the results of tests for inflammation (stool occult blood testing [Hemoccult], fecal leukocytes, fecal lactoferrin, plasma C-reactive protein), and the numbers of Campylobacter-specific antibody-secreting cells in peripheral blood failed to increase the posttest probability above 90% in this setting of Campylobacter hyperendemicity when these findings were present. Positive results by a Campylobacter-specific commercial enzyme immunoassay (EIA) and, less so, a research PCR were strong positive predictors. The negative predictive value for ruling out Campylobacter infection, defined as a posttest probability of less than 10%, was similarly observed with these Campylobacter-specific stool-based tests as well the fecal leukocyte test. Compared to the other tests evaluated, the Campylobacter EIA is a sensitive and specific rapid diagnostic test that may assist with diagnostic evaluation, with consideration of the epidemiological setting, logistics, and cost. PMID:18234869

Integrated Rapid-Diagnostic-Test Reader Platform on a Cellphone

PubMed Central

Mudanyali, Onur; Dimitrov, Stoyan; Sikora, Uzair; Padmanabhan, Swati; Navruz, Isa; Ozcan, Aydogan

2012-01-01

We demonstrate a cellphone based Rapid-Diagnostic-Test (RDT) reader platform that can work with various lateral flow immuno-chromatographic assays and similar tests to sense the presence of a target analyte in a sample. This compact and cost-effective digital RDT reader, weighing only ~65 grams, mechanically attaches to the existing camera unit of a cellphone, where various types of RDTs can be inserted to be imaged in reflection or transmission modes under light-emitting-diode (LED) based illumination. Captured raw images of these tests are then digitally processed (within less than 0.2 sec/image) through a smart application running on the cellphone for validation of the RDT as well as for automated reading of its diagnostic result. The same smart application running on the cellphone then transmits the resulting data, together with the RDT images and other related information (e.g., demographic data) to a central server, which presents the diagnostic results on a world-map through geo-tagging. This dynamic spatio-temporal map of various RDT results can then be viewed and shared using internet browsers or through the same cellphone application. We tested this platform using malaria, tuberculosis (TB) as well as HIV RDTs by installing it on both Android based smart-phones as well as an iPhone. Providing real-time spatio-temporal statistics for the prevalence of various infectious diseases, this smart RDT reader platform running on cellphones might assist health-care professionals and policy makers to track emerging epidemics worldwide and help epidemic preparedness. PMID:22596243

Diagnostic accuracy of tablet-based software for the detection of concussion.

PubMed

Yang, Suosuo; Flores, Benjamin; Magal, Rotem; Harris, Kyrsti; Gross, Jonathan; Ewbank, Amy; Davenport, Sasha; Ormachea, Pablo; Nasser, Waleed; Le, Weidong; Peacock, W Frank; Katz, Yael; Eagleman, David M

2017-01-01

Despite the high prevalence of traumatic brain injuries (TBI), there are few rapid and straightforward tests to improve its assessment. To this end, we developed a tablet-based software battery ("BrainCheck") for concussion detection that is well suited to sports, emergency department, and clinical settings. This article is a study of the diagnostic accuracy of BrainCheck. We administered BrainCheck to 30 TBI patients and 30 pain-matched controls at a hospital Emergency Department (ED), and 538 healthy individuals at 10 control test sites. We compared the results of the tablet-based assessment against physician diagnoses derived from brain scans, clinical examination, and the SCAT3 test, a traditional measure of TBI. We found consistent distributions of normative data and high test-retest reliability. Based on these assessments, we defined a composite score that distinguishes TBI from non-TBI individuals with high sensitivity (83%) and specificity (87%). We conclude that our testing application provides a rapid, portable testing method for TBI.

Medical microbiology: laboratory diagnosis of invasive pneumococcal disease.

PubMed

Werno, Anja M; Murdoch, David R

2008-03-15

The laboratory diagnosis of invasive pneumococcal disease (IPD) continues to rely on culture-based methods that have been used for many decades. The most significant recent developments have occurred with antigen detection assays, whereas the role of nucleic acid amplification tests has yet to be fully clarified. Despite developments in laboratory diagnostics, a microbiological diagnosis is still not made in most cases of IPD, particularly for pneumococcal pneumonia. The limitations of existing diagnostic tests impact the ability to obtain accurate IPD burden data and to assess the effectiveness of control measures, such as vaccination, in addition to the ability to diagnose IPD in individual patients. There is an urgent need for improved diagnostic tests for pneumococcal disease--especially tests that are suitable for use in underresourced countries.

Market assessment of tuberculosis diagnostics in Brazil in 2012.

PubMed

2014-01-01

Improved diagnostics for the diagnosis of tuberculosis (TB) are urgently needed. However, test developers and investors require market size data to support new product development. This study assessed the served available market for TB diagnostics in Brazil in 2012 and the market segmentation in the public and private sectors. Data were collected on test volumes done in the public and private sectors for the diagnosis of latent and active TB, drug susceptibility testing and treatment follow-up. Tests included were tuberculin skin tests, interferon-gamma releases assays, smear microscopy, solid and liquid cultures, nucleic acid amplification tests and phenotypic drug susceptibility tests. The data were collected by means of an electronic survey via the Brazilian State laboratories and from sales information provided by manufacturers. Test costs for the public sector were calculated using a components approach, while costs for the private sector were based on prices paid by patients. The overall market value (expenditure) for the entire country was calculated using the public sector test costs. During 2012, an estimated total of 2.4 million TB diagnostic tests were done in Brazil, resulting in an estimated overall market value of USD 17.2 million. The public sector accounted for 91% of the test volumes and 88% of the market value. Smear microscopy was the most commonly test (n = 1.3 million; 55% of total) at an estimated value of USD 3.7 million. Culture overall (n = 302,761) represented 13% of test volumes and 40% (USD 6.9 million) of the market value. On average, USD 208 was spent on TB diagnostics for every notified TB patient in Brazil, in 2012. The TB diagnostics market value in Brazil in 2012 was over USD 17 million. These study results will help test developers to understand the current and potential market for replacement or add-on diagnostic technologies.

Market Assessment of Tuberculosis Diagnostics in Brazil in 2012

PubMed Central

2014-01-01

Background Improved diagnostics for the diagnosis of tuberculosis (TB) are urgently needed. However, test developers and investors require market size data to support new product development. This study assessed the served available market for TB diagnostics in Brazil in 2012 and the market segmentation in the public and private sectors. Methods Data were collected on test volumes done in the public and private sectors for the diagnosis of latent and active TB, drug susceptibility testing and treatment follow-up. Tests included were tuberculin skin tests, interferon-gamma releases assays, smear microscopy, solid and liquid cultures, nucleic acid amplification tests and phenotypic drug susceptibility tests. The data were collected by means of an electronic survey via the Brazilian State laboratories and from sales information provided by manufacturers. Test costs for the public sector were calculated using a components approach, while costs for the private sector were based on prices paid by patients. The overall market value (expenditure) for the entire country was calculated using the public sector test costs. Results During 2012, an estimated total of 2.4 million TB diagnostic tests were done in Brazil, resulting in an estimated overall market value of USD 17.2 million. The public sector accounted for 91% of the test volumes and 88% of the market value. Smear microscopy was the most commonly test (n = 1.3 million; 55% of total) at an estimated value of USD 3.7 million. Culture overall (n = 302,761) represented 13% of test volumes and 40% (USD 6.9 million) of the market value. On average, USD 208 was spent on TB diagnostics for every notified TB patient in Brazil, in 2012. Conclusion The TB diagnostics market value in Brazil in 2012 was over USD 17 million. These study results will help test developers to understand the current and potential market for replacement or add-on diagnostic technologies. PMID:25099237

Culture-independent diagnostic testing: have we opened Pandora's box for good?

PubMed

Janda, J Michael; Abbott, Sharon A

2014-11-01

The ability to accurately and quickly identify microbial agents associated with infectious diseases has been a longstanding and continuous goal of diagnostic microbiology laboratories. Over the course of several decades, technology and testing methodologies in this field have gradually evolved from traditional- or classic-based culture and identification approaches to antigen capture systems and more molecular-oriented applications. Recently, these molecular-based applications have signaled a new era in clinical diagnostic microbiology with the commercial introduction of culture-independent diagnostic testing (CIDT) systems. The first major commercial venture into the CIDT arena involves the detection of acute bacterial gastroenteritis. Several commercial products are now on the market globally with at least 4 Food and Drug Administration approved since January of 2013. These new systems offer the direct detection of a variety of enteropathogens quickly without the need for traditional culture. In Greek mythology, Pandora opened a "jar" or "box" out of curiosity thereby releasing all of humanity's evils most notably diseases and plagues according to Hesiod's Theogony. While not ill-intentioned the only thing left in the box was Hope. Copyright © 2014 Elsevier Inc. All rights reserved.

Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus

PubMed Central

van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

2015-01-01

Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Conclusions: Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. (Hepatology 2015;61:1174–1182) PMID:25482139

Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus.

PubMed

van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

2015-04-01

Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. © 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Benefits and challenges of molecular diagnostics for childhood tuberculosis.

PubMed

Gutierrez, Cristina

2016-12-01

Expanding tuberculosis (TB)-diagnostic services, including access to rapid tests, is a World Health Organization (WHO) strategy to accelerate progress toward ending TB. Faster and more sensitive molecular tests capable of diagnosing TB and drug-resistant TB have the technical capacity to address limitations associated with smears and cultures by increasing accuracy and shortening turnaround times as compared with those of these conventional laboratory methods. Nucleic acid amplification assays used to detect and analyze Mycobacterium tuberculosis (MTB)-complex nucleic acids can be used directly on specimens from patients suspected of having TB. Recently, several commercial molecular tests were developed to detect MTB and determine the drug resistance (DR) based on detection of specific genetic mutations conferring resistance. The first to be endorsed by the WHO was molecular line-probe assay technology. This test uses polymerase chain reaction (PCR) and reverse-hybridization methods to rapidly identify MTB and DR-related mutations simultaneously. More recently, the WHO endorsed Xpert MTB/RIF, Cepheid Inc, CA, USA, a fully automated assay used for TB diagnosis that relies upon PCR techniques for detection of TB and rifampicin resistance-related mutations. Other promising molecular TB assays for simplifying PCR-based testing protocols and increasing their accuracy are under development and evaluation. Although we lack a practical gold standard for the diagnosis of childhood TB, its bacteriological confirmation is always recommended to be sought whenever possible prior to a diagnostic decision being made. Conventional diagnostic laboratory TB tests are less efficient for children as compared with adults, because sufficient sputum samples are more difficult to collect from infants and young children, and their disease is often paucibacillary, resulting in smear-negative disease. These inherent challenges associated with childhood TB are due to immunological- and pathophysiological-response differences relative to those observed in adults. Several recent meta-analyses showed low sensitivity estimates of PCR-based TB assays for paucibacillary forms of TB (extrapulmonary TB and smear-negative pulmonary disease), which represent the vast majority of childhood TB cases. Despite the lack of evidence regarding use of the rapid molecular assays to identify TB and detect DR in children, and due to the clinical nature of childhood TB, TB-expert groups recommend including rapid methods for TB identification and DR detection in diagnostic algorithms for children suspected of both smear-positive and -negative pulmonary or extrapulmonary TB, both with or without human immunodeficiency virus (HIV)-coinfection, when combined with standard methods (including clinical, microbiological, and radiological assessment) for diagnosing active TB and conventional DR. Since 2011, the WHO has specifically recommended use of the Xpert MTB/RIF test as an initial diagnostic tool for children with suspected HIV-associated TB or multidrug-resistant TB based on successful treatment data related to adults. Implementation of the rapid molecular assays for rapid detection of TB and DR should occur in laboratories with proven capability to run molecular tests and where quality control systems are implemented. Molecular approaches should be more largely tested in children, given their status as the group in whom the diagnostic dilemma is most pronounced. These tests should also be included in specific childhood TB diagnostic algorithms adapted to the local/national context in combination with other strategies for improving diagnostics, including more effective specimen collection. Copyright © 2016.

Assessing clinical reasoning (ASCLIRE): Instrument development and validation.

PubMed

Kunina-Habenicht, Olga; Hautz, Wolf E; Knigge, Michel; Spies, Claudia; Ahlers, Olaf

2015-12-01

Clinical reasoning is an essential competency in medical education. This study aimed at developing and validating a test to assess diagnostic accuracy, collected information, and diagnostic decision time in clinical reasoning. A norm-referenced computer-based test for the assessment of clinical reasoning (ASCLIRE) was developed, integrating the entire clinical decision process. In a cross-sectional study participants were asked to choose as many diagnostic measures as they deemed necessary to diagnose the underlying disease of six different cases with acute or sub-acute dyspnea and provide a diagnosis. 283 students and 20 content experts participated. In addition to diagnostic accuracy, respective decision time and number of used relevant diagnostic measures were documented as distinct performance indicators. The empirical structure of the test was investigated using a structural equation modeling approach. Experts showed higher accuracy rates and lower decision times than students. In a cross-sectional comparison, the diagnostic accuracy of students improved with the year of study. Wrong diagnoses provided by our sample were comparable to wrong diagnoses in practice. We found an excellent fit for a model with three latent factors-diagnostic accuracy, decision time, and choice of relevant diagnostic information-with diagnostic accuracy showing no significant correlation with decision time. ASCLIRE considers decision time as an important performance indicator beneath diagnostic accuracy and provides evidence that clinical reasoning is a complex ability comprising diagnostic accuracy, decision time, and choice of relevant diagnostic information as three partly correlated but still distinct aspects.

A comparison of diagnostic tests for lactose malabsorption - which one is the best?

PubMed Central

2009-01-01

Background Perceived milk intolerance is a common complaint, and tests for lactose malabsorption (LM) are unreliable. This study assesses the agreement between diagnostic tests for LM and describes the diagnostic properties of the tests. Methods Patients above 18 years of age with suspected LM were included. After oral intake of 25 g lactose, a combined test with measurement of serum glucose (s-glucose) and hydrogen (H2) and methane (CH4) in expired air was performed and symptoms were recorded. In patients with discrepancies between the results, the combined test was repeated and a gene test for lactose non-persistence was added. The diagnosis of LM was based on an evaluation of all tests. The following tests were compared: Increase in H2, CH4, H2+CH4 and H2+CH4x2 in expired air, increase in s-glucose, and symptoms. The agreement was calculated and the diagnostic properties described. Results Sixty patients were included, seven (12%) had LM. The agreement (kappa-values) between the methods varied from 0.25 to 0.91. The best test was the lactose breath test with measurement of the increase in H2 + CH4x2 in expired air. With a cut-off level < 18 ppm, the area under the ROC-curve was 0.967 and sensitivity was 100%. This shows that measurement of CH4 in addition to H2 improves the diagnostic properties of the breath test. Conclusion The agreement between commonly used methods for the diagnosis of LM was unsatisfactory. A lactose breath test with measurement of H2 + CH4x2 in expired air had the best diagnostic properties. PMID:19878587

Evidence base and future research directions in the management of low back pain.

PubMed

Abbott, Allan

2016-03-18

Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care.

[Interpretation of false positive results of biochemical prenatal tests].

PubMed

Sieroszewski, Piotr; Słowakiewicz, Katarzyna; Perenc, Małgorzata

2010-03-01

Modern, non-invasive prenatal diagnostics based on biochemical and ultrasonographic markers of fetal defects allows us to calculate the risk of fetal chromosomal aneuploidies with high sensitivity and specificity An introduction of biochemical, non-invasive prenatal tests turned out to result in frequent false positive results of these tests in cases when invasive diagnostics does not confirm fetal defects. However prospective analysis of these cases showed numerous complications in the third trimester of the pregnancies.

Trends in basic mathematical competencies of beginning undergraduates in Ireland, 2003-2013

NASA Astrophysics Data System (ADS)

Treacy, Páraic; Faulkner, Fiona

2015-11-01

Deficiencies in beginning undergraduate students' basic mathematical skills has been an issue of concern in higher education, particularly in the past 15 years. This issue has been tracked and analysed in a number of universities in Ireland and internationally through student scores recorded in mathematics diagnostic tests. Students beginning their science-based and technology-based undergraduate courses in the University of Limerick have had their basic mathematics skills tested without any prior warning through a 40 question diagnostic test during their initial service mathematics lecture since 1998. Data gathered through this diagnostic test have been recorded in a database kept at the university and explored to track trends in mathematical competency of these beginning undergraduates. This paper details findings surrounding an analysis of the database between 2003 and 2013, outlining changes in mathematical competencies of these beginning undergraduates in an attempt to determine reasons for such changes. The analysis found that the proportion of students tested through this diagnostic test that are predicted to be at risk of failing their service mathematics end-of-semester examinations has increased significantly between 2003 and 2013. Furthermore, when students' performance in secondary level mathematics was controlled, it was determined that the performance of beginning undergraduates in 2013 was statistically significantly below that of the performance of the beginning undergraduates recorded 10 years previously.

Evaluation of Machine Learning and Rules-Based Approaches for Predicting Antimicrobial Resistance Profiles in Gram-negative Bacilli from Whole Genome Sequence Data.

PubMed

Pesesky, Mitchell W; Hussain, Tahir; Wallace, Meghan; Patel, Sanket; Andleeb, Saadia; Burnham, Carey-Ann D; Dantas, Gautam

2016-01-01

The time-to-result for culture-based microorganism recovery and phenotypic antimicrobial susceptibility testing necessitates initial use of empiric (frequently broad-spectrum) antimicrobial therapy. If the empiric therapy is not optimal, this can lead to adverse patient outcomes and contribute to increasing antibiotic resistance in pathogens. New, more rapid technologies are emerging to meet this need. Many of these are based on identifying resistance genes, rather than directly assaying resistance phenotypes, and thus require interpretation to translate the genotype into treatment recommendations. These interpretations, like other parts of clinical diagnostic workflows, are likely to be increasingly automated in the future. We set out to evaluate the two major approaches that could be amenable to automation pipelines: rules-based methods and machine learning methods. The rules-based algorithm makes predictions based upon current, curated knowledge of Enterobacteriaceae resistance genes. The machine-learning algorithm predicts resistance and susceptibility based on a model built from a training set of variably resistant isolates. As our test set, we used whole genome sequence data from 78 clinical Enterobacteriaceae isolates, previously identified to represent a variety of phenotypes, from fully-susceptible to pan-resistant strains for the antibiotics tested. We tested three antibiotic resistance determinant databases for their utility in identifying the complete resistome for each isolate. The predictions of the rules-based and machine learning algorithms for these isolates were compared to results of phenotype-based diagnostics. The rules based and machine-learning predictions achieved agreement with standard-of-care phenotypic diagnostics of 89.0 and 90.3%, respectively, across twelve antibiotic agents from six major antibiotic classes. Several sources of disagreement between the algorithms were identified. Novel variants of known resistance factors and incomplete genome assembly confounded the rules-based algorithm, resulting in predictions based on gene family, rather than on knowledge of the specific variant found. Low-frequency resistance caused errors in the machine-learning algorithm because those genes were not seen or seen infrequently in the test set. We also identified an example of variability in the phenotype-based results that led to disagreement with both genotype-based methods. Genotype-based antimicrobial susceptibility testing shows great promise as a diagnostic tool, and we outline specific research goals to further refine this methodology.

Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology.

PubMed

Labourier, Emmanuel; Shifrin, Alexander; Busseniers, Anne E; Lupo, Mark A; Manganelli, Monique L; Andruss, Bernard; Wylie, Dennis; Beaudenon-Huibregtse, Sylvie

2015-07-01

Molecular testing for oncogenic mutations or gene expression in fine-needle aspirations (FNAs) from thyroid nodules with indeterminate cytology identifies a subset of benign or malignant lesions with high predictive value. This study aimed to evaluate a novel diagnostic algorithm combining mutation detection and miRNA expression to improve the diagnostic yield of molecular cytology. Surgical specimens and preoperative FNAs (n = 638) were tested for 17 validated gene alterations using the miRInform Thyroid test and with a 10-miRNA gene expression classifier generating positive (malignant) or negative (benign) results. Cross-sectional sampling of thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) cytology (n = 109) was conducted at 12 endocrinology centers across the United States. Qualitative molecular results were compared with surgical histopathology to determine diagnostic performance and model clinical effect. Mutations were detected in 69% of nodules with malignant outcome. Among mutation-negative specimens, miRNA testing correctly identified 64% of malignant cases and 98% of benign cases. The diagnostic sensitivity and specificity of the combined algorithm was 89% (95% confidence interval [CI], 73-97%) and 85% (95% CI, 75-92%), respectively. At 32% cancer prevalence, 61% of the molecular results were benign with a negative predictive value of 94% (95% CI, 85-98%). Independently of variations in cancer prevalence, the test increased the yield of true benign results by 65% relative to mRNA-based gene expression classification and decreased the rate of avoidable diagnostic surgeries by 69%. Multiplatform testing for DNA, mRNA, and miRNA can accurately classify benign and malignant thyroid nodules, increase the diagnostic yield of molecular cytology, and further improve the preoperative risk-based management of benign nodules with AUS/FLUS or FN/SFN cytology.

Evidence-based Diagnostics: Adult Septic Arthritis

PubMed Central

Carpenter, Christopher R.; Schuur, Jeremiah D.; Everett, Worth W.; Pines, Jesse M.

2011-01-01

Background Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality. Objectives The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy. Methods Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits. Results The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 109–25 × 109/ L was 0.33; for 25 × 109–50 × 109/L, 1.06; for 50 × 109–100 × 109/L, 3.59; and exceeding 100 × 109/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (−LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts of >50 × 109/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%. Conclusions Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 × 109/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate. PMID:21843213

Evidence-based diagnostics: adult septic arthritis.

PubMed

Carpenter, Christopher R; Schuur, Jeremiah D; Everett, Worth W; Pines, Jesse M

2011-08-01

Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality. The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy. Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits. The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 10(9)-25 × 10(9)/L was 0.33; for 25 × 10(9)-50 × 10(9)/L, 1.06; for 50 × 10(9)-100 × 10(9)/L, 3.59; and exceeding 100 × 10(9)/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (-LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts of >50 × 10(9)/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%. Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 × 10(9)/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate. © 2011 by the Society for Academic Emergency Medicine.

Identification student’s misconception of heat and temperature using three-tier diagnostic test

NASA Astrophysics Data System (ADS)

Suliyanah; Putri, H. N. P. A.; Rohmawati, L.

2018-03-01

The objective of this research is to develop a Three-Tier Diagnostic Test (TTDT) to identify the student's misconception of heat and temperature. Stages of development include: analysis, planning, design, development, evaluation and revise. The results of this study show that (1) the quality of the three-tier type diagnostic test instrument developed has been expressed well with the following details: (a) Internal validity of 88.19% belonging to the valid category. (b) External validity of empirical construct validity test using Pearson Product Moment obtained 0.43 is classified and result of empirical construct validity test obtained false positives 6.1% and false negatives 5.9% then the instrument was valid. (c) Test reliability by using Cronbach’s Alpha of 0.98 which means acceptable. (d) The 80% difficulty level test is quite difficult. (2) Student misconceptions on the temperature of heat and displacement materials based on the II test the highest (84%), the lowest (21%), and the non-misconceptions (7%). (3) The highest cause of misconception among students is associative thinking (22%) and the lowest is caused by incomplete or incomplete reasoning (11%). Three-Tier Diagnostic Test (TTDT) could identify the student's misconception of heat and temperature.

Molecular diagnostics: the changing culture of medical microbiology.

PubMed

Bullman, Susan; Lucey, Brigid; Sleator, Roy D

2012-01-01

Diagnostic molecular biology is arguably the fastest growing area in current laboratory-based medicine. Growth of the so called 'omics' technologies has, over the last decade, led to a gradual migration away from the 'one test, one pathogen' paradigm, toward multiplex approaches to infectious disease diagnosis, which have led to significant improvements in clinical diagnostics and ultimately improved patient care.

Diagnostic accuracy of apparent diffusion coefficient and 123I-metaiodobenzylguanidine for differentiation of multiple system atrophy and Parkinson's disease.

PubMed

Umemura, Atsushi; Oeda, Tomoko; Hayashi, Ryutaro; Tomita, Satoshi; Kohsaka, Masayuki; Yamamoto, Kenji; Sawada, Hideyuki

2013-01-01

It is often hard to differentiate Parkinson's disease (PD) and parkinsonian variant of multiple system atrophy (MSA-P), especially in the early stages. Cardiac sympathetic denervation and putaminal rarefaction are specific findings for PD and MSA-P, respectively. We investigated diagnostic accuracy of putaminal apparent diffusion coefficient (ADC) test for MSA-P and (123)I-metaiodobenzylguanidine (MIBG) scintigram for PD, especially in early-stage patients. The referral standard diagnosis of PD and MSA-P were the diagnostic criteria of the United Kingdom Parkinson's Disease Society Brain Bank Criteria and the second consensus criteria, respectively. Based on the referral standard criteria, diagnostic accuracy [area under the receiver-operator characteristic curve (AUC), sensitivity and specificity] of the ADC and MIBG tests was estimated retrospectively. Diagnostic accuracy of these tests performed within 3 years of symptom onset was also investigated. ADC and MIBG tests were performed on 138 patients (20 MSA and 118 PD). AUC was 0.95 and 0.83 for the ADC and MIBG tests, respectively. Sensitivity and specificity were 85.0% and 89.0% for MSA-P diagnosis by ADC test and 67.0% and 80.0% for PD diagnosis by MIBG test. When these tests were restricted to patients with disease duration ≤ 3 years, the sensitivity and specificity were 75.0% and 91.4% for the ADC test (MSA-P diagnosis) and 47.7% and 92.3% for the MIBG test (PD diagnosis). Both tests were useful in differentiating between PD and MSA-P, even in the early stages. In early-stage patients, elevated putaminal ADC was a diagnostic marker for MSA-P. Despite high specificity of the MIBG test, careful neurological history and examinations were required for PD diagnosis because of possible false-negative results.

Determining the Optimal Number of Core Needle Biopsy Passes for Molecular Diagnostics.

PubMed

Hoang, Nam S; Ge, Benjamin H; Pan, Lorraine Y; Ozawa, Michael G; Kong, Christina S; Louie, John D; Shah, Rajesh P

2018-03-01

The number of core biopsy passes required for adequate next-generation sequencing is impacted by needle cut, needle gauge, and the type of tissue involved. This study evaluates diagnostic adequacy of core needle lung biopsies based on number of passes and provides guidelines for other tissues based on simulated biopsies in ex vivo porcine organ tissues. The rate of diagnostic adequacy for pathology and molecular testing from lung biopsy procedures was measured for eight operators pre-implementation (September 2012-October 2013) and post-implementation (December 2013-April 2014) of a standard protocol using 20-gauge side-cut needles for ten core biopsy passes at a single academic hospital. Biopsy pass volume was then estimated in ex vivo porcine muscle, liver, and kidney using side-cut devices at 16, 18, and 20 gauge and end-cut devices at 16 and 18 gauge to estimate minimum number of passes required for adequate molecular testing. Molecular diagnostic adequacy increased from 69% (pre-implementation period) to 92% (post-implementation period) (p < 0.001) for lung biopsies. In porcine models, both 16-gauge end-cut and side-cut devices require one pass to reach the validated volume threshold to ensure 99% adequacy for molecular characterization, while 18- and 20-gauge devices require 2-5 passes depending on needle cut and tissue type. Use of 20-gauge side-cut core biopsy needles requires a significant number of passes to ensure diagnostic adequacy for molecular testing across all tissue types. To ensure diagnostic adequacy for molecular testing, 16- and 18-gauge needles require markedly fewer passes.

Programmable bio-nano-chip system for saliva diagnostics

NASA Astrophysics Data System (ADS)

Christodoulides, Nicolaos; De La Garza, Richard; Simmons, Glennon W.; McRae, Michael P.; Wong, Jorge; Kosten, Thomas R.; Miller, Craig S.; Ebersole, Jeffrey L.; McDevitt, John

2014-06-01

This manuscript describes programmable Bio-Nano-Chip (p-BNC) approach that serves as miniaturized assay platform designed for the rapid detection and quantitation of multiple analytes in biological fluids along with the specific applications in salivary diagnostics intended for the point of need (PON). Included here are oral fluid-based tests for local periodontal disease, systemic cardiac disease and multiplexed tests for drugs of abuse.

An Investigation of the Teacher Competencies Needed to Utilize Diagnostic Test Data in Prescribing Occupational Learning Experiences in Teaching EMRS. Final Report. Part II. Appendices.

ERIC Educational Resources Information Center

Nelson, Orville; And Others

These appendixes are to the final report of an action research Project conducted to determine the teacher competencies needed in order to develop valid and effective occupational learning experiences for educable mentally retarded (EMR) students based on available diagnostic test data and information. Included are (1) participant vitas and…

On determining the most appropriate test cut-off value: the case of tests with continuous results

PubMed Central

Habibzadeh, Parham; Yadollahie, Mahboobeh

2016-01-01

There are several criteria for determination of the most appropriate cut-off value in a diagnostic test with continuous results. Mostly based on receiver operating characteristic (ROC) analysis, there are various methods to determine the test cut-off value. The most common criteria are the point on ROC curve where the sensitivity and specificity of the test are equal; the point on the curve with minimum distance from the left-upper corner of the unit square; and the point where the Youden’s index is maximum. There are also methods mainly based on Bayesian decision analysis. Herein, we show that a proposed method that maximizes the weighted number needed to misdiagnose, an index of diagnostic test effectiveness we previously proposed, is the most appropriate technique compared to the aforementioned ones. For determination of the cut-off value, we need to know the pretest probability of the disease of interest as well as the costs incurred by misdiagnosis. This means that even for a certain diagnostic test, the cut-off value is not universal and should be determined for each region and for each disease condition. PMID:27812299

An audit of Cryptosporidium and Giardia detection in Scottish National Health Service Diagnostic Microbiology Laboratories.

PubMed

Alexander, C L; Currie, S; Pollock, K; Smith-Palmer, A; Jones, B L

2017-06-01

Giardia duodenalis and Cryptosporidium species are protozoan parasites capable of causing gastrointestinal disease in humans and animals through the ingestion of infective faeces. Whereas Cryptosporidium species can be acquired locally or through foreign travel, there is the mis-conception that giardiasis is considered to be largely travel-associated, which results in differences in laboratory testing algorithms. In order to determine the level of variation in testing criteria and detection methods between diagnostic laboratories for both pathogens across Scotland, an audit was performed. Twenty Scottish diagnostic microbiology laboratories were invited to participate with questions on sample acceptance criteria, testing methods, testing rates and future plans for pathogen detection. Reponses were received from 19 of the 20 laboratories representing each of the 14 territorial Health Boards. Detection methods varied between laboratories with the majority performing microscopy, one using a lateral flow immunochromatographic antigen assay, another using a manually washed plate-based enzyme immunoassay (EIA) and one laboratory trialling a plate-based EIA automated with an EIA plate washer. Whereas all laboratories except one screened every stool for Cryptosporidium species, an important finding was that significant variation in the testing algorithm for detecting Giardia was noted with only four laboratories testing all diagnostic stools. The most common criteria were 'travel history' (11 laboratories) and/or 'when requested' (14 laboratories). Despite only a small proportion of stools being examined in 15 laboratories for Giardia (2%-18% of the total number of stools submitted), of interest is the finding that a higher positivity rate was observed for Giardia than Cryptosporidium in 10 of these 15 laboratories. These findings highlight that the underreporting of Giardia in Scotland is likely based on current selection and testing algorithms.

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

PubMed

Pavlov, K A; Shkoporov, A N; Khokhlova, E V; Korchagina, A A; Sidorenkov, A V; Grigor'ev, M É; Pushkar', D Iu; Chekhonin, V P

2013-01-01

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

Bivariate random-effects meta-analysis models for diagnostic test accuracy studies using arcsine-based transformations.

PubMed

Negeri, Zelalem F; Shaikh, Mateen; Beyene, Joseph

2018-05-11

Diagnostic or screening tests are widely used in medical fields to classify patients according to their disease status. Several statistical models for meta-analysis of diagnostic test accuracy studies have been developed to synthesize test sensitivity and specificity of a diagnostic test of interest. Because of the correlation between test sensitivity and specificity, modeling the two measures using a bivariate model is recommended. In this paper, we extend the current standard bivariate linear mixed model (LMM) by proposing two variance-stabilizing transformations: the arcsine square root and the Freeman-Tukey double arcsine transformation. We compared the performance of the proposed methods with the standard method through simulations using several performance measures. The simulation results showed that our proposed methods performed better than the standard LMM in terms of bias, root mean square error, and coverage probability in most of the scenarios, even when data were generated assuming the standard LMM. We also illustrated the methods using two real data sets. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laboratory Diagnostics Market in East Africa: A Survey of Test Types, Test Availability, and Test Prices in Kampala, Uganda.

PubMed

Schroeder, Lee F; Elbireer, Ali; Jackson, J Brooks; Amukele, Timothy K

2015-01-01

Diagnostic laboratory tests are routinely defined in terms of their sensitivity, specificity, and ease of use. But the actual clinical impact of a diagnostic test also depends on its availability and price. This is especially true in resource-limited settings such as sub-Saharan Africa. We present a first-of-its-kind report of diagnostic test types, availability, and prices in Kampala, Uganda. Test types (identity) and availability were based on menus and volumes obtained from clinical laboratories in late 2011 in Kampala using a standard questionnaire. As a measure of test availability, we used the Availability Index (AI). AI is the combined daily testing volumes of laboratories offering a given test, divided by the combined daily testing volumes of all laboratories in Kampala. Test prices were based on a sampling of prices collected in person and via telephone surveys in 2015. Test volumes and menus were obtained for 95% (907/954) of laboratories in Kampala city. These 907 laboratories offered 100 different test types. The ten most commonly offered tests in decreasing order were Malaria, HCG, HIV serology, Syphilis, Typhoid, Urinalysis, Brucellosis, Stool Analysis, Glucose, and ABO/Rh. In terms of AI, the 100 tests clustered into three groups: high (12 tests), moderate (33 tests), and minimal (55 tests) availability. 50% and 36% of overall availability was provided through private and public laboratories, respectively. Point-of-care laboratories contributed 35% to the AI of high availability tests, but only 6% to the AI of the other tests. The mean price of the most commonly offered test types was $2.62 (range $1.83-$3.46). One hundred different laboratory test types were in use in Kampala in late 2011. Both public and private laboratories were critical to test availability. The tests offered in point-of-care laboratories tended to be the most available tests. Prices of the most common tests ranged from $1.83-$3.46.

Invasive candidiasis: future directions in non-culture based diagnosis.

PubMed

Posch, Wilfried; Heimdörfer, David; Wilflingseder, Doris; Lass-Flörl, Cornelia

2017-09-01

Delayed initial antifungal therapy is associated with high mortality rates caused by invasive candida infections, since accurate detection of the opportunistic pathogenic yeast and its identification display a diagnostic challenge. diagnosis of candida infections relies on time-consuming methods such as blood cultures, serologic and histopathologic examination. to allow for fast detection and characterization of invasive candidiasis, there is a need to improve diagnostic tools. trends in diagnostics switch to non-culture-based methods, which allow specified diagnosis within significantly shorter periods of time in order to provide early and appropriate antifungal treatment. Areas covered: within this review comprise novel pathogen- and host-related testing methods, e.g. multiplex-PCR analyses, T2 magnetic resonance, fungus-specific DNA microarrays, microRNA characterization or analyses of IL-17 as biomarker for early detection of invasive candidiasis. Expert commentary: Early recognition and diagnosis of fungal infections is a key issue for improved patient management. As shown in this review, a broad range of novel molecular based tests for the detection and identification of Candida species is available. However, several assays are in-house assays and lack standardization, clinical validation as well as data on sensitivity and specificity. This underscores the need for the development of faster and more accurate diagnostic tests.

Use of clinical prediction rules and D-dimer tests in the diagnostic management of pregnant patients with suspected acute pulmonary embolism.

PubMed

Van der Pol, L M; Mairuhu, A T A; Tromeur, C; Couturaud, F; Huisman, M V; Klok, F A

2017-03-01

Because pregnant women have an increased risk of venous thromboembolism (VTE) and at the same time normal pregnancy is associated with symptoms, mimicking those present in the setting of acute pulmonary embolism (PE), the latter diagnosis is frequently suspected in this patient category. Since imaging tests expose both mother and foetus to ionizing radiation, the ability to rule out PE based on non-radiological diagnostic tests is of paramount importance. However, clinical decision rules have only been scarcely evaluated in the pregnant population with suspected PE, while D-dimer levels lose diagnostic accuracy due to a physiological increase during normal pregnancy. Consequently, clinical guidelines provide contradicting and weak recommendations on this subject and the optimal diagnostic strategy remains highly debated. With this systematic review, we aimed to summarize current evidence on the safety and efficacy of clinical decision rules and biomarkers used in the diagnostic management of suspected acute PE in pregnant patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Added value of cost-utility analysis in simple diagnostic studies of accuracy: (18)F-fluoromethylcholine PET/CT in prostate cancer staging.

PubMed

Gerke, Oke; Poulsen, Mads H; Høilund-Carlsen, Poul Flemming

2015-01-01

Diagnostic studies of accuracy targeting sensitivity and specificity are commonly done in a paired design in which all modalities are applied in each patient, whereas cost-effectiveness and cost-utility analyses are usually assessed either directly alongside to or indirectly by means of stochastic modeling based on larger randomized controlled trials (RCTs). However the conduct of RCTs is hampered in an environment such as ours, in which technology is rapidly evolving. As such, there is a relatively limited number of RCTs. Therefore, we investigated as to which extent paired diagnostic studies of accuracy can be also used to shed light on economic implications when considering a new diagnostic test. We propose a simple decision tree model-based cost-utility analysis of a diagnostic test when compared to the current standard procedure and exemplify this approach with published data from lymph node staging of prostate cancer. Average procedure costs were taken from the Danish Diagnosis Related Groups Tariff in 2013 and life expectancy was estimated for an ideal 60 year old patient based on prostate cancer stage and prostatectomy or radiation and chemotherapy. Quality-adjusted life-years (QALYs) were deduced from the literature, and an incremental cost-effectiveness ratio (ICER) was used to compare lymph node dissection with respective histopathological examination (reference standard) and (18)F-fluoromethylcholine positron emission tomography/computed tomography (FCH-PET/CT). Lower bounds of sensitivity and specificity of FCH-PET/CT were established at which the replacement of the reference standard by FCH-PET/CT comes with a trade-off between worse effectiveness and lower costs. Compared to the reference standard in a diagnostic accuracy study, any imperfections in accuracy of a diagnostic test imply that replacing the reference standard generates a loss in effectiveness and utility. We conclude that diagnostic studies of accuracy can be put to a more extensive use, over and above a mere indication of sensitivity and specificity of an imaging test, and that health economic considerations should be undertaken when planning a prospective diagnostic accuracy study. These endeavors will prove especially fruitful when comparing several imaging techniques with one another, or the same imaging technique using different tracers, with an independent reference standard for the evaluation of results.

Development and Testing of an LED-Based Near-Infrared Sensor for Human Kidney Tumor Diagnostics

PubMed Central

Zabarylo, Urszula; Kirsanov, Dmitry; Belikova, Valeria; Ageev, Vladimir; Usenov, Iskander; Galyanin, Vladislav; Minet, Olaf; Sakharova, Tatiana; Danielyan, Georgy; Feliksberger, Elena; Artyushenko, Viacheslav

2017-01-01

Optical spectroscopy is increasingly used for cancer diagnostics. Tumor detection feasibility in human kidney samples using mid- and near-infrared (NIR) spectroscopy, fluorescence spectroscopy, and Raman spectroscopy has been reported (Artyushenko et al., Spectral fiber sensors for cancer diagnostics in vitro. In Proceedings of the European Conference on Biomedical Optics, Munich, Germany, 21–25 June 2015). In the present work, a simplification of the NIR spectroscopic analysis for cancer diagnostics was studied. The conventional high-resolution NIR spectroscopic method of kidney tumor diagnostics was replaced by a compact optical sensing device constructively represented by a set of four light-emitting diodes (LEDs) at selected wavelengths and one detecting photodiode. Two sensor prototypes were tested using 14 in vitro clinical samples of 7 different patients. Statistical data evaluation using principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) confirmed the general applicability of the LED-based sensing approach to kidney tumor detection. An additional validation of the results was performed by means of sample permutation. PMID:28825612

The Buffer Diagnostic Prototype: A fault isolation application using CLIPS

NASA Technical Reports Server (NTRS)

Porter, Ken

1994-01-01

This paper describes problem domain characteristics and development experiences from using CLIPS 6.0 in a proof-of-concept troubleshooting application called the Buffer Diagnostic Prototype. The problem domain is a large digital communications subsystems called the real-time network (RTN), which was designed to upgrade the launch processing system used for shuttle support at KSC. The RTN enables up to 255 computers to share 50,000 data points with millisecond response times. The RTN's extensive built-in test capability but lack of any automatic fault isolation capability presents a unique opportunity for a diagnostic expert system application. The Buffer Diagnostic Prototype addresses RTN diagnosis with a multiple strategy approach. A novel technique called 'faulty causality' employs inexact qualitative models to process test results. Experimental knowledge provides a capability to recognize symptom-fault associations. The implementation utilizes rule-based and procedural programming techniques, including a goal-directed control structure and simple text-based generic user interface that may be reusable for other rapid prototyping applications. Although limited in scope, this project demonstrates a diagnostic approach that may be adapted to troubleshoot a broad range of equipment.

Overview of ion source characterization diagnostics in INTF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bandyopadhyay, M., E-mail: mainak@iter-india.org; Sudhir, Dass; Bhuyan, M.

2016-02-15

INdian Test Facility (INTF) is envisaged to characterize ITER diagnostic neutral beam system and to establish the functionality of its eight inductively coupled RF plasma driver based negative hydrogen ion source and its beamline components. The beam quality mainly depends on the ion source performance and therefore, its diagnostics plays an important role for its safe and optimized operation. A number of diagnostics are planned in INTF to characterize the ion source performance. Negative ions and its cesium contents in the source will be monitored by optical emission spectroscopy (OES) and cavity ring down spectroscopy. Plasma near the extraction regionmore » will be studied using standard electrostatic probes. The beam divergence and negative ion stripping losses are planned to be measured using Doppler shift spectroscopy. During initial phase of ion beam characterization, carbon fiber composite based infrared imaging diagnostics will be used. Safe operation of the beam will be ensured by using standard thermocouples and electrical voltage-current measurement sensors. A novel concept, based on plasma density dependent plasma impedance measurement using RF electrical impedance matching parameters to characterize the RF driver plasma, will be tested in INTF and will be validated with OES data. The paper will discuss about the overview of the complete INTF diagnostics including its present status of procurement, experimentation, interface with mechanical systems in INTF, and integration with INTF data acquisition and control systems.« less

Overview of ion source characterization diagnostics in INTF

NASA Astrophysics Data System (ADS)

Bandyopadhyay, M.; Sudhir, Dass; Bhuyan, M.; Soni, J.; Tyagi, H.; Joshi, J.; Yadav, A.; Rotti, C.; Parmar, Deepak; Patel, H.; Pillai, S.; Chakraborty, A.

2016-02-01

INdian Test Facility (INTF) is envisaged to characterize ITER diagnostic neutral beam system and to establish the functionality of its eight inductively coupled RF plasma driver based negative hydrogen ion source and its beamline components. The beam quality mainly depends on the ion source performance and therefore, its diagnostics plays an important role for its safe and optimized operation. A number of diagnostics are planned in INTF to characterize the ion source performance. Negative ions and its cesium contents in the source will be monitored by optical emission spectroscopy (OES) and cavity ring down spectroscopy. Plasma near the extraction region will be studied using standard electrostatic probes. The beam divergence and negative ion stripping losses are planned to be measured using Doppler shift spectroscopy. During initial phase of ion beam characterization, carbon fiber composite based infrared imaging diagnostics will be used. Safe operation of the beam will be ensured by using standard thermocouples and electrical voltage-current measurement sensors. A novel concept, based on plasma density dependent plasma impedance measurement using RF electrical impedance matching parameters to characterize the RF driver plasma, will be tested in INTF and will be validated with OES data. The paper will discuss about the overview of the complete INTF diagnostics including its present status of procurement, experimentation, interface with mechanical systems in INTF, and integration with INTF data acquisition and control systems.

Remediation of petroleum hydrocarbon-contaminated sites by DNA diagnosis-based bioslurping technology.

PubMed

Kim, Seungjin; Krajmalnik-Brown, Rosa; Kim, Jong-Oh; Chung, Jinwook

2014-11-01

The application of effective remediation technologies can benefit from adequate preliminary testing, such as in lab-scale and Pilot-scale systems. Bioremediation technologies have demonstrated tremendous potential with regards to cost, but they cannot be used for all contaminated sites due to limitations in biological activity. The purpose of this study was to develop a DNA diagnostic method that reduces the time to select contaminated sites that are good candidates for bioremediation. We applied an oligonucleotide microarray method to detect and monitor genes that lead to aliphatic and aromatic degradation. Further, the bioremediation of a contaminated site, selected based on the results of the genetic diagnostic method, was achieved successfully by applying bioslurping in field tests. This gene-based diagnostic technique is a powerful tool to evaluate the potential for bioremediation in petroleum hydrocarbon contaminated soil. Copyright © 2014 Elsevier B.V. All rights reserved.

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL.

PubMed

Deans, Zandra C; Costa, Jose Luis; Cree, Ian; Dequeker, Els; Edsjö, Anders; Henderson, Shirley; Hummel, Michael; Ligtenberg, Marjolijn Jl; Loddo, Marco; Machado, Jose Carlos; Marchetti, Antonio; Marquis, Katherine; Mason, Joanne; Normanno, Nicola; Rouleau, Etienne; Schuuring, Ed; Snelson, Keeda-Marie; Thunnissen, Erik; Tops, Bastiaan; Williams, Gareth; van Krieken, Han; Hall, Jacqueline A

2017-01-01

The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services.

Gaseous electron multiplier-based soft x-ray plasma diagnostics development: Preliminary tests at ASDEX Upgrade.

PubMed

Chernyshova, M; Malinowski, K; Czarski, T; Wojeński, A; Vezinet, D; Poźniak, K T; Kasprowicz, G; Mazon, D; Jardin, A; Herrmann, A; Kowalska-Strzęciwilk, E; Krawczyk, R; Kolasiński, P; Zabołotny, W; Zienkiewicz, P

2016-11-01

A Gaseous Electron Multiplier (GEM)-based detector is being developed for soft X-ray diagnostics on tokamaks. Its main goal is to facilitate transport studies of impurities like tungsten. Such studies are very relevant to ITER, where the excessive accumulation of impurities in the plasma core should be avoided. This contribution provides details of the preliminary tests at ASDEX Upgrade (AUG) with a focus on the most important aspects for detector operation in harsh radiation environment. It was shown that both spatially and spectrally resolved data could be collected, in a reasonable agreement with other AUG diagnostics. Contributions to the GEM signal include also hard X-rays, gammas, and neutrons. First simulations of the effect of high-energy photons have helped understanding these contributions.

Gaseous electron multiplier-based soft x-ray plasma diagnostics development: Preliminary tests at ASDEX Upgrade

NASA Astrophysics Data System (ADS)

Chernyshova, M.; Malinowski, K.; Czarski, T.; Wojeński, A.; Vezinet, D.; Poźniak, K. T.; Kasprowicz, G.; Mazon, D.; Jardin, A.; Herrmann, A.; Kowalska-Strzeciwilk, E.; Krawczyk, R.; Kolasiński, P.; Zabołotny, W.; Zienkiewicz, P.

2016-11-01

A Gaseous Electron Multiplier (GEM)-based detector is being developed for soft X-ray diagnostics on tokamaks. Its main goal is to facilitate transport studies of impurities like tungsten. Such studies are very relevant to ITER, where the excessive accumulation of impurities in the plasma core should be avoided. This contribution provides details of the preliminary tests at ASDEX Upgrade (AUG) with a focus on the most important aspects for detector operation in harsh radiation environment. It was shown that both spatially and spectrally resolved data could be collected, in a reasonable agreement with other AUG diagnostics. Contributions to the GEM signal include also hard X-rays, gammas, and neutrons. First simulations of the effect of high-energy photons have helped understanding these contributions.

Diagnostics of the ITER neutral beam test facility.

PubMed

Pasqualotto, R; Serianni, G; Sonato, P; Agostini, M; Brombin, M; Croci, G; Dalla Palma, M; De Muri, M; Gazza, E; Gorini, G; Pomaro, N; Rizzolo, A; Spolaore, M; Zaniol, B

2012-02-01

The ITER heating neutral beam (HNB) injector, based on negative ions accelerated at 1 MV, will be tested and optimized in the SPIDER source and MITICA full injector prototypes, using a set of diagnostics not available on the ITER HNB. The RF source, where the H(-)∕D(-) production is enhanced by cesium evaporation, will be monitored with thermocouples, electrostatic probes, optical emission spectroscopy, cavity ring down, and laser absorption spectroscopy. The beam is analyzed by cooling water calorimetry, a short pulse instrumented calorimeter, beam emission spectroscopy, visible tomography, and neutron imaging. Design of the diagnostic systems is presented.

Diagnostic hearing testing of infants aged 0-36 months in 3 South African provinces - Comparison of audiology records to HPCSA guidelines.

PubMed

Moodley, Selvarani; Störbeck, Claudine

2016-12-01

Within the Early Hearing Detection and Intervention (EHDI) pathway, which includes the processes of screening, diagnosis and intervention for paediatric hearing loss, paediatric diagnostic audiology involves a battery of specific tests and procedures. International studies have highlighted a golden standard for diagnosis of paediatric hearing loss as based on the Joint Committee of Infant Hearing (2007) diagnostic guidelines, closely resembling the HPCSA diagnostic guidelines. There are limited South African studies on the processes and protocols followed in diagnostic paediatric audiology. This study aims to provide a comparison for how the tests used for diagnosis of paediatric hearing loss in South Africa (within both the public and private healthcare sectors) compare to the HPCSA recommended diagnostic guidelines. A retrospective record review of paediatric clients with hearing loss (recruited through nonprobability convenience sampling) was conducted. This study is part of a longitudinal study of 711 deaf or hard of hearing children referred to the HI HOPES early intervention programme from September 2006 to December 2011. Diagnostic data from audiology reports of 117 children between 0 and 36 months were coded and analysed. Large variation was found in the tests included in the diagnostic audiology reports. For 22 children (19%) a comprehensive test battery was used. Health Professions Council of South Africa (HPCSA) recommended guidelines for diagnostic testing were not followed in any of the records analysed. Components of the HPCSA recommended test battery most frequently omitted was bone conduction testing. For both electrophysiology and behavioural testing, there was limited frequency specificity information. This exclusion of information is evidence of deficiencies in data recording and management, as well as having an effect on accuracy of classification of degree and type of hearing loss. There are gaps in age-appropriate assessment protocols, which will have an effect on accurate differential diagnosis of paediatric hearing loss. Reasons for not including all testing components of the HPCSA recommended guidelines, as well as the possibility of developing guidelines more relevant to a developing world context, should be explored. There might be a need for. The impact of South African specific factors that have an effect on provision of accurate paediatric diagnostic audiology services should be determined. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diagnosis of asthma: diagnostic testing.

