Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population

PubMed Central

Mercer, N. J.; Paphitis, K.; Walters, J. M.; Wallace, D.; Kristjanson, E.; Gubbay, J.; Mazzulli, T.

2016-01-01

ABSTRACT In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals. PMID:28003216

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

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.

DIAGNOSTIC TOOL DEVELOPMENT AND APPLICATION THROUGH REGIONAL CASE STUDIES

EPA Science Inventory

Case studies are a useful vehicle for developing and testing conceptual models, classification systems, diagnostic tools and models, and stressor-response relationships. Furthermore, case studies focused on specific places or issues of interest to the Agency provide an excellent ...

SFEMG in ocular myasthenia gravis diagnosis.

PubMed

Padua, L; Stalberg, E; LoMonaco, M; Evoli, A; Batocchi, A; Tonali, P

2000-07-01

In typical cases, the patient's history and clinical examination make it possible to diagnose ocular myasthenia gravis (OMG). But, in many cases a clear clinical picture is not present and OMG diagnosis is very difficult because gold diagnostic standard tests are not available. The diagnostic tests for OMG are usually unable to display a good sensitivity and specificity simultaneously. In this paper, we studied 86 cases submitted for suspected OMG. The patients were studied clinically and with various other tests used in OMG diagnosis (SFEMG, repetitive nerve stimulation, Ab anti AChR titration, tensilon test). SFEMG showed the highest sensitivity (100%) while Ab anti AChR showed the highest specificity (100%). To our knowledge this is the largest population of suspected OMG studied using most of the diagnostic parameters, reported in the literature.

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

[An evaluation of the effectiveness of laboratory diagnostic methods for brucellosis].

PubMed

Gandara, B; Zheludkov, M M; Chernysheva, M I

1994-01-01

The diagnostic value of bacteriological and serological methods for the laboratory diagnosis of brucellosis was studied. In the analysis of milk and cheese specimens Brucella cultures were isolated and differentiated as B.melitensis, biovar I, and B.abortus, biovar 4. In 25.6% of cases B.melitensis culture, biovar 1, was isolated from the blood of persons suspected for brucellosis. The isolation of B.melitensis culture from milk showed that this infective agent migrated from small animals to cattle, which was indicative of a high risk of human infection in the state of Zacatecas, Mexico. The comparative evaluation of serological diagnostic methods (the agglutination test in test tubes, Huddleson's slide test, the acidic rose bengal test and the 2-mercaptoethanol test) showed high sensitivity of rapid tests (Huddleson's test and the rose bengal test in 93.7% and 87.9% of cases respectively). The 2-mercaptoethanol test which gave positive results in 63.8% of cases provided additional information characterizing the course of infections process.

Identification of facilitators and barriers to residents' use of a clinical reasoning tool.

PubMed

DiNardo, Deborah; Tilstra, Sarah; McNeil, Melissa; Follansbee, William; Zimmer, Shanta; Farris, Coreen; Barnato, Amber E

2018-03-28

While there is some experimental evidence to support the use of cognitive forcing strategies to reduce diagnostic error in residents, the potential usability of such strategies in the clinical setting has not been explored. We sought to test the effect of a clinical reasoning tool on diagnostic accuracy and to obtain feedback on its usability and acceptability. We conducted a randomized behavioral experiment testing the effect of this tool on diagnostic accuracy on written cases among post-graduate 3 (PGY-3) residents at a single internal medical residency program in 2014. Residents completed written clinical cases in a proctored setting with and without prompts to use the tool. The tool encouraged reflection on concordant and discordant aspects of each case. We used random effects regression to assess the effect of the tool on diagnostic accuracy of the independent case sets, controlling for case complexity. We then conducted audiotaped structured focus group debriefing sessions and reviewed the tapes for facilitators and barriers to use of the tool. Of 51 eligible PGY-3 residents, 34 (67%) participated in the study. The average diagnostic accuracy increased from 52% to 60% with the tool, a difference that just met the test for statistical significance in adjusted analyses (p=0.05). Residents reported that the tool was generally acceptable and understandable but did not recognize its utility for use with simple cases, suggesting the presence of overconfidence bias. A clinical reasoning tool improved residents' diagnostic accuracy on written cases. Overconfidence bias is a potential barrier to its use in the clinical setting.

Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study.

PubMed

Allison, Kimberly H; Rendi, Mara H; Peacock, Sue; Morgan, Tom; Elmore, Joann