PubMed

Brigham, Emily P; West, Natalie E

2015-09-01

Asthma is a heterogeneous disease, encompassing both atopic and non-atopic phenotypes. Diagnosis of asthma is based on the combined presence of typical symptoms and objective tests of lung function. Objective diagnostic testing consists of 2 components: (1) demonstration of airway obstruction, and (2) documentation of variability in degree of obstruction. A review of current guidelines and literature was performed regarding diagnostic testing for asthma. Spirometry with bronchodilator reversibility testing remains the mainstay of asthma diagnostic testing for children and adults. Repetition of the test over several time points may be necessary to confirm airway obstruction and variability thereof. Repeated peak flow measurement is relatively simple to implement in a clinical and home setting. Bronchial challenge testing is reserved for patients in whom the aforementioned testing has been unrevealing but clinical suspicion remains, though is associated with low specificity. Demonstration of eosinophilic inflammation, via fractional exhaled nitric oxide measurement, or atopy, may be supportive of atopic asthma, though diagnostic utility is limited particularly in nonatopic asthma. All efforts should be made to confirm the diagnosis of asthma in those who are being presumptively treated but have not had objective measurements of variability in the degree of obstruction. Multiple testing modalities are available for objective confirmation of airway obstruction and variability thereof, consistent with a diagnosis of asthma in the appropriate clinical context. Providers should be aware that both these characteristics may be present in other disease states, and may not be specific to a diagnosis of asthma. © 2015 ARS-AAOA, LLC.

Comparing the Diagnostic Accuracy of Six Potential Screening Instruments for Bipolar Disorder in Youths Aged 5 to 17 Years.

ERIC Educational Resources Information Center

Youngstrom, Eric A.; Findling, Robert L.; Calabrese, Joseph R.; Gracious, Barbara L.; Demeter, Christine; DelPorto Bedoya, Denise; Price, Megan

2004-01-01

Objective: To compare the diagnostic efficiency of six index tests as predictors of juvenile bipolar disorder in two large outpatient samples, aged 5 to 10 and 11 to 17 years, gathered from 1997 to 2002. Method: DSM-IV diagnosis was based on a semistructured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-Age…

Accelerating the Development and Validation of New Value-Based Diagnostics by Leveraging Biobanks.

PubMed

Schneider, Daniel; Riegman, Peter H J; Cronin, Maureen; Negrouk, Anastassia; Moch, Holger; Balling, Rudi; Penault-Llorca, Frederiques; Zatloukal, Kurt; Horgan, Denis

The challenges faced in developing value-based diagnostics has resulted in few of these tests reaching the clinic, leaving many treatment modalities without matching diagnostics to select patients for particular therapies. Many patients receive therapies from which they are unlikely to benefit, resulting in worse outcomes and wasted health care resources. The paucity of value-based diagnostics is a result of the scientific challenges in developing predictive markers, specifically: (1) complex biology, (2) a limited research infrastructure supporting diagnostic development, and (3) the lack of incentives for diagnostic developers to invest the necessary resources. Better access to biospecimens can address some of these challenges. Methodologies developed to evaluate biomarkers from biospecimens archived from patients enrolled in randomized clinical trials offer the greatest opportunity to develop and validate high-value molecular diagnostics. An alternative opportunity is to access high-quality biospecimens collected from large public and private longitudinal observational cohorts such as the UK Biobank, the US Million Veteran Program, the UK 100,000 Genomes Project, or the French E3N cohort. Value-based diagnostics can be developed to work in a range of samples including blood, serum, plasma, urine, and tumour tissue, and better access to these high-quality biospecimens with clinical data can facilitate biomarker research. © 2016 S. Karger AG, Basel.

Development of a reliable simulation-based test for diagnostic abdominal ultrasound with a pass/fail standard usable for mastery learning.

PubMed

Østergaard, Mia L; Nielsen, Kristina R; Albrecht-Beste, Elisabeth; Konge, Lars; Nielsen, Michael B

2018-01-01

This study aimed to develop a test with validity evidence for abdominal diagnostic ultrasound with a pass/fail-standard to facilitate mastery learning. The simulator had 150 real-life patient abdominal scans of which 15 cases with 44 findings were selected, representing level 1 from The European Federation of Societies for Ultrasound in Medicine and Biology. Four groups of experience levels were constructed: Novices (medical students), trainees (first-year radiology residents), intermediates (third- to fourth-year radiology residents) and advanced (physicians with ultrasound fellowship). Participants were tested in a standardized setup and scored by two blinded reviewers prior to an item analysis. The item analysis excluded 14 diagnoses. Both internal consistency (Cronbach's alpha 0.96) and inter-rater reliability (0.99) were good and there were statistically significant differences (p < 0.001) between all four groups, except the intermediate and advanced groups (p = 1.0). There was a statistically significant correlation between experience and test scores (Pearson's r = 0.82, p < 0.001). The pass/fail-standard failed all novices (no false positives) and passed all advanced (no false negatives). All intermediate participants and six out of 14 trainees passed. We developed a test for diagnostic abdominal ultrasound with solid validity evidence and a pass/fail-standard without any false-positive or false-negative scores. • Ultrasound training can benefit from competency-based education based on reliable tests. • This simulation-based test can differentiate between competency levels of ultrasound examiners. • This test is suitable for competency-based education, e.g. mastery learning. • We provide a pass/fail standard without false-negative or false-positive scores.

Development and Application of a Novel Rasch-Based Methodology for Evaluating Multi-Tiered Assessment Instruments: Validation and Utilization of an Undergraduate Diagnostic Test of the Water Cycle

ERIC Educational Resources Information Center

Romine, William L.; Schaffer, Dane L.; Barrow, Lloyd

2015-01-01

We describe the development and validation of a three-tiered diagnostic test of the water cycle (DTWC) and use it to evaluate the impact of prior learning experiences on undergraduates' misconceptions. While most approaches to instrument validation take a positivist perspective using singular criteria such as reliability and fit with a measurement…

Meta-analysis: accuracy of rapid tests for malaria in travelers returning from endemic areas.

PubMed

Marx, Arthur; Pewsner, Daniel; Egger, Matthias; Nüesch, Reto; Bucher, Heiner C; Genton, Blaise; Hatz, Christoph; Jüni, Peter

2005-05-17

Microscopic diagnosis of malaria is unreliable outside specialized centers. Rapid tests have become available in recent years, but their accuracy has not been assessed systematically. To determine the accuracy of rapid diagnostic tests for ruling out malaria in nonimmune travelers returning from malaria-endemic areas. The authors searched MEDLINE, EMBASE, CAB Health, and CINAHL (1988 to September 2004); hand-searched conference proceedings; checked reference lists; and contacted experts and manufacturers. Diagnostic accuracy studies in nonimmune individuals with suspected malaria were included if they compared rapid tests with expert microscopic examination or polymerase chain reaction tests. Data on study and patient characteristics and results were extracted in duplicate. The main outcome was the likelihood ratio for a negative test result (negative likelihood ratio) for Plasmodium falciparum malaria. Likelihood ratios were combined by using random-effects meta-analysis, stratified by the antigen targeted (histidine-rich protein-2 [HRP-2] or parasite lactate dehydrogenase [LDH]) and by test generation. Nomograms of post-test probabilities were constructed. The authors included 21 studies and 5747 individuals. For P. falciparum, HRP-2-based tests were more accurate than parasite LDH-based tests: Negative likelihood ratios were 0.08 and 0.13, respectively (P = 0.019 for difference). Three-band HRP-2 tests had similar negative likelihood ratios but higher positive likelihood ratios compared with 2-band tests (34.7 vs. 98.5; P = 0.003). For P. vivax, negative likelihood ratios tended to be closer to 1.0 for HRP-2-based tests than for parasite LDH-based tests (0.24 vs. 0.13; P = 0.22), but analyses were based on a few heterogeneous studies. Negative likelihood ratios for the diagnosis of P. malariae or P. ovale were close to 1.0 for both types of tests. In febrile travelers returning from sub-Saharan Africa, the typical probability of P. falciparum malaria is estimated at 1.1% (95% CI, 0.6% to 1.9%) after a negative 3-band HRP-2 test result and 97% (CI, 92% to 99%) after a positive test result. Few studies evaluated 3-band HRP-2 tests. The evidence is also limited for species other than P. falciparum because of the few available studies and their more heterogeneous results. Further studies are needed to determine whether the use of rapid diagnostic tests improves outcomes in returning travelers with suspected malaria. Rapid malaria tests may be a useful diagnostic adjunct to microscopy in centers without major expertise in tropical medicine. Initial decisions on treatment initiation and choice of antimalarial drugs can be based on travel history and post-test probabilities after rapid testing. Expert microscopy is still required for species identification and confirmation.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets.

PubMed

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 10 2 -10 5 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets

PubMed Central

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 102-105 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing. PMID:28740546

Tissue microarrays and quantitative tissue-based image analysis as a tool for oncology biomarker and diagnostic development.

PubMed

Dolled-Filhart, Marisa P; Gustavson, Mark D

2012-11-01

Translational oncology has been improved by using tissue microarrays (TMAs), which facilitate biomarker analysis of large cohorts on a single slide. This has allowed for rapid analysis and validation of potential biomarkers for prognostic and predictive value, as well as for evaluation of biomarker prevalence. Coupled with quantitative analysis of immunohistochemical (IHC) staining, objective and standardized biomarker data from tumor samples can further advance companion diagnostic approaches for the identification of drug-responsive or resistant patient subpopulations. This review covers the advantages, disadvantages and applications of TMAs for biomarker research. Research literature and reviews of TMAs and quantitative image analysis methodology have been surveyed for this review (with an AQUA® analysis focus). Applications such as multi-marker diagnostic development and pathway-based biomarker subpopulation analyses are described. Tissue microarrays are a useful tool for biomarker analyses including prevalence surveys, disease progression assessment and addressing potential prognostic or predictive value. By combining quantitative image analysis with TMAs, analyses will be more objective and reproducible, allowing for more robust IHC-based diagnostic test development. Quantitative multi-biomarker IHC diagnostic tests that can predict drug response will allow for greater success of clinical trials for targeted therapies and provide more personalized clinical decision making.

Point-of-care oral-based diagnostics

PubMed Central

Hart, RW; Mauk, MG; Liu, C; Qiu, X; Thompson, JA; Chen, D; Malamud, D; Abrams, WR; Bau, HH

2014-01-01

Many of the target molecules that reside in blood are also present in oral fluids, albeit at lower concentrations. Oral fluids are, however, relatively easy and safe to collect without the need for specialized equipment and training. Thus, oral fluids provide convenient samples for medical diagnostics. Recent advances in lab-on-a-chip technologies have made minute, fully integrated diagnostic systems practical for an assortment of point-of-care tests. Such systems can perform either immunoassays or molecular diagnostics outside centralized laboratories within time periods ranging from minutes to an hour. The article briefly reviews recent advances in devices for point-of-care testing with a focus on work that has been carried out by the authors as part of a NIH program. PMID:21521419

Evidence base and future research directions in the management of low back pain

PubMed Central

Abbott, Allan

2016-01-01

Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care. PMID:27004162

Canadian Helicobacter Study Group Consensus Conference: Update on the approach to Helicobacter pylori infection in children and adolescents--an evidence-based evaluation.

PubMed

Bourke, Billy; Ceponis, Peter; Chiba, Naoki; Czinn, Steve; Ferraro, Richard; Fischbach, Lori; Gold, Ben; Hyunh, Hien; Jacobson, Kevan; Jones, Nicola L; Koletzko, Sibylle; Lebel, Sylvie; Moayyedi, Paul; Ridell, Robert; Sherman, Philip; van Zanten, Sander; Beck, Ivan; Best, Linda; Boland, Margaret; Bursey, Ford; Chaun, Hugh; Cooper, Geraldine; Craig, Brian; Creuzenet, Carole; Critch, Jeffrey; Govender, Krishnasamy; Hassall, Eric; Kaplan, Alan; Keelan, Monica; Noad, Garth; Robertson, Marli; Smith, Lesley; Stein, Markus; Taylor, Diane; Walters, Thomas; Persaud, Robin; Whitaker, Scott; Woodland, Robert

2005-07-01

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H. pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H. pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H. pylori infection; recurrent abdominal pain of childhood is not an indication to test for H. pylori infection; H. pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H. pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H. pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H. pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H. pylori infection; serological antibody tests are not recommended as diagnostic tools for H. pylori infection in children; first-line therapy for H. pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics (clarithromycin plus amoxicillin or metronidazole); the optimal treatment period for H. pylori infection in children is 14 days; and H. pylori culture and antibiotic sensitivity testing should be made available to monitor population antibiotic resistance and manage treatment failures.

Mobile diagnostics: next-generation technologies for in vitro diagnostics.

PubMed

Shin, Joonchul; Chakravarty, Sudesna; Choi, Wooseok; Lee, Kyungyeon; Han, Dongsik; Hwang, Hyundoo; Choi, Jaekyu; Jung, Hyo-Il

2018-03-26

The emergence of a wide range of applications of smartphones along with advances in 'liquid biopsy' has significantly propelled medical research particularly in the field of in vitro diagnostics (IVD). Herein, we have presented a detailed analysis of IVD, its associated critical concerns and probable solutions. It also demonstrates the transition in terms of analytes from minimally invasive (blood) to non-invasive (urine, saliva and sweat) and depicts how the different features of a smartphone can be integrated for specific diagnostic purposes. This review basically highlights recent advances in the applications of smartphone-based biosensors in IVD taking into account the following factors: accuracy and portability; quantitative and qualitative analysis; and centralization and decentralization tests. Furthermore, the critical concerns and future direction of diagnostics based on smartphones are also discussed.

The rapid evolution of molecular genetic diagnostics in neuromuscular diseases.

PubMed

Volk, Alexander E; Kubisch, Christian

2017-10-01

The development of massively parallel sequencing (MPS) has revolutionized molecular genetic diagnostics in monogenic disorders. The present review gives a brief overview of different MPS-based approaches used in clinical diagnostics of neuromuscular disorders (NMDs) and highlights their advantages and limitations. MPS-based approaches like gene panel sequencing, (whole) exome sequencing, (whole) genome sequencing, and RNA sequencing have been used to identify the genetic cause in NMDs. Although gene panel sequencing has evolved as a standard test for heterogeneous diseases, it is still debated, mainly because of financial issues and unsolved problems of variant interpretation, whether genome sequencing (and to a lesser extent also exome sequencing) of single patients can already be regarded as routine diagnostics. However, it has been shown that the inclusion of parents and additional family members often leads to a substantial increase in the diagnostic yield in exome-wide/genome-wide MPS approaches. In addition, MPS-based RNA sequencing just enters the research and diagnostic scene. Next-generation sequencing increasingly enables the detection of the genetic cause in highly heterogeneous diseases like NMDs in an efficient and affordable way. Gene panel sequencing and family-based exome sequencing have been proven as potent and cost-efficient diagnostic tools. Although clinical validation and interpretation of genome sequencing is still challenging, diagnostic RNA sequencing represents a promising tool to bypass some hurdles of diagnostics using genomic DNA.

Automated knowledge generation

NASA Technical Reports Server (NTRS)

Myler, Harley R.; Gonzalez, Avelino J.

1988-01-01

The general objectives of the NASA/UCF Automated Knowledge Generation Project were the development of an intelligent software system that could access CAD design data bases, interpret them, and generate a diagnostic knowledge base in the form of a system model. The initial area of concentration is in the diagnosis of the process control system using the Knowledge-based Autonomous Test Engineer (KATE) diagnostic system. A secondary objective was the study of general problems of automated knowledge generation. A prototype was developed, based on object-oriented language (Flavors).

CMOS Cell Sensors for Point-of-Care Diagnostics

PubMed Central

Adiguzel, Yekbun; Kulah, Haluk

2012-01-01

The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and for providing health services evenly throughout the population, including the rural districts. The requirements can only be fulfilled by technologies whose productivity has already been proven, such as complementary metal-oxide-semiconductors (CMOS). CMOS-based products can enable clinical tests in a fast, simple, safe, and reliable manner, with improved sensitivities. Portability due to diminished sensor dimensions and compactness of the test set-ups, along with low sample and power consumption, is another vital feature. CMOS-based sensors for cell studies have the potential to become essential counterparts of point-of-care diagnostics technologies. Hence, this review attempts to inform on the sensors fabricated with CMOS technology for point-of-care diagnostic studies, with a focus on CMOS image sensors and capacitance sensors for cell studies. PMID:23112587

CMOS cell sensors for point-of-care diagnostics.

PubMed

Adiguzel, Yekbun; Kulah, Haluk

2012-01-01

The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and for providing health services evenly throughout the population, including the rural districts. The requirements can only be fulfilled by technologies whose productivity has already been proven, such as complementary metal-oxide-semiconductors (CMOS). CMOS-based products can enable clinical tests in a fast, simple, safe, and reliable manner, with improved sensitivities. Portability due to diminished sensor dimensions and compactness of the test set-ups, along with low sample and power consumption, is another vital feature. CMOS-based sensors for cell studies have the potential to become essential counterparts of point-of-care diagnostics technologies. Hence, this review attempts to inform on the sensors fabricated with CMOS technology for point-of-care diagnostic studies, with a focus on CMOS image sensors and capacitance sensors for cell studies.

Towards non- and minimally instrumented, microfluidics-based diagnostic devices†

PubMed Central

Weigl, Bernhard; Domingo, Gonzalo; LaBarre, Paul; Gerlach, Jay

2009-01-01

In many health care settings, it is uneconomical, impractical, or unaffordable to maintain and access a fully equipped diagnostics laboratory. Examples include home health care, developing-country health care, and emergency situations in which first responders are dealing with pandemics or biowarfare agent release. In those settings, fully disposable diagnostic devices that require no instrument support, reagent, or significant training are well suited. Although the only such technology to have found widespread adoption so far is the immunochromatographic rapid assay strip test, microfluidics holds promise to expand the range of assay technologies that can be performed in formats similar to that of a strip test. In this paper, we review progress toward development of disposable, low-cost, easy-to-use microfluidics-based diagnostics that require no instrument at all. We also present examples of microfluidic functional elements—including mixers, separators, and detectors—as well as complete microfluidic devices that function entirely without any moving parts and external power sources. PMID:19023463

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

PubMed

Tsalik, Ephraim L; Li, Yanhong; Hudson, Lori L; Chu, Vivian H; Himmel, Tiffany; Limkakeng, Alex T; Katz, Jason N; Glickman, Seth W; McClain, Micah T; Welty-Wolf, Karen E; Fowler, Vance G; Ginsburg, Geoffrey S; Woods, Christopher W; Reed, Shelby D

2016-03-01

Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved. Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development.

Detection of spring viraemia of carp virus (SVCV) by loop-mediated isothermal amplification (LAMP) in koi carp, Cyprinus carpio L

USGS Publications Warehouse

Shivappa, R.B.; Savan, R.; Kono, T.; Sakai, M.; Emmenegger, E.; Kurath, G.; Levine, Jay F.

2008-01-01

Spring viraemia of carp virus (SVCV) is a rhabdovirus associated with systemic illness and mortality in cyprinids. Several diagnostic tests are available for detection of SVCV. However, most of these tests are time consuming and are not well adapted for field-based diagnostics. In this study, a diagnostic tool for SVCV detection based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been developed. Based on the nucleotide sequence of the glycoprotein (G) gene of SVCV North Carolina (NC) isolate, four sets (each set containing two outer and two inner) of primers were designed. Temperature and time conditions were optimized to 65 ??C and 60 min, respectively, for LAMP and RT-LAMP using one primer set. In vitro specificity was evaluated using four different strains of fish rhabdoviruses and RT-LAMP was found to be specific to SVCV. Serial dilutions of SVCV NC isolate was used to evaluate the in vitro sensitivity of RT-LAMP. Sensitivity of the assays was similar to RT-PCR and detected SVCV even at the lowest dilution of 10 1 TCID50 mL-1. The ability of RT-LAMP to detect SVCV from infected carp was also tested and the assay detected SVCV from all infected fish. The isothermal temperature requirements, high specificity and sensitivity, and short incubation time of the RT-LAMP assay make it an excellent choice as a field diagnostic test for SVCV. ?? 2008 The Authors.

Health economic evaluation of a serum-based blood test for brain tumour diagnosis: exploration of two clinical scenarios.

PubMed

Gray, Ewan; Butler, Holly J; Board, Ruth; Brennan, Paul M; Chalmers, Anthony J; Dawson, Timothy; Goodden, John; Hamilton, Willie; Hegarty, Mark G; James, Allan; Jenkinson, Michael D; Kernick, David; Lekka, Elvira; Livermore, Laurent J; Mills, Samantha J; O'Neill, Kevin; Palmer, David S; Vaqas, Babar; Baker, Matthew J

2018-05-24

To determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway. A model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion. Explored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA. Calculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum. The primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost-effectiveness analysis. Results indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost-effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of £20 000-£30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately £40). Use of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The diagnostic plot analysis of artesian aquifers with case studies in Table Mountain Group of South Africa

NASA Astrophysics Data System (ADS)

Sun, Xiaobin; Xu, Yongxin; Lin, Lixiang

2015-05-01

Parameter estimates of artesian aquifers where piezometric head is above ground level are largely made through free-flowing and recovery tests. The straight-line method proposed by Jacob-Lohman is often used for interpretation of flow rate measured at flowing artesian boreholes. However, the approach fails to interpret the free-flowing test data from two artesian boreholes in the fractured-rock aquifer in Table Mountain Group (TMG) of South Africa. The diagnostic plot method using the reciprocal rate derivative is adapted to evaluate the artesian aquifer properties. The variation of the derivative helps not only identify flow regimes and discern the boundary conditions, but also facilitates conceptualization of the aquifer system and selection of an appropriate model for data interpretation later on. Test data from two free-flowing tests conducted in different sites in TMG are analysed using the diagnostic plot method. Based on the results, conceptual models and appropriate approaches are developed to evaluate the aquifer properties. The advantages and limitations of using the diagnostic plot method on free-flowing test data are discussed.

Cost-effectiveness of using a molecular diagnostic test to improve preoperative diagnosis of thyroid cancer.

PubMed

Najafzadeh, Mehdi; Marra, Carlo A; Lynd, Larry D; Wiseman, Sam M

2012-12-01

Fine-needle aspiration biopsy (FNAB) is a safe and inexpensive diagnostic procedure for evaluating thyroid nodules.Up to 25% of the results from an FNAB, however, may not be diagnostic or may be indeterminate, leading to a subsequent diagnostic thyroid surgery. A new molecularly based diagnostic test could potentially reduce indeterminate cytological results and, with high accuracy, provide a definitive diagnosis for cancer in thyroid nodules. The aim of the study was to estimate the cost-effectiveness of utilizing a molecular diagnostic (DX) test as an adjunct to FNAB, compared with NoDX, to improve the preoperative diagnosis of thyroid nodules. We constructed a patient-level simulation model to estimate the clinical and economic outcomes of using a DX test compared with current practice (NoDX) for the diagnosis of thyroid nodules. By using a cost-effectiveness framework, we measured incremental clinical benefits in terms of quality-adjusted life-years and incremental costs over a 10-year time horizon. Assuming 95% sensitivity and specificity of the Dx test when used as an adjunct to FNAB, the utilization of the DX test resulted in a gain of 0.046 quality-adjusted life-years (95% confidence interval 0.019-0.078) and a saving of $1087 (95% confidence interval $691-$1533) in direct costs per patient. If the cost of the Dx test is less than $1087 per test, we expect to save quality-adjusted life-years and reduce costs when it is utilized. Sensitivity of the DX test, compared with specificity, had a larger influence on the overall outcomes. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Diagnostic efficacy of microscopy, rapid diagnostic test and polymerase chain reaction for malaria using bayesian latent class analysis.

PubMed

Saha, Sreemanti; Narang, Rahul; Deshmukh, Pradeep; Pote, Kiran; Anvikar, Anup; Narang, Pratibha

2017-01-01

The diagnostic techniques for malaria are undergoing a change depending on the availability of newer diagnostics and annual parasite index of infection in a particular area. At the country level, guidelines are available for selection of diagnostic tests; however, at the local level, this decision is made based on malaria situation in the area. The tests are evaluated against the gold standard, and if that standard has limitations, it becomes difficult to compare other available tests. Bayesian latent class analysis computes its internal standard rather than using the conventional gold standard and helps comparison of various tests including the conventional gold standard. In a cross-sectional study conducted in a tertiary care hospital setting, we have evaluated smear microscopy, rapid diagnostic test (RDT), and polymerase chain reaction (PCR) for diagnosis of malaria using Bayesian latent class analysis. We found the magnitude of malaria to be 17.7% (95% confidence interval: 12.5%-23.9%) among the study subjects. In the present study, the sensitivity of microscopy was 63%, but it had very high specificity (99.4%). Sensitivity and specificity of RDT and PCR were high with RDT having a marginally higher sensitivity (94% vs. 90%) and specificity (99% vs. 95%). On comparison of likelihood ratios (LRs), RDT had the highest LR for positive test result (175) and the lowest LR for negative test result (0.058) among the three tests. In settings like ours conventional smear microscopy may be replaced with RDT and as we move toward elimination and facilities become available PCR may be roped into detect cases with lower parasitaemia.

Improved diagnostic testing and malaria treatment practices in Zambia.

PubMed

Hamer, Davidson H; Ndhlovu, Micky; Zurovac, Dejan; Fox, Matthew; Yeboah-Antwi, Kojo; Chanda, Pascalina; Sipilinyambe, Naawa; Simon, Jonathon L; Snow, Robert W

2007-05-23

Improving the accuracy of malaria diagnosis with rapid antigen-detection diagnostic tests (RDTs) has been proposed as an approach for reducing overtreatment of malaria in the current era of widespread implementation of artemisinin-based combination therapy in sub-Saharan Africa. To assess the association between use of microscopy and RDT and the prescription of antimalarials. Cross-sectional, cluster sample survey, carried out between March and May 2006, of all outpatients treated during 1 working day at government and mission health facilities in 4 sentinel districts in Zambia. Proportions of patients undergoing malaria diagnostic procedures and receiving antimalarial treatment. Seventeen percent of the 104 health facilities surveyed had functional microscopy, 63% had RDTs available, and 73% had 1 or more diagnostics available. Of patients with fever (suspected malaria), 27.8% (95% confidence interval [CI], 13.1%-42.5%) treated in health facilities with malaria diagnostics were tested and 44.6% had positive test results. Of patients with negative blood smear results, 58.4% (95% CI, 36.7%-80.2%) were prescribed an antimalaria drug, as were 35.5% (95% CI, 16.0%-55.0%) of those with a negative RDT result. Of patients with fever who did not have diagnostic tests done, 65.9% were also prescribed antimalarials. In facilities with artemether-lumefantrine in stock, this antimalarial was prescribed to a large proportion of febrile patients with a positive diagnostic test result (blood smear, 75.0% [95% CI, 51.7%-98.3%]; RDT, 70.4% [95% CI, 39.3%-100.0%]), but also to some of those with a negative diagnostic test result (blood smear, 30.4% [95% CI, 8.0%-52. 9%]; RDT, 26.7% [95% CI, 5.7%-47.7%]). Despite efforts to expand the provision of malaria diagnostics in Zambia, they continue to be underused and patients with negative test results frequently receive antimalarials. Provision of new tools to reduce inappropriate use of new expensive antimalarial treatments must be accompanied by a major change in clinical treatment of patients presenting with fever but lacking evidence of malaria infection.

[Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis].

PubMed

Shin, Jung Woo; Park, Neung Hwa

2016-07-25

The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis.

Improved PCR-Based Detection of Soil Transmitted Helminth Infections Using a Next-Generation Sequencing Approach to Assay Design.

PubMed

Pilotte, Nils; Papaiakovou, Marina; Grant, Jessica R; Bierwert, Lou Ann; Llewellyn, Stacey; McCarthy, James S; Williams, Steven A

2016-03-01

The soil transmitted helminths are a group of parasitic worms responsible for extensive morbidity in many of the world's most economically depressed locations. With growing emphasis on disease mapping and eradication, the availability of accurate and cost-effective diagnostic measures is of paramount importance to global control and elimination efforts. While real-time PCR-based molecular detection assays have shown great promise, to date, these assays have utilized sub-optimal targets. By performing next-generation sequencing-based repeat analyses, we have identified high copy-number, non-coding DNA sequences from a series of soil transmitted pathogens. We have used these repetitive DNA elements as targets in the development of novel, multi-parallel, PCR-based diagnostic assays. Utilizing next-generation sequencing and the Galaxy-based RepeatExplorer web server, we performed repeat DNA analysis on five species of soil transmitted helminths (Necator americanus, Ancylostoma duodenale, Trichuris trichiura, Ascaris lumbricoides, and Strongyloides stercoralis). Employing high copy-number, non-coding repeat DNA sequences as targets, novel real-time PCR assays were designed, and assays were tested against established molecular detection methods. Each assay provided consistent detection of genomic DNA at quantities of 2 fg or less, demonstrated species-specificity, and showed an improved limit of detection over the existing, proven PCR-based assay. The utilization of next-generation sequencing-based repeat DNA analysis methodologies for the identification of molecular diagnostic targets has the ability to improve assay species-specificity and limits of detection. By exploiting such high copy-number repeat sequences, the assays described here will facilitate soil transmitted helminth diagnostic efforts. We recommend similar analyses when designing PCR-based diagnostic tests for the detection of other eukaryotic pathogens.

Disposable cartridge biosensor platform for portable diagnostics

NASA Astrophysics Data System (ADS)

Yaras, Yusuf S.; Cakmak, Onur; Gunduz, Ali B.; Saglam, Gokhan; Olcer, Selim; Mostafazadeh, Aref; Baris, Ibrahim; Civitci, Fehmi; Yaralioglu, Goksen G.; Urey, Hakan

2017-03-01

We developed two types of cantilever-based biosensors for portable diagnostics applications. One sensor is based on MEMS cantilever chip mounted in a microfluidic channel and the other sensor is based on a movable optical fiber placed across a microfluidic channel. Both types of sensors were aimed at direct mechanical measurement of coagulation time in a disposable cartridge using plasma or whole blood samples. There are several similarities and also some important differences between the MEMS based and the optical fiber based solutions. The aim of this paper is to provide a comparison between the two solutions and the results. For both types of sensors, actuation of the cantilever or the moving fiber is achieved using an electro coil and the readout is optical. Since both the actuation and sensing are remote, no electrical connections are required for the cartridge. Therefore it is possible to build low cost disposable cartridges. The reader unit for the cartridge contains light sources, photodetectors, the electro coil, a heater, analog electronics, and a microprocessor. The reader unit has different optical interfaces for the cartridges that have MEMS cantilevers and moving fibers. MEMS based platform has better sensitivity but optomechanical alignment is a challenge and measurements with whole blood were not possible due to high scattering of light by the red blood cells. Fiber sensor based platform has relaxed optomechanical tolerances, ease of manufacturing, and it allows measurements in whole blood. Both sensors were tested using control plasma samples for activated-Partial-Thromboplastin-Time (aPTT) measurements. Control plasma test results matched with the manufacturer's datasheet. Optical fiber based system was tested for aPTT tests with human whole blood samples and the proposed platform provided repeatable test results making the system method of choice for portable diagnostics.

The impact of patents on the development of genome-based clinical diagnostics: an analysis of case studies

PubMed Central

Pierce, Brandon L.; Carlson, Christopher S.; Kuszler, Patricia C.; Stanford, Janet L.; Austin, Melissa A.

2010-01-01

Purpose Fragmented ownership of diagnostic gene patents has the potential to create an ‘anticommons’ in the area of genomic diagnostics, making it difficult and expensive to assemble the patent rights necessary to develop a panel of genetic tests. The objectives of this study were to identify U.S. patents that protect existing panels of genetic tests, describe how (or if) test providers acquired rights to these patents, and determine if fragmented patent ownership has inhibited the commercialization of these panels. Methods As case studies, we selected four clinical applications of genetic testing (cystic fibrosis, maturity-onset diabetes of the young, long QT syndrome, and hereditary breast cancer) that utilize tests protected by ≥3 U.S. patents. We summarized publically available information on relevant patents, test providers, licenses, and litigation. Results For each case study, all tests of major genes/mutations were patented, and at least one party held the collective rights to conduct all relevant tests, often as a result of licensing agreements. Conclusions We did not find evidence that fragmentation of patent rights has inhibited commercialization of genetic testing services. However, as knowledge of genetic susceptibility increases, it will be important to consider the potential consequences of fragmented ownership of diagnostic gene patents. PMID:19367193

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Procedural Terminology published by the American Medical Association. (vii) Diagnostic tests performed by a... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Procedural Terminology published by the American Medical Association. (vii) Diagnostic tests performed by a... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

A Predictive Model to Estimate Cost Savings of a Novel Diagnostic Blood Panel for Diagnosis of Diarrhea-predominant Irritable Bowel Syndrome.

PubMed

Pimentel, Mark; Purdy, Chris; Magar, Raf; Rezaie, Ali

2016-07-01

A high incidence of irritable bowel syndrome (IBS) is associated with significant medical costs. Diarrhea-predominant IBS (IBS-D) is diagnosed on the basis of clinical presentation and diagnostic test results and procedures that exclude other conditions. This study was conducted to estimate the potential cost savings of a novel IBS diagnostic blood panel that tests for the presence of antibodies to cytolethal distending toxin B and anti-vinculin associated with IBS-D. A cost-minimization (CM) decision tree model was used to compare the costs of a novel IBS diagnostic blood panel pathway versus an exclusionary diagnostic pathway (ie, standard of care). The probability that patients proceed to treatment was modeled as a function of sensitivity, specificity, and likelihood ratios of the individual biomarker tests. One-way sensitivity analyses were performed for key variables, and a break-even analysis was performed for the pretest probability of IBS-D. Budget impact analysis of the CM model was extrapolated to a health plan with 1 million covered lives. The CM model (base-case) predicted $509 cost savings for the novel IBS diagnostic blood panel versus the exclusionary diagnostic pathway because of the avoidance of downstream testing (eg, colonoscopy, computed tomography scans). Sensitivity analysis indicated that an increase in both positive likelihood ratios modestly increased cost savings. Break-even analysis estimated that the pretest probability of disease would be 0.451 to attain cost neutrality. The budget impact analysis predicted a cost savings of $3,634,006 ($0.30 per member per month). The novel IBS diagnostic blood panel may yield significant cost savings by allowing patients to proceed to treatment earlier, thereby avoiding unnecessary testing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A Community-Based IoT Personalized Wireless Healthcare Solution Trial.

PubMed

Catherwood, Philip A; Steele, David; Little, Mike; Mccomb, Stephen; Mclaughlin, James

2018-01-01

This paper presents an advanced Internet of Things point-of-care bio-fluid analyzer; a LoRa/Bluetooth-enabled electronic reader for biomedical strip-based diagnostics system for personalized monitoring. We undertake test simulations (technology trial without patient subjects) to demonstrate potential of long-range analysis, using a disposable test 'key' and companion Android app to form a diagnostic platform suitable for remote point-of-care screening for urinary tract infection (UTI). The 868 MHz LoRaWAN-enabled personalized monitor demonstrated sound potential with UTI test results being correctly diagnosed and transmitted to a remote secure cloud server in every case. Tests ranged over distances of 1.1-6.0 Km with radio path losses from 119-141 dB. All tests conducted were correctly and robustly received at the base station and relayed to the secure server for inspection. The UTI test strips were visually inspected for correct diagnosis based on color change and verified as 100% accurate. Results from testing across a number of regions indicate that such an Internet of Things medical solution is a robust and simple way to deliver next generation community-based smart diagnostics and disease management to best benefit patients and clinical staff alike. This significant step can be applied to any type of home or region, particularly those lacking suitable mobile signals, broadband connections, or even landlines. It brings subscription-free long-range bio-telemetry to healthcare providers and offers savings on regular clinician home visits or frequent clinic visits by the chronically ill. This paper highlights practical hurdles in establishing an Internet of Medical Things network, assisting informed deployment of similar future systems.

A Community-Based IoT Personalized Wireless Healthcare Solution Trial

PubMed Central

Steele, David; Little, Mike; Mccomb, Stephen; Mclaughlin, James

2018-01-01

This paper presents an advanced Internet of Things point-of-care bio-fluid analyzer; a LoRa/Bluetooth-enabled electronic reader for biomedical strip-based diagnostics system for personalized monitoring. We undertake test simulations (technology trial without patient subjects) to demonstrate potential of long-range analysis, using a disposable test ‘key’ and companion Android app to form a diagnostic platform suitable for remote point-of-care screening for urinary tract infection (UTI). The 868 MHz LoRaWAN-enabled personalized monitor demonstrated sound potential with UTI test results being correctly diagnosed and transmitted to a remote secure cloud server in every case. Tests ranged over distances of 1.1–6.0 Km with radio path losses from 119–141 dB. All tests conducted were correctly and robustly received at the base station and relayed to the secure server for inspection. The UTI test strips were visually inspected for correct diagnosis based on color change and verified as 100% accurate. Results from testing across a number of regions indicate that such an Internet of Things medical solution is a robust and simple way to deliver next generation community-based smart diagnostics and disease management to best benefit patients and clinical staff alike. This significant step can be applied to any type of home or region, particularly those lacking suitable mobile signals, broadband connections, or even landlines. It brings subscription-free long-range bio-telemetry to healthcare providers and offers savings on regular clinician home visits or frequent clinic visits by the chronically ill. This paper highlights practical hurdles in establishing an Internet of Medical Things network, assisting informed deployment of similar future systems. PMID:29888145

Validity Arguments for Diagnostic Assessment Using Automated Writing Evaluation

ERIC Educational Resources Information Center

Chapelle, Carol A.; Cotos, Elena; Lee, Jooyoung

2015-01-01

Two examples demonstrate an argument-based approach to validation of diagnostic assessment using automated writing evaluation (AWE). "Criterion"®, was developed by Educational Testing Service to analyze students' papers grammatically, providing sentence-level error feedback. An interpretive argument was developed for its use as part of…

When BVD doesn't look like BVD

USDA-ARS?s Scientific Manuscript database

Due to the sheer number of different clinical presentations existing under the BVD umbrella, diagnosing BVD based on clinical signs is not advisable. Thus diagnosis relies upon testing of samples in diagnostic laboratories. In the US, most of the diagnostic effort has been focused on identifying a...

How to prevent overdiagnosis.

PubMed

Chiolero, Arnaud; Paccaud, Fred; Aujesky, Drahomir; Santschi, Valérie; Rodondi, Nicolas

2015-01-01

Overdiagnosis is the diagnosis of an abnormality that is not associated with a substantial health hazard and that patients have no benefit to be aware of. It is neither a misdiagnosis (diagnostic error), nor a false positive result (positive test in the absence of a real abnormality). It mainly results from screening, use of increasingly sensitive diagnostic tests, incidental findings on routine examinations, and widening diagnostic criteria to define a condition requiring an intervention. The blurring boundaries between risk and disease, physicians' fear of missing a diagnosis and patients' need for reassurance are further causes of overdiagnosis. Overdiagnosis often implies procedures to confirm or exclude the presence of the condition and is by definition associated with useless treatments and interventions, generating harm and costs without any benefit. Overdiagnosis also diverts healthcare professionals from caring about other health issues. Preventing overdiagnosis requires increasing awareness of healthcare professionals and patients about its occurrence, the avoidance of unnecessary and untargeted diagnostic tests, and the avoidance of screening without demonstrated benefits. Furthermore, accounting systematically for the harms and benefits of screening and diagnostic tests and determining risk factor thresholds based on the expected absolute risk reduction would also help prevent overdiagnosis.

A clinical approach to diagnosis of autoimmune encephalitis

PubMed Central

Graus, Francesc; Titulaer, Maarten J; Balu, Ramani; Benseler, Susanne; Bien, Christian G; Cellucci, Tania; Cortese, Irene; Dale, Russell C; Gelfand, Jeffrey M; Geschwind, Michael; Glaser, Carol A; Honnorat, Jerome; Höftberger, Romana; Iizuka, Takahiro; Irani, Sarosh R; Lancaster, Eric; Leypoldt, Frank; Prüss, Harald; Rae-Grant, Alexander; Reindl, Markus; Rosenfeld, Myrna R; Rostásy, Kevin; Saiz, Albert; Venkatesan, Arun; Vincent, Angela; Wandinger, Klaus-Peter; Waters, Patrick; Dalmau, Josep

2016-01-01

Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy. PMID:26906964

Administrative database code accuracy did not vary notably with changes in disease prevalence.

PubMed

van Walraven, Carl; English, Shane; Austin, Peter C

2016-11-01

Previous mathematical analyses of diagnostic tests based on the categorization of a continuous measure have found that test sensitivity and specificity varies significantly by disease prevalence. This study determined if the accuracy of diagnostic codes varied by disease prevalence. We used data from two previous studies in which the true status of renal disease and primary subarachnoid hemorrhage, respectively, had been determined. In multiple stratified random samples from the two previous studies having varying disease prevalence, we measured the accuracy of diagnostic codes for each disease using sensitivity, specificity, and positive and negative predictive value. Diagnostic code sensitivity and specificity did not change notably within clinically sensible disease prevalence. In contrast, positive and negative predictive values changed significantly with disease prevalence. Disease prevalence had no important influence on the sensitivity and specificity of diagnostic codes in administrative databases. Copyright © 2016 Elsevier Inc. All rights reserved.

[Chronic diarrhoea: Definition, classification and diagnosis].

PubMed

Fernández-Bañares, Fernando; Accarino, Anna; Balboa, Agustín; Domènech, Eugeni; Esteve, Maria; Garcia-Planella, Esther; Guardiola, Jordi; Molero, Xavier; Rodríguez-Luna, Alba; Ruiz-Cerulla, Alexandra; Santos, Javier; Vaquero, Eva

2016-10-01

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Electrophysiology of Cranial Nerve Testing: Trigeminal and Facial Nerves.

PubMed

Muzyka, Iryna M; Estephan, Bachir

2018-01-01

The clinical examination of the trigeminal and facial nerves provides significant diagnostic value, especially in the localization of lesions in disorders affecting the central and/or peripheral nervous system. The electrodiagnostic evaluation of these nerves and their pathways adds further accuracy and reliability to the diagnostic investigation and the localization process, especially when different testing methods are combined based on the clinical presentation and the electrophysiological findings. The diagnostic uniqueness of the trigeminal and facial nerves is their connectivity and their coparticipation in reflexes commonly used in clinical practice, namely the blink and corneal reflexes. The other reflexes used in the diagnostic process and lesion localization are very nerve specific and add more diagnostic yield to the workup of certain disorders of the nervous system. This article provides a review of commonly used electrodiagnostic studies and techniques in the evaluation and lesion localization of cranial nerves V and VII.

Diagnostic accuracy of lymphoma established by fine-needle aspiration cytological biopsy

NASA Astrophysics Data System (ADS)

Delyuzar; Amir, Z.; Suryadi, D.

2018-03-01

Based on Globocan data in 2012, it is estimated that about 14,495 Indonesians suffer from lymphoma, both Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma. Some areas of specialization still doubt the accuracy of cytology diagnosis of fine needle aspiration biopsy.This study is a diagnostic test with a cross sectional analytic design to see how the cytology diagnostic accuracy of fine needle aspiration aspirate in lymphoma. It was in Department of Anatomical Pathology Faculty of Medicine USU, Haji Adam Malik Hospital, Dr.Pirngadi hospital, or private clinic in Medan. Peripheral cytology technique biopsy of fine needle aspiration on lymph node subsequently stained with Giemsa, when the cytology of lymphoma is obtained and confirmed by histopathologic examination. Cytology and histopathologic examination will be tested by Diagnostic Test and assessed for its sensitivity and specificity. The diagnostic of lymphoma cytology provides 93.33% sensitivity and 92.31% specificity when confirmed by histopathological examination. Positive predictive value and negative predictive value of 96.55% and 85.71% respectively. In conclusion, the cytology of fine needle aspiration biopsy is accurate enough to be used as a diagnostic tool, so it is advisable to establish a lymphoma diagnosis to perform a needle aspiration biopsy examination.

Selective testing strategies for diagnosing group A streptococcal infection in children with pharyngitis: a systematic review and prospective multicentre external validation study

PubMed Central

Cohen, Jérémie F.; Cohen, Robert; Levy, Corinne; Thollot, Franck; Benani, Mohamed; Bidet, Philippe; Chalumeau, Martin

2015-01-01

Background: Several clinical prediction rules for diagnosing group A streptococcal infection in children with pharyngitis are available. We aimed to compare the diagnostic accuracy of rules-based selective testing strategies in a prospective cohort of children with pharyngitis. Methods: We identified clinical prediction rules through a systematic search of MEDLINE and Embase (1975–2014), which we then validated in a prospective cohort involving French children who presented with pharyngitis during a 1-year period (2010–2011). We diagnosed infection with group A streptococcus using two throat swabs: one obtained for a rapid antigen detection test (StreptAtest, Dectrapharm) and one obtained for culture (reference standard). We validated rules-based selective testing strategies as follows: low risk of group A streptococcal infection, no further testing or antibiotic therapy needed; intermediate risk of infection, rapid antigen detection for all patients and antibiotic therapy for those with a positive test result; and high risk of infection, empiric antibiotic treatment. Results: We identified 8 clinical prediction rules, 6 of which could be prospectively validated. Sensitivity and specificity of rules-based selective testing strategies ranged from 66% (95% confidence interval [CI] 61–72) to 94% (95% CI 92–97) and from 40% (95% CI 35–45) to 88% (95% CI 85–91), respectively. Use of rapid antigen detection testing following the clinical prediction rule ranged from 24% (95% CI 21–27) to 86% (95% CI 84–89). None of the rules-based selective testing strategies achieved our diagnostic accuracy target (sensitivity and specificity > 85%). Interpretation: Rules-based selective testing strategies did not show sufficient diagnostic accuracy in this study population. The relevance of clinical prediction rules for determining which children with pharyngitis should undergo a rapid antigen detection test remains questionable. PMID:25487666

A new condition for assessing the clinical efficiency of a diagnostic test.

PubMed

Bokhari, Ehsan; Hubert, Lawrence

2015-09-01

When prediction using a diagnostic test outperforms simple prediction using base rates, the test is said to be "clinically efficient," a term first introduced into the literature by Meehl and Rosen (1955) in Psychological Bulletin. This article provides three equivalent conditions for determining the clinical efficiency of a diagnostic test: (a) Meehl-Rosen (Meehl & Rosen, 1955); (b) Dawes (Dawes, 1962); and (c) the Bokhari-Hubert condition, introduced here for the first time. Clinical efficiency is then generalized to situations where misclassification costs are considered unequal (for example, false negatives are more costly than false positives). As an illustration, the clinical efficiency of an actuarial device for predicting violent and dangerous behavior is examined that was developed as part of the MacArthur Violence Risk Assessment Study. (c) 2015 APA, all rights reserved.

The diagnostic test accuracy of magnetic resonance imaging, magnetic resonance arthrography and computer tomography in the detection of chondral lesions of the hip.

PubMed

Smith, Toby O; Simpson, Michael; Ejindu, Vivian; Hing, Caroline B

2013-04-01

The purpose of this study was to assess the diagnostic test accuracy of magnetic resonance imaging (MRI), magnetic resonance arthrography (MRA) and multidetector arrays in CT arthrography (MDCT) for assessing chondral lesions in the hip joint. A review of the published and unpublished literature databases was performed to identify all studies reporting the diagnostic test accuracy (sensitivity/specificity) of MRI, MRA or MDCT for the assessment of adults with chondral (cartilage) lesions of the hip with surgical comparison (arthroscopic or open) as the reference test. All included studies were reviewed using the quality assessment of diagnostic accuracy studies appraisal tool. Pooled sensitivity, specificity, likelihood ratios and diagnostic odds ratios were calculated with 95 % confidence intervals using a random-effects meta-analysis for MRI, MRA and MDCT imaging. Eighteen studies satisfied the eligibility criteria. These included 648 hips from 637 patients. MRI indicated a pooled sensitivity of 0.59 (95 % CI: 0.49-0.70) and specificity of 0.94 (95 % CI: 0.90-0.97), and MRA sensitivity and specificity values were 0.62 (95 % CI: 0.57-0.66) and 0.86 (95 % CI: 0.83-0.89), respectively. The diagnostic test accuracy for the detection of hip joint cartilage lesions is currently superior for MRI compared with MRA. There were insufficient data to perform meta-analysis for MDCT or CTA protocols. Based on the current limited diagnostic test accuracy of the use of magnetic resonance or CT, arthroscopy remains the most accurate method of assessing chondral lesions in the hip joint.

Gaseous electron multiplier-based soft x-ray plasma diagnostics development: Preliminary tests at ASDEX Upgrade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chernyshova, M., E-mail: maryna.chernyshova@ipplm.pl; Malinowski, K.; Czarski, T.

2016-11-15

A Gaseous Electron Multiplier (GEM)-based detector is being developed for soft X-ray diagnostics on tokamaks. Its main goal is to facilitate transport studies of impurities like tungsten. Such studies are very relevant to ITER, where the excessive accumulation of impurities in the plasma core should be avoided. This contribution provides details of the preliminary tests at ASDEX Upgrade (AUG) with a focus on the most important aspects for detector operation in harsh radiation environment. It was shown that both spatially and spectrally resolved data could be collected, in a reasonable agreement with other AUG diagnostics. Contributions to the GEM signalmore » include also hard X-rays, gammas, and neutrons. First simulations of the effect of high-energy photons have helped understanding these contributions.« less

Perceived risk as a barrier to appropriate diagnosis of irritable bowel syndrome.

PubMed

Ahn, Eunmi; Son, Ki Young; Shin, Dong Wook; Han, Min Kyu; Lee, Hyejin; An, Ah Reum; Kim, Eun Ho; Cho, BeLong

2014-12-28

To evaluate perceived risk, diagnostic testing, and acceptance of a diagnosis of irritable bowel syndrome (IBS) among the Korean laypersons. We designed a conceptual framework to evaluate the health-seeking behavior of subjects based on a knowledge, attitude, and practice model. We developed a vignette-based questionnaire about IBS based on a literature review and focused group interviews. The vignette described a 40-year-old woman who meets the Rome III criteria for IBS without red-flag signs. It was followed by questions about demographic characteristics, health behaviors, IBS symptoms, risk perception, perceived need for diagnostic tests, and acceptance of a positive diagnosis of IBS. We planned a nationwide survey targeting laypersons without IBS and between the ages of 20 and 69 years. Survey participants were selected by quota sampling stratified by gender, age, and nationwide location. A multivariate logistic model was constructed based on literature reviews, univariate analysis, and a stepwise selection method to investigate correlations between the perceived risk, need for diagnostic tests, and acceptance of a positive diagnosis. Of 2354 eligible households, 1000 subjects completed the survey and 983 subjects were analyzed, excluding those who met symptom criteria for IBS. After reading the IBS vignette, the majority of subjects (86.8%) responded that the patient was at increased risk of severe disease. The most frequent concern was colon cancer (59.8%), followed by surgical condition (51.5%). Most subjects responded the patient needs diagnostic tests (97.2%). Colonoscopy was the most commonly required test (79.5%). Less than half of the respondents requested a stool examination (45.0%), blood test (40.7%), abdominal ultrasound (36.0%), or computed tomography (20.2%). The subjects who felt increased risk were more likely to see a need for colonoscopy [adjusted odds ratio (aOR) = 2.10, 95%CI: 1.38-3.18]. When asked about the positive diagnosis, the most frequent response was that "the patient would not be reassured" (65.7%). The increased risk perception group was less likely to be reassured by a positive diagnosis of IBS, compared to the other respondents (aOR = 0.52, 95%CI: 0.34-0.78). For IBS diagnosis, increased risk perception is a possible barrier to the appropriate use of diagnostic tests and to the patient's acceptance of a positive diagnosis.

Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection

PubMed Central

Tchesnokova, Veronika; Avagyan, Hovhannes; Rechkina, Elena; Chan, Diana; Muradova, Mariya; Haile, Helen Ghirmai; Radey, Matthew; Weissman, Scott; Riddell, Kim; Scholes, Delia; Johnson, James R.

2017-01-01

Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients’ urine within 25–35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ≥ 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care. PMID:28350870

Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.

PubMed

Tchesnokova, Veronika; Avagyan, Hovhannes; Rechkina, Elena; Chan, Diana; Muradova, Mariya; Haile, Helen Ghirmai; Radey, Matthew; Weissman, Scott; Riddell, Kim; Scholes, Delia; Johnson, James R; Sokurenko, Evgeni V

2017-01-01

Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients' urine within 25-35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ≥ 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care.

Usefulness of component resolved analysis of cat allergy in routine clinical practice.

PubMed

Eder, Katharina; Becker, Sven; San Nicoló, Marion; Berghaus, Alexander; Gröger, Moritz

2016-01-01

Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the diagnosis of sensitization to cats is important for any allergist. 70 patients with positive skin prick tests for cats were retrospectively compared regarding their skin prick test results, as well as their specific immunoglobulin E antibody profiles with regard to their responses to the native cat extract, rFel d 1, nFel d 2 and rFel d 4. 35 patients were allergic to cats, as determined by positive anamnesis and/or nasal provocation with cat allergens, and 35 patients exhibited clinically non-relevant sensitization, as indicated by negative anamnesis and/or a negative nasal allergen challenge. Native cat extract serology testing detected 100% of patients who were allergic to cats but missed eight patients who showed sensitization in the skin prick test and did not have allergic symptoms. The median values of the skin prick test, as well as those of the specific immunoglobulin E antibodies against the native cat extract, were significantly higher for allergic patients than for patients with clinically non-relevant sensitization. Component based diagnostic testing to rFel d 1 was not as reliable. Sensitization to nFel d 2 and rFel d 4 was seen only in individual patients. Extract based diagnostic methods for identifying cat allergy and sensitization, such as the skin prick test and native cat extract serology, remain crucial in routine clinical practice. In our study, component based diagnostic testing could not replace these methods with regard to the detection of sensitization to cats and differentiation between allergy and sensitization without clinical relevance. However, component resolved allergy diagnostic tools have individual implications, and future studies may facilitate a better understanding of its use and subsequently may improve the clinical management of allergic patients.

Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency.

PubMed

Shin, Ha Kyung; Grahame, George; McCandless, Shawn E; Kerr, Douglas S; Bedoyan, Jirair K

2017-11-01

Pyruvate dehydrogenase complex (PDC) deficiency is a major cause of primary lactic acidemia in children. Prompt and correct diagnosis of PDC deficiency and differentiating between specific vs generalized, or secondary deficiencies has important implications for clinical management and therapeutic interventions. Both genetic and enzymatic testing approaches are being used in the diagnosis of PDC deficiency. However, the diagnostic efficacy of such testing approaches for individuals affected with PDC deficiency has not been systematically investigated in this disorder. We sought to evaluate the diagnostic sensitivity and variability of the various PDC enzyme assays in females and males at the Center for Inherited Disorders of Energy Metabolism (CIDEM). CIDEM data were filtered by lactic acidosis and functional PDC deficiency in at least one cell/tissue type (blood lymphocytes, cultured fibroblasts or skeletal muscle) identifying 186 subjects (51% male and 49% female), about half were genetically resolved with 78% of those determined to have a pathogenic PDHA1 mutation. Assaying PDC in cultured fibroblasts in cases where the underlying genetic etiology is PDHA1, was highly sensitive irrespective of gender; 97% (95% confidence interval [CI]: 90%-100%) and 91% (95% CI: 82%-100%) in females and males, respectively. In contrast to the fibroblast-based testing, the lymphocyte- and muscle-based testing were not sensitive (36% [95% CI: 11%-61%, p=0.0003] and 58% [95% CI: 30%-86%, p=0.014], respectively) for identifying known PDC deficient females with pathogenic PDHA1 mutations. In males with a known PDHA1 mutation, the sensitivity of the various cell/tissue assays (75% lymphocyte, 91% fibroblast and 88% muscle) were not statistically different, and the discordance frequency due to the specific cell/tissue used for assaying PDC was 0.15±0.11. Based on this data, a practical diagnostic algorithm is proposed accounting for current molecular approaches, enzyme testing sensitivity, and variability due to gender, cell/tissue type used for testing, and successive repeat testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Dual Processing Model for Medical Decision-Making: An Extension to Diagnostic Testing

PubMed Central

Tsalatsanis, Athanasios; Hozo, Iztok; Kumar, Ambuj; Djulbegovic, Benjamin

2015-01-01

Dual Processing Theories (DPT) assume that human cognition is governed by two distinct types of processes typically referred to as type 1 (intuitive) and type 2 (deliberative). Based on DPT we have derived a Dual Processing Model (DPM) to describe and explain therapeutic medical decision-making. The DPM model indicates that doctors decide to treat when treatment benefits outweigh its harms, which occurs when the probability of the disease is greater than the so called “threshold probability” at which treatment benefits are equal to treatment harms. Here we extend our work to include a wider class of decision problems that involve diagnostic testing. We illustrate applicability of the proposed model in a typical clinical scenario considering the management of a patient with prostate cancer. To that end, we calculate and compare two types of decision-thresholds: one that adheres to expected utility theory (EUT) and the second according to DPM. Our results showed that the decisions to administer a diagnostic test could be better explained using the DPM threshold. This is because such decisions depend on objective evidence of test/treatment benefits and harms as well as type 1 cognition of benefits and harms, which are not considered under EUT. Given that type 1 processes are unique to each decision-maker, this means that the DPM threshold will vary among different individuals. We also showed that when type 1 processes exclusively dominate decisions, ordering a diagnostic test does not affect a decision; the decision is based on the assessment of benefits and harms of treatment. These findings could explain variations in the treatment and diagnostic patterns documented in today’s clinical practice. PMID:26244571

Dual Processing Model for Medical Decision-Making: An Extension to Diagnostic Testing.

PubMed

Tsalatsanis, Athanasios; Hozo, Iztok; Kumar, Ambuj; Djulbegovic, Benjamin

2015-01-01

Dual Processing Theories (DPT) assume that human cognition is governed by two distinct types of processes typically referred to as type 1 (intuitive) and type 2 (deliberative). Based on DPT we have derived a Dual Processing Model (DPM) to describe and explain therapeutic medical decision-making. The DPM model indicates that doctors decide to treat when treatment benefits outweigh its harms, which occurs when the probability of the disease is greater than the so called "threshold probability" at which treatment benefits are equal to treatment harms. Here we extend our work to include a wider class of decision problems that involve diagnostic testing. We illustrate applicability of the proposed model in a typical clinical scenario considering the management of a patient with prostate cancer. To that end, we calculate and compare two types of decision-thresholds: one that adheres to expected utility theory (EUT) and the second according to DPM. Our results showed that the decisions to administer a diagnostic test could be better explained using the DPM threshold. This is because such decisions depend on objective evidence of test/treatment benefits and harms as well as type 1 cognition of benefits and harms, which are not considered under EUT. Given that type 1 processes are unique to each decision-maker, this means that the DPM threshold will vary among different individuals. We also showed that when type 1 processes exclusively dominate decisions, ordering a diagnostic test does not affect a decision; the decision is based on the assessment of benefits and harms of treatment. These findings could explain variations in the treatment and diagnostic patterns documented in today's clinical practice.

From accuracy to patient outcome and cost-effectiveness evaluations of diagnostic tests and biomarkers: an exemplary modelling study

PubMed Central

2013-01-01

Background Proper evaluation of new diagnostic tests is required to reduce overutilization and to limit potential negative health effects and costs related to testing. A decision analytic modelling approach may be worthwhile when a diagnostic randomized controlled trial is not feasible. We demonstrate this by assessing the cost-effectiveness of modified transesophageal echocardiography (TEE) compared with manual palpation for the detection of atherosclerosis in the ascending aorta. Methods Based on a previous diagnostic accuracy study, actual Dutch reimbursement data, and evidence from literature we developed a Markov decision analytic model. Cost-effectiveness of modified TEE was assessed for a life time horizon and a health care perspective. Prevalence rates of atherosclerosis were age-dependent and low as well as high rates were applied. Probabilistic sensitivity analysis was applied. Results The model synthesized all available evidence on the risk of stroke in cardiac surgery patients. The modified TEE strategy consistently resulted in more adapted surgical procedures and, hence, a lower risk of stroke and a slightly higher number of life-years. With 10% prevalence of atherosclerosis the incremental cost-effectiveness ratio was €4,651 and €481 per quality-adjusted life year in 55-year-old men and women, respectively. In all patients aged 65 years or older the modified TEE strategy was cost saving and resulted in additional health benefits. Conclusions Decision analytic modelling to assess the cost-effectiveness of a new diagnostic test based on characteristics, costs and effects of the test itself and of the subsequent treatment options is both feasible and valuable. Our case study on modified TEE suggests that it may reduce the risk of stroke in cardiac surgery patients older than 55 years at acceptable cost-effectiveness levels. PMID:23368927

Portable Health Algorithms Test System

NASA Technical Reports Server (NTRS)

Melcher, Kevin J.; Wong, Edmond; Fulton, Christopher E.; Sowers, Thomas S.; Maul, William A.

2010-01-01

A document discusses the Portable Health Algorithms Test (PHALT) System, which has been designed as a means for evolving the maturity and credibility of algorithms developed to assess the health of aerospace systems. Comprising an integrated hardware-software environment, the PHALT system allows systems health management algorithms to be developed in a graphical programming environment, to be tested and refined using system simulation or test data playback, and to be evaluated in a real-time hardware-in-the-loop mode with a live test article. The integrated hardware and software development environment provides a seamless transition from algorithm development to real-time implementation. The portability of the hardware makes it quick and easy to transport between test facilities. This hard ware/software architecture is flexible enough to support a variety of diagnostic applications and test hardware, and the GUI-based rapid prototyping capability is sufficient to support development execution, and testing of custom diagnostic algorithms. The PHALT operating system supports execution of diagnostic algorithms under real-time constraints. PHALT can perform real-time capture and playback of test rig data with the ability to augment/ modify the data stream (e.g. inject simulated faults). It performs algorithm testing using a variety of data input sources, including real-time data acquisition, test data playback, and system simulations, and also provides system feedback to evaluate closed-loop diagnostic response and mitigation control.

Accuracy of an Immunochromatographic Diagnostic Test (ICT Malaria Combo Cassette Test) Compared to Microscopy among under Five-Year-Old Children when Diagnosing Malaria in Equatorial Guinea

PubMed Central

Portero, José-Luis; Rubio-Yuste, Maria; Descalzo, Miguel Angel; Raso, Jose; Lwanga, Magdalena; Obono, Jaquelina; Nseng, Gloria; Benito, Agustin; Cano, Jorge

2010-01-01

Conventional malaria diagnosis based on microscopy raises serious difficulties in weak health systems. Cost-effective and sensitive rapid diagnostic tests have been recently proposed as alternatives to microscopy. In Equatorial Guinea, a study was conducted to assess the reliability of a rapid diagnostic test compared to microscopy. The study was designed in accordance with the directives of the Standards for Reporting Diagnostic Accuracy Initiative (STARD). Peripheral thick and thin films for the microscopy diagnosis and a rapid immunochromatographic test (ICT Malaria Combo Cassette Test) were performed on under five-year-old children with malaria suspicion. The ICT test detected Plasmodium spp. infection with a sensitivity of 81.5% and a specificity of 81.9% while P. falciparum diagnosis occurred with a sensitivity of 69.7% and a specificity of 73.7%. The sensitivity of the ICT test increased with higher parasitemias. The general results showed little concordance between the ICT test and microscopy (kappa = 0.28, se: 0.04). In Equatorial Guinea, the ICT Malaria Combo Cassette Test has proven to be an acceptable test to detect high P. falciparum parasitemias. However, the decrease of sensitivity at medium and low parasitemias hampers that ICT can replace properly performed microscopy at present in the diagnosis of malaria in children. PMID:22332024

Applications of Diagnostic Classification Models: A Literature Review and Critical Commentary

ERIC Educational Resources Information Center

Sessoms, John; Henson, Robert A.

2018-01-01

Diagnostic classification models (DCMs) classify examinees based on the skills they have mastered given their test performance. This classification enables targeted feedback that can inform remedial instruction. Unfortunately, applications of DCMs have been criticized (e.g., no validity support). Generally, these evaluations have been brief and…

Validation of a Videoconferenced Speaking Test

ERIC Educational Resources Information Center

Kim, Jungtae; Craig, Daniel A.

2012-01-01

Videoconferencing offers new opportunities for language testers to assess speaking ability in low-stakes diagnostic tests. To be considered a trusted testing tool in language testing, a test should be examined employing appropriate validation processes [Chapelle, C.A., Jamieson, J., & Hegelheimer, V. (2003). "Validation of a web-based ESL…

Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.

PubMed

Tammimies, Kristiina; Marshall, Christian R; Walker, Susan; Kaur, Gaganjot; Thiruvahindrapuram, Bhooma; Lionel, Anath C; Yuen, Ryan K C; Uddin, Mohammed; Roberts, Wendy; Weksberg, Rosanna; Woodbury-Smith, Marc; Zwaigenbaum, Lonnie; Anagnostou, Evdokia; Wang, Zhuozhi; Wei, John; Howe, Jennifer L; Gazzellone, Matthew J; Lau, Lynette; Sung, Wilson W L; Whitten, Kathy; Vardy, Cathy; Crosbie, Victoria; Tsang, Brian; D'Abate, Lia; Tong, Winnie W L; Luscombe, Sandra; Doyle, Tyna; Carter, Melissa T; Szatmari, Peter; Stuckless, Susan; Merico, Daniele; Stavropoulos, Dimitri J; Scherer, Stephen W; Fernandez, Bridget A

2015-09-01

The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). All probands underwent CMA, with WES performed for 95 proband-parent trios. The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.

Addressing the Real-World Challenges in the Development of Propulsion IVHM Technology Experiment (PITEX)

NASA Technical Reports Server (NTRS)

Maul, William A.; Chicatelli, Amy; Fulton, Christopher E.; Balaban, Edward; Sweet, Adam; Hayden, Sandra Claire; Bajwa, Anupa

2005-01-01

The Propulsion IVHM Technology Experiment (PITEX) has been an on-going research effort conducted over several years. PITEX has developed and applied a model-based diagnostic system for the main propulsion system of the X-34 reusable launch vehicle, a space-launch technology demonstrator. The application was simulation-based using detailed models of the propulsion subsystem to generate nominal and failure scenarios during captive carry, which is the most safety-critical portion of the X-34 flight. Since no system-level testing of the X-34 Main Propulsion System (MPS) was performed, these simulated data were used to verify and validate the software system. Advanced diagnostic and signal processing algorithms were developed and tested in real-time on flight-like hardware. In an attempt to expose potential performance problems, these PITEX algorithms were subject to numerous real-world effects in the simulated data including noise, sensor resolution, command/valve talkback information, and nominal build variations. The current research has demonstrated the potential benefits of model-based diagnostics, defined the performance metrics required to evaluate the diagnostic system, and studied the impact of real-world challenges encountered when monitoring propulsion subsystems.

Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population.

PubMed

Maeda, Akiko; Yoshida, Akiko; Kawai, Kanako; Arai, Yuki; Akiba, Ryutaro; Inaba, Akira; Takagi, Seiji; Fujiki, Ryoji; Hirami, Yasuhiko; Kurimoto, Yasuo; Ohara, Osamu; Takahashi, Masayo

2018-05-21

Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. Evaluation of diagnostic technology, Prospective, Clinical and experimental study. A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.

Rayleigh Scattering Diagnostics Workshop

NASA Technical Reports Server (NTRS)

Seasholtz, Richard (Compiler)

1996-01-01

The Rayleigh Scattering Diagnostics Workshop was held July 25-26, 1995 at the NASA Lewis Research Center in Cleveland, Ohio. The purpose of the workshop was to foster timely exchange of information and expertise acquired by researchers and users of laser based Rayleigh scattering diagnostics for aerospace flow facilities and other applications. This Conference Publication includes the 12 technical presentations and transcriptions of the two panel discussions. The first panel was made up of 'users' of optical diagnostics, mainly in aerospace test facilities, and its purpose was to assess areas of potential applications of Rayleigh scattering diagnostics. The second panel was made up of active researchers in Rayleigh scattering diagnostics, and its purpose was to discuss the direction of future work.

A Gram Stain Hands-On Workshop Enhances First Year Medical Students' Technique Competency in Comprehension and Memorization.

PubMed

Delfiner, Matthew S; Martinez, Luis R; Pavia, Charles S

2016-01-01

Laboratory diagnostic tests have an essential role in patient care, and the increasing number of medical and health professions schools focusing on teaching laboratory medicine to pre-clinical students reflects this importance. However, data validating the pedagogical methods that best influence students' comprehension and interpretation of diagnostic tests have not been well described. The Gram stain is a simple yet significant and frequently used diagnostic test in the clinical setting that helps classify bacteria into two major groups, Gram positive and negative, based on their cell wall structure. We used this technique to assess which educational strategies may improve students' learning and competency in medical diagnostic techniques. Hence, in this randomized controlled study, we compared the effectiveness of several educational strategies (e.g. workshop, discussion, or lecture) in first year medical students' competency in comprehension and interpretation of the Gram stain procedure. We demonstrated that a hands-on practical workshop significantly enhances students' competency in memorization and overall comprehension of the technique. Interestingly, most students irrespective of their cohort showed difficulty in answering Gram stain-related analytical questions, suggesting that more emphasis should be allocated by the instructors to clearly explain the interpretation of the diagnostic test results to students in medical and health professional schools. This proof of principle study highlights the need of practical experiences on laboratory medical techniques during pre-clinical training to facilitate future medical doctors' and healthcare professionals' basic understanding and competency in diagnostic testing for better patient care.

An accurate automated technique for quasi-optics measurement of the microwave diagnostics for fusion plasma

NASA Astrophysics Data System (ADS)

Hu, Jianqiang; Liu, Ahdi; Zhou, Chu; Zhang, Xiaohui; Wang, Mingyuan; Zhang, Jin; Feng, Xi; Li, Hong; Xie, Jinlin; Liu, Wandong; Yu, Changxuan

2017-08-01

A new integrated technique for fast and accurate measurement of the quasi-optics, especially for the microwave/millimeter wave diagnostic systems of fusion plasma, has been developed. Using the LabVIEW-based comprehensive scanning system, we can realize not only automatic but also fast and accurate measurement, which will help to eliminate the effects of temperature drift and standing wave/multi-reflection. With the Matlab-based asymmetric two-dimensional Gaussian fitting method, all the desired parameters of the microwave beam can be obtained. This technique can be used in the design and testing of microwave diagnostic systems such as reflectometers and the electron cyclotron emission imaging diagnostic systems of the Experimental Advanced Superconducting Tokamak.

Challenges in Routine Implementation and Quality Control of Rapid Diagnostic Tests for Malaria–Rufiji District, Tanzania

PubMed Central

McMorrow, Meredith L.; Masanja, M. Irene; Abdulla, Salim M. K.; Kahigwa, Elizeus; Kachur, S. Patrick

2018-01-01

Rapid diagnostic tests (RDTs) represent an alternative to microscopy for malaria diagnosis and have shown high sensitivity and specificity in a variety of study settings. Current World Health Organization (WHO) guidelines for quality control of RDTs provide detailed instructions on pre-field testing, but offer little guidance for quality assurance once RDTs are deployed in health facilities. From September 2006 to April 2007, we introduced a histidine-rich protein II (HRP2)-based RDT (Paracheck) for suspected malaria cases five years of age and older in nine health facilities in Rufiji District, Tanzania, to assess sensitivity and specificity of RDTs in routine use at rural health facilities. Thick blood smears were collected for all patients tested with RDTs and stained and read by laboratory personnel in each facility. Thick smears were subsequently reviewed by a reference microscopist to determine RDT sensitivity and specificity. In all nine health facilities, there were significant problems with the quality of staining and microscopy. Sensitivity and specificity of RDTs were difficult to assess given the poor quality of routine blood smear staining. Mean operational sensitivity of RDTs based on reference microscopy was 64.8%, but varied greatly by health facility, range 18.8–85.9%. Sensitivity of RDTs increased with increasing parasite density. Specificity remained high at 87.8% despite relatively poor slide quality. Institution of quality control of RDTs based on poor quality blood smear staining may impede reliable measurement of sensitivity and specificity and undermine confidence in the new diagnostic. There is an urgent need for the development of alternative quality control procedures for rapid diagnostic tests that can be performed at the facility level. PMID:18784230

Diagnostic tools for post-gastric bypass hypoglycaemia.

PubMed

Emous, M; Ubels, F L; van Beek, A P

2015-10-01

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature. © 2015 World Obesity.

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

PubMed

Yu, Stephanie C Y; Chan, K C Allen; Zheng, Yama W L; Jiang, Peiyong; Liao, Gary J W; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y; Go, Attie T J I; van Vugt, John M G; Minekawa, Ryoko; Oudejans, Cees B M; Nicolaides, Kypros H; Chiu, Rossa W K; Lo, Y M Dennis

2014-06-10

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing

PubMed Central

Yu, Stephanie C. Y.; Chan, K. C. Allen; Zheng, Yama W. L.; Jiang, Peiyong; Liao, Gary J. W.; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y.; Go, Attie T. J. I.; van Vugt, John M. G.; Minekawa, Ryoko; Oudejans, Cees B. M.; Nicolaides, Kypros H.; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2014-01-01

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring. PMID:24843150

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

PubMed

Conwell, Darwin L; Lee, Linda S; Yadav, Dhiraj; Longnecker, Daniel S; Miller, Frank H; Mortele, Koenraad J; Levy, Michael J; Kwon, Richard; Lieb, John G; Stevens, Tyler; Toskes, Phillip P; Gardner, Timothy B; Gelrud, Andres; Wu, Bechien U; Forsmark, Christopher E; Vege, Santhi S

2014-11-01

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Interpreting IgE sensitization tests in food allergy.

PubMed

Chokshi, Niti Y; Sicherer, Scott H

2016-01-01

Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.

Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative.

PubMed

Loibner, Martina; Buzina, Walter; Viertler, Christian; Groelz, Daniel; Hausleitner, Anja; Siaulyte, Gintare; Kufferath, Iris; Kölli, Bettina; Zatloukal, Kurt

2016-01-01

Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene), was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples. Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV). Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays. All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity. PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment.

40 CFR 85.2223 - On-board diagnostic test report.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false On-board diagnostic test report. 85... Tests § 85.2223 On-board diagnostic test report. (a) Motorists whose vehicles fail the on-board diagnostic test described in § 85.2222 shall be provided with the on-board diagnostic test results, including...

40 CFR 85.2223 - On-board diagnostic test report.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false On-board diagnostic test report. 85... Tests § 85.2223 On-board diagnostic test report. (a) Motorists whose vehicles fail the on-board diagnostic test described in § 85.2222 shall be provided with the on-board diagnostic test results, including...

Incorporating uncertainty into medical decision making: an approach to unexpected test results.

PubMed

Bianchi, Matt T; Alexander, Brian M; Cash, Sydney S

2009-01-01

The utility of diagnostic tests derives from the ability to translate the population concepts of sensitivity and specificity into information that will be useful for the individual patient: the predictive value of the result. As the array of available diagnostic testing broadens, there is a temptation to de-emphasize history and physical findings and defer to the objective rigor of technology. However, diagnostic test interpretation is not always straightforward. One significant barrier to routine use of probability-based test interpretation is the uncertainty inherent in pretest probability estimation, the critical first step of Bayesian reasoning. The context in which this uncertainty presents the greatest challenge is when test results oppose clinical judgment. It is this situation when decision support would be most helpful. The authors propose a simple graphical approach that incorporates uncertainty in pretest probability and has specific application to the interpretation of unexpected results. This method quantitatively demonstrates how uncertainty in disease probability may be amplified when test results are unexpected (opposing clinical judgment), even for tests with high sensitivity and specificity. The authors provide a simple nomogram for determining whether an unexpected test result suggests that one should "switch diagnostic sides.'' This graphical framework overcomes the limitation of pretest probability uncertainty in Bayesian analysis and guides decision making when it is most challenging: interpretation of unexpected test results.

Symptoms, Diagnosis, and Treatment of Cow's Milk Allergy.

PubMed

Vandenplas, Yvan; Marchand, Johan; Meyns, Lien

2015-01-01

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate because there are no specific symptoms and reliable diagnostic tests. Literature was searched using databases to find original papers and reviews on this topic. A "challenge test" is still recommended as the most specific and sensitive diagnostic test, although a positive challenge test does not proof the involvement of the immune system. Only in the rare case of anaphylaxis, the challenge tests is not recommended. The Cow's Milk Symptom Score (CoMiSS) is an awareness tool for health care professionals to better recognize symptoms caused by the ingestion of cow's milk, but still needs validation. Today, the recommended diagnostic approach consists of an elimination diet with an extensive cow's milk based hydrolysate, followed by a challenge test. Amino acid based formula is reserved for the severe cases. Rice hydrolysates are gaining popularity, because they have been shown to be effective, have a better acceptability, and to be cheaper than the extensive cow's milk based hydrolysates. Soy infant formula may offer an additional alternative option as reviews concluded that about 10-15% of infants allergic to cow's milk will also react to soy. Gastro-intestinal microbiota manipulation may be of additional benefit in the treatment of CMA. The development of rice hydrolysates challenge the use of Today, extensive cow's milk based extensive hydrolysates remain the first option for the majority of patients and amino acid formula for the most severe cases. Rice hydrolysates and soy infant formula are considered as second choice options.

Oral vaccination of cattle with heat inactivated Mycobacterium bovis does not compromise bovine TB diagnostic tests.

PubMed

Jones, Gareth J; Steinbach, Sabine; Sevilla, Iker A; Garrido, Joseba M; Juste, Ramon; Vordermeier, H Martin

2016-12-01

In this study we investigated whether oral uptake of a heat inactivated M. bovis wildlife vaccine by domestic cattle induced systemic immune responses that compromised the use of tuberculin or defined antigens in diagnostic tests for bovine TB. Positive skin test and blood-based IFN-γ release assay (IGRA) results were observed in all calves vaccinated via the parenteral route (i.e. intramuscular). In contrast, no positive responses to tuberculin or defined antigens were observed in either the skin test or IGRA test when performed in calves vaccinated via the oral route. In conclusion, our results suggest that the heat inactivated M. bovis vaccine could be used to vaccinate wildlife in a baited form in conjunction with the following in cattle: (i) continuation of existing tuberculin skin testing or novel skin test formats based on defined antigens; and (ii) the use of IGRA tests utilizing tuberculin or defined antigens. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Dry Eye Disease: Concordance Between the Diagnostic Tests in African Eyes.

PubMed

Onwubiko, Stella N; Eze, Boniface I; Udeh, Nnenma N; Onwasigwe, Ernest N; Umeh, Rich E

2016-11-01

To assess the concordance between the diagnostic tests for dry eye disease (DED) in a Nigerian hospital population. The study was a hospital-based cross-sectional survey of adults (≥18 years) presenting at the eye clinic of the University of Nigeria Teaching Hospital (UNTH), Enugu; September-December, 2011. Participants' socio-demographic data were collected. Each subject was assessed for DED using the "Ocular Surface Disease Index" (OSDI) questionnaire, tear-film breakup time (TBUT), and Schirmer test. The intertest concordance was assessed using kappa statistic, correlation, and regression coefficients. The participants (n=402; men: 193) were aged 50.1±19.1 standard deviation years (range: 18-94 years). Dry eye disease was diagnosed in 203 by TBUT, 170 by Schirmer test, and 295 by OSDI; the concordance between the tests were OSDI versus TBUT (Kappa, κ=-0.194); OSDI versus Schirmer (κ=-0.276); and TBUT versus Schirmer (κ=0.082). Ocular Surface Disease Index was inversely correlated with Schirmer test (Spearman ρ=-0.231, P<0.001) and TBUT (ρ=-0.237, P<0.001). In the linear regression model, OSDI was poorly predicted by TBUT (β=-0.09; 95% confidence interval (CI): -0.26 to -0.03, P=0.14) and Schirmer test (β=-0.35, 95% CI: -0.53 to -0.18, P=0.18). At UNTH, there is poor agreement, and almost equal correlation, between the subjective and objective tests for DED. Therefore, the selection of diagnostic test for DED should be informed by cost-effectiveness and diagnostic resource availability, not diagnostic efficiency or utility.

[Assessment of a rapid diagnostic test and portable fluorescent microscopy for malaria diagnosis in Cotonou (Bénin)].

PubMed

Ogouyèmi-Hounto, A; Kinde-Gazard, D; Keke, C; Gonçalves, E; Alapini, N; Adjovi, F; Adisso, L; Bossou, C; Denon, Y V; Massougbodji, A

2013-02-01

The aim of the study was to determine the accuracy of a rapid diagnostic test (SD Bioline Malaria Ag P.f/ Pan®) and fluorescent microscopy (CyScope®) in confirming presumptive malaria diagnosis in Cotonou. Thick blood smear was used as the reference technique for comparison. Testing was conducted on persons between the ages of 6 months and 70 years at two hospitals from June to October 2010. If malaria was suspected in the sample by the nurse based on clinical findings and sent to laboratory for confirmation, one thick smear, one rapid diagnostic test and one slide for the fluorescent microscopy were performed. All tests were read in hospital laboratories involved with the quality control of thick blood smear in the parasitology laboratory of National University Hospital of Cotonou. A total of 354 patients with clinical diagnosis of malaria were included. Malaria prevalence determined by thick smear, rapid diagnostic test and fluorescent microscopy was 22.8%, 25.4%, and 25.1% respectively. The sensitivity, specificity, positive and negative predictive values compared to the thick smears were 96.3, 95.6, 86.7, and 98.9% for rapid diagnostic test; and 97.5, 96.7, 89.8, and 99.27% for fluorescent microscopy. With these performances, these tests meet acceptability standards recommended by WHO for rapid tests (sensitivity > 95%). These two methods have advantages for the confirmation of malaria diagnosis in peripheral health structures that lack the resources to conduct diagnosis confirmation by the thick blood smear.

Emerging dilemmas in the diagnosis and management of gastroesophageal reflux disease

PubMed Central

Kahrilas, Peter; Yadlapati, Rena; Roman, Sabine

2017-01-01

Gastroesophageal reflux disease (GERD) is common, but less so than widely reported because of inconsistencies in definition. In clinical practice, the diagnosis is usually based on a symptom assessment without testing, and the extent of diagnostic testing pursued should be limited to that which guides management or which protects the patient from the risks of a potentially morbid treatment or an undetected early (or imminent) esophageal adenocarcinoma or which does both. When testing is pursued, upper gastrointestinal endoscopy is the most useful initial diagnostic test because it evaluates for the major potential morbidities (Barrett’s, stricture, and cancer) associated with GERD and facilitates the identification of some alternative diagnostic possibilities such as eosinophilic esophagitis. However, endoscopy is insensitive for diagnosing GERD because most patients with GERD have non-erosive reflux disease, a persistent diagnostic dilemma. Although many studies have tried to objectify the diagnosis of GERD with improved technology, this is ultimately a pragmatic diagnosis based on response to proton pump inhibitor (PPI) therapy, and, in the end, response to PPI therapy becomes the major indication for continued PPI therapy. Conversely, in the absence of objective criteria for GERD and the absence of apparent clinical benefit, PPI therapy is not indicated and should be discontinued. PPIs are well tolerated and safe, but nothing is perfectly safe, and in the absence of measurable benefit, even a miniscule risk dominates the risk-benefit assessment. PMID:29034088

A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

PubMed

Cho, Sung Jin; Lee, Jihoo; Lee, Hyun Jae; Jo, Hyun-Young; Sinniah, Mangalam; Kim, Hak-Yong; Chong, Chom-Kyu; Song, Hyun-Ok

2016-01-01

Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas. However, only a few malaria antibody tests are available in the microwell-based assay format and these are not suitable for field application. A novel malaria antibody (Ab)-based RDT using a differential diagnostic marker for falciparum and vivax malaria was developed as a suitable high-throughput assay that is sensitive and practical for blood screening. The marker, merozoite surface protein 1 (MSP1) was discovered by generation of a Plasmodium-specific network and the hierarchical organization of modularity in the network. Clinical evaluation revealed that the novel Malaria Pf/Pv Ab RDT shows improved sensitivity (98%) and specificity (99.7%) compared with the performance of a commercial kit, SD BioLine Malaria P.f/P.v (95.1% sensitivity and 99.1% specificity). The novel Malaria Pf/Pv Ab RDT has potential for use as a cost-effective blood-screening tool for malaria and in turn, reduces TTM risk in endemic areas.

Repeated significance tests of linear combinations of sensitivity and specificity of a diagnostic biomarker

PubMed Central

Wu, Mixia; Shu, Yu; Li, Zhaohai; Liu, Aiyi

2016-01-01

A sequential design is proposed to test whether the accuracy of a binary diagnostic biomarker meets the minimal level of acceptance. The accuracy of a binary diagnostic biomarker is a linear combination of the marker’s sensitivity and specificity. The objective of the sequential method is to minimize the maximum expected sample size under the null hypothesis that the marker’s accuracy is below the minimal level of acceptance. The exact results of two-stage designs based on Youden’s index and efficiency indicate that the maximum expected sample sizes are smaller than the sample sizes of the fixed designs. Exact methods are also developed for estimation, confidence interval and p-value concerning the proposed accuracy index upon termination of the sequential testing. PMID:26947768

Long-term Cost-Effectiveness of Diagnostic Tests for Assessing Stable Chest Pain: Modeled Analysis of Anatomical and Functional Strategies.

PubMed

Bertoldi, Eduardo G; Stella, Steffan F; Rohde, Luis E; Polanczyk, Carisi A

2016-05-01

Several tests exist for diagnosing coronary artery disease, with varying accuracy and cost. We sought to provide cost-effectiveness information to aid physicians and decision-makers in selecting the most appropriate testing strategy. We used the state-transitions (Markov) model from the Brazilian public health system perspective with a lifetime horizon. Diagnostic strategies were based on exercise electrocardiography (Ex-ECG), stress echocardiography (ECHO), single-photon emission computed tomography (SPECT), computed tomography coronary angiography (CTA), or stress cardiac magnetic resonance imaging (C-MRI) as the initial test. Systematic review provided input data for test accuracy and long-term prognosis. Cost data were derived from the Brazilian public health system. Diagnostic test strategy had a small but measurable impact in quality-adjusted life-years gained. Switching from Ex-ECG to CTA-based strategies improved outcomes at an incremental cost-effectiveness ratio of 3100 international dollars per quality-adjusted life-year. ECHO-based strategies resulted in cost and effectiveness almost identical to CTA, and SPECT-based strategies were dominated because of their much higher cost. Strategies based on stress C-MRI were most effective, but the incremental cost-effectiveness ratio vs CTA was higher than the proposed willingness-to-pay threshold. Invasive strategies were dominant in the high pretest probability setting. Sensitivity analysis showed that results were sensitive to costs of CTA, ECHO, and C-MRI. Coronary CT is cost-effective for the diagnosis of coronary artery disease and should be included in the Brazilian public health system. Stress ECHO has a similar performance and is an acceptable alternative for most patients, but invasive strategies should be reserved for patients at high risk. © 2016 Wiley Periodicals, Inc.

42 CFR 415.180 - Teaching setting requirements for the interpretation of diagnostic radiology and other diagnostic...

Code of Federal Regulations, 2011 CFR

2011-10-01

... interpretation of diagnostic radiology and other diagnostic tests. 415.180 Section 415.180 Public Health CENTERS... for the interpretation of diagnostic radiology and other diagnostic tests. (a) General rule. Physician fee schedule payment is made for the interpretation of diagnostic radiology and other diagnostic tests...

42 CFR 415.180 - Teaching setting requirements for the interpretation of diagnostic radiology and other diagnostic...

Code of Federal Regulations, 2010 CFR

2010-10-01

... interpretation of diagnostic radiology and other diagnostic tests. 415.180 Section 415.180 Public Health CENTERS... for the interpretation of diagnostic radiology and other diagnostic tests. (a) General rule. Physician fee schedule payment is made for the interpretation of diagnostic radiology and other diagnostic tests...

The evaluation of GM6-based ELISA and ICT as diagnostic methods on a Mongolian farm with an outbreak of non-tsetse transmitted horse trypanosomosis.

PubMed

Davaasuren, Batdorj; Amgalanbaatar, Tovuu; Musinguzi, Simon Peter; Suganuma, Keisuke; Otgonsuren, Davaajav; Mossaad, Ehab; Narantsatsral, Sandagdorj; Battur, Banzragch; Battsetseg, Badgar; Xuan, Xuenan; Inoue, Noboru

2017-09-15

Trypanosoma equiperdum, which is the etiological agent of dourine, spreads through sexual intercourse in equines. Dourine (T. equiperdum) has been reported in Mongolia, where it is considered an economically important disease of horses. T. evansi has also been reported in Mongolian domestic animals. The objective of this study was to evaluate the potential application of recombinant T. evansi GM6 (rTeGM6-4r)-based diagnostic methods on a farm with an outbreak of non-tsetse transmitted horse trypanosomosis. Ninety-seven percent homology was found between the amino acid sequences of T. equiperdum GM6 and the GM6 of another Trypanozoon, which also shared the same cellular localization. This finding suggests the utility of rTeGM6-4r-based serodiagnostic methods for epidemiological studies and the diagnosis of both surra and dourine in Equidae. Fifty blood samples were examined from a herd of horses. The diagnostic value of an rTeGM6-4r-based ELISA and an rTeGM6-4r-based immunochromatographic test (ICT) were measured in comparison to a T. evansi crude antigen-based ELISA, which is a diagnostic method recommended by the OIE. However, this is not a perfect diagnostic method for trypanosomosis. Positive serum samples were detected in 46%, 42% and 28% of the tested horses using an rTeGM6-4r-based ELISA, crude antigen-based ELISA and rTeGM6-4r-based ICT, respectively. The sensitivity of rTeGM6-based ELISA was 81%, the specificity was 79%, and the agreement was moderate. We conclude that rTeGM6-4r-based ELISA and ICT represent alternative options for baseline epidemiological studies and the on-site diagnosis of horse trypanosomoses in the field, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

A new diagnostic approach for bilious pleural effusion.

PubMed

Saraya, Takeshi; Light, Richard W; Sakuma, Sho; Nakamoto, Yasuo; Wada, Shoko; Ishida, Manabu; Inui, Toshiya; Koide, Takashi; Ishii, Haruyuki; Takizawa, Hajime

2016-09-01

Bilious pleural effusion is an extremely rare condition associated with liver diseases, subphrenic or subhepatic abscess formation, biliary peritonitis, and invasive procedures (i.e., percutaneous biliary drainage or liver biopsy). The current diagnostic test is based on the measurement of the ratio of pleural total bilirubin to serum total bilirubin, which is greater than 1 in patients with bilious pleural effusion. Given the low incidence of bilious pleural effusion, the precise diagnostic yield of this ratio based test has not been evaluated. We retrospectively reviewed the medical records of our institution and searched the PubMed database for reports of bilious pleural effusion. We identified a total of 12 cases of bilious pleural effusion (9 from 8 Pubmed reports and 3 from our institutional records). The factors causing this condition were broadly classified into three categories based on the pathophysiology: 1) liver diseases (echinococcosis, tuberculosis and amebiasis); 2) subhepatic/subphrenic abscess or biliary peritonitis, with or without biliary tract obstruction; and 3) iatrogenic disease after percutaneous biliary drainage and/or liver biopsy. The sensitivity of detection was 76.9% when the ratio of pleural total bilirubin to serum total bilirubin was greater than 1. The sensitivity increased to 100% when a combination test including pleural glycoholic acid was adopted. This study demonstrates the high diagnostic yield for bilious pleural effusion using a combination of two test criteria; a ratio of pleural total bilirubin to serum total bilirubin greater than 1 and the presence of pleural glycoholic acid. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Potential Application of Digitally Linked Tuberculosis Diagnostics for Real-Time Surveillance of Drug-Resistant Tuberculosis Transmission: Validation and Analysis of Test Results.

PubMed

Ng, Kamela Charmaine; Meehan, Conor Joseph; Torrea, Gabriela; Goeminne, Léonie; Diels, Maren; Rigouts, Leen; de Jong, Bouke Catherine; André, Emmanuel

2018-02-27

Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results. However, these connected diagnostics and readily available test results are not used to their full capacity, as we have yet to capitalize on fully understanding the relationship between test results and specific rpoB mutations to elucidate its potential application to real-time surveillance. We aimed to validate and analyze RDT data in detail, and propose the potential use of connected diagnostics and associated test results for real-time evaluation of RR-TB transmission. We selected 107 RR-TB strains harboring 34 unique rpoB mutations, including 30 within the rifampicin resistance-determining region (RRDR), from the Belgian Coordinated Collections of Microorganisms, Antwerp, Belgium. We subjected these strains to Xpert MTB/RIF, GenoType MTBDRplus v2.0, and Genoscholar NTM + MDRTB II, the results of which were validated against the strains' available rpoB gene sequences. We determined the reproducibility of the results, analyzed and visualized the probe reactions, and proposed these for potential use in evaluating transmission. The RDT probe reactions detected most RRDR mutations tested, although we found a few critical discrepancies between observed results and manufacturers' claims. Based on published frequencies of probe reactions and RRDR mutations, we found specific probe reactions with high potential use in transmission studies: Xpert MTB/RIF probes A, Bdelayed, C, and Edelayed; Genotype MTBDRplus v2.0 WT2, WT5, and WT6; and Genoscholar NTM + MDRTB II S1 and S3. Inspection of probe reactions of disputed mutations may potentially resolve discordance between genotypic and phenotypic test results. We propose a novel approach for potential real-time detection of RR-TB transmission through fully using digitally linked TB diagnostics and shared repository of test results. To our knowledge, this is the first pragmatic and scalable work in response to the consensus of world-renowned TB experts in 2016 on the potential of diagnostic connectivity to accelerate efforts to eliminate TB. This is evidenced by the ability of our proposed approach to facilitate comparison of probe reactions between different RDTs used in the same setting. Integrating this proposed approach as a plug-in module to a connectivity platform will increase usefulness of connected TB diagnostics for RR-TB outbreak detection through real-time investigation of suspected RR-TB transmission cases based on epidemiologic linking. ©Kamela Charmaine Ng, Conor Joseph Meehan, Gabriela Torrea, Léonie Goeminne, Maren Diels, Leen Rigouts, Bouke Catherine de Jong, Emmanuel André. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 27.02.2018.

Comparison of isolated-check visual evoked potential and standard automated perimetry in early glaucoma and high-risk ocular hypertension

PubMed Central

Chen, Xiang-Wu; Zhao, Ying-Xi

2017-01-01

AIM To compare the diagnostic performance of isolated-check visual evoked potential (icVEP) and standard automated perimetry (SAP), for evaluating the application values of icVEP in the detection of early glaucoma. METHODS Totally 144 subjects (288 eyes) were enrolled in this study. icVEP testing was performed with the Neucodia visual electrophysiological diagnostic system. A 15% positive-contrast (bright) condition pattern was used in this device to differentiate between glaucoma patients and healthy control subjects. Signal-to-noise ratios (SNR) were derived based on a multivariate statistic. The eyes were judged as abnormal if the test yielded an SNR≤1. SAP testing was performed with the Humphrey Field Analyzer II. The visual fields were deemed as abnormality if the glaucoma hemifield test results outside normal limits; or the pattern standard deviation with P<0.05; or the cluster of three or more non-edge points on the pattern deviation plot in a single hemifield with P<0.05, one of which must have a P<0.01. Disc photographs were graded as either glaucomatous optic neuropathy or normal by two experts who were masked to all other patient information. Moorfields regression analysis (MRA) used as a separate diagnostic classification was performed by Heidelberg retina tomograph (HRT). RESULTS When the disc photograph grader was used as diagnostic standard, the sensitivity for SAP and icVEP was 32.3% and 38.5% respectively and specificity was 82.3% and 77.8% respectively. When the MRA Classifier was used as the diagnostic standard, the sensitivity for SAP and icVEP was 48.6% and 51.4% respectively and specificity was 84.1% and 78.0% respectively. When the combined structural assessment was used as the diagnostic standard, the sensitivity for SAP and icVEP was 59.2% and 53.1% respectively and specificity was 84.2% and 84.6% respectivlely. There was no statistical significance between the sensitivity or specificity of SAP and icVEP, regardless of which diagnostic standard was based on. CONCLUSION The diagnostic performance of icVEP is not better than that of SAP in the detection of early glaucoma. PMID:28503434

Diagnostic Testing and Hospital Outcomes of Children with Neurologic Impairment and Bacterial Pneumonia.

PubMed

Thomson, Joanna; Hall, Matt; Berry, Jay G; Stone, Bryan; Ambroggio, Lilliam; Srivastava, Rajendu; Shah, Samir S

2016-11-01

To assess hospital-level variability in diagnostic testing and outcomes for children with neurologic impairment hospitalized with pneumonia. A retrospective cohort study of 27 455 children ages 1-18 years with neurologic impairment hospitalized with pneumonia at 39 children's hospitals. K-means clustering was used to assign each hospital to 1 of 3 groups (termed A, B, and C) based on similar diagnostic testing patterns. Outcomes of hospital-level median length of stay (LOS), 30-day readmissions, and pneumonia-associated complications were compared while controlling for patient differences. Overall, 48.5% had comorbid complex chronic conditions, and 25.4% were assisted with medical technology. Outcomes and diagnostic testing varied across hospitals: median hospital-level LOS, 3.2 days (IQR 2.8-3.8); median readmission, 8.4% (IQR 6.8,-10.0); and median pneumonia-associated complication rate, 23.1% (IQR 18.7-26.8). Despite similar populations, hospitals in group A tended to perform fewer tests than those in groups B and C. Across hospital groups, there was a significant difference in adjusted readmission rates (group A 7.2%, group B 9.0%, group C 7.7%, P = .003). There was no significant difference in adjusted median LOS (group A 3.4 days, group B 3.2 days, group C 3.3 days, P = .3) or adjusted pneumonia-associated complication rates (group A 22.5%, group B 22.5%, group C 25.0%, P = .6). For children with neurologic impairment hospitalized with pneumonia, across hospital differences in diagnostic testing were not associated with clinically meaningful differences in outcomes. High-utilizing hospitals may be able to decrease diagnostic testing for children with neurologic impairment hospitalized with pneumonia without adversely impacting outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD-'Assessing QbTest Utility in ADHD' (AQUA): a randomised controlled trial.

PubMed

Hall, Charlotte L; Walker, Gemma M; Valentine, Althea Z; Guo, Boliang; Kaylor-Hughes, Catherine; James, Marilyn; Daley, David; Sayal, Kapil; Hollis, Chris

2014-12-01

The National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current 'gold standard' ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome. This multisite randomised controlled trial will recruit young people (aged 6-17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice. The findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval. NCT02209116. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD—‘Assessing QbTest Utility in ADHD’ (AQUA): a randomised controlled trial

PubMed Central

Hall, Charlotte L; Walker, Gemma M; Valentine, Althea Z; Guo, Boliang; Kaylor-Hughes, Catherine; James, Marilyn; Daley, David; Sayal, Kapil; Hollis, Chris

2014-01-01

Introduction The National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current ‘gold standard’ ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome. Methods and analysis This multisite randomised controlled trial will recruit young people (aged 6–17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice. Ethics and dissemination The findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval. Trial registration number NCT02209116. PMID:25448628

Highly Effective Serodiagnosis for Chagas' Disease ▿

PubMed Central

Hernández, Pilar; Heimann, Michael; Riera, Cristina; Solano, Marco; Santalla, José; Luquetti, Alejandro O.; Beck, Ewald

2010-01-01

Many proteins of Trypanosoma cruzi, the causative agent of Chagas' disease, contain characteristic arrays of highly repetitive immunogenic amino acid motifs. Diagnostic tests using these motifs in monomeric or dimeric form have proven to provide markedly improved specificity compared to conventional tests based on crude parasite extracts. However, in many cases the available tests still suffer from limited sensitivity. In this study we produced stable synthetic genes with maximal codon variability for the four diagnostic antigens, B13, CRA, TcD, and TcE, each containing between three and nine identical amino acid repeats. These genes were combined by linker sequences encoding short proline-rich peptides, giving rise to a 24-kDa fusion protein which was used as a novel diagnostic antigen in an enzyme-linked immunosorbent assay setup. Validation of the assay with a large number of well-characterized patient sera from Bolivia and Brazil revealed excellent diagnostic performance. The high sensitivity of the new test may allow future studies to use blood collected by finger prick and dried on filter paper, thus dramatically reducing the costs and effort for the detection of T. cruzi infection. PMID:20668136

Prevalence of PCR detectable malaria infection among febrile patients with a negative Plasmodium falciparum specific rapid diagnostic test in Zanzibar.

PubMed

Baltzell, Kimberly A; Shakely, Deler; Hsiang, Michelle; Kemere, Jordan; Ali, Abdullah Suleiman; Björkman, Anders; Mårtensson, Andreas; Omar, Rahila; Elfving, Kristina; Msellem, Mwinyi; Aydin-Schmidt, Berit; Rosenthal, Philip J; Greenhouse, Bryan

2013-02-01

We screened for malaria in 594 blood samples from febrile patients who tested negative by a Plasmodium falciparum-specific histidine-rich protein-2-based rapid diagnostic test at 12 health facilities in Zanzibar districts North A and Micheweni, from May to August 2010. Screening was with microscopy, polymerase chain reaction (PCR) targeting the cytochrome b gene (cytbPCR) of the four major human malaria species, and quantitative PCR (qPCR). The prevalence of cytbPCR-detectable malaria infection was 2% (12 of 594), including 8 P. falciparum, 3 Plasmodium malariae, and 1 Plasmodium vivax infections. Microscopy identified 4 of 8 P. falciparum infections. Parasite density as estimated by microscopy or qPCR was > 4,000 parasites/μL in 5 of 8 cytbPCR-detectable P. falciparum infections. The infections that were missed by the rapid diagnostic test represent a particular challenge in malaria elimination settings and highlight the need for more sensitive point-of-care diagnostic tools to improve case detection of all human malaria species in febrile patients.

New molecular medicine: Diagnomics and pharmacogenomics

NASA Astrophysics Data System (ADS)

Kauffman, Michael G.

1999-04-01

Millennium Predictive Medicine (MPMx), a subsidiary of Millennium Pharmaceuticals, is focusing on the discovery and clinical validation of Diagnomic and Pharmacogenomic Tests which will replace many of the subjective elements of clinical decision making. Diagnomics are molecular diagnostic markers with prognostic and economic impact. While the majority of currently available diagnostics represent data points, Diagnomics allow patients and physicians to make scientifically based, individualized decisions about their disease and its therapy. Pharmacogenomics are diagnostics that specify the use or avoidance of specific therapeutics based on an individual genotype and/or disease subtype. MPMx uses the broad Millennium genomics, proteomics, and bioinformatics technologies in the analysis of human disease and drug response. These technologies permit global and unbiased approaches towards the elucidation of disease pathways and mechanisms at the molecular level. Germline or somatic mutations, RNA levels, or protein levels comprising these pathways and mechanisms are currently being evaluated as markers for disease predisposition, stage, aggressiveness, and likely drug response or drug toxicity. Diagnomic and Pharmacogenomic Tests are part of the new molecular medicine that is transforming clinical practice forma symptom/pathology-based art into a pre-symptom, mechanism- based science.

ALK evaluation in the world of multiplex testing: Network Genomic Medicine (NGM): the Cologne model for implementing personalised oncology.

PubMed

Heydt, C; Kostenko, A; Merkelbach-Bruse, S; Wolf, J; Büttner, R

2016-09-01

Comprehensive molecular genotyping of lung cancers has become a key requirement for guiding therapeutic decisions. As a paradigm model of implementing next-generation comprehensive diagnostics, Network Genomic Medicine (NGM) has established central diagnostic and clinical trial platforms for centralised testing and decentralised personalised treatment in clinical practice. Here, we describe the structures of the NGM network and give a summary of technologies to identify patients with anaplastic lymphoma kinase (ALK) fusion-positive lung adenocarcinomas. As unifying test platforms will become increasingly important for delivering reliable, quick and affordable tests, the NGM diagnostic platform is currently implementing a comprehensive hybrid capture-based parallel sequencing pan-cancer assay. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

An Exploration of the Base Rate Scores of the Millon Clinical Multiaxial Inventory-III

ERIC Educational Resources Information Center

Grove, William M.; Vrieze, Scott I.

2009-01-01

The Millon Clinical Multiaxial Inventory (3rd ed.; MCMI-III) is a widely used psychological assessment of clinical and personality disorders. Unlike typical tests, the MCMI-III uses a base-rate score transformation to incorporate prior probabilities of disorder (i.e., base rates) in test output and diagnostic thresholds. The authors describe the…

Antigen persistence of rapid diagnostic tests in pregnant women in Nanoro, Burkina Faso, and the implications for the diagnosis of malaria in pregnancy.

PubMed

Kattenberg, Johanna H; Tahita, Christian M; Versteeg, Inge A J; Tinto, Halidou; Traoré-Coulibaly, Maminata; Schallig, Henk D F H; Mens, Petra F

2012-05-01

To evaluate persistence of several Plasmodium antigens in pregnant women after treatment and compare diagnostics during treatment follow-up. Thirty-two pregnant women (N = 32) with confirmed malaria infection by a histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) and microscopy were followed for 28 days after artemisinin-based combination therapy (ACT). A Plasmodium lactate dehydrogenase (pLDH)-based RDT and two ELISAs based on the detection of dihydrofolate reductase-thymidylate synthase (DHFR-TS) and haeme detoxification protein (HDP) were compared with each other and to RT-PCR at each visit. The mean visit number (95% confidence interval) on which the HRP2-based RDT was still positive after treatment was 3.4 (2.7-4.1) visits with some patients still positive at day 28. This is significantly later than the pLDH-based RDT [0.84 (0.55-1.1)], microscopy (median 1, range 1-3), DHFR-TS-ELISA [1.7 (1.1-2.3)] and RT-PCR (median 2, range 1-5) (P < 0.05), but not significantly later than HDP-ELISA [2.1 (1.6-2.7)]. Lower gravidity and higher parasite density at day 0 resulted in significantly longer positive results with most tests (P < 0.05). HRP2 can persist up to 28 days after ACT treatment; therefore, this test is not suitable for treatment follow-up in pregnant women and can generate problems when using this test during intermittent preventive treatment (IPTp). DHFR-TS is less persistent than HRP2, making it a potentially interesting target for diagnosis. © 2012 Blackwell Publishing Ltd.

The implications of using Hemoglobin A1C for diagnosing Diabetes Mellitus

PubMed Central

Malkani, Samir; Mordes, John P

2011-01-01

Until 2010 the diagnosis of diabetes mellitus was based solely on glucose concentration, but American Diabetes Association (ADA) recommendations now include a new criterion: hemoglobin A1C ≥6.5%. Because this change may have significant implications for diabetes diagnosis, we conducted a comprehensive literature review including peer-reviewed articles not referenced in the ADA report. We conclude that A1C and plasma glucose tests are frequently discordant for diagnosing diabetes. A1C ≥6.5% identifies fewer individuals as having diabetes than glucose-based criteria. Convenience of A1C test might increase the number of patients diagnosed, but this is unproven. Diagnostic cut-points for both glucose and A1C are based on consensus judgments regarding optimal sensitivity and specificity for the complications of hyperglycemia. A1C may not accurately reflect levels of glycemia in some situations, but in comparison with glucose measurements, it has greater analytic stability and less temporal variability. When choosing a diagnostic test for diabetes, the limitations of each choice must be understood. Clinical judgment and consideration of patient preference are required to appropriately select among the diagnostic alternatives. PMID:21531226

eSensor: an electrochemical detection-based DNA microarray technology enabling sample-to-answer molecular diagnostics

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Longiaru, Mathew

2009-05-01

DNA microarrays are becoming a widespread tool used in life science and drug screening due to its many benefits of miniaturization and integration. Microarrays permit a highly multiplexed DNA analysis. Recently, the development of new detection methods and simplified methodologies has rapidly expanded the use of microarray technologies from predominantly gene expression analysis into the arena of diagnostics. Osmetech's eSensor® is an electrochemical detection platform based on a low-to- medium density DNA hybridization array on a cost-effective printed circuit board substrate. eSensor® has been cleared by FDA for Warfarin sensitivity test and Cystic Fibrosis Carrier Detection. Other genetic-based diagnostic and infectious disease detection tests are under development. The eSensor® platform eliminates the need for an expensive laser-based optical system and fluorescent reagents. It allows one to perform hybridization and detection in a single and small instrument without any fluidic processing and handling. Furthermore, the eSensor® platform is readily adaptable to on-chip sample-to-answer genetic analyses using microfluidics technology. The eSensor® platform provides a cost-effective solution to direct sample-to-answer genetic analysis, and thus have a potential impact in the fields of point-of-care genetic analysis, environmental testing, and biological warfare agent detection.

Higher cost of implementing Xpert(®) MTB/RIF in Ugandan peripheral settings: implications for cost-effectiveness.

PubMed

Hsiang, E; Little, K M; Haguma, P; Hanrahan, C F; Katamba, A; Cattamanchi, A; Davis, J L; Vassall, A; Dowdy, D

2016-09-01

Initial cost-effectiveness evaluations of Xpert(®) MTB/RIF for tuberculosis (TB) diagnosis have not fully accounted for the realities of implementation in peripheral settings. To evaluate costs and diagnostic outcomes of Xpert testing implemented at various health care levels in Uganda. We collected empirical cost data from five health centers utilizing Xpert for TB diagnosis, using an ingredients approach. We reviewed laboratory and patient records to assess outcomes at these sites and10 sites without Xpert. We also estimated incremental cost-effectiveness of Xpert testing; our primary outcome was the incremental cost of Xpert testing per newly detected TB case. The mean unit cost of an Xpert test was US$21 based on a mean monthly volume of 54 tests per site, although unit cost varied widely (US$16-58) and was primarily determined by testing volume. Total diagnostic costs were 2.4-fold higher in Xpert clinics than in non-Xpert clinics; however, Xpert only increased diagnoses by 12%. The diagnostic costs of Xpert averaged US$119 per newly detected TB case, but were as high as US$885 at the center with the lowest volume of tests. Xpert testing can detect TB cases at reasonable cost, but may double diagnostic budgets for relatively small gains, with cost-effectiveness deteriorating with lower testing volumes.

Developing a modular architecture for creation of rule-based clinical diagnostic criteria.

PubMed

Hong, Na; Pathak, Jyotishman; Chute, Christopher G; Jiang, Guoqian

2016-01-01

With recent advances in computerized patient records system, there is an urgent need for producing computable and standards-based clinical diagnostic criteria. Notably, constructing rule-based clinical diagnosis criteria has become one of the goals in the International Classification of Diseases (ICD)-11 revision. However, few studies have been done in building a unified architecture to support the need for diagnostic criteria computerization. In this study, we present a modular architecture for enabling the creation of rule-based clinical diagnostic criteria leveraging Semantic Web technologies. The architecture consists of two modules: an authoring module that utilizes a standards-based information model and a translation module that leverages Semantic Web Rule Language (SWRL). In a prototype implementation, we created a diagnostic criteria upper ontology (DCUO) that integrates ICD-11 content model with the Quality Data Model (QDM). Using the DCUO, we developed a transformation tool that converts QDM-based diagnostic criteria into Semantic Web Rule Language (SWRL) representation. We evaluated the domain coverage of the upper ontology model using randomly selected diagnostic criteria from broad domains (n = 20). We also tested the transformation algorithms using 6 QDM templates for ontology population and 15 QDM-based criteria data for rule generation. As the results, the first draft of DCUO contains 14 root classes, 21 subclasses, 6 object properties and 1 data property. Investigation Findings, and Signs and Symptoms are the two most commonly used element types. All 6 HQMF templates are successfully parsed and populated into their corresponding domain specific ontologies and 14 rules (93.3 %) passed the rule validation. Our efforts in developing and prototyping a modular architecture provide useful insight into how to build a scalable solution to support diagnostic criteria representation and computerization.

Cost-effectiveness analysis of rapid diagnostic test, microscopy and syndromic approach in the diagnosis of malaria in Nigeria: implications for scaling-up deployment of ACT.

PubMed

Uzochukwu, Benjamin S C; Obikeze, Eric N; Onwujekwe, Obinna E; Onoka, Chima A; Griffiths, Ulla K

2009-11-23

The diagnosis and treatment of malaria is often based on syndromic presentation (presumptive treatment) and microscopic examination of blood films. Treatment based on syndromic approach has been found to be costly, and contributes to the development of drug resistance, while microscopic diagnosis of malaria is time-consuming and labour-intensive. Also, there is lack of trained microscopists and reliable equipment especially in rural areas of Nigeria. However, although rapid diagnostic tests (RDTs) have improved the ease of appropriate diagnosis of malaria diagnosis, the cost-effectiveness of RDTs in case management of malaria has not been evaluated in Nigeria. The study hence compares the cost-effectiveness of RDT versus syndromic diagnosis and microscopy. A total of 638 patients with fever, clinically diagnosed as malaria (presumptive malaria) by health workers, were selected for examination with both RDT and microscopy. Patients positive on RDT received artemisinin-based combination therapy (ACT) and febrile patients negative on RDT received an antibiotic treatment. Using a decision tree model for a hypothetical cohort of 100,000 patients, the diagnostic alternatives considered were presumptive treatment (base strategy), RDT and microscopy. Costs were based on a consumer and provider perspective while the outcome measure was deaths averted. Information on costs and malaria epidemiology were locally generated, and along with available data on effectiveness of diagnostic tests, adherence level to drugs for treatment, and drug efficacy levels, cost-effectiveness estimates were computed using TreeAge programme. Results were reported based on costs and effects per strategy, and incremental cost-effectiveness ratios. The cost-effectiveness analysis at 43.1% prevalence level showed an incremental cost effectiveness ratio (ICER) of 221 per deaths averted between RDT and presumptive treatment, while microscopy is dominated at that level. There was also a lesser cost of RDT ($0.34 million) compared to presumptive treatment ($0.37 million) and microscopy ($0.39 million), with effectiveness values of 99,862, 99,735 and 99,851 for RDT, presumptive treatment and microscopy, respectively. Cost-effectiveness was affected by malaria prevalence level, ACT adherence level, cost of ACT, proportion of non-malaria febrile illness cases that were bacterial, and microscopy and RDT sensitivity. RDT is cost-effective when compared to other diagnostic strategies for malaria treatment at malaria prevalence of 43.1% and, therefore, a very good strategy for diagnosis of malaria in Nigeria. There is opportunity for cost savings if rapid diagnostic tests are introduced in health facilities in Nigeria for case management of malaria.

Battery operated preconcentration-assisted lateral flow assay.

PubMed

Kim, Cheonjung; Yoo, Yong Kyoung; Han, Sung Il; Lee, Junwoo; Lee, Dohwan; Lee, Kyungjae; Hwang, Kyo Seon; Lee, Kyu Hyoung; Chung, Seok; Lee, Jeong Hoon

2017-07-11

Paper-based analytical devices (e.g. lateral flow assays) are highly advantageous as portable diagnostic systems owing to their low costs and ease of use. Because of their low sensitivity and detection limits for biomolecules, these devices have several limitations in applications for real-field diagnosis. Here, we demonstrate a paper-based preconcentration enhanced lateral flow assay using a commercial β-hCG-based test. Utilizing a simple 9 V battery operation with a low power consumption of approximately 81 μW, we acquire a 25-fold preconcentration factor, demonstrating a clear sensitivity enhancement in the colorimetric lateral flow assay; consequently, clear colors are observed in a rapid kit test line, which cannot be monitored without preconcentration. This device can also facilitate a semi-quantitative platform using the saturation value and/or color intensity in both paper-based colorimetric assays and smartphone-based diagnostics.

Progress towards implementation of ACT malaria case-management in public health facilities in the Republic of Sudan: a cluster-sample survey

PubMed Central

2012-01-01

Background Effective malaria case-management based on artemisinin-based combination therapy (ACT) and parasitological diagnosis is a major pillar within the 2007-2012 National Malaria Strategic Plan in the Sudan. Three years after the launch of the strategy a health facility survey was undertaken to evaluate case-management practices and readiness of the health facilities and health workers to implement a new malaria case-management strategy. Methods A cross-sectional, cluster sample survey was undertaken at public health facilities in 15 states of Sudan. Data were collected using quality-of-care assessment methods. The main outcomes were the proportions of facilities with ACTs and malaria diagnostics; proportions of health workers exposed to malaria related health systems support activities; and composite and individual indicators of case-management practices for febrile outpatients stratified by age, availability of ACTs and diagnostics, use of malaria diagnostics, and test result. Results We evaluated 244 facilities, 294 health workers and 1,643 consultations for febrile outpatients (425 < 5 years and 1,218 ≥ 5 years). Health facility and health worker readiness was variable: chloroquine was available at only 5% of facilities, 73% stocked recommended artesunate and sulfadoxine/pyrimethamine (AS+SP), 51% had the capacity to perform parasitological diagnosis, 53% of health workers had received in-service training on ACTs, 24% were trained in the use of malaria Rapid Diagnostic Tests, and 19% had received a supervisory visit including malaria case-management. At all health facilities 46% of febrile patients were parasitologically tested and 35% of patients were both, tested and treated according to test result. At facilities where AS+SP and malaria diagnostics were available 66% of febrile patients were tested and 51% were both, tested and treated according to test result. Among test positive patients 64% were treated with AS+SP but 24% were treated with artemether monotherapy. Among test negative patients only 17% of patients were treated for malaria. The majority of ACT dispensing and counseling practices were suboptimal. Conclusions Five years following change of the policy from chloroquine to ACTs and 3 years before the end of the new malaria strategic plan chloroquine was successfully phased out from public facilities in Sudan, however, an important gap remained in the availability of ACTs, diagnostic capacities and coverage with malaria case-management activities. The national scale-up of diagnostics, using the findings of this survey as well as future qualitative research, should present an opportunity not only to expand existing testing capacities but also to implement effective support interventions to bridge the health systems gaps and support corrective case-management measures, including the discontinuation of artemether monotherapy treatment. PMID:22221821

[Promoting evidence-based gastroenterology: back to the future.

PubMed

Koch, Maurizio

2018-01-01

Evidence-based medicine continues to thrive thanks to the publication of a considerable amount of papers focusing on data collection and sharing. Assessment of the accuracy of diagnostic tests still remains highly deficient, often leading to inappropriate clinical decision-making. Like most other doctors, gastroenterologists as well have to face the ever-growing availability of complex and expensive exams, being charged with the task of choosing the best diagnostic option and interpreting test results. It is therefore advisable to provide specialists with the tools they need to evaluate the available literature data. Among these, it deserves mentioning the residential courses organized by the Evidence-based Gastroenterology & Hepatology Club, which have been attended by hundreds of participants over the last years.

Photoplethysmography using a smartphone application for assessment of ulnar artery patency: a randomized clinical trial

PubMed Central

Di Santo, Pietro; Harnett, David T.; Simard, Trevor; Ramirez, F. Daniel; Pourdjabbar, Ali; Yousef, Altayyeb; Moreland, Robert; Bernick, Jordan; Wells, George; Dick, Alexander; Le May, Michel; Labinaz, Marino; So, Derek; Motazedian, Pouya; Jung, Richard G.; Chandrasekhar, Jaya; Mehran, Roxana; Chong, Aun-Yeong

2018-01-01

BACKGROUND: Radial artery access is commonly performed for coronary angiography and invasive hemodynamic monitoring. Despite limitations in diagnostic accuracy, the modified Allen test (manual occlusion of radial and ulnar arteries followed by release of the latter and assessment of palmar blush) is used routinely to evaluate the collateral circulation to the hand and, therefore, to determine patient eligibility for radial artery access. We sought to evaluate whether a smartphone application may provide a superior alternative to the modified Allen test. METHODS: We compared the modified Allen test with a smartphone heart rate–monitoring application (photoplethysmography readings detected using a smartphone camera lens placed on the patient’s index finger) in patients undergoing a planned cardiac catheterization. Test order was randomly assigned in a 1:1 fashion. All patients then underwent conventional plethysmography of the index finger, followed by Doppler ultrasonography of the radial and ulnar arteries (the diagnostic standard). The primary outcome was diagnostic accuracy of the heart rate–monitoring application. RESULTS: Among 438 patients who were included in the study, we found that the heart rate–monitoring application had a superior diagnostic accuracy compared with the modified Allen test (91.8% v. 81.7%, p = 0.002), attributable to its greater specificity (93.0% v. 82.8%, p = 0.001). We also found that this application had greater diagnostic accuracy for assessment of radial or ulnar artery patency in the ipsilateral and contralateral wrist (94.0% v. 84.0%, p < 0.001). INTERPRETATION: A smartphone application used at the bedside was diagnostically superior to traditional physical examination for confirming ulnar patency before radial artery access. This study highlights the potential for smartphone-based diagnostics to aid in clinical decision-making at the patient’s bedside. Trial registration: Clinicaltrials.gov, no. NCT02519491. PMID:29615421

Photoplethysmography using a smartphone application for assessment of ulnar artery patency: a randomized clinical trial.

PubMed

Di Santo, Pietro; Harnett, David T; Simard, Trevor; Ramirez, F Daniel; Pourdjabbar, Ali; Yousef, Altayyeb; Moreland, Robert; Bernick, Jordan; Wells, George; Dick, Alexander; Le May, Michel; Labinaz, Marino; So, Derek; Motazedian, Pouya; Jung, Richard G; Chandrasekhar, Jaya; Mehran, Roxana; Chong, Aun-Yeong; Hibbert, Benjamin

2018-04-03

Radial artery access is commonly performed for coronary angiography and invasive hemodynamic monitoring. Despite limitations in diagnostic accuracy, the modified Allen test (manual occlusion of radial and ulnar arteries followed by release of the latter and assessment of palmar blush) is used routinely to evaluate the collateral circulation to the hand and, therefore, to determine patient eligibility for radial artery access. We sought to evaluate whether a smartphone application may provide a superior alternative to the modified Allen test. We compared the modified Allen test with a smartphone heart rate-monitoring application (photoplethysmography readings detected using a smartphone camera lens placed on the patient's index finger) in patients undergoing a planned cardiac catheterization. Test order was randomly assigned in a 1:1 fashion. All patients then underwent conventional plethysmography of the index finger, followed by Doppler ultrasonography of the radial and ulnar arteries (the diagnostic standard). The primary outcome was diagnostic accuracy of the heart rate-monitoring application. Among 438 patients who were included in the study, we found that the heart rate-monitoring application had a superior diagnostic accuracy compared with the modified Allen test (91.8% v. 81.7%, p = 0.002), attributable to its greater specificity (93.0% v. 82.8%, p = 0.001). We also found that this application had greater diagnostic accuracy for assessment of radial or ulnar artery patency in the ipsilateral and contralateral wrist (94.0% v. 84.0%, p < 0.001). A smartphone application used at the bedside was diagnostically superior to traditional physical examination for confirming ulnar patency before radial artery access. This study highlights the potential for smartphone-based diagnostics to aid in clinical decision-making at the patient's bedside. Trial registration: Clinicaltrials.gov, no. NCT02519491. © 2018 Joule Inc. or its licensors.

Update on diagnostics for Phytophthora ramorum

Treesearch

Philip Berger

2006-01-01

Diagnostics used by the U.S. Department of Agriculture (USDA), to determine absence or presence of Phytophthora ramorum in plant samples, are based on a combination of tests and depend on collaboration with external laboratories. The system currently in place attempts to maximize limited resources and at the same time provide the most scientifically...

Are the classic diagnostic methods in mycology still state of the art?

PubMed

Wiegand, Cornelia; Bauer, Andrea; Brasch, Jochen; Nenoff, Pietro; Schaller, Martin; Mayser, Peter; Hipler, Uta-Christina; Elsner, Peter

2016-05-01

The diagnostic workup of cutaneous fungal infections is traditionally based on microscopic KOH preparations as well as culturing of the causative organism from sample material. Another possible option is the detection of fungal elements by dermatohistology. If performed correctly, these methods are generally suitable for the diagnosis of mycoses. However, the advent of personalized medicine and the tasks arising therefrom require new procedures marked by simplicity, specificity, and swiftness. The additional use of DNA-based molecular techniques further enhances sensitivity and diagnostic specificity, and reduces the diagnostic interval to 24-48 hours, compared to weeks required for conventional mycological methods. Given the steady evolution in the field of personalized medicine, simple analytical PCR-based systems are conceivable, which allow for instant diagnosis of dermatophytes in the dermatology office (point-of-care tests). © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Electrochemistry-based Approaches to Low Cost, High Sensitivity, Automated, Multiplexed Protein Immunoassays for Cancer Diagnostics

PubMed Central

Dixit, Chandra K.; Kadimisetty, Karteek; Otieno, Brunah A.; Tang, Chi; Malla, Spundana; Krause, Colleen E.; Rusling, James F.

2015-01-01

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. Simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that doesn’t require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for highly sensitive detection of the panel of cancer-specific biomarkers with high specificity and at the same time have the potential to be translated into a POC. PMID:26525998

Electrochemistry-based approaches to low cost, high sensitivity, automated, multiplexed protein immunoassays for cancer diagnostics.

PubMed

Dixit, Chandra K; Kadimisetty, Karteek; Otieno, Brunah A; Tang, Chi; Malla, Spundana; Krause, Colleen E; Rusling, James F

2016-01-21

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. The simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that does not require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for the highly sensitive detection of a panel of cancer-specific biomarkers with high specificity which at the same time has the potential to be translated into POC applications.

Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe.

PubMed

Dubbink, Hendrikus J; Deans, Zandra C; Tops, Bastiaan B J; van Kemenade, Folkert J; Koljenović, S; van Krieken, Han J M; Blokx, Willeke A M; Dinjens, Winand N M; Groenen, Patricia J T A

2014-06-01

Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

2D imaging X-ray diagnostic for measuring the current density distribution in a wide-area electron beam produced in a multiaperture diode with plasma cathode

NASA Astrophysics Data System (ADS)

Kurkuchekov, V.; Kandaurov, I.; Trunev, Y.

2018-05-01

A simple and inexpensive X-ray diagnostic tool was designed for measuring the cross-sectional current density distribution in a low-relativistic pulsed electron beam produced in a source based on an arc-discharge plasma cathode and multiaperture diode-type electron optical system. The beam parameters were as follows: Uacc = 50–110 kV, Ibeam = 20–100 A, τbeam = 0.1–0.3 ms. The beam effective diameter was ca. 7 cm. Based on a pinhole camera, the diagnostic allows one to obtain a 2D profile of electron beam flux distribution on a flat metal target in a single shot. The linearity of the diagnostic system response to the electron flux density was established experimentally. Spatial resolution of the diagnostic was also estimated in special test experiments. The optimal choice of the main components of the diagnostic technique is discussed.

The role of diagnostic laboratories in support of animal disease surveillance systems.

PubMed

Zepeda, C

2007-01-01

Diagnostic laboratories are an essential component of animal disease surveillance systems. To understand the occurrence of disease in populations, surveillance systems rely on random or targeted surveys using three approaches: clinical, serological and virological surveillance. Clinical surveillance is the basis for early detection of disease and is usually centered on the detection of syndromes and clinical findings requiring confirmation by diagnostic laboratories. Although most of the tests applied usually perform to an acceptable standard, several have not been properly validated in terms of their diagnostic sensitivity and specificity. Sensitivity and specificity estimates can vary according to local conditions and, ideally, should be determined by national laboratories where the tests are to be applied. The importance of sensitivity and specificity estimates in the design and interpretation of statistically based surveys and risk analysis is fundamental to establish appropriate disease control and prevention strategies. The World Organisation for Animal Health's (OIE) network of reference laboratories acts as centers of expertise for the diagnosis of OIE listed diseases and have a role in promoting the validation of OIE prescribed tests for international trade. This paper discusses the importance of the epidemiological evaluation of diagnostic tests and the role of the OIE Reference Laboratories and Collaborating Centres in this process.

A principled approach to setting optimal diagnostic thresholds: where ROC and indifference curves meet.

PubMed

Irwin, R John; Irwin, Timothy C

2011-06-01

Making clinical decisions on the basis of diagnostic tests is an essential feature of medical practice and the choice of the decision threshold is therefore crucial. A test's optimal diagnostic threshold is the threshold that maximizes expected utility. It is given by the product of the prior odds of a disease and a measure of the importance of the diagnostic test's sensitivity relative to its specificity. Choosing this threshold is the same as choosing the point on the Receiver Operating Characteristic (ROC) curve whose slope equals this product. We contend that a test's likelihood ratio is the canonical decision variable and contrast diagnostic thresholds based on likelihood ratio with two popular rules of thumb for choosing a threshold. The two rules are appealing because they have clear graphical interpretations, but they yield optimal thresholds only in special cases. The optimal rule can be given similar appeal by presenting indifference curves, each of which shows a set of equally good combinations of sensitivity and specificity. The indifference curve is tangent to the ROC curve at the optimal threshold. Whereas ROC curves show what is feasible, indifference curves show what is desirable. Together they show what should be chosen. Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Development of immune-diagnostic reagents to diagnose bovine tuberculosis in cattle.

PubMed

Vordermeier, H Martin; Jones, Gareth J; Buddle, Bryce M; Hewinson, R Glyn

2016-11-15

Bovine tuberculosis remains a major economic and animal welfare concern worldwide. As part of control strategies, cattle vaccination is being considered. This approach, used alongside conventional control policies, also requires the development of vaccine compatible diagnostic assays to distinguish infected from vaccinated animals (DIVA). In this review we discuss recent advances in DIVA development based on the detection of host cellular immune responses by blood testing or skin testing approaches. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

The role of molecular genetic analysis in the diagnosis of primary ciliary dyskinesia.

PubMed

Kim, Raymond H; A Hall, David; Cutz, Ernest; Knowles, Michael R; Nelligan, Kathleen A; Nykamp, Keith; Zariwala, Maimoona A; Dell, Sharon D

2014-03-01

Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disorder of motile cilia. The diagnosis of PCD has previously relied on ciliary analysis with transmission electron microscopy or video microscopy. However, patients with PCD may have normal ultrastructural appearance, and ciliary analysis has limited accessibility. Alternatively, PCD can be diagnosed by demonstrating biallelic mutations in known PCD genes. Genetic testing is emerging as a diagnostic tool to complement ciliary analysis where interpretation and access may delay diagnosis. To determine the diagnostic yield of genetic testing of patients with a confirmed or suspected diagnosis of PCD in a multiethnic urban center. Twenty-eight individuals with confirmed PCD on transmission electron microscopy of ciliary ultrastructure and 24 individuals with a probable diagnosis of PCD based on a classical PCD phenotype and low nasal nitric oxide had molecular analysis of 12 genes associated with PCD. Of 49 subjects who underwent ciliary biopsy, 28 (57%) were diagnosed with PCD through an ultrastructural defect. Of the 52 individuals who underwent molecular genetic analysis, 22 (42%) individuals had two mutations in known PCD genes. Twenty-four previously unreported mutations in known PCD genes were observed. Combining both diagnostic modalities of biopsy and molecular genetics, the diagnostic yield increased to 69% compared with 57% based on biopsy alone. The diagnosis of PCD is challenging and has traditionally relied on ciliary biopsy, which is unreliable as the sole criterion for a definitive diagnosis. Molecular genetic analysis can be used as a complementary test to increase the diagnostic yield.

Structured syncope care pathways based on lean six sigma methodology optimises resource use with shorter time to diagnosis and increased diagnostic yield.

PubMed

Martens, Leon; Goode, Grahame; Wold, Johan F H; Beck, Lionel; Martin, Georgina; Perings, Christian; Stolt, Pelle; Baggerman, Lucas

2014-01-01

To conduct a pilot study on the potential to optimise care pathways in syncope/Transient Loss of Consciousness management by using Lean Six Sigma methodology while maintaining compliance with ESC and/or NICE guidelines. Five hospitals in four European countries took part. The Lean Six Sigma methodology consisted of 3 phases: 1) Assessment phase, in which baseline performance was mapped in each centre, processes were evaluated and a new operational model was developed with an improvement plan that included best practices and change management; 2) Improvement phase, in which optimisation pathways and standardised best practice tools and forms were developed and implemented. Staff were trained on new processes and change-management support provided; 3) Sustaining phase, which included support, refinement of tools and metrics. The impact of the implementation of new pathways was evaluated on number of tests performed, diagnostic yield, time to diagnosis and compliance with guidelines. One hospital with focus on geriatric populations was analysed separately from the other four. With the new pathways, there was a 59% reduction in the average time to diagnosis (p = 0.048) and a 75% increase in diagnostic yield (p = 0.007). There was a marked reduction in repetitions of diagnostic tests and improved prioritisation of indicated tests. Applying a structured Lean Six Sigma based methodology to pathways for syncope management has the potential to improve time to diagnosis and diagnostic yield.

Structured Syncope Care Pathways Based on Lean Six Sigma Methodology Optimises Resource Use with Shorter Time to Diagnosis and Increased Diagnostic Yield

PubMed Central

Martens, Leon; Goode, Grahame; Wold, Johan F. H.; Beck, Lionel; Martin, Georgina; Perings, Christian; Stolt, Pelle; Baggerman, Lucas

2014-01-01

Aims To conduct a pilot study on the potential to optimise care pathways in syncope/Transient Loss of Consciousness management by using Lean Six Sigma methodology while maintaining compliance with ESC and/or NICE guidelines. Methods Five hospitals in four European countries took part. The Lean Six Sigma methodology consisted of 3 phases: 1) Assessment phase, in which baseline performance was mapped in each centre, processes were evaluated and a new operational model was developed with an improvement plan that included best practices and change management; 2) Improvement phase, in which optimisation pathways and standardised best practice tools and forms were developed and implemented. Staff were trained on new processes and change-management support provided; 3) Sustaining phase, which included support, refinement of tools and metrics. The impact of the implementation of new pathways was evaluated on number of tests performed, diagnostic yield, time to diagnosis and compliance with guidelines. One hospital with focus on geriatric populations was analysed separately from the other four. Results With the new pathways, there was a 59% reduction in the average time to diagnosis (p = 0.048) and a 75% increase in diagnostic yield (p = 0.007). There was a marked reduction in repetitions of diagnostic tests and improved prioritisation of indicated tests. Conclusions Applying a structured Lean Six Sigma based methodology to pathways for syncope management has the potential to improve time to diagnosis and diagnostic yield. PMID:24927475

Review: Diagnostic accuracy of PCR-based detection tests for Helicobacter Pylori in stool samples.

PubMed

Khadangi, Fatemeh; Yassi, Maryam; Kerachian, Mohammad Amin

2017-12-01

Although different methods have been established to detect Helicobacter pylori (H. pylori) infection, identifying infected patients is an ongoing challenge. The aim of this meta-analysis was to provide pooled diagnostic accuracy measures for stool PCR test in the diagnosis of H. pylori infection. In this study, a systematic review and meta-analysis were carried out on various sources, including MEDLINE, Web of Sciences, and the Cochrane Library from April 1, 1999, to May 1, 2016. This meta-analysis adheres to the guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses report (PRISMA Statement). The clinical value of DNA stool PCR test was based on the pooled false positive, false negative, true positive, and true negative of different genes. Twenty-six of 328 studies identified met the eligibility criteria. Stool PCR test had a performance of 71% (95% CI: 68-73) sensitivity, 96% (95% CI: 94-97) specificity, and 65.6 (95% CI: 30.2-142.5) diagnostic odds ratio (DOR) in diagnosis of H. pylori. The DOR of genes which showed the highest performance of stool PCR tests was as follows: 23S rRNA 152.5 (95% CI: 55.5-418.9), 16S rRNA 67.9 (95%CI: 6.4-714.3), and glmM 68.1 (95%CI: 20.1-231.7). The sensitivity and specificity of stool PCR test are relatively in the same spectrum of other diagnostic methods for the detection of H. pylori infection. In descending order of significance, the most diagnostic candidate genes using PCR detection were 23S rRNA, 16S rRNA, and glmM. PCR for 23S rRNA gene which has the highest performance could be applicable to detect H. pylori infection. © 2017 John Wiley & Sons Ltd.

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

PubMed

Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

2016-03-22

To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

Fault Tree Based Diagnosis with Optimal Test Sequencing for Field Service Engineers

NASA Technical Reports Server (NTRS)

Iverson, David L.; George, Laurence L.; Patterson-Hine, F. A.; Lum, Henry, Jr. (Technical Monitor)

1994-01-01

When field service engineers go to customer sites to service equipment, they want to diagnose and repair failures quickly and cost effectively. Symptoms exhibited by failed equipment frequently suggest several possible causes which require different approaches to diagnosis. This can lead the engineer to follow several fruitless paths in the diagnostic process before they find the actual failure. To assist in this situation, we have developed the Fault Tree Diagnosis and Optimal Test Sequence (FTDOTS) software system that performs automated diagnosis and ranks diagnostic hypotheses based on failure probability and the time or cost required to isolate and repair each failure. FTDOTS first finds a set of possible failures that explain exhibited symptoms by using a fault tree reliability model as a diagnostic knowledge to rank the hypothesized failures based on how likely they are and how long it would take or how much it would cost to isolate and repair them. This ordering suggests an optimal sequence for the field service engineer to investigate the hypothesized failures in order to minimize the time or cost required to accomplish the repair task. Previously, field service personnel would arrive at the customer site and choose which components to investigate based on past experience and service manuals. Using FTDOTS running on a portable computer, they can now enter a set of symptoms and get a list of possible failures ordered in an optimal test sequence to help them in their decisions. If facilities are available, the field engineer can connect the portable computer to the malfunctioning device for automated data gathering. FTDOTS is currently being applied to field service of medical test equipment. The techniques are flexible enough to use for many different types of devices. If a fault tree model of the equipment and information about component failure probabilities and isolation times or costs are available, a diagnostic knowledge base for that device can be developed easily.

Bayesian multivariate hierarchical transformation models for ROC analysis.

PubMed

O'Malley, A James; Zou, Kelly H

2006-02-15

A Bayesian multivariate hierarchical transformation model (BMHTM) is developed for receiver operating characteristic (ROC) curve analysis based on clustered continuous diagnostic outcome data with covariates. Two special features of this model are that it incorporates non-linear monotone transformations of the outcomes and that multiple correlated outcomes may be analysed. The mean, variance, and transformation components are all modelled parametrically, enabling a wide range of inferences. The general framework is illustrated by focusing on two problems: (1) analysis of the diagnostic accuracy of a covariate-dependent univariate test outcome requiring a Box-Cox transformation within each cluster to map the test outcomes to a common family of distributions; (2) development of an optimal composite diagnostic test using multivariate clustered outcome data. In the second problem, the composite test is estimated using discriminant function analysis and compared to the test derived from logistic regression analysis where the gold standard is a binary outcome. The proposed methodology is illustrated on prostate cancer biopsy data from a multi-centre clinical trial.

Bayesian multivariate hierarchical transformation models for ROC analysis

PubMed Central

O'Malley, A. James; Zou, Kelly H.

2006-01-01

SUMMARY A Bayesian multivariate hierarchical transformation model (BMHTM) is developed for receiver operating characteristic (ROC) curve analysis based on clustered continuous diagnostic outcome data with covariates. Two special features of this model are that it incorporates non-linear monotone transformations of the outcomes and that multiple correlated outcomes may be analysed. The mean, variance, and transformation components are all modelled parametrically, enabling a wide range of inferences. The general framework is illustrated by focusing on two problems: (1) analysis of the diagnostic accuracy of a covariate-dependent univariate test outcome requiring a Box–Cox transformation within each cluster to map the test outcomes to a common family of distributions; (2) development of an optimal composite diagnostic test using multivariate clustered outcome data. In the second problem, the composite test is estimated using discriminant function analysis and compared to the test derived from logistic regression analysis where the gold standard is a binary outcome. The proposed methodology is illustrated on prostate cancer biopsy data from a multi-centre clinical trial. PMID:16217836

[Assessment of a rapid diagnostic test for malaria in rural health care facilities in Senegal].

PubMed

Munier, A; Diallo, A; Sokhna, C; Chippaux, J P

2009-10-01

The aim of the study was to determine the accuracy of a rapid diagnostic test in confirming presumptive malaria diagnosis in a rural zone of Senegal. Thick blood smear was used as the reference technique for comparison. METHOHDOLOGY: Testing was conducted on children between the ages of 1 and 14 years at three health care facilities located in the Niakhar are from August 2006 to June 2007. If malaria was suspected by the nurse based on clinical findings, two thick smears and one rapid diagnostic test (Core Malaria Pf) were performed. Blood slides were stained in Niakhar and read in Dakar. A total of 474 patients were examined. Three-fourths (75%) of these patients were seen during the rainy season. Malaria was suspected in 335 patients (71%). Rapid tests and thick smears were obtained in 330 of these patients with positive results in 194 (59%) and 180 (55%) respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the rapid test were 96%, 87%, 90% and 95% respectively. Our data show that the rapid diagnostic test used in this study exhibits good sensitivity and positive predictive value. Despite its cost this test could be helpful in confirming malaria diagnosis in outlying health care facilities without the necessary resources to perform blood smears. Confirmation is necessary to avoid unwarranted prescription of malaria treatment due to inaccurate clinical diagnosis

Bayesian modeling and inference for diagnostic accuracy and probability of disease based on multiple diagnostic biomarkers with and without a perfect reference standard.

PubMed

Jafarzadeh, S Reza; Johnson, Wesley O; Gardner, Ian A

2016-03-15

The area under the receiver operating characteristic (ROC) curve (AUC) is used as a performance metric for quantitative tests. Although multiple biomarkers may be available for diagnostic or screening purposes, diagnostic accuracy is often assessed individually rather than in combination. In this paper, we consider the interesting problem of combining multiple biomarkers for use in a single diagnostic criterion with the goal of improving the diagnostic accuracy above that of an individual biomarker. The diagnostic criterion created from multiple biomarkers is based on the predictive probability of disease, conditional on given multiple biomarker outcomes. If the computed predictive probability exceeds a specified cutoff, the corresponding subject is allocated as 'diseased'. This defines a standard diagnostic criterion that has its own ROC curve, namely, the combined ROC (cROC). The AUC metric for cROC, namely, the combined AUC (cAUC), is used to compare the predictive criterion based on multiple biomarkers to one based on fewer biomarkers. A multivariate random-effects model is proposed for modeling multiple normally distributed dependent scores. Bayesian methods for estimating ROC curves and corresponding (marginal) AUCs are developed when a perfect reference standard is not available. In addition, cAUCs are computed to compare the accuracy of different combinations of biomarkers for diagnosis. The methods are evaluated using simulations and are applied to data for Johne's disease (paratuberculosis) in cattle. Copyright © 2015 John Wiley & Sons, Ltd.

Design standards for experimental and field studies to evaluate diagnostic accuracy of tests for infectious diseases in aquatic animals.

PubMed

Laurin, E; Thakur, K K; Gardner, I A; Hick, P; Moody, N J G; Crane, M S J; Ernst, I

2018-05-01

Design and reporting quality of diagnostic accuracy studies (DAS) are important metrics for assessing utility of tests used in animal and human health. Following standards for designing DAS will assist in appropriate test selection for specific testing purposes and minimize the risk of reporting biased sensitivity and specificity estimates. To examine the benefits of recommending standards, design information from published DAS literature was assessed for 10 finfish, seven mollusc, nine crustacean and two amphibian diseases listed in the 2017 OIE Manual of Diagnostic Tests for Aquatic Animals. Of the 56 DAS identified, 41 were based on field testing, eight on experimental challenge studies and seven on both. Also, we adapted human and terrestrial-animal standards and guidelines for DAS structure for use in aquatic animal diagnostic research. Through this process, we identified and addressed important metrics for consideration at the design phase: study purpose, targeted disease state, selection of appropriate samples and specimens, laboratory analytical methods, statistical methods and data interpretation. These recommended design standards for DAS are presented as a checklist including risk-of-failure points and actions to mitigate bias at each critical step. Adherence to standards when designing DAS will also facilitate future systematic review and meta-analyses of DAS research literature. © 2018 John Wiley & Sons Ltd.

Lyssaviruses: special emphasis on rabies virus and other members of the lyssavirus genus.

PubMed

Harkess, Graeme; Fooks, Anthony R

2011-01-01

Rabies is routinely diagnosed based on the clinical description and history of exposure in a rabies-endemic country. A negative diagnostic test for rabies virus or a related lyssavirus does not exclude the clinical diagnosis. Diagnostic tests are never optimal and are entirely dependent on the nature and quality of the sample supplied. Often, only a sample from a single time point is investigated reducing the overall sensitivity of any diagnosis. With the advent of molecular biology, tests have been developed that are rapid, robust, and sensitive in support of the rapid detection and strain identification of rabies virus from clinical specimens. These molecular tests complement conventional tests in rabies diagnosis, particularly for human cases, for which an early laboratory diagnosis is critical and may decrease the number of unnecessary contacts with the patient, reduce the requirement for invasive and costly interventions, and enable the appropriate medical treatment regimen to be administered for the patient. The barrier to success is in transferring the technology for the latest techniques in rabies diagnosis to rabies-endemic countries. These barriers are not insurmountable and in liaison with international organisations, especially OIE, FAO, and WHO, these diagnostic tests will be validated for rabies diagnosis and surveillance, and implemented in modern and well-equipped diagnostic laboratories throughout the world.

Comprehensive evaluation of the child with intellectual disability or global developmental delays.

PubMed

Moeschler, John B; Shevell, Michael

2014-09-01

Global developmental delay and intellectual disability are relatively common pediatric conditions. This report describes the recommended clinical genetics diagnostic approach. The report is based on a review of published reports, most consisting of medium to large case series of diagnostic tests used, and the proportion of those that led to a diagnosis in such patients. Chromosome microarray is designated as a first-line test and replaces the standard karyotype and fluorescent in situ hybridization subtelomere tests for the child with intellectual disability of unknown etiology. Fragile X testing remains an important first-line test. The importance of considering testing for inborn errors of metabolism in this population is supported by a recent systematic review of the literature and several case series recently published. The role of brain MRI remains important in certain patients. There is also a discussion of the emerging literature on the use of whole-exome sequencing as a diagnostic test in this population. Finally, the importance of intentional comanagement among families, the medical home, and the clinical genetics specialty clinic is discussed. Copyright © 2014 by the American Academy of Pediatrics.

[A new system of testing visual performance based on the cylindrical lens screen].

PubMed

Doege, E; Krause, O

1983-09-01

Using a special microoptical screen as a test-picture coating, a method for testing binocular function was developed. It offers the advantage of providing a separate visual impression to each eye from a diagnostic picture without using any device in front of the eyes. The person tested is unaware of this procedure, of which the diagnostic plate gives no hint. In addition to a description of its numerous uses and diagnostic possibilities, fusion pictures suitable for screening tests are described: Each eye is offered a separate impression with a completely different content. If fusion occurs correctly, a third motif with an entirely new meaning emerges. Several years of experience with this effective system (naked-eye tests) resulted in aids which are listed in the final section of the paper: exercise aids used for preparing the persons tested (especially infants) in the waiting room, recognition aids for the examination, and a partially kinetic picture for rapid, simple and very convincing representation of adjusting movements and of the squint position in cases of concomitant squint.

GENOSENSE Diagnostics GmbH.

PubMed

Schneeberger, Christian

2004-07-01

GENOSENSE Diagnostics GmbH, a company specialized in preventive genetic diagnostics, has committed itself to applying molecular medical knowledge to realizing the vision of individual, preventive and patient-tailored medicine. GENOSENSE offers a unique line of preventive genomic diagnostic profiles. Each profile focuses on a carefully selected set of polymorphisms associated with particular diseases or physiologic imbalances. GENOSENSE does not only provide the genetic test results, but highly capable medical experts 'translate' the results into a clinical language and assist the customer with established support regarding their medical interpretation. In addition, the company provides academic institutions and pharmaceutical companies with turnkey solutions for research-based projects.

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... in the 80000 series of the Current Procedural Terminology published by the American Medical... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Procedural Terminology published by the American Medical Association. (3) Levels of supervision. Except where... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

Clinical overlap between malaria and pneumonia: can malaria rapid diagnostic test play a role?

PubMed

Ukwaja, Kingsley Nnanna; Aina, Olufemi B; Talabi, Ademola A

2011-03-21

Malaria and pneumonia account for 40% of mortality among children under five years of age in sub-Saharan Africa. Due to lack of diagnostic facilities, their management is based on the integrated management of childhood illnesses (IMCI) strategy. Symptoms of malaria and pneumonia overlap in African children, necessitating dual IMCI classifications at health centres and treatment with both antibiotics and antimalarials. This study determined the prevalence of malaria-pneumonia symptom overlap and confirmed the diagnosis of malaria in these cases using a rapid diagnostic test. Consecutive consultations of 1,216 children (two months to five years old) were documented over a three-month period in a comprehensive health centre. Malaria rapid diagnostic tests were conducted only for children who had symptom overlap. Of the 1,216 children enrolled, 1,090 (90%) reported cough or fever. Among the children fulfilling the malaria case definition, 284 (30%) also met the pneumonia case definition. Twenty-three percent (284) of all children enrolled met the criteria for both malaria and pneumonia. However, only 130 (46%) of them had a positive result for malaria using a malaria rapid diagnostic test. During a malaria-pneumonia overlap, female children (chi-square 5.9, P = 0.01) and children ≥ one year (chi-square 4.8, P = 0.003) were more likely to seek care within two days of fever. Dual treatment with antimalarials and antibiotics in children with malaria-pneumonia overlap may result in unnecessary over-prescription of antimalarial medications. Use of rapid diagnostic tests in their management can potentially avoid over-prescribing of malaria medications.

Spinal meningioma, aortic aneurysms and the missing link of observation: the anchoring heuristic approach.

PubMed

Floros, Nikolaos; Papadakis, Marios; Schelzig, Hubert; Oberhuber, Alexander

2018-03-10

Over the last three decades, the development of systematic and protocol-based algorithms, and advances in available diagnostic tests have become the indispensable parts of practising medicine. Naturally, despite the implementation of meticulous protocols involving diagnostic tests or even trials of empirical therapies, the cause of one's symptoms may still not be obvious. We herein report a case of chronic back pain, which took about 5 years to get accurately diagnosed. The case challenges the diagnostic assumptions and sets ground of discussion for the diagnostic reasoning pitfalls and heuristic biases that mislead the caring physicians and cost years of low quality of life to our patient. This case serves as an example of how anchoring heuristics can interfere in the diagnostic process of a complex and rare entity when combined with a concurrent potentially life-threatening condition. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Computer Vision Malaria Diagnostic Systems-Progress and Prospects.

PubMed

Pollak, Joseph Joel; Houri-Yafin, Arnon; Salpeter, Seth J

2017-01-01

Accurate malaria diagnosis is critical to prevent malaria fatalities, curb overuse of antimalarial drugs, and promote appropriate management of other causes of fever. While several diagnostic tests exist, the need for a rapid and highly accurate malaria assay remains. Microscopy and rapid diagnostic tests are the main diagnostic modalities available, yet they can demonstrate poor performance and accuracy. Automated microscopy platforms have the potential to significantly improve and standardize malaria diagnosis. Based on image recognition and machine learning algorithms, these systems maintain the benefits of light microscopy and provide improvements such as quicker scanning time, greater scanning area, and increased consistency brought by automation. While these applications have been in development for over a decade, recently several commercial platforms have emerged. In this review, we discuss the most advanced computer vision malaria diagnostic technologies and investigate several of their features which are central to field use. Additionally, we discuss the technological and policy barriers to implementing these technologies in low-resource settings world-wide.

Demise of Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry as an Infectious Diseases Diagnostic Tool.

PubMed

Özenci, Volkan; Patel, Robin; Ullberg, Måns; Strålin, Kristoffer

2018-01-18

Although there are several US Food and Drug Administration (FDA)-approved/cleared molecular microbiology diagnostics for direct analysis of patient samples, all are single target or panel-based tests. There is no FDA-approved/cleared diagnostic for broad microbial detection. Polymerase chain reaction (PCR)/electrospray ionization-mass spectrometry (PCR/ESI-MS), commercialized as the IRIDICA system (Abbott) and formerly PLEX-ID, had been under development for over a decade and had become CE-marked and commercially available in Europe in 2014. Capable of detecting a large number of microorganisms, it was under review at the FDA when, in April 2017, Abbott discontinued it. This turn of events represents not only the loss of a potential diagnostic tool for infectious diseases but may be a harbinger of similar situations with other emerging and expensive microbial diagnostics, especially genomic tests. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Effect of Watermarking on Diagnostic Preservation of Atherosclerotic Ultrasound Video in Stroke Telemedicine.

PubMed

Dey, Nilanjan; Bose, Soumyo; Das, Achintya; Chaudhuri, Sheli Sinha; Saba, Luca; Shafique, Shoaib; Nicolaides, Andrew; Suri, Jasjit S

2016-04-01

Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA-AtheroPoint™ (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application.

Emerging Rapid Resistance Testing Methods for Clinical Microbiology Laboratories and Their Potential Impact on Patient Management

PubMed Central

Frickmann, Hagen; Zautner, Andreas E.

2014-01-01

Atypical and multidrug resistance, especially ESBL and carbapenemase expressing Enterobacteriaceae, is globally spreading. Therefore, it becomes increasingly difficult to achieve therapeutic success by calculated antibiotic therapy. Consequently, rapid antibiotic resistance testing is essential. Various molecular and mass spectrometry-based approaches have been introduced in diagnostic microbiology to speed up the providing of reliable resistance data. PCR- and sequencing-based approaches are the most expensive but the most frequently applied modes of testing, suitable for the detection of resistance genes even from primary material. Next generation sequencing, based either on assessment of allelic single nucleotide polymorphisms or on the detection of nonubiquitous resistance mechanisms might allow for sequence-based bacterial resistance testing comparable to viral resistance testing on the long term. Fluorescence in situ hybridization (FISH), based on specific binding of fluorescence-labeled oligonucleotide probes, provides a less expensive molecular bridging technique. It is particularly useful for detection of resistance mechanisms based on mutations in ribosomal RNA. Approaches based on MALDI-TOF-MS, alone or in combination with molecular techniques, like PCR/electrospray ionization MS or minisequencing provide the fastest resistance results from pure colonies or even primary samples with a growing number of protocols. This review details the various approaches of rapid resistance testing, their pros and cons, and their potential use for the diagnostic laboratory. PMID:25343142

Method of Testing and Predicting Failures of Electronic Mechanical Systems

NASA Technical Reports Server (NTRS)

Iverson, David L.; Patterson-Hine, Frances A.

1996-01-01

A method employing a knowledge base of human expertise comprising a reliability model analysis implemented for diagnostic routines is disclosed. The reliability analysis comprises digraph models that determine target events created by hardware failures human actions, and other factors affecting the system operation. The reliability analysis contains a wealth of human expertise information that is used to build automatic diagnostic routines and which provides a knowledge base that can be used to solve other artificial intelligence problems.

GryphSens: A Smartphone-Based Portable Diagnostic Reader for the Rapid Detection of Progesterone in Milk

PubMed Central

Jang, Hyunwook; Ahmed, Syed Rahin; Neethirajan, Suresh

2017-01-01

Enzyme-linked immunosorbent assay (ELISA) is a popular assay technique for the detection and quantification of various biological substances due its high sensitivity and specificity. More often, it requires large and expensive laboratory instruments, which makes it difficult to conduct when the tests must be performed quickly at the point-of-care (POC). To increase portability and ease of use, we propose a portable diagnostic system based on a Raspberry Pi imaging sensor for the rapid detection of progesterone in milk samples. We designed, assembled, and tested a standalone portable diagnostic reader and validated it for progesterone detection against a standard ELISA assay using a commercial plate reader. The portable POC device yielded consistent results, regardless of differences in the cameras and flashlights between various smartphone devices. An Android application was built to provide front-end access to users, control the diagnostic reader, and display and store the progesterone measurement on the smartphone. The diagnostic reader takes images of the samples, reads the pixel values, processes the results, and presents the results on the handheld device. The proposed POC reader can perform to superior levels of performance as a plate reader, while adding the desirable qualities of portability and ease of use. PMID:28489036

GryphSens: A Smartphone-Based Portable Diagnostic Reader for the Rapid Detection of Progesterone in Milk.

PubMed

Jang, Hyunwook; Ahmed, Syed Rahin; Neethirajan, Suresh

2017-05-10

Enzyme-linked immunosorbent assay (ELISA) is a popular assay technique for the detection and quantification of various biological substances due its high sensitivity and specificity. More often, it requires large and expensive laboratory instruments, which makes it difficult to conduct when the tests must be performed quickly at the point-of-care (POC). To increase portability and ease of use, we propose a portable diagnostic system based on a Raspberry Pi imaging sensor for the rapid detection of progesterone in milk samples. We designed, assembled, and tested a standalone portable diagnostic reader and validated it for progesterone detection against a standard ELISA assay using a commercial plate reader. The portable POC device yielded consistent results, regardless of differences in the cameras and flashlights between various smartphone devices. An Android application was built to provide front-end access to users, control the diagnostic reader, and display and store the progesterone measurement on the smartphone. The diagnostic reader takes images of the samples, reads the pixel values, processes the results, and presents the results on the handheld device. The proposed POC reader can perform to superior levels of performance as a plate reader, while adding the desirable qualities of portability and ease of use.

Correlation between bithermal caloric test results and vestibular evoked myogenic potentials (VEMPs) in normal subjects.

PubMed

Andrade, Isabel Vaamonde Sanchez; Santos-Perez, Sofia; Diz, Pilar Gayoso; Caballero, Torcuato Labella; Soto-Varela, Andrés

2013-05-01

Bithermal caloric testing and vestibular evoked myogenic potentials (VEMPs) are both diagnostic tools for the study of the vestibular system. The first tests the horizontal semicircular canal and the second evaluates the saccule and lower vestibular nerve. The results of these two tests can therefore be expected to be correlated. The aim of this study was to compare bithermal caloric test results with VEMP records in normal subjects to verify whether they are correlated. A prospective study was conducted in 60 healthy subjects (30 men and 30 women) who underwent otoscopy, pure tone audiometry, bithermal caloric testing and VEMPs. From the caloric test, we assessed the presence of possible vestibular hypofunction, whether there was directional preponderance and reflectivity of each ear (all based on both slow phase velocity and nystagmus frequency). The analysed VEMPs variables were: p1 and n1 latency, corrected amplitude, interaural p1 latency difference and p1 interaural amplitude asymmetry. We compared the reflectivity, hypofunction and directional preponderance of the caloric tests with the corrected amplitudes and amplitude asymmetries of the VEMPs. No correlations were found in the different comparisons between bithermal caloric testing results and VEMPs except for a weak correlation (p = 0.039) when comparing preponderance based on the number of nystagmus in the caloric test and amplitude asymmetry with 99 dB tone burst in the VEMPs test. The results indicate that the two diagnostic tests are not comparable, so one of them cannot replace the other, but the use of both increases diagnostic success in some conditions.

Study on Practical Application of Turboprop Engine Condition Monitoring and Fault Diagnostic System Using Fuzzy-Neuro Algorithms

NASA Astrophysics Data System (ADS)

Kong, Changduk; Lim, Semyeong; Kim, Keunwoo

2013-03-01

The Neural Networks is mostly used to engine fault diagnostic system due to its good learning performance, but it has a drawback due to low accuracy and long learning time to build learning data base. This work builds inversely a base performance model of a turboprop engine to be used for a high altitude operation UAV using measuring performance data, and proposes a fault diagnostic system using the base performance model and artificial intelligent methods such as Fuzzy and Neural Networks. Each real engine performance model, which is named as the base performance model that can simulate a new engine performance, is inversely made using its performance test data. Therefore the condition monitoring of each engine can be more precisely carried out through comparison with measuring performance data. The proposed diagnostic system identifies firstly the faulted components using Fuzzy Logic, and then quantifies faults of the identified components using Neural Networks leaned by fault learning data base obtained from the developed base performance model. In leaning the measuring performance data of the faulted components, the FFBP (Feed Forward Back Propagation) is used. In order to user's friendly purpose, the proposed diagnostic program is coded by the GUI type using MATLAB.

QUADAS and STARD: evaluating the quality of diagnostic accuracy studies.

PubMed

Oliveira, Maria Regina Fernandes de; Gomes, Almério de Castro; Toscano, Cristiana Maria

2011-04-01

To compare the performance of two approaches, one based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and another on the Standards for Reporting Studies of Diagnostic Accuracy (STARD), in evaluating the quality of studies validating the OptiMal® rapid malaria diagnostic test. Articles validating the rapid test published until 2007 were searched in the Medline/PubMed database. This search retrieved 13 articles. A combination of 12 QUADAS criteria and three STARD criteria were compared with the 12 QUADAS criteria alone. Articles that fulfilled at least 50% of QUADAS criteria were considered as regular to good quality. Of the 13 articles retrieved, 12 fulfilled at least 50% of QUADAS criteria, and only two fulfilled the STARD/QUADAS criteria combined. Considering the two criteria combination (> 6 QUADAS and > 3 STARD), two studies (15.4%) showed good methodological quality. The articles selection using the proposed combination resulted in two to eight articles, depending on the number of items assumed as cutoff point. The STARD/QUADAS combination has the potential to provide greater rigor when evaluating the quality of studies validating malaria diagnostic tests, given that it incorporates relevant information not contemplated in the QUADAS criteria alone.

Propulsion Diagnostic Method Evaluation Strategy (ProDiMES) User's Guide

NASA Technical Reports Server (NTRS)

Simon, Donald L.

2010-01-01

This report is a User's Guide for the Propulsion Diagnostic Method Evaluation Strategy (ProDiMES). ProDiMES is a standard benchmarking problem and a set of evaluation metrics to enable the comparison of candidate aircraft engine gas path diagnostic methods. This Matlab (The Mathworks, Inc.) based software tool enables users to independently develop and evaluate diagnostic methods. Additionally, a set of blind test case data is also distributed as part of the software. This will enable the side-by-side comparison of diagnostic approaches developed by multiple users. The Users Guide describes the various components of ProDiMES, and provides instructions for the installation and operation of the tool.

Diagnostic accuracy and applicability of a PCR system for the detection of Schistosoma mansoni DNA in human urine samples from an endemic area.

PubMed

Enk, Martin Johannes; Oliveira e Silva, Guilherme; Rodrigues, Nilton Barnabé

2012-01-01

Schistosomiasis caused by Schistosoma mansoni, one of the most neglected human parasitoses in Latin America and Africa, is routinely confirmed by microscopic visualization of eggs in stool. The main limitation of this diagnostic approach is its lack of sensitivity in detecting individual low worm burdens and consequently data on infection rates in low transmission settings are little reliable. According to the scientific literature, PCR assays are characterized by high sensitivity and specificity in detecting parasite DNA in biological samples. A simple and cost effective extraction method for DNA of Schistosoma mansoni from urine samples in combination with a conventional PCR assay was developed and applied in an endemic area. This urine based PCR system was tested for diagnostic accuracy among a population of a small village in an endemic area, comparing it to a reference test composed of three different parasitological techniques. The diagnostic parameters revealed a sensitivity of 100%, a specificity of 91.20%, positive and negative predictive values of 86.25% and 100%, respectively, and a test accuracy of 94.33%. Further statistical analysis showed a k index of 0.8806, indicating an excellent agreement between the reference test and the PCR system. Data obtained from the mouse model indicate the infection can be detected one week after cercariae penetration, opening a new perspective for early detection and patient management during this stage of the disease. The data indicate that this innovative PCR system provides a simple to handle and robust diagnostic tool for the detection of S. mansoni DNA from urine samples and a promising approach to overcome the diagnostic obstacles in low transmission settings. Furthermore the principals of this molecular technique, based on the examination of human urine samples may be useful for the diagnosis of other neglected tropical diseases that can be detected by trans-renal DNA.

Evaluating Malaria Prevalence Using Clinical Diagnosis Compared with Microscopy and Rapid Diagnostic Tests in a Tertiary Healthcare Facility in Rivers State, Nigeria.

PubMed

Wogu, M N; Nduka, F O

2018-01-01

The World Health Organization's policy on laboratory test of all suspected malaria cases before treatment has not yielded significant effects in several rural areas of Sub-Saharan Africa due to inadequate diagnostic infrastructure, leading to high morbidity and mortality rates. A cross-sectional randomized study was conducted to evaluate the validity of clinical malaria diagnosis through comparison with microscopy and rapid diagnostic test kits (RDTs) using 1000 consenting outpatients of a tertiary hospital in Nigeria. Physicians conducted clinical diagnosis, and blood samples were collected through venous procedure and analyzed for malaria parasites using Giemsa microscopy and RDT kits. Microscopy was considered the diagnostic "gold standard" and all data obtained were statistically analyzed using Chi-square test with a P value <0.05 considered significant. Malaria prevalence values of 20.1%, 43.1%, and 29.7% were obtained for clinical diagnosis, microscopy, and RDTs, respectively ( P < 0.05). Values of 47.2%, 95.9%, and 77.8% were obtained for sensitivity, specificity, and diagnostic accuracy, respectively, in clinical diagnosis, while RDTs had sensitivity, specificity, and diagnostic accuracy values of 73.7%, 97.3%, and 88.3%, respectively, when compared to microscopy ( P < 0.05). Clinical diagnosed malaria cases should be confirmed with a parasite-based laboratory diagnosis and more qualitative research is needed to explore why clinicians still use clinical diagnosis despite reported cases of its ineffectiveness.

Inference of Antibiotic Resistance and Virulence Among Diverse Group A Streptococcus Strains Using emm Sequencing and Multilocus Genotyping Methods

DTIC Science & Technology

2009-09-04

apparent GAS-associated conditions were sampled by oropharyn- geal swab. Swabs were streaked on blood agar plates using Table 3. Isolate properties by...testing, samples were re-streaked on blood agar plates (5% sheep blood in TSA base) (Hardy Diagnostics, Santa Maria, CA), and incubated at 35–37uC with 5–10...sensitivity (A-disk method, Hardy Diagnostics) and positive GAS latex agglutination reaction (Hardy Diagnostics). Confirmed GAS isolates were then

Rocket engine diagnostics using qualitative modeling techniques

NASA Technical Reports Server (NTRS)

Binder, Michael; Maul, William; Meyer, Claudia; Sovie, Amy

1992-01-01

Researchers at NASA Lewis Research Center are presently developing qualitative modeling techniques for automated rocket engine diagnostics. A qualitative model of a turbopump interpropellant seal system has been created. The qualitative model describes the effects of seal failures on the system steady-state behavior. This model is able to diagnose the failure of particular seals in the system based on anomalous temperature and pressure values. The anomalous values input to the qualitative model are generated using numerical simulations. Diagnostic test cases include both single and multiple seal failures.

Rocket engine diagnostics using qualitative modeling techniques

NASA Technical Reports Server (NTRS)

Binder, Michael; Maul, William; Meyer, Claudia; Sovie, Amy

1992-01-01

Researchers at NASA Lewis Research Center are presently developing qualitative modeling techniques for automated rocket engine diagnostics. A qualitative model of a turbopump interpropellant seal system was created. The qualitative model describes the effects of seal failures on the system steady state behavior. This model is able to diagnose the failure of particular seals in the system based on anomalous temperature and pressure values. The anomalous values input to the qualitative model are generated using numerical simulations. Diagnostic test cases include both single and multiple seal failures.

Nanotechnology-Based Surface Plasmon Resonance Affinity Biosensors for In Vitro Diagnostics

PubMed Central

Antiochia, Riccarda; Bollella, Paolo; Favero, Gabriele

2016-01-01

In the last decades, in vitro diagnostic devices (IVDDs) became a very important tool in medicine for an early and correct diagnosis, a proper screening of targeted population, and also assessing the efficiency of a specific therapy. In this review, the most recent developments regarding different configurations of surface plasmon resonance affinity biosensors modified by using several nanostructured materials for in vitro diagnostics are critically discussed. Both assembly and performances of the IVDDs tested in biological samples are reported and compared. PMID:27594884

Imperfect practice makes perfect: error management training improves transfer of learning.

PubMed

Dyre, Liv; Tabor, Ann; Ringsted, Charlotte; Tolsgaard, Martin G

2017-02-01

Traditionally, trainees are instructed to practise with as few errors as possible during simulation-based training. However, transfer of learning may improve if trainees are encouraged to commit errors. The aim of this study was to assess the effects of error management instructions compared with error avoidance instructions during simulation-based ultrasound training. Medical students (n = 60) with no prior ultrasound experience were randomised to error management training (EMT) (n = 32) or error avoidance training (EAT) (n = 28). The EMT group was instructed to deliberately make errors during training. The EAT group was instructed to follow the simulator instructions and to commit as few errors as possible. Training consisted of 3 hours of simulation-based ultrasound training focusing on fetal weight estimation. Simulation-based tests were administered before and after training. Transfer tests were performed on real patients 7-10 days after the completion of training. Primary outcomes were transfer test performance scores and diagnostic accuracy. Secondary outcomes included performance scores and diagnostic accuracy during the simulation-based pre- and post-tests. A total of 56 participants completed the study. On the transfer test, EMT group participants attained higher performance scores (mean score: 67.7%, 95% confidence interval [CI]: 62.4-72.9%) than EAT group members (mean score: 51.7%, 95% CI: 45.8-57.6%) (p < 0.001; Cohen's d = 1.1, 95% CI: 0.5-1.7). There was a moderate improvement in diagnostic accuracy in the EMT group compared with the EAT group (16.7%, 95% CI: 10.2-23.3% weight deviation versus 26.6%, 95% CI: 16.5-36.7% weight deviation [p = 0.082; Cohen's d = 0.46, 95% CI: -0.06 to 1.0]). No significant interaction effects between group and performance improvements between the pre- and post-tests were found in either performance scores (p = 0.25) or diagnostic accuracy (p = 0.09). The provision of error management instructions during simulation-based training improves the transfer of learning to the clinical setting compared with error avoidance instructions. Rather than teaching to avoid errors, the use of errors for learning should be explored further in medical education theory and practice. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Senior high school students’ need analysis of Three-Tier Multiple Choice (3TMC) diagnostic test about acid-base and solubility equilibrium

NASA Astrophysics Data System (ADS)

Ardiansah; Masykuri, M.; Rahardjo, S. B.

2018-05-01

Students’ conceptual understanding is the most important comprehension to obtain related comprehension. However, they held their own conception. With this need analysis, we will elicit student need of 3TMC diagnostic test to measure students’ conception about acid-base and solubility equilibrium. The research done by a mixed method using questionnaire analysis based on descriptive of quantitative and qualitative. The research subject was 96 students from 4 senior high schools and 4 chemistry teachers chosen by random sampling technique. Data gathering used a questionnaire with 10 questions for student and 28 questions for teachers. The results showed that 97% of students stated that the development this instrument is needed. In addition, there were several problems obtained in this questionnaire include learning activity, teacher’s test and guessing. In conclusion, this is necessary to develop the 3TMC instrument that can diagnose and measure the student’s conception in acid-base and solubility equilibrium.

42 CFR 414.508 - Payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Payment for a new clinical diagnostic laboratory... SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.508 Payment for a new clinical diagnostic laboratory test. For a new clinical diagnostic laboratory test that is assigned a new or...

20 CFR 404.1519m - Diagnostic tests or procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Diagnostic tests or procedures. 404.1519m... Report Content § 404.1519m Diagnostic tests or procedures. We will request the results of any diagnostic... will not order diagnostic tests or procedures that involve significant risk to you, such as myelograms...

42 CFR 414.508 - Payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Payment for a new clinical diagnostic laboratory... SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.508 Payment for a new clinical diagnostic laboratory test. For a new clinical diagnostic laboratory test that is assigned a new or...

Acquiring, Representing, and Evaluating a Competence Model of Diagnostic Strategy.

ERIC Educational Resources Information Center

Clancey, William J.

This paper describes NEOMYCIN, a computer program that models one physician's diagnostic reasoning within a limited area of medicine. NEOMYCIN's knowledge base and reasoning procedure constitute a model of how human knowledge is organized and how it is used in diagnosis. The hypothesis is tested that such a procedure can be used to simulate both…

Emotion Perception in Asperger's Syndrome and High-Functioning Autism: The Importance of Diagnostic Criteria and Cue Intensity

ERIC Educational Resources Information Center

Mazefsky, Carla A.; Oswald, Donald P.

2007-01-01

This study compared emotion perception accuracy between children with Asperger's syndrome (AS) and high-functioning autism (HFA). Thirty children were diagnosed with AS or HFA based on empirically supported diagnostic criteria and administered an emotion perception test consisting of facial expressions and tone of voice cues that varied in…

Development of an intelligent diagnostic system for reusable rocket engine control

NASA Technical Reports Server (NTRS)

Anex, R. P.; Russell, J. R.; Guo, T.-H.

1991-01-01

A description of an intelligent diagnostic system for the Space Shuttle Main Engines (SSME) is presented. This system is suitable for incorporation in an intelligent controller which implements accommodating closed-loop control to extend engine life and maximize available performance. The diagnostic system architecture is a modular, hierarchical, blackboard system which is particularly well suited for real-time implementation of a system which must be repeatedly updated and extended. The diagnostic problem is formulated as a hierarchical classification problem in which the failure hypotheses are represented in terms of predefined data patterns. The diagnostic expert system incorporates techniques for priority-based diagnostics, the combination of analytical and heuristic knowledge for diagnosis, integration of different AI systems, and the implementation of hierarchical distributed systems. A prototype reusable rocket engine diagnostic system (ReREDS) has been implemented. The prototype user interface and diagnostic performance using SSME test data are described.

A Framework to Debug Diagnostic Matrices

NASA Technical Reports Server (NTRS)

Kodal, Anuradha; Robinson, Peter; Patterson-Hine, Ann

2013-01-01

Diagnostics is an important concept in system health and monitoring of space operations. Many of the existing diagnostic algorithms utilize system knowledge in the form of diagnostic matrix (D-matrix, also popularly known as diagnostic dictionary, fault signature matrix or reachability matrix) gleaned from physical models. But, sometimes, this may not be coherent to obtain high diagnostic performance. In such a case, it is important to modify this D-matrix based on knowledge obtained from other sources such as time-series data stream (simulated or maintenance data) within the context of a framework that includes the diagnostic/inference algorithm. A systematic and sequential update procedure, diagnostic modeling evaluator (DME) is proposed to modify D-matrix and wrapper logic considering least expensive solution first. This iterative procedure includes conditions ranging from modifying 0s and 1s in the matrix, or adding/removing the rows (failure sources) columns (tests). We will experiment this framework on datasets from DX challenge 2009.

Point of care testing: The impact of nanotechnology.

PubMed

Syedmoradi, Leila; Daneshpour, Maryam; Alvandipour, Mehrdad; Gomez, Frank A; Hajghassem, Hassan; Omidfar, Kobra

2017-01-15

Point-of-care (POC) diagnostic devices are integral in the health care system and particularly for the diagnosis and monitoring of diseases. POC testing has a variety of advantages including the ability to provide rapid and accurate results, ease of use, low cost, and little need for specialized equipment. One of the goals of POC testing is the development of a chip-based, miniaturized, portable, and self-containing system that allows for the assay of different analytes in complex samples. To achieve these goals, many researchers have focused on paper-based and printed electrode technologies as the material for fabricating POC diagnostic systems. These technologies are affordable, sensitive, user-friendly, rapid, and scalable for manufacturing. Moreover, the combination such devices with nanomaterials provide a path for the development of highly sensitive and selective biosensors for future generation POC tools. This review article discusses present technologies in on-site or at home POC diagnostic assays implemented in paper-based microfluidic and screen printing devices over the past decade as well as in the near future. In addition, recent advances in the application of nanomaterials such as gold nanoparticles, carbon nanotubes (CNTs), magnetic nanoparticles, and graphene in POC devices will be reviewed. The factors that limit POC testing to become real world products and future directions are also identified. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid diagnostic test for G6PD deficiency in Plasmodium vivax-infected men: a budget impact analysis based in Brazilian Amazon.

PubMed

Peixoto, Henry Maia; Brito, Marcelo Augusto Mota; Romero, Gustavo Adolfo Sierra; Monteiro, Wuelton Marcelo; de Lacerda, Marcus Vinícius Guimarães; de Oliveira, Maria Regina Fernandes

2017-01-01

The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon. © 2016 John Wiley & Sons Ltd.

Clinical Evaluation of Rapid Diagnostic Test Kit for Scrub Typhus with Improved Performance.

PubMed

Kim, Young-Jin; Park, Sungman; Premaratna, Ranjan; Selvaraj, Stephen; Park, Sang-Jin; Kim, Sora; Kim, Donghwan; Kim, Min Soo; Shin, Dong Hoon; Choi, Kyung-Chan; Kwon, Soon-Hwan; Seo, Wonjun; Lee, Nam Taek; Kim, Seung-Han; Kang, Heui Keun; Kim, Yoon-Won

2016-08-01

Diagnosis of scrub typhus is challenging due to its more than twenty serotypes and the similar clinical symptoms with other acute febrile illnesses including leptospirosis, murine typhus and hemorrhagic fever with renal syndrome. Accuracy and rapidity of a diagnostic test to Orientia tsutsugamushi is an important step to diagnose this disease. To discriminate scrub typhus from other diseases, the improved ImmuneMed Scrub Typhus Rapid Diagnostic Test (RDT) was evaluated in Korea and Sri Lanka. The sensitivity at the base of each IgM and IgG indirect immunofluorescent assay (IFA) in Korean patients was 98.6% and 97.1%, and the specificity was 98.2% and 97.7% respectively. The sensitivity and specificity for retrospective diagnosis at the base of IFA in Sri Lanka was 92.1% and 96.1%. ImmuneMed RDT was not reactive to any serum from seventeen diseases including hemorrhagic fever with renal syndrome (n = 48), leptospirosis (n = 23), and murine typhus (n = 48). ImmuneMed RDT shows superior sensitivity (98.6% and 97.1%) compared with SD Bioline RDT (84.4% at IgM and 83.3% at IgG) in Korea. The retrospective diagnosis of ImmuneMed RDT exhibits 94.0% identity with enzyme-linked Immunosorbent assay (ELISA) using South India patient serum samples. These results suggest that this RDT can replace other diagnostic tests and is applicable for global diagnosis of scrub typhus. This rapid and accurate diagnosis will be beneficial for diagnosing and managing scrub typhus.

Field evaluation of a recombinase polymerase amplification assay for the diagnosis of Schistosoma japonicum infection in Hunan province of China.

PubMed

Xing, Weiwei; Yu, Xinling; Feng, Jingtao; Sun, Kui; Fu, Wenliang; Wang, Yuanyuan; Zou, Minji; Xia, Wenrong; Luo, Zhihong; He, Hongbin; Li, Yuesheng; Xu, Donggang

2017-02-21

Current diagnostic methods for Schistosoma japonicum infection are insensitive for low-density infections. Therefore, a new diagnostic assay based on recombinase polymerase amplification (RPA) technology was established and assessed for field applification. The S.japonicum RPA assay was developed to target highly repetitive retrotransposon SjR2 gene of S japonicum, and its sensitivity and specificity were assessed by serial dilution of S. japonicum genomic DNA and other related worm genomic DNA respectively. The RPA diagnostic validity was first evaluated in 60 fecal samples from healthy people and patients, and then compared with other diagnostic tests in 200 high-risk individuals living in endemic areas. The real time RPA assay could detect 0.9 fg S. japonicum DNA within 15 min and distinguish S. japonicum from other worms. The validity analysis of RPA for the detection of S. japonicum in stool samples from 30 S. japonicum-infected patients and 30 healthy persons indicated 100% sensitivity and specificity. When testing 200 fecal or serum samples from a high-risk population, the percentage sensitivity of RPA was 100%, whereas that of indirect hemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA) were 80.3% and 85.2% respectively. In addition, the RPA presented better consistency with the stool-based tests than IHA and ELISA. Overall, the RPA was superior to other detection methods with respect to detection time, sensitivity, and convenience. This is the first time we applied the RPA technology to the field evaluation of S. japonicum infection. And the results suggest that RPA-based assays can be used as a promising point-of-care test for the diagnosis of schistosomiasis.

Residual gas analyzer mass spectrometry for human breath analysis: a new tool for the non-invasive diagnosis of Helicobacter pylori infection.

PubMed

Maity, Abhijit; Banik, Gourab D; Ghosh, Chiranjit; Som, Suman; Chaudhuri, Sujit; Daschakraborty, Sunil B; Ghosh, Shibendu; Ghosh, Barnali; Raychaudhuri, Arup K; Pradhan, Manik

2014-03-01

A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection through ¹³C-urea breath analysis. The present RGA-based mass spectrometry (MS) method is capable of measuring high-precision ¹³CO₂ isotope enrichments in exhaled breath samples from individuals harboring the H. pylori infection. The system exhibited 100% diagnostic sensitivity, and 93% specificity alongside positive and negative predictive values of 95% and 100%, respectively, compared with invasive endoscopy-based biopsy tests. A statistically sound diagnostic cut-off value for the presence of H. pylori was determined to be 3.0‰ using a receiver operating characteristic curve analysis. The diagnostic accuracy and validity of the results are also supported by optical off-axis integrated cavity output spectroscopy measurements. The δ¹³(DOB)C‰ values of both methods correlated well (R² = 0.9973 at 30 min). The RGA-based instrumental setup described here is simple, robust, easy-to-use and more portable and cost-effective compared to all other currently available detection methods, thus making it a new point-of-care medical diagnostic tool for the purpose of large-scale screening of the H. pylori infection in real time. The RGA-MS technique should have broad applicability for ¹³C-breath tests in a wide range of biomedical research and clinical diagnostics for many other diseases and metabolic disorders.

Evaluation of phenotypic detection methods for metallo-β-lactamases (MBLs) in clinical isolates of Pseudomonas aeruginosa.

PubMed

Peter, S; Lacher, A; Marschal, M; Hölzl, F; Buhl, M; Autenrieth, I; Kaase, M; Willmann, M

2014-07-01

Metallo-beta-lactamase (MBL) production in Pseudomonas aeruginosa is a growing issue across the globe. Fast and reliable diagnostic tools are needed for appropriate implementation of infection control measures. In this study we evaluated the performance of three commercial combined disk tests, two EDTA based in-house combined disk tests and the Carba NP test in comparison to molecular detection of MBL genes on 133 meropenem non-susceptible non-duplicate P. aeruginosa clinical isolates. The meropenem/DPA based commercial KPC + MBL-confirm ID kit (Rosco Diagnostica, Denmark) and the MASTDISCS™ ID carbapenemase (Enterobacteriaceae) detection disc set (MAST Diagnostics, UK) showed sensitivities of 31.1 % and 28.8 % and specificities of 69.3 % and 79.6 %, respectively. The total MBL confirm kit (Rosco Diagnostica, Denmark) contains imipenem/DPA and imipenem/EDTA combination disks. Evaluation of the single disk combinations revealed 84.4 % sensitivity and 81.8 % specificity for the imipenem/DPA assay and 86.7 % sensitivity and 51.1 % specificity for the imipenem/EDTA test. Applying both tests simultaneously resulted in a slightly higher sensitivity of 88.9 % but a lower specificity of 48.9 % when compared to the single tests alone. The Carba NP test showed 93.3 % sensitivity and 96.6 % specificity. All phenotypic combined disk tests lacked either sensitivity or specificity for the detection of MBL in P. aeruginosa. The Carba NP test showed excellent test properties, but suffers from drawbacks in handling and high costs. The optimal diagnostic approach needs to be chosen depending on the epidemiological situation, laboratory resources and availability of molecular confirmation tests.

Evaluation and comparison of native and recombinant LipL21 protein-based ELISAs for diagnosis of bovine leptospirosis.

PubMed

Joseph, Siju; Thomas, Naicy; Thangapandian, E; Singh, Vijendra P; Verma, Rishendra; Srivastava, S K

2012-03-01

A 21-kDa leptospiral lipoprotein (LipL21) was evaluated for its diagnostic potential to detect bovine leptospirosis by ELISA. Both native LipL21 (nLipL21) and recombinant LipL21 (rLipL21) proteins were tested and compared regarding diagnostic efficiency, and no statistically significant difference was observed. The sensitivity of rLipL21 ELISA for 62 microscopic agglutination test (MAT) positive sera was 100% and the specificity with 378 MAT negative sera was 97.09%. Thus, rLipL21 protein-based ELISA could be used as an alternative to MAT for the diagnosis of bovine leptospirosis.

Getting expert systems off the ground: Lessons learned from integrating model-based diagnostics with prototype flight hardware

NASA Technical Reports Server (NTRS)

Stephan, Amy; Erikson, Carol A.

1991-01-01

As an initial attempt to introduce expert system technology into an onboard environment, a model based diagnostic system using the TRW MARPLE software tool was integrated with prototype flight hardware and its corresponding control software. Because this experiment was designed primarily to test the effectiveness of the model based reasoning technique used, the expert system ran on a separate hardware platform, and interactions between the control software and the model based diagnostics were limited. While this project met its objective of showing that model based reasoning can effectively isolate failures in flight hardware, it also identified the need for an integrated development path for expert system and control software for onboard applications. In developing expert systems that are ready for flight, artificial intelligence techniques must be evaluated to determine whether they offer a real advantage onboard, identify which diagnostic functions should be performed by the expert systems and which are better left to the procedural software, and work closely with both the hardware and the software developers from the beginning of a project to produce a well designed and thoroughly integrated application.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: Evidence-Based Report on Diagnostic Guidelines

PubMed Central

Conwell, Darwin L.; Lee, Linda S.; Yadav, Dhiraj; Longnecker, Daniel S.; Miller, Frank H.; Mortele, Koenraad J.; Levy, Michael J.; Kwon, Richard; Lieb, John G.; Stevens, Tyler; Toskes, Philip P.; Gardner, Timothy B.; Gelrud, Andres; Wu, Bechien U.; Forsmark, Christopher E.; Vege, Santhi S.

2016-01-01

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed and evidence based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable or insufficient evidence. A diagnostic (STEP-wise; S-survey, T-tomography, E-endoscopy and P-pancreas function testing) algorithm is proposed that proceeds from a non-invasive to a more invasive approach. This algorithm maximizes specificity (low false positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Futhermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (T-toxic, I-idiopathic, G-genetic, A- autoimmune, R-recurrent and O-obstructive) etiology, gland morphology (Cambridge criteria) and physiologic state (exocrine, endocrine function) for uniformity across future multi-center research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves. PMID:25333398

Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics.

PubMed

Jiang, Li; Mancuso, Matthew; Lu, Zhengda; Akar, Gunkut; Cesarman, Ethel; Erickson, David

2014-02-20

Nucleic acid-based diagnostic techniques such as polymerase chain reaction (PCR) are used extensively in medical diagnostics due to their high sensitivity, specificity and quantification capability. In settings with limited infrastructure and unreliable electricity, however, access to such devices is often limited due to the highly specialized and energy-intensive nature of the thermal cycling process required for nucleic acid amplification. Here we integrate solar heating with microfluidics to eliminate thermal cycling power requirements as well as create a simple device infrastructure for PCR. Tests are completed in less than 30 min, and power consumption is reduced to 80 mW, enabling a standard 5.5 Wh iPhone battery to provide 70 h of power to this system. Additionally, we demonstrate a complete sample-to-answer diagnostic strategy by analyzing human skin biopsies infected with Kaposi's Sarcoma herpesvirus (KSHV/HHV-8) through the combination of solar thermal PCR, HotSHOT DNA extraction and smartphone-based fluorescence detection. We believe that exploiting the ubiquity of solar thermal energy as demonstrated here could facilitate broad availability of nucleic acid-based diagnostics in resource-limited areas.

Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics

NASA Astrophysics Data System (ADS)

Jiang, Li; Mancuso, Matthew; Lu, Zhengda; Akar, Gunkut; Cesarman, Ethel; Erickson, David

2014-02-01

Nucleic acid-based diagnostic techniques such as polymerase chain reaction (PCR) are used extensively in medical diagnostics due to their high sensitivity, specificity and quantification capability. In settings with limited infrastructure and unreliable electricity, however, access to such devices is often limited due to the highly specialized and energy-intensive nature of the thermal cycling process required for nucleic acid amplification. Here we integrate solar heating with microfluidics to eliminate thermal cycling power requirements as well as create a simple device infrastructure for PCR. Tests are completed in less than 30 min, and power consumption is reduced to 80 mW, enabling a standard 5.5 Wh iPhone battery to provide 70 h of power to this system. Additionally, we demonstrate a complete sample-to-answer diagnostic strategy by analyzing human skin biopsies infected with Kaposi's Sarcoma herpesvirus (KSHV/HHV-8) through the combination of solar thermal PCR, HotSHOT DNA extraction and smartphone-based fluorescence detection. We believe that exploiting the ubiquity of solar thermal energy as demonstrated here could facilitate broad availability of nucleic acid-based diagnostics in resource-limited areas.

Temperature Measurements in Compressed and Uncompressed SPECTOR Plasmas at General Fusion

NASA Astrophysics Data System (ADS)

Young, William; Carter, Neil; Howard, Stephen; Carle, Patrick; O'Shea, Peter; Fusion Team, General

2017-10-01

Accurate temperature measurements are critical to establishing the behavior of General Fusion's SPECTOR plasma injector, both before and during compression. As compression tests impose additional constraints on diagnostic access to the plasma, a two-color, filter-based soft x-ray electron temperature diagnostic has been implemented. Ion Doppler spectroscopy measurements also provide impurity ion temperatures on compression tests. The soft x-ray and ion Doppler spectroscopy measurements are being validated against a Thomson scattering system on an uncompressed version of SPECTOR with more diagnostic access. The multipoint Thomson scattering diagnostic also provides up to a six point temperature and density profile, with the density measurements validated against a far infrared interferometer. Temperatures above 300 eV have been demonstrated to be sustained for over 500 microseconds in uncompressed plasmas. Optimization of soft x-ray filters is ongoing, in order to balance blocking of impurity line radiation with signal strength.

30 CFR 250.525 - What do I submit if my casing diagnostic test requires action?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What do I submit if my casing diagnostic test... if my casing diagnostic test requires action? Within 14 days after you perform a casing diagnostic... Corrective Action Plan within 30 days of the diagnostic test. (b) a casing pressure request, Regional...

MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: A study from the tertiary care hospital in Zanzibar.

PubMed

Jørstad, Melissa Davidsen; Marijani, Msafiri; Dyrhol-Riise, Anne Ma; Sviland, Lisbet; Mustafa, Tehmina

2018-01-01

Extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting. Patients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases. Patients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%). We show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.

Recommended reporting standards for test accuracy studies of infectious diseases of finfish, amphibians, molluscs and crustaceans: the STRADAS-aquatic checklist

USGS Publications Warehouse

Gardner, Ian A; Whittington, Richard J; Caraguel, Charles G B; Hick, Paul; Moody, Nicholas J G; Corbeil, Serge; Garver, Kyle A.; Warg, Janet V.; Arzul, Isabelle; Purcell, Maureen; St. J. Crane, Mark; Waltzek, Thomas B.; Olesen, Niels J; Lagno, Alicia Gallardo

2016-01-01

Complete and transparent reporting of key elements of diagnostic accuracy studies for infectious diseases in cultured and wild aquatic animals benefits end-users of these tests, enabling the rational design of surveillance programs, the assessment of test results from clinical cases and comparisons of diagnostic test performance. Based on deficiencies in the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines identified in a prior finfish study (Gardner et al. 2014), we adapted the Standards for Reporting of Animal Diagnostic Accuracy Studies—paratuberculosis (STRADAS-paraTB) checklist of 25 reporting items to increase their relevance to finfish, amphibians, molluscs, and crustaceans and provided examples and explanations for each item. The checklist, known as STRADAS-aquatic, was developed and refined by an expert group of 14 transdisciplinary scientists with experience in test evaluation studies using field and experimental samples, in operation of reference laboratories for aquatic animal pathogens, and in development of international aquatic animal health policy. The main changes to the STRADAS-paraTB checklist were to nomenclature related to the species, the addition of guidelines for experimental challenge studies, and the designation of some items as relevant only to experimental studies and ante-mortem tests. We believe that adoption of these guidelines will improve reporting of primary studies of test accuracy for aquatic animal diseases and facilitate assessment of their fitness-for-purpose. Given the importance of diagnostic tests to underpin the Sanitary and Phytosanitary agreement of the World Trade Organization, the principles outlined in this paper should be applied to other World Organisation for Animal Health (OIE)-relevant species.

Healthcare Fragmentation and the Frequency of Radiology and Other Diagnostic Tests: A Cross-Sectional Study.

PubMed

Kern, Lisa M; Seirup, Joanna K; Casalino, Lawrence P; Safford, Monika M

2017-02-01

Fragmented ambulatory care has been associated with high rates of emergency department visits and hospitalizations, but effects on other types of utilization are unclear. To determine whether more fragmented care is associated with more radiology and other diagnostic tests, compared to less fragmented care. We conducted a cross-sectional study using claims from five commercial payers for 2010. The study took place in the Hudson Valley, a seven-county region in New York State. We included adult patients who were insured through the participating payers and were attributed to a primary care physician in the region. We restricted the cohort to those with ≥4 ambulatory visits, as measures of fragmentation are not reliable if based on ≤3 visits (N = 126,801). For each patient, we calculated fragmentation using a reversed Bice-Boxerman Index, which we divided into seven categories. We used negative binomial regression to determine the association between fragmentation category and rates of radiology and other diagnostic tests, stratified by number of chronic conditions and adjusting for patient age, gender, and number of visits. Patients with the most fragmented care had approximately twice as many radiology and other diagnostic tests as patients with the least fragmented care, across all groups stratified by number of chronic conditions (each adjusted p < 0.0001). For example, among patients with ≥5 chronic conditions, those with the least fragmented care had 258 tests per 100 patients, and those with the most fragmented care had 542 tests per 100 patients (+284 tests per 100 patients, or +110 %, adjusted p < 0.0001). More fragmented care was independently associated with higher rates of radiology and other diagnostic tests than less fragmented care.

Recommended reporting standards for test accuracy studies of infectious diseases of finfish, amphibians, molluscs and crustaceans: the STRADAS-aquatic checklist.

PubMed

Gardner, Ian A; Whittington, Richard J; Caraguel, Charles G B; Hick, Paul; Moody, Nicholas J G; Corbeil, Serge; Garver, Kyle A; Warg, Janet V; Arzul, Isabelle; Purcell, Maureen K; Crane, Mark St J; Waltzek, Thomas B; Olesen, Niels J; Gallardo Lagno, Alicia

2016-02-25

Complete and transparent reporting of key elements of diagnostic accuracy studies for infectious diseases in cultured and wild aquatic animals benefits end-users of these tests, enabling the rational design of surveillance programs, the assessment of test results from clinical cases and comparisons of diagnostic test performance. Based on deficiencies in the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines identified in a prior finfish study (Gardner et al. 2014), we adapted the Standards for Reporting of Animal Diagnostic Accuracy Studies-paratuberculosis (STRADAS-paraTB) checklist of 25 reporting items to increase their relevance to finfish, amphibians, molluscs, and crustaceans and provided examples and explanations for each item. The checklist, known as STRADAS-aquatic, was developed and refined by an expert group of 14 transdisciplinary scientists with experience in test evaluation studies using field and experimental samples, in operation of reference laboratories for aquatic animal pathogens, and in development of international aquatic animal health policy. The main changes to the STRADAS-paraTB checklist were to nomenclature related to the species, the addition of guidelines for experimental challenge studies, and the designation of some items as relevant only to experimental studies and ante-mortem tests. We believe that adoption of these guidelines will improve reporting of primary studies of test accuracy for aquatic animal diseases and facilitate assessment of their fitness-for-purpose. Given the importance of diagnostic tests to underpin the Sanitary and Phytosanitary agreement of the World Trade Organization, the principles outlined in this paper should be applied to other World Organisation for Animal Health (OIE)-relevant species.

Children Becoming More Intelligent: Can the Flynn Effect Be Generalized to Other Child Intelligence Tests?

ERIC Educational Resources Information Center

Resing, Wilma C. M.; Tunteler, Erika

2007-01-01

In this article, time effects on intelligence test scores have been investigated. In particular, we examined whether the "Flynn effect" is manifest in children from the middle and higher IQ distribution range, measured with a child intelligence test based on information processing principles--the Leiden Diagnostic Test. The test was administered…

Company Profile: Selventa, Inc.

PubMed

Fryburg, David A; Latino, Louis J; Tagliamonte, John; Kenney, Renee D; Song, Diane H; Levine, Arnold J; de Graaf, David

2012-08-01

Selventa, Inc. (MA, USA) is a biomarker discovery company that enables personalized healthcare. Originally founded as Genstruct, Inc., Selventa has undergone significant evolution from a technology-based service provider to an active partner in the development of diagnostic tests, functioning as a molecular dashboard of disease activity using a unique platform. As part of that evolution, approximately 2 years ago the company was rebranded as Selventa to reflect its new identity and mission. The contributions to biomedical research by Selventa are based on in silico, reverse-engineering methods to determine biological causality. That is, given a set of in vitro or in vivo biological observations, which biological mechanisms can explain the measured results? Facilitated by a large and carefully curated knowledge base, these in silico methods generated new insights into the mechanisms driving a disease. As Selventa's methods would enable biomarker discovery and be directly applicable to generating novel diagnostics, the scientists at Selventa have focused on the development of predictive biomarkers of response in autoimmune and oncologic diseases. Selventa is presently building a portfolio of independent, as well as partnered, biomarker projects with the intention to create diagnostic tests that predict response to therapy.

Rapid-Testing Technology and Systems Improvement for the Elimination of Congenital Syphilis in Haiti: Overcoming the “Technology to Systems Gap”

PubMed Central

Benoit, Daphne; Zhou, Xi K.; Pape, Jean W.; Peeling, Rosanna W.; Fitzgerald, Daniel W.; Mate, Kedar S.

2013-01-01

Background. Despite the availability of rapid diagnostic tests and inexpensive treatment for pregnant women, maternal-child syphilis transmission remains a leading cause of perinatal morbidity and mortality in developing countries. In Haiti, more than 3000 babies are born with congenital syphilis annually. Methods and Findings. From 2007 to 2011, we used a sequential time series, multi-intervention study design in fourteen clinics throughout Haiti to improve syphilis testing and treatment in pregnancy. The two primary interventions were the introduction of a rapid point-of-care syphilis test and systems strengthening based on quality improvement (QI) methods. Syphilis testing increased from 91.5% prediagnostic test to 95.9% after (P < 0.001) and further increased to 96.8% (P < 0.001) after the QI intervention. Despite high rates of testing across all time periods, syphilis treatment lagged behind and only increased from 70.3% to 74.7% after the introduction of rapid tests (P = 0.27), but it improved significantly from 70.2% to 84.3% (P < 0.001) after the systems strengthening QI intervention. Conclusion. Both point-of-care diagnostic testing and health systems-based quality improvement interventions can improve the delivery of specific evidence-based healthcare interventions to prevent congenital syphilis at scale in Haiti. Improved treatment rates for syphilis were seen only after the use of systems-based quality improvement approaches. PMID:26316955

Rapid-Testing Technology and Systems Improvement for the Elimination of Congenital Syphilis in Haiti: Overcoming the "Technology to Systems Gap".

PubMed

Severe, Linda; Benoit, Daphne; Zhou, Xi K; Pape, Jean W; Peeling, Rosanna W; Fitzgerald, Daniel W; Mate, Kedar S

2013-01-01

Background. Despite the availability of rapid diagnostic tests and inexpensive treatment for pregnant women, maternal-child syphilis transmission remains a leading cause of perinatal morbidity and mortality in developing countries. In Haiti, more than 3000 babies are born with congenital syphilis annually. Methods and Findings. From 2007 to 2011, we used a sequential time series, multi-intervention study design in fourteen clinics throughout Haiti to improve syphilis testing and treatment in pregnancy. The two primary interventions were the introduction of a rapid point-of-care syphilis test and systems strengthening based on quality improvement (QI) methods. Syphilis testing increased from 91.5% prediagnostic test to 95.9% after (P < 0.001) and further increased to 96.8% (P < 0.001) after the QI intervention. Despite high rates of testing across all time periods, syphilis treatment lagged behind and only increased from 70.3% to 74.7% after the introduction of rapid tests (P = 0.27), but it improved significantly from 70.2% to 84.3% (P < 0.001) after the systems strengthening QI intervention. Conclusion. Both point-of-care diagnostic testing and health systems-based quality improvement interventions can improve the delivery of specific evidence-based healthcare interventions to prevent congenital syphilis at scale in Haiti. Improved treatment rates for syphilis were seen only after the use of systems-based quality improvement approaches.

Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.

PubMed

Laskowitz, Daniel T; Kasner, Scott E; Saver, Jeffrey; Remmel, Kerri S; Jauch, Edward C

2009-01-01

One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.

An Integrated Architecture for Aircraft Engine Performance Monitoring and Fault Diagnostics: Engine Test Results

NASA Technical Reports Server (NTRS)

Rinehart, Aidan W.; Simon, Donald L.

2015-01-01

This paper presents a model-based architecture for performance trend monitoring and gas path fault diagnostics designed for analyzing streaming transient aircraft engine measurement data. The technique analyzes residuals between sensed engine outputs and model predicted outputs for fault detection and isolation purposes. Diagnostic results from the application of the approach to test data acquired from an aircraft turbofan engine are presented. The approach is found to avoid false alarms when presented nominal fault-free data. Additionally, the approach is found to successfully detect and isolate gas path seeded-faults under steady-state operating scenarios although some fault misclassifications are noted during engine transients. Recommendations for follow-on maturation and evaluation of the technique are also presented.

An Integrated Architecture for Aircraft Engine Performance Monitoring and Fault Diagnostics: Engine Test Results

NASA Technical Reports Server (NTRS)

Rinehart, Aidan W.; Simon, Donald L.

2014-01-01

This paper presents a model-based architecture for performance trend monitoring and gas path fault diagnostics designed for analyzing streaming transient aircraft engine measurement data. The technique analyzes residuals between sensed engine outputs and model predicted outputs for fault detection and isolation purposes. Diagnostic results from the application of the approach to test data acquired from an aircraft turbofan engine are presented. The approach is found to avoid false alarms when presented nominal fault-free data. Additionally, the approach is found to successfully detect and isolate gas path seeded-faults under steady-state operating scenarios although some fault misclassifications are noted during engine transients. Recommendations for follow-on maturation and evaluation of the technique are also presented.

Greater Real-Life Diagnostic Efficacy of Allergen Molecule-Based Diagnosis for Prescription of Immunotherapy in an Area with Multiple Pollen Exposure

PubMed Central

Saltabayeva, Ulbosin; Garib, Victoria; Morenko, Marina; Rosenson, Rafail; Ispayeva, Zhanat; Gatauova, Madina; Zulus, Loreta; Karaulov, Alexander; Gastager, Felix; Valenta, Rudolf

2017-01-01

Background Allergen molecule-based diagnosis has been suggested to facilitate the identification of disease-causing allergen sources and the prescription of allergen-specific immunotherapy (AIT). The aim of the current study was to compare allergen molecule-based IgE serology with allergen extract-based skin testing for the identification of the disease-causing allergen sources. The study was conducted in an area where patients are exposed to pollen from multiple sources (trees, grasses, and weeds) at the same time to compare the diagnostic efficiency of the 2 forms of diagnosis. Methods Patients from Astana, Kazakhstan, who suffered from pollen-induced allergy (n = 95) were subjected to skin prick testing (SPT) with a local panel of tree pollen, grass pollen, and weed pollen allergen extracts and IgE antibodies specific for marker allergen molecules (nArt v 1, nArt v 3, rAmb a 1, rPhl p 1, rPhl p 5, rBet v 1) were measured by ImmunoCAP. Direct and indirect costs for diagnosis based on SPT and marker allergen-based IgE serology as well as direct costs for immunotherapy depending on SPT and serological test results were calculated. Results The costs for SPT-based diagnosis per patient were lower than the costs for allergen molecule-based IgE serology. However, allergen molecule-based serology was more precise in detecting the disease-causing allergen sources. A lower number of immunotherapy treatments (n = 119) was needed according to molecular diagnosis as compared to extract-based diagnosis (n = 275), which considerably reduced the total costs for diagnosis and for a 3-year treatment from EUR 1,112.30 to 521.77 per patient. Conclusions The results from this real-life study show that SPT is less expensive than allergen molecule-based diagnostic testing, but molecular diagnosis allowed more precise prescription of immunotherapy which substantially reduced treatment costs and combined costs for diagnosis and treatment. PMID:28654920

In vivo study of the effectiveness of quantitative percussion diagnostics as an indicator of the level of structural pathology of teeth after restoration.

PubMed

Sheets, Cherilyn G; Wu, Jean C; Rashad, Samer; Phelan, Michael; Earthman, James C

2017-02-01

Conventional diagnostic aids based upon imagery and patient symptoms do not indicate whether restorative treatments have eliminated structural pathology. The purpose of this clinical study was to evaluate quantitative percussion diagnostics (QPD), a mechanics-based methodology that tests the structural integrity of teeth noninvasively. The study hypothesis was that QPD would provide knowledge of the structural instability of teeth after restorative work. Eight participants with 60 sites needing restoration were enrolled in an IRB-approved clinical study. Each participant was examined comprehensively, including QPD testing. Each site was disassembled and microscopically video documented, and the results were recorded on a defect assessment sheet. A predictive model was developed for the pathology rating based on normalized fit error (NFE) values using data from the before treatment phase of the study published previously. Each restored site was then tested using QPD. The mean change in NFE values after restoration was evaluated by the pathology rating before treatment. The model was then used to predictively classify the rating after restoration based on the NFE values after treatment. The diagnostic potential of the rating was explored as a marker for risk of pathology after restoration. After restoration, 51 of the 60 sites fell below an NFE of 0.04, representing a greatly stabilized tooth site sample group. Several sites remained in the high-risk category and some increased in pathologic micromovement. Two models were used to determine severity with indicative cutoff points to group sites with similar values. The data support the hypothesis that QPD can indicate a revised level of structural instability of teeth after restoration. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

A hierarchical fuzzy rule-based approach to aphasia diagnosis.

PubMed

Akbarzadeh-T, Mohammad-R; Moshtagh-Khorasani, Majid

2007-10-01

Aphasia diagnosis is a particularly challenging medical diagnostic task due to the linguistic uncertainty and vagueness, inconsistencies in the definition of aphasic syndromes, large number of measurements with imprecision, natural diversity and subjectivity in test objects as well as in opinions of experts who diagnose the disease. To efficiently address this diagnostic process, a hierarchical fuzzy rule-based structure is proposed here that considers the effect of different features of aphasia by statistical analysis in its construction. This approach can be efficient for diagnosis of aphasia and possibly other medical diagnostic applications due to its fuzzy and hierarchical reasoning construction. Initially, the symptoms of the disease which each consists of different features are analyzed statistically. The measured statistical parameters from the training set are then used to define membership functions and the fuzzy rules. The resulting two-layered fuzzy rule-based system is then compared with a back propagating feed-forward neural network for diagnosis of four Aphasia types: Anomic, Broca, Global and Wernicke. In order to reduce the number of required inputs, the technique is applied and compared on both comprehensive and spontaneous speech tests. Statistical t-test analysis confirms that the proposed approach uses fewer Aphasia features while also presenting a significant improvement in terms of accuracy.

The diagnostic performance of coronary artery angiography with 64-MSCT and post 64-MSCT: systematic review and meta-analysis.

PubMed

Li, Min; Du, Xiang-Min; Jin, Zhi-Tao; Peng, Zhao-Hui; Ding, Juan; Li, Li

2014-01-01

To comprehensively investigate the diagnostic performance of coronary artery angiography with 64-MDCT and post 64-MDCT. PubMed was searched for all published studies that evaluated coronary arteries with 64-MDCT and post 64-MDCT. The clinical diagnostic role was evaluated by applying the likelihood ratios (LRs) to calculate the post-test probability based on Bayes' theorem. 91 studies that met our inclusion criteria were ultimately included in the analysis. The pooled positive and negative LRs at patient level were 8.91 (95% CI, 7.53, 10.54) and 0.02 (CI, 0.01, 0.03), respectively. For studies that did not claim that non-evaluable segments were included, the pooled positive and negative LRs were 11.16 (CI, 8.90, 14.00) and 0.01 (CI, 0.01, 0.03), respectively. For studies including uninterruptable results, the diagnostic performance decreased, with the pooled positive LR 7.40 (CI, 6.00, 9.13) and negative LR 0.02 (CI, 0.01, 0.03). The areas under the summary ROC curve were 0.98 (CI, 0.97 to 0.99) for 64-MDCT and 0.96 (CI, 0.94 to 0.98) for post 64-MDCT, respectively. For references explicitly stating that the non-assessable segments were included during analysis, a post-test probability of negative results >95% and a positive post-test probability <95% could be obtained for patients with a pre-test probability of <73% for coronary artery disease (CAD). On the other hand, when the pre-test probability of CAD was >73%, the diagnostic role was reversed, with a positive post-test probability of CAD >95% and a negative post-test probability of CAD <95%. The diagnostic performance of post 64-MDCT does not increase as compared with 64-MDCT. CTA, overall, is a test of exclusion for patients with a pre-test probability of CAD<73%, while for patients with a pre-test probability of CAD>73%, CTA is a test used to confirm the presence of CAD.

How to diagnose food allergy.

PubMed

Sato, Sakura; Yanagida, Noriyuki; Ebisawa, Motohiro

2018-06-01

To assess the recent studies that focus on specific immunoglobulin E (sIgE) testing and basophil activation test (BAT) for diagnosing IgE-mediated food allergies. The sIgE to allergen extract or component can predict reactivity to food. The cutoff value based on the positive predictive value (PPV) of sIgE can be considered whenever deciding whether oral food challenge (OFC) is required to diagnose hen's egg, cow's milk, wheat, peanut, and cashew nut allergy. However, PPV varies depending on the patients' background, OFC methodology, challenge foods, and assay methodology. Component-resolved diagnostics (CRD) has been used for food allergy diagnosis. Ovomucoid and omega-5 gliadin are good diagnostic markers for heated egg and wheat allergy. More recently, CRD of peanut, tree nuts, and seed have been investigated. Ara h 2 showed the best diagnostic accuracy for peanut allergy; other storage proteins, such as Jug r 1 for walnut, Ana o 3 for cashew nut, Ses i 1 for sesame, and Fag e 3 for buckwheat, are also better markers than allergen extracts. Some studies suggested that BAT has superior specificity than skin prick test and sIgE testing. The sIgE testing and BAT can improve diagnostic accuracy. CRD provides additional information that can help determine whether OFCs should be performed to diagnose food allergy.

[Evaluation of quality of HIV diagnostic procedures in Poland].

PubMed

Parczewski, Miłosz; Madaliński, Kazimierz; Leszczyszyn-Pynka, Magdalena; Boroń-Kaczmarska, Anna

2010-01-01

The aim of this work was quality assessment of HIV diagnostic procedures in Poland, including human and technical resources as well as laboratory practice. Sixty questionnaires were distributed among diagnostic centers to obtain qualitative data. Basing on the survey data serological control using coded panels of HIV-1/2 samples was performed. Thirty-one filled questionnaires were received (50.8%). Surveyed laboratories perform from 350 to 5500 serological screening tests per year. In most of laboratories fourth generation assays are available, while Blood Donation Centers screen the blood both with serological assays and by HIV-RNA detection. Sanitary and Epidemiological Stations and academic laboratories hold the ISO/IEC 17025 or IS0 9001:2001 accreditation, five of the surveyed centers participate in Labquality assurance and two in Quality Control in Molecular Diagnostics programs. Data of control serological testing were received from 21 centers. In the quality control assessment 194 analyses were performed with 91 true negative, 2 false negative, 96 true positive and 5 false positive results. False negative rate of % and false positive rate of 5.2% was noted for this study. Currently, virtually no guidelines related to the HIV-diagnostics quality assurance and control in Poland are in delineated. Development of the national unified quality control system, basing on the central institution is highly desirable. National certification within the frames of the quality control and assurance program should be mandatory for all the diagnostic labs, and aim at improvement of reliability of the result distributed among clinicians and patients.

Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

PubMed Central

van de Stolpe, Anja; den Toonder, Jaap M. J.

2014-01-01

Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics. PMID:24879438

Evaluation of a PfHRP2 and a pLDH-based Rapid Diagnostic Test for the Diagnosis of Severe Malaria in 2 Populations of African Children

PubMed Central

Hendriksen, Ilse C. E.; Mtove, George; Pedro, Alínia José; Gomes, Ermelinda; Silamut, Kamolrat; Lee, Sue J.; Mwambuli, Abraham; Gesase, Samwel; Reyburn, Hugh; Day, Nicholas P. J.; White, Nicholas J.; von Seidlein, Lorenz

2011-01-01

Background. Rapid diagnostic tests (RDTs) now play an important role in the diagnosis of falciparum malaria in many countries where the disease is endemic. Although these tests have been extensively evaluated in uncomplicated falciparum malaria, reliable data on their performance for diagnosing potentially lethal severe malaria is lacking. Methods. We compared a Plasmodium falciparum histidine-rich-protein2 (PfHRP2)–based RDT and a Plasmodium lactate dehydrogenase (pLDH)–based RDT with routine microscopy of a peripheral blood slide and expert microscopy as a reference standard for the diagnosis of severe malaria in 1898 children who presented with severe febrile illness at 2 centers in Mozambique and Tanzania. Results. The overall sensitivity, specificity, positive predictive value, and negative predictive values of the PfHRP2-based test were 94.0%, 70.9%, 85.4%, and 86.8%, respectively, and for the pLDH-based test, the values were 88.0%, 88.3%, 93.2%, and 80.3%, respectively. At parasite counts <1000 parasites/μL (n = 173), sensitivity of the pLDH-based test was low (45.7%), compared with that of the PfHRP2-based test (69.9%). Both RDTs performed better than did the routine slide reading in a clinical laboratory as assessed in 1 of the centers. Conclusion. The evaluated PfHRP2-based RDT is an acceptable alternative to routine microscopy for diagnosing severe malaria in African children and performed better than did the evaluated pLDH-based RDT. PMID:21467015

Molecular Methods and Platforms for Infectious Diseases Testing

PubMed Central

Emmadi, Rajyasree; Boonyaratanakornkit, Jerry B.; Selvarangan, Rangaraj; Shyamala, Venkatakrishna; Zimmer, Barbara L.; Williams, Laurina; Bryant, Bonita; Schutzbank, Ted; Schoonmaker, Michele M.; Amos Wilson, Jean A.; Hall, Leslie; Pancholi, Preeti; Bernard, Kathryn

2011-01-01

The superior sensitivity and specificity associated with the use of molecular assays has greatly improved the field of infectious disease diagnostics by providing clinicians with results that are both accurate and rapidly obtained. Herein, we review molecularly based infectious disease diagnostic tests that are Food and Drug Administration approved or cleared and commercially available in the United States as of December 31, 2010. We describe specific assays and their performance, as stated in the Food and Drug Administration's Summary of Safety and Effectiveness Data or the Office of In Vitro Diagnostic Device Evaluation and Safety's decision summaries, product inserts, or peer-reviewed literature. We summarize indications for testing, limitations, and challenges related to implementation in a clinical laboratory setting for a wide variety of common pathogens. The information presented in this review will be particularly useful for laboratories that plan to implement or expand their molecular offerings in the near term. PMID:21871973

40 CFR 85.2222 - On-board diagnostic test procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 19 2013-07-01 2013-07-01 false On-board diagnostic test procedures... Warranty Short Tests § 85.2222 On-board diagnostic test procedures. The test sequence for the inspection of on-board diagnostic systems on 1996 and newer light-duty vehicles and light-duty trucks shall consist...

40 CFR 85.2222 - On-board diagnostic test procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false On-board diagnostic test procedures... Warranty Short Tests § 85.2222 On-board diagnostic test procedures. The test sequence for the inspection of on-board diagnostic systems on 1996 and newer light-duty vehicles and light-duty trucks shall consist...

40 CFR 85.2231 - On-board diagnostic test equipment requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false On-board diagnostic test equipment... Warranty Short Tests § 85.2231 On-board diagnostic test equipment requirements. (a) The test system interface to the vehicle shall include a plug that conforms to SAE J1962 “Diagnostic Connector.” The...

40 CFR 85.2222 - On-board diagnostic test procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false On-board diagnostic test procedures... Warranty Short Tests § 85.2222 On-board diagnostic test procedures. The test sequence for the inspection of on-board diagnostic systems on 1996 and newer light-duty vehicles and light-duty trucks shall consist...

40 CFR 85.2231 - On-board diagnostic test equipment requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false On-board diagnostic test equipment... Warranty Short Tests § 85.2231 On-board diagnostic test equipment requirements. (a) The test system interface to the vehicle shall include a plug that conforms to SAE J1962 “Diagnostic Connector.” The...

40 CFR 85.2231 - On-board diagnostic test equipment requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 19 2013-07-01 2013-07-01 false On-board diagnostic test equipment... Warranty Short Tests § 85.2231 On-board diagnostic test equipment requirements. (a) The test system interface to the vehicle shall include a plug that conforms to SAE J1962 “Diagnostic Connector.” The...

Establishment and Comparison of Two Different Diagnostic Platforms for Detection of DENV1 NS1 Protein

PubMed Central

Tang, Yin-Liang; Chiu, Chien-Yu; Lin, Chun-Yu; Huang, Chung-Hao; Chen, Yen-Hsu; Destura, Raul V.; Chao, Day-Yu; Wu, Han-Chung

2015-01-01

Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of the disease is urgently needed. Serotype-specific monoclonal antibodies (mAbs) against the DENV1 nonstructural protein 1 (NS1), DA12-4, DA13-2, and DA15-3, which were recently generated using the hybridoma technique, are suitable for use in diagnostic platforms. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis further confirmed the serotype specificity of these three monoclonal antibodies. The ELISA-based diagnostic platform was established using the combination of two highly sensitive mAbs (DA15-3 and DB20-6). The same combination was also used for the flow cytometry-based diagnostic platform. We report here the detection limits of flow cytometry-based and ELISA-based diagnostic platforms using these mAbs to be 0.1 and 1 ng/mL, respectively. The collected clinical patient serum samples were also assayed by these two serotyping diagnostic platforms. The sensitivity and specificity for detecting NS1 protein of DENV1 are 90% and 96%, respectively. The accuracy of our platform for testing clinical samples is more advanced than that of the two commercial NS1 diagnostic platforms. In conclusion, our platforms are suitable for the early detection of NS1 protein in DENV1 infected patients. PMID:26610481

Testing Measurement Invariance across Groups of Children with and without Attention-Deficit/ Hyperactivity Disorder: Applications for Word Recognition and Spelling Tasks

PubMed Central

Lúcio, Patrícia S.; Salum, Giovanni; Swardfager, Walter; Mari, Jair de Jesus; Pan, Pedro M.; Bressan, Rodrigo A.; Gadelha, Ary; Rohde, Luis A.; Cogo-Moreira, Hugo

2017-01-01

Although studies have consistently demonstrated that children with attention-deficit/hyperactivity disorder (ADHD) perform significantly lower than controls on word recognition and spelling tests, such studies rely on the assumption that those groups are comparable in these measures. This study investigates comparability of word recognition and spelling tests based on diagnostic status for ADHD through measurement invariance methods. The participants (n = 1,935; 47% female; 11% ADHD) were children aged 6–15 with normal IQ (≥70). Measurement invariance was investigated through Confirmatory Factor Analysis and Multiple Indicators Multiple Causes models. Measurement invariance was attested in both methods, demonstrating the direct comparability of the groups. Children with ADHD were 0.51 SD lower in word recognition and 0.33 SD lower in spelling tests than controls. Results suggest that differences in performance on word recognition and spelling tests are related to true mean differences based on ADHD diagnostic status. Implications for clinical practice and research are discussed. PMID:29118733

Testing Measurement Invariance across Groups of Children with and without Attention-Deficit/ Hyperactivity Disorder: Applications for Word Recognition and Spelling Tasks.

PubMed

Lúcio, Patrícia S; Salum, Giovanni; Swardfager, Walter; Mari, Jair de Jesus; Pan, Pedro M; Bressan, Rodrigo A; Gadelha, Ary; Rohde, Luis A; Cogo-Moreira, Hugo

2017-01-01

Although studies have consistently demonstrated that children with attention-deficit/hyperactivity disorder (ADHD) perform significantly lower than controls on word recognition and spelling tests, such studies rely on the assumption that those groups are comparable in these measures. This study investigates comparability of word recognition and spelling tests based on diagnostic status for ADHD through measurement invariance methods. The participants ( n = 1,935; 47% female; 11% ADHD) were children aged 6-15 with normal IQ (≥70). Measurement invariance was investigated through Confirmatory Factor Analysis and Multiple Indicators Multiple Causes models. Measurement invariance was attested in both methods, demonstrating the direct comparability of the groups. Children with ADHD were 0.51 SD lower in word recognition and 0.33 SD lower in spelling tests than controls. Results suggest that differences in performance on word recognition and spelling tests are related to true mean differences based on ADHD diagnostic status. Implications for clinical practice and research are discussed.

Effectiveness of rapid prescreening and 10% rescreening in liquid-based Papanicolaou testing.

PubMed

Currens, Heather S; Nejkauf, Katharine; Wagner, Lynn; Raab, Stephen S

2012-01-01

Although rapid prescreening (RPS) has been shown to be an effective quality control procedure for detecting false-negative conventional Papanicolaou (Pap) tests, RPS has not been widely implemented in the United States. In our laboratory, cytotechnologists performed RPS in 3,567 liquid-based Pap tests: 1,911 SurePath (BD Diagnostics-TriPath, Burlington, NC) preparations that were manually screened and 1,656 ThinPrep Pap tests (Hologic, Bedford, MA) that were imaged using the ThinPrep Imaging System (Hologic). We compared the sensitivity of RPS, 10% rescreening (R-10%), and routine screening (RS). In contrast with previously published findings, we found that RS + RPS did not improve screening sensitivity compared with RS + R-10%. These results support the following hypotheses: (1) Higher baseline RS sensitivity as a result of Pap test diagnoses standardization implemented for quality improvement purposes decreases the performance impact of RPS. (2) R-10% and RPS quality assurance methods detect diagnostic failures caused by different types of cognitive errors.

Prognostic relevance of motor talent predictors in early adolescence: A group- and individual-based evaluation considering different levels of achievement in youth football.

PubMed

Höner, Oliver; Votteler, Andreas

2016-12-01

In the debate about the usefulness of motor diagnostics in the talent identification process, the prognostic validity for tests conducted in early adolescence is of critical interest. Using a group- and individual-based statistical approach, this prospective cohort study evaluated a nationwide assessment of speed abilities and technical skills regarding its relevance for future achievement levels. The sample consisted of 22,843 U12-players belonging to the top 4% in German football. The U12-results in five tests served as predictors for players' selection levels in U16-U19 (youth national team, regional association, youth academy, not selected). Group-mean differences proved the prognostic relevance for all predictors. Low individual selection probabilities demonstrated limited predictive values, while excellent test results proved their particular prognostic relevance. Players scoring percentile ranks (PRs) ≥ 99 had a 12 times higher chance to become youth national team players than players scoring PR < 99. Simulating increasing score cut-off values not only enhanced specificity (correctly identified non-talents) but also led to lower sensitivity (loss of talents). Extending the current research, these different approaches revealed the ambiguity of the diagnostics' prognostic relevance, representing both the usefulness and several pitfalls of nationwide diagnostics. Therefore, the present diagnostics can support but not substitute for coaches' subjective decisions for talent identification, and multidisciplinary designs are required.

Diagnostic Accuracy of Global Pharma Health Fund Minilab™ in Assessing Pharmacopoeial Quality of Antimicrobials.

PubMed

Pan, Hui; Ba-Thein, William

2018-01-01

Global Pharma Health Fund (GPHF) Minilab™, a semi-quantitative thin-layer chromatography (TLC)-based commercially available test kit, is widely used in drug quality surveillance globally, but its diagnostic accuracy is unclear. We investigated the diagnostic accuracy of Minilab system for antimicrobials, using high-performance liquid chromatography (HPLC) as reference standard. Following the Minilab protocols and the Pharmacopoeia of the People's Republic of China protocols, Minilab-TLC and HPLC were used to test five common antimicrobials (506 batches) for relative concentration of active pharmaceutical ingredients. The prevalence of poor-quality antimicrobials determined, respectively, by Minilab TLC and HPLC was amoxicillin (0% versus 14.9%), azithromycin (0% versus 17.4%), cefuroxime axetil (14.3% versus 0%), levofloxacin (0% versus 3.0%), and metronidazole (0% versus 38.0%). The Minilab TLC had false-positive and false-negative detection rates of 2.6% (13/506) and 15.2% (77/506) accordingly, resulting in the following test characteristics: sensitivity 0%, specificity 97.0%, positive predictive value 0, negative predictive value 0.8, positive likelihood ratio 0, negative likelihood ratio 1.0, diagnostic odds ratio 0, and adjusted diagnostic odds ratio 0.2. This study demonstrates unsatisfying diagnostic accuracy of Minilab system in screening poor-quality antimicrobials of common use. Using Minilab as a stand-alone system for monitoring drug quality should be reconsidered.

Chemical sensors for breath gas analysis: the latest developments at the Breath Analysis Summit 2013.

PubMed

Tisch, Ulrike; Haick, Hossam

2014-06-01

Profiling the body chemistry by means of volatile organic compounds (VOCs) in the breath opens exciting new avenues in medical diagnostics. Gas sensors could provide ideal platforms for realizing portable, hand-held breath testing devices in the near future. This review summarizes the latest developments and applications in the field of chemical sensors for diagnostic breath testing that were presented at the Breath Analysis Summit 2013 in Wallerfangen, Germany. Considerable progress has been made towards clinically applicable breath testing devices, especially by utilizing chemo-sensitive nanomaterials. Examples of several specialized breath testing applications are presented that are either based on stand-alone nanomaterial-based sensors being highly sensitive and specific to individual breath compounds over others, or on combinations of several highly specific sensors, or on experimental nanomaterial-based sensors arrays. Other interesting approaches include the adaption of a commercially available MOx-based sensor array to indirect breath testing applications, using a sample pre-concentration method, and the development of compact integrated GC-sensor systems. The recent trend towards device integration has led to the development of fully integrated prototypes of point-of-care devices. We describe and compare the performance of several prototypes that are based on different sensing technologies and evaluate their potential as low-cost and readily available next-generation medical devices.

Sequential Test Strategies for Multiple Fault Isolation

NASA Technical Reports Server (NTRS)

Shakeri, M.; Pattipati, Krishna R.; Raghavan, V.; Patterson-Hine, Ann; Kell, T.

1997-01-01

In this paper, we consider the problem of constructing near optimal test sequencing algorithms for diagnosing multiple faults in redundant (fault-tolerant) systems. The computational complexity of solving the optimal multiple-fault isolation problem is super-exponential, that is, it is much more difficult than the single-fault isolation problem, which, by itself, is NP-hard. By employing concepts from information theory and Lagrangian relaxation, we present several static and dynamic (on-line or interactive) test sequencing algorithms for the multiple fault isolation problem that provide a trade-off between the degree of suboptimality and computational complexity. Furthermore, we present novel diagnostic strategies that generate a static diagnostic directed graph (digraph), instead of a static diagnostic tree, for multiple fault diagnosis. Using this approach, the storage complexity of the overall diagnostic strategy reduces substantially. Computational results based on real-world systems indicate that the size of a static multiple fault strategy is strictly related to the structure of the system, and that the use of an on-line multiple fault strategy can diagnose faults in systems with as many as 10,000 failure sources.

Surface enhanced Raman spectroscopy (SERS) for in vitro diagnostic testing at the point of care

NASA Astrophysics Data System (ADS)

Marks, Haley; Schechinger, Monika; Garza, Javier; Locke, Andrea; Coté, Gerard

2017-06-01

Point-of-care (POC) device development is a growing field that aims to develop low-cost, rapid, sensitive in-vitro diagnostic testing platforms that are portable, self-contained, and can be used anywhere - from modern clinics to remote and low resource areas. In this review, surface enhanced Raman spectroscopy (SERS) is discussed as a solution to facilitating the translation of bioanalytical sensing to the POC. The potential for SERS to meet the widely accepted "ASSURED" (Affordable, Sensitive, Specific, User-friendly, Rapid, Equipment-free, and Deliverable) criterion provided by the World Health Organization is discussed based on recent advances in SERS in vitro assay development. As SERS provides attractive characteristics for multiplexed sensing at low concentration limits with a high degree of specificity, it holds great promise for enhancing current efforts in rapid diagnostic testing. In outlining the progression of SERS techniques over the past years combined with recent developments in smart nanomaterials, high-throughput microfluidics, and low-cost paper diagnostics, an extensive number of new possibilities show potential for translating SERS biosensors to the POC.

Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis.

PubMed

Nolan, Danielle; Carlson, Martha

2016-06-01

Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype-based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations. © The Author(s) 2016.

Laboratory evaluation on the sensitivity and specificity of a novel and rapid detection method for malaria diagnosis based on magneto-optical technology (MOT).

PubMed

Mens, Petra F; Matelon, Raphael J; Nour, Bakri Y M; Newman, Dave M; Schallig, Henk D F H

2010-07-19

This study describes the laboratory evaluation of a novel diagnostic platform for malaria. The Magneto Optical Test (MOT) is based on the bio-physical detection of haemozoin in clinical samples. Having an assay time of around one minute, it offers the potential of high throughput screening. Blood samples of confirmed malaria patients from different regions of Africa, patients with other diseases and healthy non-endemic controls were used in the present study. The samples were analysed with two reference tests, i.e. an histidine rich protein-2 based rapid diagnostic test (RDT) and a conventional Pan-Plasmodium PCR, and the MOT as index test. Data were entered in 2 x 2 tables and analysed for sensitivity and specificity. The agreement between microscopy, RDT and PCR and the MOT assay was determined by calculating Kappa values with a 95% confidence interval. The observed sensitivity/specificity of the MOT test in comparison with clinical description, RDT or PCR ranged from 77.2 - 78.8% (sensitivity) and from 72.5 - 74.6% (specificity). In general, the agreement between MOT and the other assays is around 0.5 indicating a moderate agreement between the reference and the index test. However, when RDT and PCR are compared to each other, an almost perfect agreement can be observed (k = 0.97) with a sensitivity and specificity of >95%. Although MOT sensitivity and specificity are currently not yet at a competing level compared to other diagnostic test, such as PCR and RDTs, it has a potential to rapidly screen patients for malaria in endemic as well as non-endemic countries.

Oak Ridge Reservation Public Warning Siren System Annual Test Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

R. F. Gee

2000-10-01

The full operational test of the Oak Ridge Reservation (ORR) Public Warning Siren System (PWSS) was successfully conducted on September 27, 2000. The annual test is a full-scale sounding of the individual siren systems around each of the three Department of Energy (DOE) sites in Oak Ridge, Tennessee. The purpose of the annual test is to demonstrate and validate the siren systems' ability to alert personnel outdoors in the Immediate Notification Zones (INZ) (approximately two miles) around each site. The success of this test is based on two critical functions of the siren system. The first function is system operability.more » The system is considered operable if 90% of the sirens are operational. System diagnostics and direct field observations were used to validate the operability of the siren systems. Based on the diagnostic results and field observations, greater than 90% of the sirens were considered operational. The second function is system audibility. The system is considered audible if the siren could be heard in the immediate notification zones around each of the three sites. Direct field observations, along with sound level measurements, were used to validate the audibility of the siren system. Based on the direct field observations and sound level measurements, the siren system was considered audible. The combination of field observations, system diagnostic status reports, and sound level measurements provided a high level of confidence that the system met and would meet operational requirements upon demand. As part of the overall system test, the Tennessee Emergency Management Agency (TEMA) activated the Emergency Alerting System (EAS), which utilized area radio stations to make announcements regarding the test and to remind residents of what to do in the event of an actual emergency.« less

Mast cell activation test in the diagnosis of allergic disease and anaphylaxis.

PubMed

Bahri, Rajia; Custovic, Adnan; Korosec, Peter; Tsoumani, Marina; Barron, Martin; Wu, Jiakai; Sayers, Rebekah; Weimann, Alf; Ruiz-Garcia, Monica; Patel, Nandinee; Robb, Abigail; Shamji, Mohamed H; Fontanella, Sara; Silar, Mira; Mills, E N Clare; Simpson, Angela; Turner, Paul J; Bulfone-Paus, Silvia

2018-03-05

Food allergy is an increasing public health issue and the most common cause of life-threatening anaphylactic reactions. Conventional allergy tests assess for the presence of allergen-specific IgE, significantly overestimating the rate of true clinical allergy and resulting in overdiagnosis and adverse effect on health-related quality of life. To undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT). Primary human blood-derived mast cells (MCs) were generated from peripheral blood precursors, sensitized with patients' sera, and then incubated with allergen. MC degranulation was assessed by means of flow cytometry and mediator release. We compared the diagnostic performance of MATs with that of existing diagnostic tools to assess in a cohort of peanut-sensitized subjects undergoing double-blind, placebo-controlled challenge. Human blood-derived MCs sensitized with sera from patients with peanut, grass pollen, and Hymenoptera (wasp venom) allergy demonstrated allergen-specific and dose-dependent degranulation, as determined based on both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandin D 2 and β-hexosaminidase release). In this cohort of peanut-sensitized subjects, the MAT was found to have superior discrimination performance compared with other testing modalities, including component-resolved diagnostics and basophil activation tests. Using functional principle component analysis, we identified 5 clusters or patterns of reactivity in the resulting dose-response curves, which at preliminary analysis corresponded to the reaction phenotypes seen at challenge. The MAT is a robust tool that can confer superior diagnostic performance compared with existing allergy diagnostics and might be useful to explore differences in effector cell function between basophils and MCs during allergic reactions. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Disk Crack Detection for Seeded Fault Engine Test

NASA Technical Reports Server (NTRS)

Luo, Huageng; Rodriguez, Hector; Hallman, Darren; Corbly, Dennis; Lewicki, David G. (Technical Monitor)

2004-01-01

Work was performed to develop and demonstrate vibration diagnostic techniques for the on-line detection of engine rotor disk cracks and other anomalies through a real engine test. An existing single-degree-of-freedom non-resonance-based vibration algorithm was extended to a multi-degree-of-freedom model. In addition, a resonance-based algorithm was also proposed for the case of one or more resonances. The algorithms were integrated into a diagnostic system using state-of-the- art commercial analysis equipment. The system required only non-rotating vibration signals, such as accelerometers and proximity probes, and the rotor shaft 1/rev signal to conduct the health monitoring. Before the engine test, the integrated system was tested in the laboratory by using a small rotor with controlled mass unbalances. The laboratory tests verified the system integration and both the non-resonance and the resonance-based algorithm implementations. In the engine test, the system concluded that after two weeks of cycling, the seeded fan disk flaw did not propagate to a large enough size to be detected by changes in the synchronous vibration. The unbalance induced by mass shifting during the start up and coast down was still the dominant response in the synchronous vibration.

Diagnostic performance of serological tests to detect antibodies against acute scrub typhus infection in central India.

PubMed

Pote, Kiran; Narang, Rahul; Deshmukh, Pradeep

2018-01-01

Differentiating scrub typhus from other acute febrile illness is difficult due to non specificity of clinical symptoms and relative absence of eschar in Indian population. The diagnosis thus relies mainly on laboratory tests. Antibody based serological tests are mainstay of scrub typhus diagnosis. Here, we evaluated the diagnostic performance of IgM ELISA, IgM IFA and ICT to detect antibodies against O. tsutsugamushi in acute serum of febrile patients. The serum samples from 600 randomly selected patients suffering from acute undifferentiated fever were tested by all the three tests mentioned above. We used latent class analysis to generate unbiased results as all the tests for scrub typhus diagnosis are imperfect and none of them can be considered as reference standard. We found that IgM ELISA with cutoff titer 0.5 OD has high diagnostic accuracy (sensitivity 99.9% and specificity 99.15) than IgM IFA (sensitivity 96.8% and specificity 99.7%) for scrub typhus diagnosis. ICT used in our study had very high specificity 100% but low sensitivity (38%) which would limit its use for acute serum samples. ICT being a screening or point of care test, has to be more sensitive while some compromise with specificity is affordable. Hence, optimal cutoff for ICT should be evaluated under different settings. IgM ELISA being simple and affordable could be an alternative diagnostic test to IgM IFA which is subjective and costly.

Diagnosis of stinging insect allergy: utility of cellular in-vitro tests.

PubMed

Scherer, Kathrin; Bircher, Andreas J; Heijnen, Ingmar Afm

2009-08-01

Diagnosis of stinging insect allergy is based on a detailed history, venom skin tests, and detection of venom-specific IgE. As an additional diagnostic tool, basophil responsiveness to venom allergens has been shown to be helpful in selected patients. This review summarizes the current diagnostic procedures for stinging insect allergy and discusses the latest developments in cellular in-vitro tests. Cellular assays have been evaluated in patients with Hymenoptera venom allergy. The diagnostic performance of the cellular mediator release test is similar to that of the flow cytometric basophil activation test (BAT), but the BAT has been the most intensively studied. BAT offers the possibility to assess basophil reactivity to allergens in their natural environment and to simultaneously analyze surface marker expression and intracellular signaling. It has been demonstrated that BAT represents a valuable additional diagnostic tool in selected patients when used in combination with other well established tests. A major limitation is the current lack of unified, standardized protocols. Flow cytometry offers huge possibilities to enhance knowledge of basophil functions. The BAT may be used as an additional test to confirm the diagnosis of stinging insect allergy in selected patients, provided that it is performed by an experienced laboratory using a validated assay. Test results have to be interpreted by clinicians familiar with the methodological aspects. The utility of the BAT to confirm allergy diagnosis and to predict the risk of subsequent systemic reactions may be improved by combined analysis of multiple surface markers and intracellular signaling pathways.

The Targeted Reading Intervention (TRI): A Classroom Teacher Tier 2 Intervention to Help Struggling Readers in Early Elementary School

ERIC Educational Resources Information Center

Vernon-Feagans, Lynne; Amendum, Steve; Kainz, Kirsten; Ginsburg, Marnie

2009-01-01

The two studies presented in this report were designed to test the effectiveness of a new diagnostic-based reading intervention for classroom teachers, called the Targeted Reading Intervention (TRI). This TRI Tier 2 intervention stressed diagnostic teaching as the key to helping struggling readers make rapid progress in reading in the regular…

A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria.

PubMed

Burden-Teh, E; Phillips, R C; Thomas, K S; Ratib, S; Grindlay, D; Murphy, R

2017-11-06

The diagnosis of psoriasis in adults and children is made clinically, for both patient management and the selection of participants in research. Diagnostic criteria provide a structure for clinical assessment, which in turn helps standardize patient recruitment into clinical trials and case definitions in observational studies. The aim of this systematic review was to identify and critically appraise the published studies to date that had a primary research aim to develop or validate diagnostic criteria for psoriasis. A search of Ovid MEDLINE and Ovid Embase was conducted in October 2016. The primary objective was to record the sensitivity and specificity of diagnostic criteria for psoriasis. Secondary objectives included diagnostic recommendations, applicability to children and study characteristics. Diagnostic accuracy studies were critically appraised for risk of bias using the QUADAS-2 tool. Twenty-three studies met the inclusion criteria. None detailed clinical examination-based diagnostic criteria. The included criteria varied from genetic and molecular diagnostic models to skin imaging, histopathology, and questionnaire-based, computer-aided and traditional Chinese medicine criteria. High sensitivity and specificity (> 90%) were reported in many studies. However, the study authors often did not specify how the criteria would be used clinically or in research. This review identified studies with varying risk of bias, and due to each study developing separate criteria meta-analysis was not possible. Clinical examination-based diagnostic criteria are currently lacking for psoriasis. Future research could follow an international collaborative approach and employ study designs allowing high-quality diagnostic accuracy testing. Existing and newly developed criteria require validation. © 2017 British Association of Dermatologists.

Benchmarking Diagnostic Algorithms on an Electrical Power System Testbed

NASA Technical Reports Server (NTRS)

Kurtoglu, Tolga; Narasimhan, Sriram; Poll, Scott; Garcia, David; Wright, Stephanie

2009-01-01

Diagnostic algorithms (DAs) are key to enabling automated health management. These algorithms are designed to detect and isolate anomalies of either a component or the whole system based on observations received from sensors. In recent years a wide range of algorithms, both model-based and data-driven, have been developed to increase autonomy and improve system reliability and affordability. However, the lack of support to perform systematic benchmarking of these algorithms continues to create barriers for effective development and deployment of diagnostic technologies. In this paper, we present our efforts to benchmark a set of DAs on a common platform using a framework that was developed to evaluate and compare various performance metrics for diagnostic technologies. The diagnosed system is an electrical power system, namely the Advanced Diagnostics and Prognostics Testbed (ADAPT) developed and located at the NASA Ames Research Center. The paper presents the fundamentals of the benchmarking framework, the ADAPT system, description of faults and data sets, the metrics used for evaluation, and an in-depth analysis of benchmarking results obtained from testing ten diagnostic algorithms on the ADAPT electrical power system testbed.

Comparative application of IS711-based polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) for canine brucellosis diagnosis.

PubMed

Batinga, Maria Cryskely Agra; de Lima, Julia Teresa Ribeiro; Gregori, Fabio; Diniz, Jaqueline Assumpção; Muner, Kerstin; Oliveira, Trícia M F S; Ferreira, Helena Lage; Soares, Rodrigo Martins; Keid, Lara Borges

2018-06-01

Canine brucellosis is caused by Brucella canis, a gram negative and facultative intracellular bacterium that is commonly associated with reproductive failures in dogs. The accurate diagnosis of the infection relies on the use of serological tests associated with blood culturing to guarantee sensitivity. The polymerase chain reaction (PCR) can replace the culturing procedure for the direct diagnosis of the infection because of its speed, high specificity and sensitivity values; however, it depends on some laboratory infrastructure to be conducted. The loop-mediated isothermal amplification (LAMP) may be an alternative method for DNA amplification in a shorter period, using simpler equipment, and with a lower cost. This study evaluated the potential of molecular tools based on PCR and LAMP using primers targeting the insertion sequence IS711 for Brucella detection in three groups of dogs (infected, non-infected and suspected of brucellosis), which were determined according to the results of blood culturing and clinical examination. The performance of the three diagnostic tests was also determined using McNemar test and Kappa coefficient. The proportion of positive samples detected by blood culturing, PCR and LAMP was respectively 31.57% (18/57), 33.34% (19/57), and 14.03% (8/57). The agreement between blood culturing and PCR was almost perfect, while the agreement of PCR and blood culturing compared to LAMP was fair. The diagnostic sensitivity of PCR and LAMP was respectively 100% (18/18) and 44.44% (8/18), while the diagnostic specificity of both tests was 100% (21/21). LAMP performance was not satisfactory for canine brucellosis diagnosis because of the low diagnostic sensitivity of the test. The IS711 based PCR, otherwise, showed high values of sensitivity and specificity, which makes it a good alternative for use for the rapid diagnosis of canine brucellosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

[New Radiopharmaceuticals Based on Prostate-Specific Inhibitors of Membrane Antigen for Diagnostics and Therapy of Metastatic Prostate Cancer].

PubMed

Vlasova, O P; German, K E; Krilov, V V; Petriev, V M; Epstein, N B

2015-01-01

About 10.7% cases of prostate cancer were registered in Russia in 2011 (40,000 patients). More than half of cancer cases were revealed in advanced (III-IV) stages when metastases inevitably developed quickly. Clinical problem of early diagnostics and treatment of metastatic prostate cancer is still not solved. Anatomical imaging techniques have low sensitivity and specificity for the detection of this disease. Metabolic visualization methods which use prostate specific antigen (PSA) as a marker are also ineffective. This article describes prostate-specific membrane antigens (PSMA) that are proposed as a marker for diagnostics and therapy of prostate cancer. The most promising PSMA-based radiopharmaceutical agent for diagnostics has been developed and clinically tested in the European countries. These pharmaceuticals are based on small peptide molecules modified with urea, and have the highest affinity to PSMA. Favorable phannacokinetics, rapid accumulation in the tumor and rapid excretion from the body are beneficial features of these pharmaceuticals.

Study of a high power hydrogen beam diagnostic based on secondary electron emission.

PubMed

Sartori, E; Panasenkov, A; Veltri, P; Serianni, G; Pasqualotto, R

2016-11-01

In high power neutral beams for fusion, beam uniformity is an important figure of merit. Knowing the transverse power profile is essential during the initial phases of beam source operation, such as those expected for the ITER heating neutral beam (HNB) test facility. To measure it a diagnostic technique is proposed, based on the collection of secondary electrons generated by beam-surface and beam-gas interactions, by an array of positively biased collectors placed behind the calorimeter tubes. This measurement showed in the IREK test stand good proportionality to the primary beam current. To investigate the diagnostic performances in different conditions, we developed a numerical model of secondary electron emission, induced by beam particle impact on the copper tubes, and reproducing the cascade of secondary emission caused by successive electron impacts. The model is first validated against IREK measurements. It is then applied to the HNB case, to assess the locality of the measurement, the proportionality to the beam current density, and the influence of beam plasma.

Diagnostic test accuracy and prevalence inferences based on joint and sequential testing with finite population sampling.

PubMed

Su, Chun-Lung; Gardner, Ian A; Johnson, Wesley O

2004-07-30

The two-test two-population model, originally formulated by Hui and Walter, for estimation of test accuracy and prevalence estimation assumes conditionally independent tests, constant accuracy across populations and binomial sampling. The binomial assumption is incorrect if all individuals in a population e.g. child-care centre, village in Africa, or a cattle herd are sampled or if the sample size is large relative to population size. In this paper, we develop statistical methods for evaluating diagnostic test accuracy and prevalence estimation based on finite sample data in the absence of a gold standard. Moreover, two tests are often applied simultaneously for the purpose of obtaining a 'joint' testing strategy that has either higher overall sensitivity or specificity than either of the two tests considered singly. Sequential versions of such strategies are often applied in order to reduce the cost of testing. We thus discuss joint (simultaneous and sequential) testing strategies and inference for them. Using the developed methods, we analyse two real and one simulated data sets, and we compare 'hypergeometric' and 'binomial-based' inferences. Our findings indicate that the posterior standard deviations for prevalence (but not sensitivity and specificity) based on finite population sampling tend to be smaller than their counterparts for infinite population sampling. Finally, we make recommendations about how small the sample size should be relative to the population size to warrant use of the binomial model for prevalence estimation. Copyright 2004 John Wiley & Sons, Ltd.

Evaluating Diagnostic Point-of-Care Tests in Resource-Limited Settings

PubMed Central

Drain, Paul K; Hyle, Emily P; Noubary, Farzad; Freedberg, Kenneth A; Wilson, Douglas; Bishai, William; Rodriguez, William; Bassett, Ingrid V

2014-01-01

Diagnostic point-of-care (POC) testing is intended to minimize the time to obtain a test result, thereby allowing clinicians and patients to make an expeditious clinical decision. As POC tests expand into resource-limited settings (RLS), the benefits must outweigh the costs. To optimize POC testing in RLS, diagnostic POC tests need rigorous evaluations focused on relevant clinical outcomes and operational costs, which differ from evaluations of conventional diagnostic tests. Here, we reviewed published studies on POC testing in RLS, and found no clearly defined metric for the clinical utility of POC testing. Therefore, we propose a framework for evaluating POC tests, and suggest and define the term “test efficacy” to describe a diagnostic test’s capacity to support a clinical decision within its operational context. We also proposed revised criteria for an ideal diagnostic POC test in resource-limited settings. Through systematic evaluations, comparisons between centralized diagnostic testing and novel POC technologies can be more formalized, and health officials can better determine which POC technologies represent valuable additions to their clinical programs. PMID:24332389

The after breakfast 50-g, 1-hour glucose challenge test in urban Mexican pregnant women: its sensitivity and specificity evaluated by three diagnostic criteria for gestational diabetes mellitus.

PubMed

Espinosa de los Monteros, A; Parra, A; Hidalgo, R; Zambrana, M

1999-04-01

To study the sensitivity and specificity of the 50-g, 1-hour gestational glucose challenge test performed 1 to 2 hours after a non-standardized home breakfast in urban Mexican women by using three different gestational diabetes mellitus diagnostic criteria. Four hundred and forty-five consecutive women of 24-28 weeks gestation were studied. The glucose challenge test was performed in the fed state and a week later a fasting 100-g, 3-hours oral glucose tolerance test was carried out in all of them. Duplicate serum glucose concentrations were determined by a glucose-oxidase method. Sensitivity and specificity were calculated using three different diagnostic criteria for gestational diabetes mellitus. The glucose challenge test performed as indicated, with a cutoff of 7.8 mmol/L, had 88-89% sensitivity and 85-87% specificity when using as diagnostic criteria those proposed by the National Diabetes Data Group and by Carpenter & Coustan; by using Sacks et al. criteria, the values were 82% and 88%, respectively. Considering only pregnant women > or = 25 years of age, the sensitivity increased to 92% with the National Diabetes Data Group criteria. Pregnant women < 25 years of age had significantly lower blood glucose values than those with age > or = 25 years during the glucose tolerance test. For the general group the sensitivity of the glucose challenge test performed 1 to 2 hours after breakfast was similar, based on the National Diabetes Data Group and the Carpenter & Coustan's diagnostic criteria for gestational diabetes mellitus. However, when pregnant women > or = 25 years of age were considered, the use of the former criteria yielded a slightly better sensitivity.

Evaluation of an Intelligent Tutoring System in Pathology: Effects of External Representation on Performance Gains, Metacognition, and Acceptance

PubMed Central

Crowley, Rebecca S.; Legowski, Elizabeth; Medvedeva, Olga; Tseytlin, Eugene; Roh, Ellen; Jukic, Drazen

2007-01-01

Objective Determine effects of computer-based tutoring on diagnostic performance gains, meta-cognition, and acceptance using two different problem representations. Describe impact of tutoring on spectrum of diagnostic skills required for task performance. Identify key features of student-tutor interaction contributing to learning gains. Design Prospective, between-subjects study, controlled for participant level of training. Resident physicians in two academic pathology programs spent four hours using one of two interfaces which differed mainly in external problem representation. The case-focused representation provided an open-learning environment in which students were free to explore evidence-hypothesis relationships within a case, but could not visualize the entire diagnostic space. The knowledge-focused representation provided an interactive representation of the entire diagnostic space, which more tightly constrained student actions. Measurements Metrics included results of pretest, post-test and retention-test for multiple choice and case diagnosis tests, ratios of performance to student reported certainty, results of participant survey, learning curves, and interaction behaviors during tutoring. Results Students had highly significant learning gains after one tutoring session. Learning was retained at one week. There were no differences between the two interfaces in learning gains on post-test or retention test. Only students in the knowledge-focused interface exhibited significant metacognitive gains from pretest to post-test and pretest to retention test. Students rated the knowledge-focused interface significantly higher than the case-focused interface. Conclusions Cognitive tutoring is associated with improved diagnostic performance in a complex medical domain. The effect is retained at one-week post-training. Knowledge-focused external problem representation shows an advantage over case-focused representation for metacognitive effects and user acceptance. PMID:17213494

Evaluation of an intelligent tutoring system in pathology: effects of external representation on performance gains, metacognition, and acceptance.

PubMed

Crowley, Rebecca S; Legowski, Elizabeth; Medvedeva, Olga; Tseytlin, Eugene; Roh, Ellen; Jukic, Drazen

2007-01-01

Determine effects of computer-based tutoring on diagnostic performance gains, meta-cognition, and acceptance using two different problem representations. Describe impact of tutoring on spectrum of diagnostic skills required for task performance. Identify key features of student-tutor interaction contributing to learning gains. Prospective, between-subjects study, controlled for participant level of training. Resident physicians in two academic pathology programs spent four hours using one of two interfaces which differed mainly in external problem representation. The case-focused representation provided an open-learning environment in which students were free to explore evidence-hypothesis relationships within a case, but could not visualize the entire diagnostic space. The knowledge-focused representation provided an interactive representation of the entire diagnostic space, which more tightly constrained student actions. Metrics included results of pretest, post-test and retention-test for multiple choice and case diagnosis tests, ratios of performance to student reported certainty, results of participant survey, learning curves, and interaction behaviors during tutoring. Students had highly significant learning gains after one tutoring session. Learning was retained at one week. There were no differences between the two interfaces in learning gains on post-test or retention test. Only students in the knowledge-focused interface exhibited significant metacognitive gains from pretest to post-test and pretest to retention test. Students rated the knowledge-focused interface significantly higher than the case-focused interface. Cognitive tutoring is associated with improved diagnostic performance in a complex medical domain. The effect is retained at one-week post-training. Knowledge-focused external problem representation shows an advantage over case-focused representation for metacognitive effects and user acceptance.

German translation, cross-cultural adaptation and diagnostic test accuracy of three frailty screening tools : PRISMA-7, FRAIL scale and Groningen Frailty Indicator.

PubMed

Braun, Tobias; Grüneberg, Christian; Thiel, Christian

2018-04-01

Routine screening for frailty could be used to timely identify older people with increased vulnerability und corresponding medical needs. The aim of this study was the translation and cross-cultural adaptation of the PRISMA-7 questionnaire, the FRAIL scale and the Groningen Frailty Indicator (GFI) into the German language as well as a preliminary analysis of the diagnostic test accuracy of these instruments used to screen for frailty. A diagnostic cross-sectional study was performed. The instrument translation into German followed a standardized process. Prefinal versions were clinically tested on older adults who gave structured in-depth feedback on the scales in order to compile a final revision of the German language scale versions. For the analysis of diagnostic test accuracy (criterion validity), PRISMA-7, FRAIL scale and GFI were considered the index tests. Two reference tests were applied to assess frailty, either based on Fried's model of a Physical Frailty Phenotype or on the model of deficit accumulation, expressed in a Frailty Index. Prefinal versions of the German translations of each instrument were produced and completed by 52 older participants (mean age: 73 ± 6 years). Some minor issues concerning comprehensibility and semantics of the scales were identified and resolved. Using the Physical Frailty Phenotype (frailty prevalence: 4%) criteria as a reference standard, the accuracy of the instruments was excellent (area under the curve AUC >0.90). Taking the Frailty Index (frailty prevalence: 23%) as the reference standard, the accuracy was good (AUC between 0.73 and 0.88). German language versions of PRISMA-7, FRAIL scale and GFI have been established and preliminary results indicate sufficient diagnostic test accuracy that needs to be further established.

Bead-based immunoassay allows sub-picogram detection of histidine-rich protein 2 from Plasmodium falciparum and estimates reliability of malaria rapid diagnostic tests

PubMed Central

Rogier, Eric; Plucinski, Mateusz; Lucchi, Naomi; Mace, Kimberly; Chang, Michelle; Lemoine, Jean Frantz; Candrinho, Baltazar; Colborn, James; Dimbu, Rafael; Fortes, Filomeno; Udhayakumar, Venkatachalam; Barnwell, John

2017-01-01

Detection of histidine-rich protein 2 (HRP2) from the malaria parasite Plasmodium falciparum provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for HRP2 are hindered by low sensitivities and high costs. Here we present a new HRP2 immunoassay based on antigen capture through a bead-based system capable of detecting HRP2 at sub-picogram levels. The assay is highly specific and cost-effective, allowing fast processing and screening of large numbers of samples. We utilized the assay to assess results of HRP2-based rapid diagnostic tests (RDTs) in different P. falciparum transmission settings, generating estimates for true performance in the field. Through this method of external validation, HRP2 RDTs were found to perform well in the high-endemic areas of Mozambique and Angola with 86.4% and 73.9% of persons with HRP2 in their blood testing positive by RDTs, respectively, and false-positive rates of 4.3% and 0.5%. However, in the low-endemic setting of Haiti, only 14.5% of persons found to be HRP2 positive by the bead assay were RDT positive. Additionally, 62.5% of Haitians showing a positive RDT test had no detectable HRP2 by the bead assay, likely indicating that these were false positive tests. In addition to RDT validation, HRP2 biomass was assessed for the populations in these different settings, and may provide an additional metric by which to estimate P. falciparum transmission intensity and measure the impact of interventions. PMID:28192523

How to Use the DX SYSTEM of Diagnostic Testing. Methodology Project.

ERIC Educational Resources Information Center

McArthur, David; Cabello, Beverly

The DX SYSTEM of Diagnostic Testing is an easy-to-use computerized system for developing and administering diagnostic tests. A diagnostic test measures a student's mastery of a specific domain (skill or content area). It examines the necessary subskills hierarchically from the most to the least complex. The DX SYSTEM features tailored testing with…

Cost-effectiveness analysis of microscopic observation drug susceptibility test versus Xpert MTB/Rif test for diagnosis of pulmonary tuberculosis in HIV patients in Uganda.

PubMed

Walusimbi, Simon; Kwesiga, Brendan; Rodrigues, Rashmi; Haile, Melles; de Costa, Ayesha; Bogg, Lennart; Katamba, Achilles

2016-10-10

Microscopic Observation Drug Susceptibility (MODS) and Xpert MTB/Rif (Xpert) are highly sensitive tests for diagnosis of pulmonary tuberculosis (PTB). This study evaluated the cost effectiveness of utilizing MODS versus Xpert for diagnosis of active pulmonary TB in HIV infected patients in Uganda. A decision analysis model comparing MODS versus Xpert for TB diagnosis was used. Costs were estimated by measuring and valuing relevant resources required to perform the MODS and Xpert tests. Diagnostic accuracy data of the tests were obtained from systematic reviews involving HIV infected patients. We calculated base values for unit costs and varied several assumptions to obtain the range estimates. Cost effectiveness was expressed as costs per TB patient diagnosed for each of the two diagnostic strategies. Base case analysis was performed using the base estimates for unit cost and diagnostic accuracy of the tests. Sensitivity analysis was performed using a range of value estimates for resources, prevalence, number of tests and diagnostic accuracy. The unit cost of MODS was US$ 6.53 versus US$ 12.41 of Xpert. Consumables accounted for 59 % (US$ 3.84 of 6.53) of the unit cost for MODS and 84 % (US$10.37 of 12.41) of the unit cost for Xpert. The cost effectiveness ratio of the algorithm using MODS was US$ 34 per TB patient diagnosed compared to US$ 71 of the algorithm using Xpert. The algorithm using MODS was more cost-effective compared to the algorithm using Xpert for a wide range of different values of accuracy, cost and TB prevalence. The cost (threshold value), where the algorithm using Xpert was optimal over the algorithm using MODS was US$ 5.92. MODS versus Xpert was more cost-effective for the diagnosis of PTB among HIV patients in our setting. Efforts to scale-up MODS therefore need to be explored. However, since other non-economic factors may still favour the use of Xpert, the current cost of the Xpert cartridge still needs to be reduced further by more than half, in order to make it economically competitive with MODS.

Differential Diagnosis of Malaria on Truelab Uno®, a Portable, Real-Time, MicroPCR Device for Point-Of-Care Applications.

PubMed

Nair, Chandrasekhar Bhaskaran; Manjula, Jagannath; Subramani, Pradeep Annamalai; Nagendrappa, Prakash B; Manoj, Mulakkapurath Narayanan; Malpani, Sukriti; Pullela, Phani Kumar; Subbarao, Pillarisetti Venkata; Ramamoorthy, Siva; Ghosh, Susanta K

2016-01-01

Sensitive and specific detection of malarial parasites is crucial in controlling the significant malaria burden in the developing world. Also important is being able to identify life threatening Plasmodium falciparum malaria quickly and accurately to reduce malaria related mortality. Existing methods such as microscopy and rapid diagnostic tests (RDTs) have major shortcomings. Here, we describe a new real-time PCR-based diagnostic test device at point-of-care service for resource-limited settings. Truenat® Malaria, a chip-based microPCR test, was developed by bigtec Labs, Bangalore, India, for differential identification of Plasmodium falciparum and Plasmodium vivax parasites. The Truenat Malaria tests runs on bigtec's Truelab Uno® microPCR device, a handheld, battery operated, and easy-to-use real-time microPCR device. The performance of Truenat® Malaria was evaluated versus the WHO nested PCR protocol. The Truenat® Malaria was further evaluated in a triple-blinded study design using a sample panel of 281 specimens created from the clinical samples characterized by expert microscopy and a rapid diagnostic test kit by the National Institute of Malaria Research (NIMR). A comparative evaluation was done on the Truelab Uno® and a commercial real-time PCR system. The limit of detection of the Truenat Malaria assay was found to be <5 parasites/μl for both P. falciparum and P. vivax. The Truenat® Malaria test was found to have sensitivity and specificity of 100% each, compared to the WHO nested PCR protocol based on the evaluation of 100 samples. The sensitivity using expert microscopy as the reference standard was determined to be around 99.3% (95% CI: 95.5-99.9) at the species level. Mixed infections were identified more accurately by Truenat Malaria (32 samples identified as mixed) versus expert microscopy and RDTs which detected 4 and 5 mixed samples, respectively. The Truenat® Malaria microPCR test is a valuable diagnostic tool and implementation should be considered not only for malaria diagnosis but also for active surveillance and epidemiological intervention.

Differential Diagnosis of Malaria on Truelab Uno®, a Portable, Real-Time, MicroPCR Device for Point-Of-Care Applications

PubMed Central

Nair, Chandrasekhar Bhaskaran; Manjula, Jagannath; Subramani, Pradeep Annamalai; Nagendrappa, Prakash B.; Manoj, Mulakkapurath Narayanan; Malpani, Sukriti; Pullela, Phani Kumar; Subbarao, Pillarisetti Venkata; Ramamoorthy, Siva; Ghosh, Susanta K.

2016-01-01

Background Sensitive and specific detection of malarial parasites is crucial in controlling the significant malaria burden in the developing world. Also important is being able to identify life threatening Plasmodium falciparum malaria quickly and accurately to reduce malaria related mortality. Existing methods such as microscopy and rapid diagnostic tests (RDTs) have major shortcomings. Here, we describe a new real-time PCR-based diagnostic test device at point-of-care service for resource-limited settings. Methods Truenat® Malaria, a chip-based microPCR test, was developed by bigtec Labs, Bangalore, India, for differential identification of Plasmodium falciparum and Plasmodium vivax parasites. The Truenat Malaria tests runs on bigtec’s Truelab Uno® microPCR device, a handheld, battery operated, and easy-to-use real-time microPCR device. The performance of Truenat® Malaria was evaluated versus the WHO nested PCR protocol. The Truenat® Malaria was further evaluated in a triple-blinded study design using a sample panel of 281 specimens created from the clinical samples characterized by expert microscopy and a rapid diagnostic test kit by the National Institute of Malaria Research (NIMR). A comparative evaluation was done on the Truelab Uno® and a commercial real-time PCR system. Results The limit of detection of the Truenat Malaria assay was found to be <5 parasites/μl for both P. falciparum and P. vivax. The Truenat® Malaria test was found to have sensitivity and specificity of 100% each, compared to the WHO nested PCR protocol based on the evaluation of 100 samples. The sensitivity using expert microscopy as the reference standard was determined to be around 99.3% (95% CI: 95.5–99.9) at the species level. Mixed infections were identified more accurately by Truenat Malaria (32 samples identified as mixed) versus expert microscopy and RDTs which detected 4 and 5 mixed samples, respectively. Conclusion The Truenat® Malaria microPCR test is a valuable diagnostic tool and implementation should be considered not only for malaria diagnosis but also for active surveillance and epidemiological intervention. PMID:26784111

Challenges to Laser-Based Imaging Techniques in Gas Turbine Combustor Systems for Aerospace Applications

NASA Technical Reports Server (NTRS)

Locke, Randy J.; Anderson, Robert C.; Zaller, Michelle M.; Hicks, Yolanda R.

1998-01-01

Increasingly severe constraints on emissions, noise and fuel efficiency must be met by the next generation of commercial aircraft powerplants. At NASA Lewis Research Center (LeRC) a cooperative research effort with industry is underway to design and test combustors that will meet these requirements. To accomplish these tasks, it is necessary to gain both a detailed understanding of the combustion processes and a precise knowledge of combustor and combustor sub-component performance at close to actual conditions. To that end, researchers at LeRC are engaged in a comprehensive diagnostic investigation of high pressure reacting flowfields that duplicate conditions expected within the actual engine combustors. Unique, optically accessible flame-tubes and sector rig combustors, designed especially for these tests. afford the opportunity to probe these flowfields with the most advanced, laser-based optical diagnostic techniques. However, these same techniques, tested and proven on comparatively simple bench-top gaseous flame burners, encounter numerous restrictions and challenges when applied in these facilities. These include high pressures and temperatures, large flow rates, liquid fuels, remote testing, and carbon or other material deposits on combustor windows. Results are shown that document the success and versatility of these nonintrusive optical diagnostics despite the challenges to their implementation in realistic systems.

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... Nonphysician practitioners (that is, clinical nurse specialists, clinical psychologists, clinical social... that do not involve the use of contrast media; and (iii) Diagnostic mammograms if the approved portable...

What Do Diagnostic Reading Tests Really Diagnose?

ERIC Educational Resources Information Center

Winkley, Carol K.

A study was made of nine reading tests, including both group and individually-administered measures, which are claimed to be chiefly diagnostic. Instruments analyzed were the following: Silent Reading Diagnostic Tests (Bond, Balow, and Hoyt), Botel Reading Inventory, Durrell Analysis of Reading Difficulty, Gates-McKillop Reading Diagnostic Tests,…

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2012 CFR

2012-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2013 CFR

2013-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2014 CFR

2014-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2010 CFR

2010-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2011 CFR

2011-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

Rapid and Accurate Behavioral Health Diagnostic Screening: Initial Validation Study of a Web-Based, Self-Report Tool (the SAGE-SR)

PubMed Central

Purcell, Susan E; Rhea, Karen; Maier, Philip; First, Michael; Zweede, Lisa; Sinisterra, Manuela; Nunn, M Brad; Austin, Marie-Paule; Brodey, Inger S

2018-01-01

Background The Structured Clinical Interview for DSM (SCID) is considered the gold standard assessment for accurate, reliable psychiatric diagnoses; however, because of its length, complexity, and training required, the SCID is rarely used outside of research. Objective This paper aims to describe the development and initial validation of a Web-based, self-report screening instrument (the Screening Assessment for Guiding Evaluation-Self-Report, SAGE-SR) based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the SCID-5-Clinician Version (CV) intended to make accurate, broad-based behavioral health diagnostic screening more accessible within clinical care. Methods First, study staff drafted approximately 1200 self-report items representing individual granular symptoms in the diagnostic criteria for the 8 primary SCID-CV modules. An expert panel iteratively reviewed, critiqued, and revised items. The resulting items were iteratively administered and revised through 3 rounds of cognitive interviewing with community mental health center participants. In the first 2 rounds, the SCID was also administered to participants to directly compare their Likert self-report and SCID responses. A second expert panel evaluated the final pool of items from cognitive interviewing and criteria in the DSM-5 to construct the SAGE-SR, a computerized adaptive instrument that uses branching logic from a screener section to administer appropriate follow-up questions to refine the differential diagnoses. The SAGE-SR was administered to healthy controls and outpatient mental health clinic clients to assess test duration and test-retest reliability. Cutoff scores for screening into follow-up diagnostic sections and criteria for inclusion of diagnoses in the differential diagnosis were evaluated. Results The expert panel reduced the initial 1200 test items to 664 items that panel members agreed collectively represented the SCID items from the 8 targeted modules and DSM criteria for the covered diagnoses. These 664 items were iteratively submitted to 3 rounds of cognitive interviewing with 50 community mental health center participants; the expert panel reviewed session summaries and agreed on a final set of 661 clear and concise self-report items representing the desired criteria in the DSM-5. The SAGE-SR constructed from this item pool took an average of 14 min to complete in a nonclinical sample versus 24 min in a clinical sample. Responses to individual items can be combined to generate DSM criteria endorsements and differential diagnoses, as well as provide indices of individual symptom severity. Preliminary measures of test-retest reliability in a small, nonclinical sample were promising, with good to excellent reliability for screener items in 11 of 13 diagnostic screening modules (intraclass correlation coefficient [ICC] or kappa coefficients ranging from .60 to .90), with mania achieving fair test-retest reliability (ICC=.50) and other substance use endorsed too infrequently for analysis. Conclusions The SAGE-SR is a computerized adaptive self-report instrument designed to provide rigorous differential diagnostic information to clinicians. PMID:29572204

Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome.

PubMed

Jaques, Alice M; Collins, Veronica R; Muggli, Evelyne E; Amor, David J; Francis, Ivan; Sheffield, Leslie J; Halliday, Jane L

2010-06-01

To map prenatal screening and diagnostic testing pathways in Victorian pregnant women during 2003 to 2004; measure the impact of prenatal diagnostic testing uptake on the effectiveness of prenatal screening for Down syndrome; and assess factors influencing uptake of diagnostic testing following screening. State-wide data collections of prenatal screening and diagnostic tests were linked to all Victorian births and pregnancy terminations for birth defects. Overall, 52% of women had a prenatal test (65 692/126 305); screening (44.9%), diagnostic testing (3.9%), or both (3.2%). Uptake of diagnostic testing was 71.4% (2390/3349) after an increased risk screen result, and 2.5% (1381/54 286) after a low risk result. Variation in uptake of diagnostic testing reduced the effectiveness of the screening program by 11.2%: from 87.4% (sensitivity - 125/143) to 76.2% (prenatal diagnoses of Down syndrome - 109/143). In both the increased and low risk groups, uptake was influenced by absolute numerical risk, as well as by the change in numerical risk from a priori risk. This comprehensive follow-up demonstrates clearly that numerical risk is being used to aid in decision making about confirmatory diagnostic testing. Collectively, these fundamental individual decisions will impact on the overall effectiveness of screening programmes for Down syndrome.

The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria.

PubMed

Gunay-Aygun, M; Schwartz, S; Heeger, S; O'Riordan, M A; Cassidy, S B

2001-11-01

Prader-Willi syndrome (PWS) is a complex, multisystem disorder. Its major clinical features include neonatal hypotonia, developmental delay, short stature, behavioral abnormalities, childhood-onset obesity, hypothalamic hypogonadism, and characteristic appearance. The genetic basis of PWS is also complex. It is caused by absence of expression of the paternally active genes in the PWS critical region on 15q11-q13. In approximately 70% of cases this is the result of deletion of this region from the paternal chromosome 15. In approximately 28%, it is attributable to maternal uniparental disomy (UPD; inheritance of 2 copies of a chromosome from the mother and no copies from the father, as opposed to the normal 1 copy from each parent) of chromosome 15, and in <2%, it is the result of a mutation, deletion, or other defect in the imprinting center. Clinical diagnostic criteria were established by consensus in 1993. Subsequently, definitive molecular genetic testing became available for laboratory diagnosis of PWS. However, identification of appropriate patients for testing remains a challenge for most practitioners because many features of the disorder are nonspecific and others can be subtle or evolve over time. For example, hypotonic infants who are still in the failure to thrive phase of the disorder often do not have sufficient features for recognition of PWS and often are not tested. Initial screening with these diagnostic criteria can increase the yield of molecular testing for older children and adults with nonspecific obesity and mental retardation. Therefore, the purpose of clinical diagnostic criteria has shifted from assisting in making the definitive diagnosis to raising diagnostic suspicion, thereby prompting testing. We conducted a retrospective review of patients with PWS confirmed with genetic testing to assess the validity and sensitivity of clinical diagnostic criteria published before the widespread availability of testing for all affected patients and recommend revised clinical criteria. Charts of all 90 patients with laboratory-confirmed PWS were reviewed. For each patient, the presence or absence of the major, minor, and supportive features listed in the published diagnostic criteria was recorded. The sensitivity of each criterion, mean of the total number of major and minor criteria, and mean total score for each patient were calculated. There were 68 patients with a deletion (del 15q11-q13), 21 with maternal UPD of chromosome 15, and 1 with a presumed imprinting defect. Age range at the time of the most recent evaluation was 5 months to 60 years (median: 14.5 years; del median: 14 years; range: 5 months-60 years; UPD median: 18 years; range: 5-42 years). The sensitivities of the major criteria ranged from 49% (characteristic facial features) to 98% (developmental delay). Global developmental delay and neonatal hypotonia were the 2 most consistently positive major criteria and were positive in >97% of the patients. Feeding problems in infancy, excessive weight gain after 1 year, hypogonadism, and hyperphagia were all present in 93% or more of patients. Sensitivities of the minor criteria ranged form 37% (sleep disturbance and apneas) to 93% (speech and articulation defects). Interestingly, the sensitivities of 8 of the minor criteria were higher than the sensitivity of characteristic facial features, which is a major criterion. Fifteen out of 90 patients with molecular diagnosis did not meet the clinical diagnostic criteria retrospectively. When definitive diagnostic testing is not available, as was the case for PWS when the 1993 criteria were developed, diagnostic criteria are important to avoid overdiagnosis and to ensure that diagnostic test development is performed on appropriate samples. When diagnostic testing is available, as is now the case for PWS, diagnostic criteria should serve to raise diagnostic suspicion, ensure that all appropriate people are tested, and avoid the expense of testing unnecessarily. Our results indicate that the sensitivities of most of the published criteria are acceptable. However, 16.7% of patients with molecular diagnosis did not meet the 1993 clinical diagnostic criteria retrospectively, suggesting that the published criteria may be too exclusive. A less strict scoring system may ensure that all appropriate people are tested. Accordingly, we suggest revised clinical criteria to help identify the appropriate patients for DNA testing for PWS. The suggested age groupings are based on characteristic phases of the natural history of PWS. Some of the features (eg, neonatal hypotonia, feeding problems in infancy) serve to diagnose the syndrome in the first few years of life, whereas others (eg, excessive eating) are useful during early childhood. Similarly, hypogonadism is most useful during and after adolescence. Some of the features like neonatal hypotonia and infantile feeding problems are less likely to be missed, whereas others such as characteristic facial features and hypogonadism (especially in prepubertal females) may require more careful and/or expert examination. The issue of who should have diagnostic testing is distinct from the determination of features among confirmed patients. Based on the sensitivities of the published criteria and our experience, we suggest testing all newborns/infants with otherwise unexplained hypotonia with poor suck. For children between 2 and 6 years of age, we consider hypotonia with history of poor suck associated with global developmental delay sufficient criteria to prompt testing. Between 6 and 12 years of age, we suggest testing those with hypotonia (or history of hypotonia with poor suck), global developmental delay, and excessive eating with central obesity (if uncontrolled). At the ages of 13 years and above, we recommend testing patients with cognitive impairment, excessive eating with central obesity (if uncontrolled), and hypogonadotropic hypogonadism and/or typical behavior problems (including temper tantrums and obsessive-compulsive features). Thus, we propose a lower threshold to prompt diagnostic DNA testing, leading to a higher likelihood of diagnosis of this disorder in which anticipatory guidance and intervention can significantly influence outcome.

DEVELOPMENT OF DIAGNOSTIC ANALYTICAL AND MECHANICAL ABILITY TESTS THROUGH FACET DESIGN AND ANALYSIS.

ERIC Educational Resources Information Center

GUTTMAN, LOUIS,; SCHLESINGER, I.M.

METHODOLOGY BASED ON FACET THEORY (MODIFIED SET THEORY) WAS USED IN TEST CONSTRUCTION AND ANALYSIS TO PROVIDE AN EFFICIENT TOOL OF EVALUATION FOR VOCATIONAL GUIDANCE AND VOCATIONAL SCHOOL USE. THE TYPE OF TEST DEVELOPMENT UNDERTAKEN WAS LIMITED TO THE USE OF NONVERBAL PICTORIAL ITEMS. ITEMS FOR TESTING ABILITY TO IDENTIFY ELEMENTS BELONGING TO AN…

Moving toward rapid and low-cost point-of-care molecular diagnostics with a repurposed 3D printer and RPA.

PubMed

Chan, Kamfai; Wong, Pui-Yan; Parikh, Chaitanya; Wong, Season

2018-03-15

Traditionally, the majority of nucleic acid amplification-based molecular diagnostic tests are done in centralized settings. In recent years, point-of-care tests have been developed for use in low-resource settings away from central laboratories. While most experts agree that point-of-care molecular tests are greatly needed, their availability as cost-effective and easy-to-operate tests remains an unmet goal. In this article, we discuss our efforts to develop a recombinase polymerase amplification reaction-based test that will meet these criteria. First, we describe our efforts in repurposing a low-cost 3D printer as a platform that can carry out medium-throughput, rapid, and high-performing nucleic acid extraction. Next, we address how these purified templates can be rapidly amplified and analyzed using the 3D printer's heated bed or the deconstructed, low-cost thermal cycler we have developed. In both approaches, real-time isothermal amplification and detection of template DNA or RNA can be accomplished using a low-cost portable detector or smartphone camera. Last, we demonstrate the capability of our technologies using foodborne pathogens and the Zika virus. Our low-cost approach does not employ complicated and high-cost components, making it suitable for resource-limited settings. When integrated and commercialized, it will offer simple sample-to-answer molecular diagnostics. Copyright © 2018 Elsevier Inc. All rights reserved.

Performance of an HRP-2 Rapid Diagnostic Test in Nigerian Children Less Than 5 Years of Age

PubMed Central

Ajumobi, Olufemi; Sabitu, Kabir; Nguku, Patrick; Kwaga, Jacob; Ntadom, Godwin; Gitta, Sheba; Elizeus, Rutebemberwa; Oyibo, Wellington; Nsubuga, Peter; Maire, Mark; Poggensee, Gabriele

2015-01-01

The diagnostic performance of histidine-rich protein 2 (HRP-2)–based malaria rapid diagnostic test (RDT) was evaluated in a mesoendemic area for malaria, Kaduna, Nigeria. We compared RDT results with expert microscopy results of blood samples from 295 febrile children under 5 years. Overall, 11.9% (35/295) tested positive with RDT compared with 10.5% (31/295) by microscopy: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 98.5%, 88.6%, and 100%, respectively. The RDT sensitivity was not affected by transmission season, parasite density, and age. Specificity and positive PV decreased slightly during the high-transmission season (97.5% and 83.3%). The RDT test positivity rates in the low- and high-transmission seasons were 9.4% and 13.5%, respectively. Overall, the test performance of this RDT was satisfactory. The findings of a low proportion of RDT false positives, no invalid and no false-negative results should validate the performance of RDTs in this context. PMID:25711608

[What is hidden behind the Baking Tray Task? Study of sensibility and specificity in right-hemispheric stroke patients].

PubMed

Garcia-Fernandez, Juan; Garcia-Molina, Alberto; Aparicio-Lopez, Celeste; Sanchez-Carrion, Rocío; Ensenat, Antònia; Pena-Casanova, Jordi; Roig-Rovira, Teresa

2015-12-16

Tham and Tegner proposed the Baking Tray Task (BTT) as a fast simple assessment test for detecting spatial negligence. However, very few studies have examined its validity as a diagnostic test. To analyse the diagnostic validity of the BTT by measuring its specificity and sensitivity in a sample of subjects with right hemisphere strokes. Forty-eight patients with right hemisphere vascular lesions were distributed in two groups (negligence group, n = 35; non-negligence group, n = 13) according to the scores obtained in a battery of visuospatial examination tests. The participants' performance on the BTT was compared with that of a healthy control group (n = 12). The results showed a high level of sensitivity of the BTT, but low specificity. The performance on the BTT of eight of the 13 members of the non-negligence group was suggestive of negligence. The BTT has proved to be a sensitive test for the detection of spatial negligence. Yet, based on its low specificity, its use alone as a single diagnostic test is not recommended.

Preliminary assessment of the diagnostic performances of a new rapid diagnostic test for the serodiagnosis of human cystic echinococcosis.

PubMed

Vola, Ambra; Tamarozzi, Francesca; Noordin, Rahmah; Yunus, Muhammad Hafiznur; Khanbabaie, Sam; De Silvestri, Annalisa; Brunetti, Enrico; Mariconti, Mara

2018-04-14

Rapid diagnostic tests for cystic echinococcosis (CE) are convenient to support ultrasound diagnosis in uncertain cases, especially in resource-limited settings. We found comparable diagnostic performances of the experimental Hyd Rapid Test and the commercial VIRapid HYDATIDOSIS Test, used in our diagnostic laboratory, using samples from well-characterized hepatic CE cases. Copyright © 2018 Elsevier Inc. All rights reserved.

Vacuum system design and tritium inventory for the charge exchange diagnostic on the Tokamak Fusion Test Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medley, S.S.

The application of charge exchange analyzers for the measurement of ion temperature in fusion plasma experiments requires a direct connection between the diagnostic and plasma-discharge vacuum chambers. Differential pumping of the gas load from the diagnostic stripping cell operated at > or approx. = 10/sup -3/ Torr is required to maintain the analyzer chamber at a pressure of < or approx. = 10/sup -6/ Torr. The migration of gases between the diagnostic and plasma vacuum chambers must be minimized. In particular, introduction of the analyzer stripping cell gas into the plasma chamber having a base pressure of < or approx.more » = 10/sup -8/ Torr must be suppressed. The charge exchange diagnostic for the Tokamak Fusion Test Reactor (TFTR) is comprised of two analyzer systems designed to contain a total of 18 independent mass/energy analyzers and one diagnostic neutral beam rated at 80 keV, 15 A. The associated arrays of multiple, interconnected vacuum systems were analyzed using the Vacuum System Transient Simulator (Vsts) computer program which models the transient transport of multigas species through complex networks of ducts, valves, traps, vacuum pumps, and other related vacuum system components. In addition to providing improved design performance at reduced costs, the analysis yields estimates for the exchange of tritium from the torus to the diagnostic components and of the diagnostic working gases to the torus.« less

Advantages of virulotyping foodborne pathogens over traditional identification and characterization methods

USDA-ARS?s Scientific Manuscript database

This chapter provides an overview regarding the advantages of virulotyping over historic serology-based, PCR-based on genes that identify an organism, or enzymatic and biochemical-based analyses of foodborne pathogens in clinical diagnostics and food industry microbiology testing. Traditional ident...

Yield and cost of individual common diagnostic tests in new primary care outpatients in Japan.

PubMed

Takemura, Yuzuru; Ishida, Haku; Inoue, Yuji; Beck, J Robert

2002-01-01

Appropriate diagnostic testing involves considerations of cost-effectiveness. We examined the cost-effectiveness of individual tests in a panel of tests defined by the Japan Society of Clinical Pathology. We studied 540 new, symptomatic primary care outpatients with a set of 30 common diagnostic tests [the Essential Laboratory Tests (2); ELT(2) panel] for clinical evaluation and identification of occult disease. A useful result (UR) of testing was defined as a finding that contributed to a change in a physician's diagnosis or decision-making relating to a "tentative initial diagnosis" obtained from history and physical examination alone. The ELT(2) panel testing yielded 398 URs and uncovered 261 occult diseases among 540 patients. In total, 1592 tests contributed to either UR-generation or discovery of occult disease. The cost per effective test (cost required per test that contributed to either definition of effectiveness) ranged from 108 yen (approximately 0.92 US dollars) for total cholesterol to 6200 yen (approximately 52.50 dollars) for chest x-ray. Contribution rates and the cost per effective test varied among disease categories. We restructured panel components considering the effectiveness of each test. Subsets of the ELT(2) would have improved cost-effectiveness and achieved cost savings in five of eight disease categories. Assembly of tests based on cost-effectiveness can improve clinical efficiency and decrease total cost of panel testing for selected patient groups.

Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement.

PubMed

McInnes, Matthew D F; Moher, David; Thombs, Brett D; McGrath, Trevor A; Bossuyt, Patrick M; Clifford, Tammy; Cohen, Jérémie F; Deeks, Jonathan J; Gatsonis, Constantine; Hooft, Lotty; Hunt, Harriet A; Hyde, Christopher J; Korevaar, Daniël A; Leeflang, Mariska M G; Macaskill, Petra; Reitsma, Johannes B; Rodin, Rachel; Rutjes, Anne W S; Salameh, Jean-Paul; Stevens, Adrienne; Takwoingi, Yemisi; Tonelli, Marcello; Weeks, Laura; Whiting, Penny; Willis, Brian H

2018-01-23

Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy. To develop the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagnostic test accuracy guideline as a stand-alone extension of the PRISMA statement. Modifications to the PRISMA statement reflect the specific requirements for reporting of systematic reviews and meta-analyses of diagnostic test accuracy studies and the abstracts for these reviews. Established standards from the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network were followed for the development of the guideline. The original PRISMA statement was used as a framework on which to modify and add items. A group of 24 multidisciplinary experts used a systematic review of articles on existing reporting guidelines and methods, a 3-round Delphi process, a consensus meeting, pilot testing, and iterative refinement to develop the PRISMA diagnostic test accuracy guideline. The final version of the PRISMA diagnostic test accuracy guideline checklist was approved by the group. The systematic review (produced 64 items) and the Delphi process (provided feedback on 7 proposed items; 1 item was later split into 2 items) identified 71 potentially relevant items for consideration. The Delphi process reduced these to 60 items that were discussed at the consensus meeting. Following the meeting, pilot testing and iterative feedback were used to generate the 27-item PRISMA diagnostic test accuracy checklist. To reflect specific or optimal contemporary systematic review methods for diagnostic test accuracy, 8 of the 27 original PRISMA items were left unchanged, 17 were modified, 2 were added, and 2 were omitted. The 27-item PRISMA diagnostic test accuracy checklist provides specific guidance for reporting of systematic reviews. The PRISMA diagnostic test accuracy guideline can facilitate the transparent reporting of reviews, and may assist in the evaluation of validity and applicability, enhance replicability of reviews, and make the results from systematic reviews of diagnostic test accuracy studies more useful.

Isotope-selective sensor for medical diagnostics based on PAS

NASA Astrophysics Data System (ADS)

Wolff, M.; Groninga, H. G.; Harde, H.

2005-06-01

Development of new optical sensor technologies has a major impact on the progression of diagnostic methods. Of the permanently increasing number of non-invasive 13C-breath tests, the Urea Breath Test for detection of Helicobacter pylori is the most prominent. However, many recent developments go beyond gastroenterological applications. We present a new detection scheme for breath analysis that employs an especially compact and simple set-up based on Photoacoustic Spectroscopy. Using a wavelength-modulated DFB-diode laser and taking advantage of acoustical resonances of the sample cell, we performed very sensitive isotope-selective measurements on CO2. Detection limits for 13CO2 of a few ppm and for the variation of the 13CO2 concentration of approximately 1% were achieved.

[Express diagnostics of bovine leucosis by immune sensor based on surface plasmon resonance].

PubMed

Pyrohova, L V; Starodub, M F; Artiukh, V P; Nahaieva, L I; Dobrosol, H I

2002-01-01

An immune sensor based on the surface plasmon resonance (SPR) was developed for express diagnostics of bovine leucosis. The sensor was used for detection of the level of antibodies against bovine leukaemia virus (BLV) in the blood serum. The industrially manufactured BLV antigen for screening test in the agar gel immunodiffusion (AGID) required the additional purification in order to be used in immune sensor analysis. It was shown that immune sensor analysis was more sensitive, rapid and simple in comparison with the traditional AGID test. It was stated that the developed immune sensor was capable to be used for performance of bovine leucosis screening at the farms and the minimal dilution of the serum should be 1:500.

Continuous stacking computational approach based automated microscope slide scanner

NASA Astrophysics Data System (ADS)

Murali, Swetha; Adhikari, Jayesh Vasudeva; Jagannadh, Veerendra Kalyan; Gorthi, Sai Siva

2018-02-01

Cost-effective and automated acquisition of whole slide images is a bottleneck for wide-scale deployment of digital pathology. In this article, a computation augmented approach for the development of an automated microscope slide scanner is presented. The realization of a prototype device built using inexpensive off-the-shelf optical components and motors is detailed. The applicability of the developed prototype to clinical diagnostic testing is demonstrated by generating good quality digital images of malaria-infected blood smears. Further, the acquired slide images have been processed to identify and count the number of malaria-infected red blood cells and thereby perform quantitative parasitemia level estimation. The presented prototype would enable cost-effective deployment of slide-based cyto-diagnostic testing in endemic areas.

Damage tolerance modeling and validation of a wireless sensory composite panel for a structural health monitoring system

NASA Astrophysics Data System (ADS)

Talagani, Mohamad R.; Abdi, Frank; Saravanos, Dimitris; Chrysohoidis, Nikos; Nikbin, Kamran; Ragalini, Rose; Rodov, Irena

2013-05-01

The paper proposes the diagnostic and prognostic modeling and test validation of a Wireless Integrated Strain Monitoring and Simulation System (WISMOS). The effort verifies a hardware and web based software tool that is able to evaluate and optimize sensorized aerospace composite structures for the purpose of Structural Health Monitoring (SHM). The tool is an extension of an existing suite of an SHM system, based on a diagnostic-prognostic system (DPS) methodology. The goal of the extended SHM-DPS is to apply multi-scale nonlinear physics-based Progressive Failure analyses to the "as-is" structural configuration to determine residual strength, remaining service life, and future inspection intervals and maintenance procedures. The DPS solution meets the JTI Green Regional Aircraft (GRA) goals towards low weight, durable and reliable commercial aircraft. It will take advantage of the currently developed methodologies within the European Clean sky JTI project WISMOS, with the capability to transmit, store and process strain data from a network of wireless sensors (e.g. strain gages, FBGA) and utilize a DPS-based methodology, based on multi scale progressive failure analysis (MS-PFA), to determine structural health and to advice with respect to condition based inspection and maintenance. As part of the validation of the Diagnostic and prognostic system, Carbon/Epoxy ASTM coupons were fabricated and tested to extract the mechanical properties. Subsequently two composite stiffened panels were manufactured, instrumented and tested under compressive loading: 1) an undamaged stiffened buckling panel; and 2) a damaged stiffened buckling panel including an initial diamond cut. Next numerical Finite element models of the two panels were developed and analyzed under test conditions using Multi-Scale Progressive Failure Analysis (an extension of FEM) to evaluate the damage/fracture evolution process, as well as the identification of contributing failure modes. The comparisons between predictions and test results were within 10% accuracy.

Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi - a systematic review and economic evaluation.

PubMed

Stevenson, Matt; Pandor, Abdullah; Martyn-St James, Marrissa; Rafia, Rachid; Uttley, Lesley; Stevens, John; Sanderson, Jean; Wong, Ruth; Perkins, Gavin D; McMullan, Ronan; Dark, Paul

2016-06-01

Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE(®) (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest(TM) (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-of-flight mass spectrometry). Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable. The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required. This study is registered as PROSPERO CRD42015016724. The National Institute for Health Research Health Technology Assessment programme.

A novel indirect ELISA based on glycoprotein Gn for the detection of IgG antibodies against Rift Valley fever virus in small ruminants.

PubMed

Jäckel, S; Eiden, M; Balkema-Buschmann, A; Ziller, M; van Vuren, P Jansen; Paweska, J T; Groschup, M H

2013-10-01

Rift Valley fever virus (RVFV) is an emerging zoonotic pathogen that causes high morbidity and mortality in humans and livestock. In this paper, we describe the cloning, expression and purification of RVFV glycoprotein Gn and its application as a diagnostic antigen in an indirect ELISA for the specific detection of RVF IgG antibodies in sheep and goats. The performance of this Gn based ELISA is validated using a panel of almost 2000 field samples from sheep and goats from Mozambique, Senegal, Uganda and Yemen. All serum samples were also tested by virus neutralization test (VNT), the gold standard method for RVFV serological testing. Compared to the VNT results the Gn based ELISA proved to have an excellent sensitivity (94.56%) and specificity (95.57%). Apart from establishing this new diagnostic assay, these results also demonstrate a close correlation between the presence of RVFV Gn and neutralizing antibodies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Expanding the Taxonomy of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD)

PubMed Central

Peck, Christopher C.; Goulet, Jean-Paul; Lobbezoo, Frank; Schiffman, Eric L.; Alstergren, Per; Anderson, Gary C.; de Leeuw, Reny; Jensen, Rigmor; Michelotti, Ambra; Ohrbach, Richard; Petersson, Arne; List, Thomas

2014-01-01

Background There is a need to expand the current temporomandibular disorder (TMD) classification to include less common, but clinically important disorders. The immediate aim was to develop a consensus-based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long-term aim was to establish a foundation, vis-à-vis this classification system, that will stimulate data collection, validity testing, and further criteria refinement. Methods A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria, and the ability to operationalize and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMD taxonomy was presented for feedback at international meetings. Results Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders, and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalized diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. Conclusions The expanded TMD taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalize and test the proposed taxonomy and diagnostic criteria. PMID:24443898

Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders.

PubMed

Peck, C C; Goulet, J-P; Lobbezoo, F; Schiffman, E L; Alstergren, P; Anderson, G C; de Leeuw, R; Jensen, R; Michelotti, A; Ohrbach, R; Petersson, A; List, T

2014-01-01

There is a need to expand the current temporomandibular disorders' (TMDs) classification to include less common but clinically important disorders. The immediate aim was to develop a consensus-based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long-term aim was to establish a foundation, vis-à-vis this classification system, that will stimulate data collection, validity testing and further criteria refinement. A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria and the ability to operationalise and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMDs taxonomy was presented for feedback at international meetings. Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalised diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. The expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalise and test the proposed taxonomy and diagnostic criteria. © 2014 John Wiley & Sons Ltd.

Enhanced CT images by the wavelet transform improving diagnostic accuracy of chest nodules.

PubMed

Guo, Xiuhua; Liu, Xiangye; Wang, Huan; Liang, Zhigang; Wu, Wei; He, Qian; Li, Kuncheng; Wang, Wei

2011-02-01

The objective of this study was to compare the diagnostic accuracy in the interpretation of chest nodules using original CT images versus enhanced CT images based on the wavelet transform. The CT images of 118 patients with cancers and 60 with benign nodules were used in this study. All images were enhanced through an algorithm based on the wavelet transform. Two experienced radiologists interpreted all the images in two reading sessions. The reading sessions were separated by a minimum of 1 month in order to minimize the effect of observer's recall. The Mann-Whitney U nonparametric test was used to analyze the interpretation results between original and enhanced images. The Kruskal-Wallis H nonparametric test of K independent samples was used to investigate the related factors which could affect the diagnostic accuracy of observers. The area under the ROC curves for the original and enhanced images was 0.681 and 0.736, respectively. There is significant difference in diagnosing the malignant nodules between the original and enhanced images (z = 7.122, P < 0.001), whereas there is no significant difference in diagnosing the benign nodules (z = 0.894, P = 0.371). The results showed that there is significant difference between original and enhancement images when the size of nodules was larger than 2 cm (Z = -2.509, P = 0.012, indicating the size of the nodules is a critical evaluating factor of the diagnostic accuracy of observers). This study indicated that the image enhancement based on wavelet transform could improve the diagnostic accuracy of radiologists for the malignant chest nodules.

Validation of wet mount microscopy against Trichomonas culture among women of reproductive age group in Western province, Sri Lanka.

PubMed

Banneheke, H; Fernandopulle, R; Gunasekara, U; Barua, A; Fernando, N; Wickremasinghe, R

2015-06-01

Wet mount microscopy is the most commonly used diagnostic method for trichomoniasis in clinical diagnostic services all over the world including Sri Lanka due to its availability, simplicity and is relatively inexpensive. However, Trichomonas culture and PCR are the gold standard tests. Unfortunately, neither the culture nor PCR is available for the diagnosis of trichomoniasis in Sri Lanka. Thus, it is important to validate the wet mount microscopy as it is the only available diagnostic test and has not been validated to date in Sri Lanka. The objective was to evaluate the validity and reliability of wet mount microscopy against gold standard Trichomonas culture among clinic based population of reproductive age group women in Western province, Sri Lanka. Women attending hospital and institutional based clinics were enrolled. They were interviewed and high vaginal swabs were taken for laboratory diagnosis by culture and wet mount microscopy. There were 601 participants in the age group of 15-45 years. Wet mount microscopy showed 68% sensitivity, 100% specificity, 100% positive (PPV) and 98% negative predictive values (NPV) (P=0.001, kappa=0.803) respectively against the gold standard culture. The area under the ROC curve was 0.840. Sensitivity of wet mount microscopy is low. However it has high validity and reliability as a specific diagnostic test for trichomoniasis. If it is to be used among women of reproductive age group in Western province, Sri Lanka, a culture method could be adopted as a second test to confirm the negative wet mount for symptomatic patients.

Applying team-based learning of diagnostics for undergraduate students: assessing teaching effectiveness by a randomized controlled trial study

PubMed Central

Zeng, Rui; Xiang, Lian-rui; Zeng, Jing; Zuo, Chuan

2017-01-01

Background We aimed to introduce team-based learning (TBL) as one of the teaching methods for diagnostics and to compare its teaching effectiveness with that of the traditional teaching methods. Methods We conducted a randomized controlled trial on diagnostics teaching involving 111 third-year medical undergraduates, using TBL as the experimental intervention, compared with lecture-based learning as the control, for teaching the two topics of symptomatology. Individual Readiness Assurance Test (IRAT)-baseline and Group Readiness Assurance Test (GRAT) were performed in members of each TBL subgroup. The scores in Individual Terminal Test 1 (ITT1) immediately after class and Individual Terminal Test 2 (ITT2) 1 week later were compared between the two groups. The questionnaire and interview were also implemented to survey the attitude of students and teachers toward TBL. Results There was no significant difference between the two groups in ITT1 (19.85±4.20 vs 19.70±4.61), while the score of the TBL group was significantly higher than that of the control group in ITT2 (19.15±3.93 vs 17.46±4.65). In the TBL group, the scores of the two terminal tests after the teaching intervention were significantly higher than the baseline test score of individuals. IRAT-baseline, ITT1, and ITT2 scores of students at different academic levels in the TBL teaching exhibited significant differences, but the ITT1-IRAT-baseline and ITT2-IRAT-baseline indicated no significant differences among the three subgroups. Conclusion Our TBL in symptomatology approach was highly accepted by students in the improvement of interest and self-directed learning and resulted in an increase in knowledge acquirements, which significantly improved short-term test scores compared with lecture-based learning. TBL is regarded as an effective teaching method worthy of promoting. PMID:28331383

Applying team-based learning of diagnostics for undergraduate students: assessing teaching effectiveness by a randomized controlled trial study.

PubMed

Zeng, Rui; Xiang, Lian-Rui; Zeng, Jing; Zuo, Chuan

2017-01-01

We aimed to introduce team-based learning (TBL) as one of the teaching methods for diagnostics and to compare its teaching effectiveness with that of the traditional teaching methods. We conducted a randomized controlled trial on diagnostics teaching involving 111 third-year medical undergraduates, using TBL as the experimental intervention, compared with lecture-based learning as the control, for teaching the two topics of symptomatology. Individual Readiness Assurance Test (IRAT)-baseline and Group Readiness Assurance Test (GRAT) were performed in members of each TBL subgroup. The scores in Individual Terminal Test 1 (ITT1) immediately after class and Individual Terminal Test 2 (ITT2) 1 week later were compared between the two groups. The questionnaire and interview were also implemented to survey the attitude of students and teachers toward TBL. There was no significant difference between the two groups in ITT1 (19.85±4.20 vs 19.70±4.61), while the score of the TBL group was significantly higher than that of the control group in ITT2 (19.15±3.93 vs 17.46±4.65). In the TBL group, the scores of the two terminal tests after the teaching intervention were significantly higher than the baseline test score of individuals. IRAT-baseline, ITT1, and ITT2 scores of students at different academic levels in the TBL teaching exhibited significant differences, but the ITT1-IRAT-baseline and ITT2-IRAT-baseline indicated no significant differences among the three subgroups. Our TBL in symptomatology approach was highly accepted by students in the improvement of interest and self-directed learning and resulted in an increase in knowledge acquirements, which significantly improved short-term test scores compared with lecture-based learning. TBL is regarded as an effective teaching method worthy of promoting.

Infection with Pathogens Transmitted Commonly Through Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on Surveillance--Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2012-2015.

PubMed

Huang, Jennifer Y; Henao, Olga L; Griffin, Patricia M; Vugia, Duc J; Cronquist, Alicia B; Hurd, Sharon; Tobin-D'Angelo, Melissa; Ryan, Patricia; Smith, Kirk; Lathrop, Sarah; Zansky, Shelley; Cieslak, Paul R; Dunn, John; Holt, Kristin G; Wolpert, Beverly J; Patrick, Mary E

2016-04-15

To evaluate progress toward prevention of enteric and foodborne illnesses in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) monitors the incidence of laboratory-confirmed infections caused by nine pathogens transmitted commonly through food in 10 U.S. sites. This report summarizes preliminary 2015 data and describes trends since 2012. In 2015, FoodNet reported 20,107 confirmed cases (defined as culture-confirmed bacterial infections and laboratory-confirmed parasitic infections), 4,531 hospitalizations, and 77 deaths. FoodNet also received reports of 3,112 positive culture-independent diagnostic tests (CIDTs) without culture-confirmation, a number that has markedly increased since 2012. Diagnostic testing practices for enteric pathogens are rapidly moving away from culture-based methods. The continued shift from culture-based methods to CIDTs that do not produce the isolates needed to distinguish between strains and subtypes affects the interpretation of public health surveillance data and ability to monitor progress toward prevention efforts. Expanded case definitions and strategies for obtaining bacterial isolates are crucial during this transition period.

Vaccine allergy and pseudo-allergy.

PubMed

Ponvert, Claude; Scheinmann, Pierre

2003-01-01

Allergic and pseudo-allergic reactions to vaccines frequently involve the skin, and can be generalized systemic symptoms (urticaria/angioedema, serum sickness, flares of eczema) or localized at the sites of vaccination (persistent nodules, abcesses, granulomas). Diagnosis of Arthus-type reactions is based on clinical history and specific IgM/IgG anti-toxoid determination. For other local reactions, diagnostic value of non-immediate responses in skin tests varies with clinical symptoms and substances involved. Immediate responses in skin tests and specific IgE determination have good diagnostic and/or predictive value in anaphylaxis and immediate/accelerated urticaria/angioedema to toxoid-, pneumococcus-, and egg- and gelatin-containing vaccines. Diagnosis of reactions to dextran in BCG is based on specific IgM/IgG determination. Most non-immediate generalized reactions result from non-specific inflammation, except for gelatin-containing vaccines, but the diagnostic value of immuno-allergological tests with the vaccines and gelatin are controversial. Withholding booster injections is advised if specific IgM/IgG levels are high. If the levels are low, sequential injections of vaccines containing a single vaccinating agent are usually tolerated. However, injections of the vaccine should be performed using a " desensitization " procedure in patients reporting anaphylaxis and immediate/accelerated urticaria/angioedema.

42 CFR 414.506 - Procedures for public consultation for payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... a new clinical diagnostic laboratory test. 414.506 Section 414.506 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.506 Procedures for public consultation for payment for a new clinical diagnostic laboratory test...

42 CFR 414.506 - Procedures for public consultation for payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... a new clinical diagnostic laboratory test. 414.506 Section 414.506 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.506 Procedures for public consultation for payment for a new clinical diagnostic laboratory test...

Understanding the properties of diagnostic tests - Part 2: Likelihood ratios.

PubMed

Ranganathan, Priya; Aggarwal, Rakesh

2018-01-01

Diagnostic tests are used to identify subjects with and without disease. In a previous article in this series, we examined some attributes of diagnostic tests - sensitivity, specificity, and predictive values. In this second article, we look at likelihood ratios, which are useful for the interpretation of diagnostic test results in everyday clinical practice.

Barriers to community case management of malaria in Saraya, Senegal: training, and supply-chains.

PubMed

Blanas, Demetri A; Ndiaye, Youssoupha; Nichols, Kim; Jensen, Andrew; Siddiqui, Ammar; Hennig, Nils

2013-03-14

Health workers in sub-Saharan Africa can now diagnose and treat malaria in the field, using rapid diagnostic tests and artemisinin-based combination therapy in areas without microscopy and widespread resistance to previously effective drugs. This study evaluates communities' perceptions of a new community case management of malaria programme in the district of Saraya, south-eastern Senegal, the effectiveness of lay health worker trainings, and the availability of rapid diagnostic tests and artemisinin-based combination therapy in the field. The study employed qualitative and quantitative methods including focus groups with villagers, and pre- and post-training questionnaires with lay health workers. Communities approved of the community case management programme, but expressed concern about other general barriers to care, particularly transportation challenges. Most lay health workers acquired important skills, but a sizeable minority did not understand the rapid diagnostic test algorithm and were not able to correctly prescribe arteminisin-based combination therapy soon after the training. Further, few women lay health workers participated in the programme. Finally, the study identified stock-outs of rapid tests and anti-malaria medication products in over half of the programme sites two months after the start of the programme, thought due to a regional shortage. This study identified barriers to implementation of the community case management of malaria programme in Saraya that include lay health worker training, low numbers of women participants, and generalized stock-outs. These barriers warrant investigation into possible solutions of relevance to community case management generally.

Diagnostic validation of selected serological tests for detecting scrub typhus.

PubMed

Koraluru, Munegowda; Bairy, Indira; Varma, Muralidhar; Vidyasagar, Sudha

2015-07-01

Clinical diagnosis of scrub typhus is often difficult because the symptoms are very similar to those of other febrile illness such as dengue, leptospirosis, malaria and other viral hemorrhagic fevers. Though better diagnostic tests are available for rickettsial diseases and scrub typhus elsewhere, the Weil-Felix test is still commonly used in India, mainly because microimmunofluorescence assays (M-IFA) were not available in India till recently and relevant staff had insufficient training. The present study was performed to investigate the performance of M-IFA, IgM ELISA, and Weil-Felix test on 546 non-repeated serum samples from subjects suspected of having scrub typhus. One hundred and forty-three of these 546 samples were positive by M-IFA; these cases were also confirmed clinically to have scrub typhus based on their dramatic responses to doxycycline therapy. IgM ELISA was positive in 122 of the 143 M-IFA positive cases and the Weil-Felix test in 96. Though the Weil-Felix test is a heterophile agglutination test, it was found in this study to have good specificity but far too little sensitivity to use as a routine diagnostic test. IgM ELISA can be a good substitute for M-IFA. Incorporation of multiple prototype antigens on M-IFA slides is likely one of the reasons for its superior performance. As newer and better diagnostic assays become available for scrub typhus diagnosis in developed countries, it will be imperative to also use such tests in other endemic countries to prevent over- or under-diagnosis of scrub typhus. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

The challenges of oral-based diagnostics in extending the role of dentistry as a health care profession: property rights, privacy, and informed consent.

PubMed

Vernillo, Anthony; Welie, Jos V M; Naidoo, Sudeshni; Malamud, Daniel

2011-01-01

Saliva may be a legal and ethical counterpart of other bodily fluids in diagnostic testing to blood and urine, with regard to its role in diagnostic testing. Two paradigms that have been proposed in the literature to address these challenges are reviewed in this paper. The first is centered on ownership and property rights to saliva, including financial compensation from commercially developed products using saliva. The commodification of saliva as property is also discussed. The second paradigm is related to privacy and the potential for genetic discrimination, given the unwarranted disclosure of confidential information. The management of saliva specimens from dental patients and research participants will also require the implementation of innovative approaches to obtain informed consent.

Accuracy of clinical neurological examination in diagnosing lumbo-sacral radiculopathy: a systematic literature review.

PubMed

Tawa, Nassib; Rhoda, Anthea; Diener, Ina

2017-02-23

Lumbar radiculopathy remains a clinical challenge among primary care clinicians in both assessment and diagnosis. This often leads to misdiagnosis and inappropriate treatment of patients resulting in poor health outcomes, exacerbating this already debilitating condition. This review evaluated 12 primary diagnostic accuracy studies that specifically assessed the performance of various individual and grouped clinical neurological tests in detecting nerve root impingement, as established in the current literature. Eight electronic data bases were searched for relevant articles from inception until July 2016. All primary diagnostic studies which investigated the accuracy of clinical neurological test (s) in diagnosing lumbar radiculopathy among patients with low back and referred leg symptoms were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the 'Quality Assessment of Diagnostic tests Accuracy Studies' criteria. A total of 12 studies which investigated standard components of clinical neurological examination of (sensory, motor, tendon reflex and neuro-dynamics) of the lumbo-sacral spine were included. The mean inter-observer agreement on quality assessment by two independent reviewers was fair (k = 0.3 - 0.7). The diagnostic performance of sensory testing using MR imaging as a reference standard demonstrated a sensitivity (confidence interval 95%) 0.61 (0.47-0.73) and a specificity of 0.63 (0.38-0.84). Motor tests sensitivity was poor to moderate, ranging from 0.13 (0.04-0.31) to 0.61 (0.36-0.83). Generally, the diagnostic performance of reflex testing was notably good with specificity ranging from (confidence interval 95%) 0.60 (0.51-0.69) to 0.93 (0.87-0.97) and sensitivity ranging from 0.14 (0.09-0.21) to 0.67 (0.21-0.94). Femoral nerve stretch test had a high sensitivity of (confidence interval 95%) 1.00 (0.40-1.00) and specificity of 0.83 (0.52-0.98) while SLR test recorded a mean sensitivity of 0.84 (0.72-0.92) and specificity of 0.78 (0.67-0.87). There is a scarcity of studies on the diagnostic accuracy of clinical neurological examination testing. Furthermore there seem to be a disconnect among researchers regarding the diagnostic utility of lower limb neuro-dynamic tests which include the Straight Leg Raise and Femoral Nerve tests for sciatic and femoral nerve respectively. Whether these tests are able to detect the presence of disc herniation and subsequent nerve root compression or hyper-sensitivity of the sacral and femoral plexus due to mechanical irritation still remains debatable.

Estimation of infection prevalence and sensitivity in a stratified two-stage sampling design employing highly specific diagnostic tests when there is no gold standard.

PubMed

Miller, Ezer; Huppert, Amit; Novikov, Ilya; Warburg, Alon; Hailu, Asrat; Abbasi, Ibrahim; Freedman, Laurence S

2015-11-10

In this work, we describe a two-stage sampling design to estimate the infection prevalence in a population. In the first stage, an imperfect diagnostic test was performed on a random sample of the population. In the second stage, a different imperfect test was performed in a stratified random sample of the first sample. To estimate infection prevalence, we assumed conditional independence between the diagnostic tests and develop method of moments estimators based on expectations of the proportions of people with positive and negative results on both tests that are functions of the tests' sensitivity, specificity, and the infection prevalence. A closed-form solution of the estimating equations was obtained assuming a specificity of 100% for both tests. We applied our method to estimate the infection prevalence of visceral leishmaniasis according to two quantitative polymerase chain reaction tests performed on blood samples taken from 4756 patients in northern Ethiopia. The sensitivities of the tests were also estimated, as well as the standard errors of all estimates, using a parametric bootstrap. We also examined the impact of departures from our assumptions of 100% specificity and conditional independence on the estimated prevalence. Copyright © 2015 John Wiley & Sons, Ltd.

A low cost, safe, disposable, rapid and self-sustainable paper-based platform for diagnostic testing: lab-on-paper.

PubMed

Costa, M N; Veigas, B; Jacob, J M; Santos, D S; Gomes, J; Baptista, P V; Martins, R; Inácio, J; Fortunato, E

2014-03-07

There is a strong interest in the use of biopolymers in the electronic and biomedical industries, mainly towards low-cost applications. The possibility of developing entirely new kinds of products based on cellulose is of current interest, in order to enhance and to add new functionalities to conventional paper-based products. We present our results towards the development of paper-based microfluidics for molecular diagnostic testing. Paper properties were evaluated and compared to nitrocellulose, the most commonly used material in lateral flow and other rapid tests. Focusing on the use of paper as a substrate for microfluidic applications, through an eco-friendly wax-printing technology, we present three main and distinct colorimetric approaches: (i) enzymatic reactions (glucose detection); (ii) immunoassays (antibodies anti-Leishmania detection); (iii) nucleic acid sequence identification (Mycobacterium tuberculosis complex detection). Colorimetric glucose quantification was achieved through enzymatic reactions performed within specific zones of the paper-based device. The colouration achieved increased with growing glucose concentration and was highly homogeneous, covering all the surface of the paper reaction zones in a 3D sensor format. These devices showed a major advantage when compared to the 2D lateral flow glucose sensors, where some carryover of the coloured products usually occurs. The detection of anti-Leishmania antibodies in canine sera was conceptually achieved using a paper-based 96-well enzyme-linked immunosorbent assay format. However, optimization is still needed for this test, regarding the efficiency of the immobilization of antigens on the cellulose fibres. The detection of Mycobacterium tuberculosis nucleic acids integrated with a non-cross-linking gold nanoprobe detection scheme was also achieved in a wax-printed 384-well paper-based microplate, by the hybridization with a species-specific probe. The obtained results with the above-mentioned proof-of-concept sensors are thus promising towards the future development of simple and cost-effective paper-based diagnostic devices.

A low cost, safe, disposable, rapid and self-sustainable paper-based platform for diagnostic testing: lab-on-paper

NASA Astrophysics Data System (ADS)

Costa, M. N.; Veigas, B.; Jacob, J. M.; Santos, D. S.; Gomes, J.; Baptista, P. V.; Martins, R.; Inácio, J.; Fortunato, E.

2014-03-01

There is a strong interest in the use of biopolymers in the electronic and biomedical industries, mainly towards low-cost applications. The possibility of developing entirely new kinds of products based on cellulose is of current interest, in order to enhance and to add new functionalities to conventional paper-based products. We present our results towards the development of paper-based microfluidics for molecular diagnostic testing. Paper properties were evaluated and compared to nitrocellulose, the most commonly used material in lateral flow and other rapid tests. Focusing on the use of paper as a substrate for microfluidic applications, through an eco-friendly wax-printing technology, we present three main and distinct colorimetric approaches: (i) enzymatic reactions (glucose detection); (ii) immunoassays (antibodies anti-Leishmania detection); (iii) nucleic acid sequence identification (Mycobacterium tuberculosis complex detection). Colorimetric glucose quantification was achieved through enzymatic reactions performed within specific zones of the paper-based device. The colouration achieved increased with growing glucose concentration and was highly homogeneous, covering all the surface of the paper reaction zones in a 3D sensor format. These devices showed a major advantage when compared to the 2D lateral flow glucose sensors, where some carryover of the coloured products usually occurs. The detection of anti-Leishmania antibodies in canine sera was conceptually achieved using a paper-based 96-well enzyme-linked immunosorbent assay format. However, optimization is still needed for this test, regarding the efficiency of the immobilization of antigens on the cellulose fibres. The detection of Mycobacterium tuberculosis nucleic acids integrated with a non-cross-linking gold nanoprobe detection scheme was also achieved in a wax-printed 384-well paper-based microplate, by the hybridization with a species-specific probe. The obtained results with the above-mentioned proof-of-concept sensors are thus promising towards the future development of simple and cost-effective paper-based diagnostic devices.

Current practice in laboratory diagnostics of autoimmune diseases in Croatia. 
Survey of the Working group for laboratory diagnostics of autoimmune diseases of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

PubMed

Kuna, Andrea Tešija; Đerek, Lovorka; Kozmar, Ana; Drvar, Vedrana

2016-10-15

With the trend of increasing incidence of autoimmune diseases, laboratories are faced with exponential growth of the requests for tests relating the diagnosis of these diseases. Unfortunately, the lack of laboratory personnel experienced in this specific discipline of laboratory diagnostic, as well as an unawareness of a method limitation often results in confusion for clinicians. The aim was to gain insight into number and type of Croatian laboratories that perform humoral diagnostics with the final goal to improve and harmonize laboratory diagnostics of autoimmune diseases in Croatia. In order to get insight into current laboratory practice two questionnaires, consisting of 42 questions in total, were created. Surveys were conducted using SurveyMonkey application and were sent to 88 medical biochemistry laboratories in Croatia for the first survey. Out of 33 laboratories that declared to perform diagnostic from the scope, 19 were selected for the second survey based on the tests they pleaded to perform. The survey comprised questions regarding autoantibody hallmarks of systemic autoimmune diseases while regarding organ-specific autoimmune diseases was limited to diseases of liver, gastrointestinal and nervous system. Response rate was high with 80 / 88 (91%) laboratories which answered the first questionnaire, and 19 / 19 (1.0) for the second questionnaire. Obtained results of surveys indicate high heterogeneity in the performance of autoantibody testing among laboratories in Croatia. Results indicate the need of creating recommendations and algorithms in order to harmonize the approach to laboratory diagnostics of autoimmune diseases in Croatia.

Comparing diagnostic tests on benefit-risk.

PubMed

Pennello, Gene; Pantoja-Galicia, Norberto; Evans, Scott

2016-01-01

Comparing diagnostic tests on accuracy alone can be inconclusive. For example, a test may have better sensitivity than another test yet worse specificity. Comparing tests on benefit risk may be more conclusive because clinical consequences of diagnostic error are considered. For benefit-risk evaluation, we propose diagnostic yield, the expected distribution of subjects with true positive, false positive, true negative, and false negative test results in a hypothetical population. We construct a table of diagnostic yield that includes the number of false positive subjects experiencing adverse consequences from unnecessary work-up. We then develop a decision theory for evaluating tests. The theory provides additional interpretation to quantities in the diagnostic yield table. It also indicates that the expected utility of a test relative to a perfect test is a weighted accuracy measure, the average of sensitivity and specificity weighted for prevalence and relative importance of false positive and false negative testing errors, also interpretable as the cost-benefit ratio of treating non-diseased and diseased subjects. We propose plots of diagnostic yield, weighted accuracy, and relative net benefit of tests as functions of prevalence or cost-benefit ratio. Concepts are illustrated with hypothetical screening tests for colorectal cancer with test positive subjects being referred to colonoscopy.

Quality Assurance Assessment of Diagnostic and Radiation Therapy–Simulation CT Image Registration for Head and Neck Radiation Therapy: Anatomic Region of Interest–based Comparison of Rigid and Deformable Algorithms

PubMed Central

Mohamed, Abdallah S. R.; Ruangskul, Manee-Naad; Awan, Musaddiq J.; Baron, Charles A.; Kalpathy-Cramer, Jayashree; Castillo, Richard; Castillo, Edward; Guerrero, Thomas M.; Kocak-Uzel, Esengul; Yang, Jinzhong; Court, Laurence E.; Kantor, Michael E.; Gunn, G. Brandon; Colen, Rivka R.; Frank, Steven J.; Garden, Adam S.; Rosenthal, David I.

2015-01-01

Purpose To develop a quality assurance (QA) workflow by using a robust, curated, manually segmented anatomic region-of-interest (ROI) library as a benchmark for quantitative assessment of different image registration techniques used for head and neck radiation therapy–simulation computed tomography (CT) with diagnostic CT coregistration. Materials and Methods Radiation therapy–simulation CT images and diagnostic CT images in 20 patients with head and neck squamous cell carcinoma treated with curative-intent intensity-modulated radiation therapy between August 2011 and May 2012 were retrospectively retrieved with institutional review board approval. Sixty-eight reference anatomic ROIs with gross tumor and nodal targets were then manually contoured on images from each examination. Diagnostic CT images were registered with simulation CT images rigidly and by using four deformable image registration (DIR) algorithms: atlas based, B-spline, demons, and optical flow. The resultant deformed ROIs were compared with manually contoured reference ROIs by using similarity coefficient metrics (ie, Dice similarity coefficient) and surface distance metrics (ie, 95% maximum Hausdorff distance). The nonparametric Steel test with control was used to compare different DIR algorithms with rigid image registration (RIR) by using the post hoc Wilcoxon signed-rank test for stratified metric comparison. Results A total of 2720 anatomic and 50 tumor and nodal ROIs were delineated. All DIR algorithms showed improved performance over RIR for anatomic and target ROI conformance, as shown for most comparison metrics (Steel test, P < .008 after Bonferroni correction). The performance of different algorithms varied substantially with stratification by specific anatomic structures or category and simulation CT section thickness. Conclusion Development of a formal ROI-based QA workflow for registration assessment demonstrated improved performance with DIR techniques over RIR. After QA, DIR implementation should be the standard for head and neck diagnostic CT and simulation CT allineation, especially for target delineation. © RSNA, 2014 Online supplemental material is available for this article. PMID:25380454

Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

PubMed Central

Parkash, Om; Hanim Shueb, Rafidah

2015-01-01

Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed. PMID:26492265

Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants

PubMed Central

Metzgar, David; Myers, Christopher A.; Russell, Kevin L.; Faix, Dennis; Blair, Patrick J.; Brown, Jason; Vo, Scott; Swayne, David E.; Thomas, Colleen; Stenger, David A.; Lin, Baochuan; Malanoski, Anthony P.; Wang, Zheng; Blaney, Kate M.; Long, Nina C.; Schnur, Joel M.; Saad, Magdi D.; Borsuk, Lisa A.; Lichanska, Agnieszka M.; Lorence, Matthew C.; Weslowski, Brian; Schafer, Klaus O.; Tibbetts, Clark

2010-01-01

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents. PMID:20140251

Single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.

PubMed

Metzgar, David; Myers, Christopher A; Russell, Kevin L; Faix, Dennis; Blair, Patrick J; Brown, Jason; Vo, Scott; Swayne, David E; Thomas, Colleen; Stenger, David A; Lin, Baochuan; Malanoski, Anthony P; Wang, Zheng; Blaney, Kate M; Long, Nina C; Schnur, Joel M; Saad, Magdi D; Borsuk, Lisa A; Lichanska, Agnieszka M; Lorence, Matthew C; Weslowski, Brian; Schafer, Klaus O; Tibbetts, Clark

2010-02-03

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.

Study on validity of a rapid diagnostic test kit versus light microscopy for malaria diagnosis in Ahmedabad city, India.

PubMed

Vyas, S; Puwar, B; Patel, V; Bhatt, G; Kulkarni, S; Fancy, M

2014-05-01

Light microscopy of blood smears for diagnosis of malaria in the field has several limitations, notably delays in diagnosis. This study in Ahmedabad in Gujarat State, India, evaluated the diagnostic performance of a rapid diagnostic test for malaria (SD Bioline Malaria Ag P.f/Pan) versus blood smear examination as the gold standard. All fever cases presenting at 13 urban health centres were subjected to rapid diagnostic testing and thick and thin blood smears. A total of 677 cases with fever were examined; 135 (20.0%) tested positive by rapid diagnostic test and 86 (12.7%) by blood smear. The sensitivity of the rapid diagnostic test for malaria was 98.8%, specificity was 91.5%, positive predictive value 63.0% and negative predictive value 99.8%. For detection of Plasmodium falciparum the sensitivity of rapid diagnostic test was 100% and specificity was 97.3%. The results show the acceptability of the rapid test as an alternative to light microscopy in the field setting.

Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics

PubMed Central

Jiang, Li; Mancuso, Matthew; Lu, Zhengda; Akar, Gunkut; Cesarman, Ethel; Erickson, David

2014-01-01

Nucleic acid-based diagnostic techniques such as polymerase chain reaction (PCR) are used extensively in medical diagnostics due to their high sensitivity, specificity and quantification capability. In settings with limited infrastructure and unreliable electricity, however, access to such devices is often limited due to the highly specialized and energy-intensive nature of the thermal cycling process required for nucleic acid amplification. Here we integrate solar heating with microfluidics to eliminate thermal cycling power requirements as well as create a simple device infrastructure for PCR. Tests are completed in less than 30 min, and power consumption is reduced to 80 mW, enabling a standard 5.5 Wh iPhone battery to provide 70 h of power to this system. Additionally, we demonstrate a complete sample-to-answer diagnostic strategy by analyzing human skin biopsies infected with Kaposi's Sarcoma herpesvirus (KSHV/HHV-8) through the combination of solar thermal PCR, HotSHOT DNA extraction and smartphone-based fluorescence detection. We believe that exploiting the ubiquity of solar thermal energy as demonstrated here could facilitate broad availability of nucleic acid-based diagnostics in resource-limited areas. PMID:24553130

Intelligent Condition Diagnosis Method Based on Adaptive Statistic Test Filter and Diagnostic Bayesian Network

PubMed Central

Li, Ke; Zhang, Qiuju; Wang, Kun; Chen, Peng; Wang, Huaqing

2016-01-01

A new fault diagnosis method for rotating machinery based on adaptive statistic test filter (ASTF) and Diagnostic Bayesian Network (DBN) is presented in this paper. ASTF is proposed to obtain weak fault features under background noise, ASTF is based on statistic hypothesis testing in the frequency domain to evaluate similarity between reference signal (noise signal) and original signal, and remove the component of high similarity. The optimal level of significance α is obtained using particle swarm optimization (PSO). To evaluate the performance of the ASTF, evaluation factor Ipq is also defined. In addition, a simulation experiment is designed to verify the effectiveness and robustness of ASTF. A sensitive evaluation method using principal component analysis (PCA) is proposed to evaluate the sensitiveness of symptom parameters (SPs) for condition diagnosis. By this way, the good SPs that have high sensitiveness for condition diagnosis can be selected. A three-layer DBN is developed to identify condition of rotation machinery based on the Bayesian Belief Network (BBN) theory. Condition diagnosis experiment for rolling element bearings demonstrates the effectiveness of the proposed method. PMID:26761006

Intelligent Condition Diagnosis Method Based on Adaptive Statistic Test Filter and Diagnostic Bayesian Network.

PubMed

Li, Ke; Zhang, Qiuju; Wang, Kun; Chen, Peng; Wang, Huaqing

2016-01-08

A new fault diagnosis method for rotating machinery based on adaptive statistic test filter (ASTF) and Diagnostic Bayesian Network (DBN) is presented in this paper. ASTF is proposed to obtain weak fault features under background noise, ASTF is based on statistic hypothesis testing in the frequency domain to evaluate similarity between reference signal (noise signal) and original signal, and remove the component of high similarity. The optimal level of significance α is obtained using particle swarm optimization (PSO). To evaluate the performance of the ASTF, evaluation factor Ipq is also defined. In addition, a simulation experiment is designed to verify the effectiveness and robustness of ASTF. A sensitive evaluation method using principal component analysis (PCA) is proposed to evaluate the sensitiveness of symptom parameters (SPs) for condition diagnosis. By this way, the good SPs that have high sensitiveness for condition diagnosis can be selected. A three-layer DBN is developed to identify condition of rotation machinery based on the Bayesian Belief Network (BBN) theory. Condition diagnosis experiment for rolling element bearings demonstrates the effectiveness of the proposed method.

Development of Two-Tier Diagnostic Test Pictorial-Based for Identifying High School Students Misconceptions on the Mole Concept

NASA Astrophysics Data System (ADS)

Siswaningsih, W.; Firman, H.; Zackiyah; Khoirunnisa, A.

2017-02-01

The aim of this study was to develop the two-tier pictorial-based diagnostic test for identifying student misconceptions on mole concept. The method of this study is used development and validation. The development of the test Obtained through four phases, development of any items, validation, determination key, and application test. Test was developed in the form of pictorial consisting of two tier, the first tier Consist of four possible answers and the second tier Consist of four possible reasons. Based on the results of content validity of 20 items using the CVR (Content Validity Ratio), a number of 18 items declared valid. Based on the results of the reliability test using SPSS, Obtained 17 items with Cronbach’s Alpha value of 0703, the which means that items have accepted. A total of 10 items was conducted to 35 students of senior high school students who have studied the mole concept on one of the high schools in Cimahi. Based on the results of the application test, student misconceptions were identified in each label concept in mole concept with the percentage of misconceptions on the label concept of mole (60.15%), Avogadro’s number (34.28%), relative atomic mass (62, 84%), relative molecule mass (77.08%), molar mass (68.53%), molar volume of gas (57.11%), molarity (71.32%), chemical equation (82.77%), limiting reactants (91.40%), and molecular formula (77.13%).

The 2016 Academic Emergency Medicine Consensus Conference, "Shared Decision Making in the Emergency Department: Development of a Policy-relevant Patient-centered Research Agenda" Diagnostic Testing Breakout Session Report.

PubMed

Barrett, Tyler W; Rising, Kristin L; Bellolio, M Fernanda; Hall, M Kennedy; Brody, Aaron; Dodd, Kenneth W; Grieser, Mira; Levy, Phillip D; Raja, Ali S; Self, Wesley H; Weingarten, Gail; Hess, Erik P; Hollander, Judd E

2016-12-01

Diagnostic testing is an integral component of patient evaluation in the emergency department (ED). Emergency clinicians frequently use diagnostic testing to more confidently exclude "worst-case" diagnoses rather than to determine the most likely etiology for a presenting complaint. Increased utilization of diagnostic testing has not been associated with reductions in disease-related mortality but has led to increased overall healthcare costs and other unintended consequences (e.g., incidental findings requiring further workup, unnecessary exposure to ionizing radiation or potentially nephrotoxic contrast). Shared decision making (SDM) presents an opportunity for clinicians to discuss the benefits and harms associated with diagnostic testing with patients to more closely tailor testing to patient risk. This article introduces the challenges and opportunities associated with incorporating SDM into emergency care by summarizing the conclusions of the diagnostic testing group at the 2016 Academic Emergency Medicine Consensus Conference on SDM. Three primary domains emerged: 1) characteristics of a condition or test appropriate for SDM, 2) critical elements of and potential barriers to SDM discussions on diagnostic testing, and 3) financial aspects of SDM applied to diagnostic testing. The most critical research questions to improve engagement of patients in their acute care diagnostic decisions were determined by consensus. © 2016 by the Society for Academic Emergency Medicine.

Pre- and post-test genetic counseling for chromosomal and Mendelian disorders.

PubMed

Fonda Allen, Jill; Stoll, Katie; Bernhardt, Barbara A

2016-02-01

Genetic carrier screening, prenatal screening for aneuploidy, and prenatal diagnostic testing have expanded dramatically over the past 2 decades. Driven in part by powerful market forces, new complex testing modalities have become available after limited clinical research. The responsibility for offering these tests lies primarily on the obstetrical care provider and has become more burdensome as the number of testing options expands. Genetic testing in pregnancy is optional, and decisions about undergoing tests, as well as follow-up testing, should be informed and based on individual patients' values and needs. Careful pre- and post-test counseling is central to supporting informed decision-making. This article explores three areas of technical expansion in genetic testing: expanded carrier screening, non-invasive prenatal screening for fetal aneuploidies using cell-free DNA, and diagnostic testing using fetal chromosomal microarray testing, and provides insights aimed at enabling the obstetrical practitioner to better support patients considering these tests. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT).

PubMed

Lee, Adria D; Cassiday, Pamela K; Pawloski, Lucia C; Tatti, Kathleen M; Martin, Monte D; Briere, Elizabeth C; Tondella, M Lucia; Martin, Stacey W

2018-01-01

The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2-4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods-pertussis culture as the "gold standard," composite reference standard analysis (CRS), and latent class analysis (LCA). Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics

PubMed Central

Bianchi, Paola; Fermo, Elisa; Vercellati, Cristina; Marcello, Anna P.; Porretti, Laura; Cortelezzi, Agostino; Barcellini, Wilma; Zanella, Alberto

2012-01-01

Background The laboratory diagnosis of hereditary spherocytosis commonly relies on NaCl-based or glycerol-based red cell osmotic fragility tests; more recently, an assay directly targeting the hereditary spherocytosis molecular defect (eosin-5′-maleimide-binding test) has been proposed. None of the available tests identifies all cases of hereditary spherocytosis. Design and Methods We compared the performances of the eosin-5′-maleimide-binding test, NaCl-osmotic fragility studies on fresh and incubated blood, the glycerol lysis test, the acidified glycerol lysis test, and the Pink test on a series of 150 patients with hereditary spherocytosis grouped according to clinical phenotype and the defective protein, with the final aim of finding the combination of tests associated with the highest diagnostic power, even in the mildest cases of hereditary spherocytosis. Results The eosin-5′-maleimide-binding test had a sensitivity of 93% and a specificity of 98% for detecting hereditary spherocytosis: the sensitivity was independent of the type and amount of molecular defect and of the clinical phenotype. The acidified glycerol lysis test and Pink test showed comparable sensitivity (95% and 91%). The sensitivity of NaCl osmotic fragility tests, commonly considered the gold standard for the diagnosis of hereditary spherocytosis, was 68% on fresh blood and 81% on incubated blood, and further decreased in compensated cases (53% and 64%, respectively). The combination of the eosin-5′-maleimide-binding test and acidified glycerol lysis test enabled all patients with hereditary spherocytosis to be identified. The eosin-5′-maleimide-binding test showed the greatest disease specificity. Conclusions Each type of test fails to diagnose some cases of hereditary spherocytosis. The association of an eosin-5′-maleimide-binding test and an acidified glycerol lysis test enabled identification of all patients with hereditary spherocytosis in this series and, therefore, represents a currently effective diagnostic strategy for hereditary spherocytosis including mild/compensated cases. PMID:22058213

Risk, Benefit, and Cost Thresholds for Emergency Department Testing: A Cross-sectional, Scenario-based Study.

PubMed

Meka, Arjun Prasad; Porath, Jonathan Douglas; Iyengar, Rahul; Morrow, Chelsea; Fagerlin, Angela; Meurer, William J

2017-06-01

While diagnostic testing is common in the emergency department, the value of some testing is questionable. The purpose of this study was to assess how varying levels of benefit, risk, and costs influenced an individual's desire to have diagnostic testing. A survey through Amazon Mechanical Turk presented hypothetical clinical situations: low-risk chest pain and minor traumatic brain injury. Each scenario included three given variables (benefit, risk, and cost), that was independently randomly varied over four possible values (0.1, 1, 5, and 10% for benefit and risk and $0, $100, $500, and $1,000 for the individual's personal cost for receiving the test). Benefit was defined as the probability of finding the target disease (traumatic intracranial hemorrhage or acute coronary syndrome). One-thousand unique respondents completed the survey. With an increased benefit from 0.1% to 10%, the percentage of respondents who accepted a diagnostic test went from 28.4% to 53.1%. (odds ratio [OR] = 3.42; 95% confidence interval [CI] = 2.57-4.54). As risk increased from 0.1% to 10%, this number decreased from 52.5% to 28.5%. (OR = 0.33; 95% CI = 0.25-0.44). Increasing cost from $0 to $1,000 had the greatest change of those accepting the test from 61.1% to 21.4%, respectively (OR = 0.15; 95% CI = 0.11-0.2). The desire for testing was strongly sensitive to the benefits, risks, and costs. Many participants wanted a test when there was no added cost, regardless of benefit or risk levels, but far fewer elected to receive the test as cost increased incrementally. This suggests that out-of-pocket costs may deter patients from undergoing diagnostic testing with low potential benefit. © 2016 by the Society for Academic Emergency Medicine.

Accuracy of the radioactive copper incorporation test in the diagnosis of Wilson disease.

PubMed

Członkowska, Anna; Rodo, Maria; Wierzchowska-Ciok, Agata; Smolinski, Lukasz; Litwin, Tomasz

2018-02-08

In Wilson disease (WD), copper accumulates in the liver and other tissues because of mutations in the ATP7B copper transporter gene. Early and effective anticopper treatment is crucial. However, routine diagnostic methods based on clinical findings, copper metabolism tests, liver biopsies and DNA analyses do not always provide a conclusive diagnosis. The aim was to evaluate radioactive copper incorporation as a diagnostic test. We included cases with a diagnosis of WD supported by radiocopper testing and later, when available, confirmed by DNA analysis. Incorporation of 64 Cu was measured at 2, 24 and 48 hours following intravenous injection. Diagnostic accuracy (area under the receiver operating characteristic curve [AUC]), sensitivity, specificity and predictive value were assessed for 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios and compared with serum measurements of ceruloplasmin, copper, non-ceruloplasmin-bound copper and urinary 24-hours copper excretion. Patients having two pathogenic ATP7B mutations (homozygotes/compound heterozygotes) (n = 74) had significantly lower 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios than heterozygote controls (n = 21) (mean 0.14 and 0.12 vs 0.49 and 0.63, respectively; both P < .001). Of note, 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios had excellent diagnostic accuracy, with AUCs approaching 1, and only 24-hours urinary copper excretion displayed similar positive features. Other copper metabolism tests studied had lower accuracy, specificity and sensitivity. The radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring ATP7B function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

20 CFR 416.919m - Diagnostic tests or procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Diagnostic tests or procedures. 416.919m... for Report Content § 416.919m Diagnostic tests or procedures. We will request the results of any diagnostic tests or procedures that have been performed as part of a workup by your treating source or other...

Qualitative and quantitative detection of T7 bacteriophages using paper based sandwich ELISA.

PubMed

Khan, Mohidus Samad; Pande, Tripti; van de Ven, Theo G M

2015-08-01

Viruses cause many infectious diseases and consequently epidemic health threats. Paper based diagnostics and filters can offer attractive options for detecting and deactivating pathogens. However, due to their infectious characteristics, virus detection using paper diagnostics is more challenging compared to the detection of bacteria, enzymes, DNA or antigens. The major objective of this study was to prepare reliable, degradable and low cost paper diagnostics to detect viruses, without using sophisticated optical or microfluidic analytical instruments. T7 bacteriophage was used as a model virus. A paper based sandwich ELISA technique was developed to detect and quantify the T7 phages in solution. The paper based sandwich ELISA detected T7 phage concentrations as low as 100 pfu/mL to as high as 10(9) pfu/mL. The compatibility of paper based sandwich ELISA with the conventional titre count was tested using T7 phage solutions of unknown concentrations. The paper based sandwich ELISA technique is faster and economical compared to the traditional detection techniques. Therefore, with proper calibration and right reagents, and by following the biosafety regulations, the paper based technique can be said to be compatible and economical to the sophisticated laboratory diagnostic techniques applied to detect pathogenic viruses and other microorganisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid diagnosis of tinea incognito using handheld reflectance confocal microscopy: a paradigm shift in dermatology?

PubMed

Navarrete-Dechent, Cristián; Bajaj, Shirin; Marghoob, Ashfaq A; Marchetti, Michael A

2015-06-01

Dermatophytoses are common skin infections. Traditional diagnostic tests such as skin scrapings for light microscopy examination, fungal cultures and biopsies remain imperfect due to false-negative test results, cost, time required to perform the procedure, time delays in test results and/or a requirement for an invasive procedure. Herein, we present a case of an 80-year-old female whose tinea incognito was non-invasively diagnosed within seconds using handheld reflectance confocal microscopy (RCM). As non-invasive skin imaging continues to improve, we expect light-based office microscopy to be replaced with technologies such as RCM, which has multiple and continually expanding diagnostic applications. © 2015 Blackwell Verlag GmbH.

Fan fault diagnosis based on symmetrized dot pattern analysis and image matching

NASA Astrophysics Data System (ADS)

Xu, Xiaogang; Liu, Haixiao; Zhu, Hao; Wang, Songling

2016-07-01

To detect the mechanical failure of fans, a new diagnostic method based on the symmetrized dot pattern (SDP) analysis and image matching is proposed. Vibration signals of 13 kinds of running states are acquired on a centrifugal fan test bed and reconstructed by the SDP technique. The SDP pattern templates of each running state are established. An image matching method is performed to diagnose the fault. In order to improve the diagnostic accuracy, the single template, multiple templates and clustering fault templates are used to perform the image matching.

Rolling bearing fault diagnosis based on information fusion using Dempster-Shafer evidence theory

NASA Astrophysics Data System (ADS)

Pei, Di; Yue, Jianhai; Jiao, Jing

2017-10-01

This paper presents a fault diagnosis method for rolling bearing based on information fusion. Acceleration sensors are arranged at different position to get bearing vibration data as diagnostic evidence. The Dempster-Shafer (D-S) evidence theory is used to fuse multi-sensor data to improve diagnostic accuracy. The efficiency of the proposed method is demonstrated by the high speed train transmission test bench. The results of experiment show that the proposed method in this paper improves the rolling bearing fault diagnosis accuracy compared with traditional signal analysis methods.

Assessing the value-adding impact of diagnostic-type tests on drug development and marketing.

PubMed

Blair, Edward D

2008-01-01

We explore the cash value of the companion diagnostics opportunity from the perspective of the pharmaceutical partner. Cashflow-based modeling is used to demonstrate the potential financial benefits of key relationships between the pharmaceutical and diagnostics industries. In four scenarios, the uplift in the net present value (NPV) of a proprietary medicine can exceed $US1.8 billion. By simple extrapolation, the uplifted NPV calculations allow realistic and plausible estimates of the companion diagnostic opportunity to be in the region of $US40 billion to $US90 billion. It is expected that such market valuation could drive a macroeconomic change that shifts healthcare practice from reactionary disease-treatment to proactive health maintenance.

Is there a role for antibody testing in the diagnosis of invasive candidiasis?

PubMed

Quindós, Guillermo; Moragues, María Dolores; Pontón, José

2004-03-01

During the last decades, the use of antibody tests for the diagnosis of invasive mycoses has declined as a consequence of the general belief that they are insensitive and non-specific. However, there is a clear evidence that antibodies can be detected in highly immunodeficient patients (such as bone marrow transplant recipients), and that those antibodies are useful for the diagnosis. Antibody tests are currently in use as diagnostic tools for some primary mycoses, such as the endemic mycoses, aspergilloma, allergic bronchopulmonary aspergilosis and sporothrichosis. For invasive candidiasis, diagnostic methods must differentiate Candida colonization of mucous membranes or superficial infection from tissue invasion by this microorganism. Substantial progress has been made in diagnosis of invasive candidiasis with the development of a variety of methods for the detection of antibodies and antigens. However, no single test has found widespread clinical use and there is a consensus that diagnosis based on a single specimen lacks sensitivity. It is necessary to test sequential samples taken while the patient is at greatest risk for developing invasive candidiasis to optimize the diagnosis. Results obtained from a panel of diagnostic tests in association with clinical aspects will likely be the most useful strategy for early diagnosis and therapy.

A general diagnostic model applied to language testing data.

PubMed

von Davier, Matthias

2008-11-01

Probabilistic models with one or more latent variables are designed to report on a corresponding number of skills or cognitive attributes. Multidimensional skill profiles offer additional information beyond what a single test score can provide, if the reported skills can be identified and distinguished reliably. Many recent approaches to skill profile models are limited to dichotomous data and have made use of computationally intensive estimation methods such as Markov chain Monte Carlo, since standard maximum likelihood (ML) estimation techniques were deemed infeasible. This paper presents a general diagnostic model (GDM) that can be estimated with standard ML techniques and applies to polytomous response variables as well as to skills with two or more proficiency levels. The paper uses one member of a larger class of diagnostic models, a compensatory diagnostic model for dichotomous and partial credit data. Many well-known models, such as univariate and multivariate versions of the Rasch model and the two-parameter logistic item response theory model, the generalized partial credit model, as well as a variety of skill profile models, are special cases of this GDM. In addition to an introduction to this model, the paper presents a parameter recovery study using simulated data and an application to real data from the field test for TOEFL Internet-based testing.

Inverse probability weighting estimation of the volume under the ROC surface in the presence of verification bias.

PubMed

Zhang, Ying; Alonzo, Todd A

2016-11-01

In diagnostic medicine, the volume under the receiver operating characteristic (ROC) surface (VUS) is a commonly used index to quantify the ability of a continuous diagnostic test to discriminate between three disease states. In practice, verification of the true disease status may be performed only for a subset of subjects under study since the verification procedure is invasive, risky, or expensive. The selection for disease examination might depend on the results of the diagnostic test and other clinical characteristics of the patients, which in turn can cause bias in estimates of the VUS. This bias is referred to as verification bias. Existing verification bias correction in three-way ROC analysis focuses on ordinal tests. We propose verification bias-correction methods to construct ROC surface and estimate the VUS for a continuous diagnostic test, based on inverse probability weighting. By applying U-statistics theory, we develop asymptotic properties for the estimator. A Jackknife estimator of variance is also derived. Extensive simulation studies are performed to evaluate the performance of the new estimators in terms of bias correction and variance. The proposed methods are used to assess the ability of a biomarker to accurately identify stages of Alzheimer's disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasmodium glyceraldehyde-3-phosphate dehydrogenase: A potential malaria diagnostic target.

PubMed

Krause, Robert G E; Hurdayal, Ramona; Choveaux, David; Przyborski, Jude M; Coetzer, Theresa H T; Goldring, J P Dean

2017-08-01

Malaria rapid diagnostic tests (RDTs) are immunochromatographic tests detecting Plasmodial histidine-rich protein 2 (HRP2), lactate dehydrogenase (LDH) and aldolase. HRP2 is only expressed by Plasmodium falciparum parasites and the protein is not expressed in several geographic isolates. LDH-based tests lack sensitivity compared to HRP2 tests. This study explored the potential of the Plasmodial glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as a new malaria diagnostic biomarker. The P. falciparum and P. yoelii proteins were recombinantly expressed in BL21(DE3) Escherischia coli host cells and affinity purified. Two epitopes (CADGFLLIGEKKVSVFA and CAEKDPSQIPWGKCQV) specific to P. falciparum GAPDH and one common to all mammalian malaria species (CKDDTPIYVMGINH) were identified. Antibodies were raised in chickens against the two recombinant proteins and the three epitopes and affinity purified. The antibodies detected the native protein in parasite lysates as a 38 kDa protein and immunofluorescence verified a parasite cytosolic localization for the native protein. The antibodies suggested a 4-6 fold higher concentration of native PfGAPDH compared to PfLDH in immunoprecipitation and ELISA formats, consistent with published proteomic data. PfGAPDH shows interesting potential as a malaria diagnostic biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

The ITER Neutral Beam Test Facility towards SPIDER operation

NASA Astrophysics Data System (ADS)

Toigo, V.; Dal Bello, S.; Gaio, E.; Luchetta, A.; Pasqualotto, R.; Zaccaria, P.; Bigi, M.; Chitarin, G.; Marcuzzi, D.; Pomaro, N.; Serianni, G.; Agostinetti, P.; Agostini, M.; Antoni, V.; Aprile, D.; Baltador, C.; Barbisan, M.; Battistella, M.; Boldrin, M.; Brombin, M.; Dalla Palma, M.; De Lorenzi, A.; Delogu, R.; De Muri, M.; Fellin, F.; Ferro, A.; Gambetta, G.; Grando, L.; Jain, P.; Maistrello, A.; Manduchi, G.; Marconato, N.; Pavei, M.; Peruzzo, S.; Pilan, N.; Pimazzoni, A.; Piovan, R.; Recchia, M.; Rizzolo, A.; Sartori, E.; Siragusa, M.; Spada, E.; Spagnolo, S.; Spolaore, M.; Taliercio, C.; Valente, M.; Veltri, P.; Zamengo, A.; Zaniol, B.; Zanotto, L.; Zaupa, M.; Boilson, D.; Graceffa, J.; Svensson, L.; Schunke, B.; Decamps, H.; Urbani, M.; Kushwah, M.; Chareyre, J.; Singh, M.; Bonicelli, T.; Agarici, G.; Garbuglia, A.; Masiello, A.; Paolucci, F.; Simon, M.; Bailly-Maitre, L.; Bragulat, E.; Gomez, G.; Gutierrez, D.; Mico, G.; Moreno, J.-F.; Pilard, V.; Chakraborty, A.; Baruah, U.; Rotti, C.; Patel, H.; Nagaraju, M. V.; Singh, N. P.; Patel, A.; Dhola, H.; Raval, B.; Fantz, U.; Fröschle, M.; Heinemann, B.; Kraus, W.; Nocentini, R.; Riedl, R.; Schiesko, L.; Wimmer, C.; Wünderlich, D.; Cavenago, M.; Croci, G.; Gorini, G.; Rebai, M.; Muraro, A.; Tardocchi, M.; Hemsworth, R.

2017-08-01

SPIDER is one of two projects of the ITER Neutral Beam Test Facility under construction in Padova, Italy, at the Consorzio RFX premises. It will have a 100 keV beam source with a full-size prototype of the radiofrequency ion source for the ITER neutral beam injector (NBI) and also, similar to the ITER diagnostic neutral beam, it is designed to operate with a pulse length of up to 3600 s, featuring an ITER-like magnetic filter field configuration (for high extraction of negative ions) and caesium oven (for high production of negative ions) layout as well as a wide set of diagnostics. These features will allow a reproduction of the ion source operation in ITER, which cannot be done in any other existing test facility. SPIDER realization is well advanced and the first operation is expected at the beginning of 2018, with the mission of achieving the ITER heating and diagnostic NBI ion source requirements and of improving its performance in terms of reliability and availability. This paper mainly focuses on the preparation of the first SPIDER operations—integration and testing of SPIDER components, completion and implementation of diagnostics and control and formulation of operation and research plan, based on a staged strategy.

Development and evaluation of a Loop Mediated Isothermal Amplification (LAMP) technique for the detection of hookworm (Necator americanus) infection in fecal samples.

PubMed

Mugambi, Robert Muriuki; Agola, Eric L; Mwangi, Ibrahim N; Kinyua, Johnson; Shiraho, Esther Andia; Mkoji, Gerald M

2015-11-06

Hookworm infection is a major concern in sub-Saharan Africa, particularly in children and pregnant women. Necator americanus and Ancylostoma duodenale are responsible for this condition. Hookworm disease is one of the Neglected tropical diseases (NTDs) that are targeted for elimination through global mass chemotherapy. To support this there is a need for reliable diagnostic tools. The conventional diagnostic test, Kato-Katz that is based on microscopic detection of parasite ova in faecal samples, is not effective due to its low sensitivity that is brought about mainly by non-random distribution of eggs in stool and day to day variation in egg output. It is tedious, cumbersome to perform and requires experience for correct diagnosis. LAMP-based tests are simple, relatively cheap, offer greater sensitivity, specificity than existing tests, have high throughput capability, and are ideal for use at the point of care. We have developed a LAMP diagnostic test for detection of hookworm infection in faecal samples. LAMP relies on auto cycling strand displacement DNA synthesis performed at isothermal temperature by Bst polymerase and a set of 4 specific primers. The primers used in the LAMP assay were based on the second Internal Transcribed Spacer (ITS-2) region and designed using Primer Explorer version 4 Software. The ITS-2 region of the ribosomal gene (rDNA) was identified as a suitable target due to its low mutation rates and substantial differences between species. DNA was extracted directly from human faecal samples, followed by LAMP amplification at isothermal temperature of 63 °C for 1 h. Amplicons were visualized using gel electrophoresis and SYBR green dye. Both specificity and sensitivity of the assay were determined. The LAMP based technique developed was able to detect N. americanus DNA in faecal samples. The assay showed 100 % specificity and no cross-reaction was observed with other helminth parasites (S. mansoni, A. lumbricoides or T. trichiura). The developed LAMP assay was 97 % sensitive and DNA at concentrations as low as 0.4 fg were amplified. The LAMP assay developed is an appropriate diagnostic method for the detection of N. americanus DNA in human stool samples because of its simplicity, low cost, sensitivity, and specificity. It holds great promise as a useful diagnostic tool for use in disease control where infection intensities have been significantly reduced.

Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis.

PubMed

Shirahata, Mitsuaki; Iwao-Koizumi, Kyoko; Saito, Sakae; Ueno, Noriko; Oda, Masashi; Hashimoto, Nobuo; Takahashi, Jun A; Kato, Kikuya

2007-12-15

Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

Carpal tunnel syndrome: Investigating the sensitivity of initial-diagnosis with electro-diagnostic tests in 600 cases and associated risk factors especially manual milking.

PubMed

Tunç, Abdulkadir; Güngen, Belma Doğan

2017-01-01

Electro-diagnostic studies are the most reliable methods in diagnosis of carpal tunnel syndrome (CTS). Although there are many risk factors associated with CTS, there are a limited number of studies in the literature indicating that manual milking, which is frequently seen in Turkey, is a risk factor for CTS. The purpose of this study was to evaluate demographic findings of cases referred due to initial diagnosis of CTS as well as aetiological data especially manual milking and to investigate the sensitivity of initial diagnosis of CTS. Six hundred patients, who were referred to our electromyography laboratory due to initial diagnosis of CTS, were included. Demographic findings, duration of complaints, existence of diabetes mellitus, and manual milking histories of all patients were recorded. Sensitivity of initial diagnosis was investigated based on electro-diagnostic test results. According to electro-diagnostic test results, 289 of the patients were diagnosed with CTS (48.17%). 110 (18.3%) of 600 patients had a history of manual milking. In 94 of this group (85.4%), CTS was detected. Statistically significant correlation was found between CTS and age, female gender, duration of complaints, obesity and manual milking. This study confirms that manual milking is an important risk factor for CTS in addition to female gender, age, symptom duration and obesity. The fact that sensitivity of initial diagnosis of CTS was found to be low according to electro-diagnostic test results indicates importance of detailed clinical evaluation.

40 CFR 86.1806-05 - On-board diagnostics for vehicles less than or equal to 14,000 pounds GVWR.

Code of Federal Regulations, 2012 CFR

2012-07-01

... once per applicable certification test cycle as defined in paragraphs (a) and (d) of Appendix I of this...-based test procedures), excluding those test procedures defined as “Supplemental” test procedures in... infeasibility. Malfunctions are defined as a failure of the system or component to meet the electrical circuit...

40 CFR 86.1806-05 - On-board diagnostics for vehicles less than or equal to 14,000 pounds GVWR.

Code of Federal Regulations, 2013 CFR

2013-07-01

... once per applicable certification test cycle as defined in paragraphs (a) and (d) of Appendix I of this...-based test procedures), excluding those test procedures defined as “Supplemental” test procedures in... infeasibility. Malfunctions are defined as a failure of the system or component to meet the electrical circuit...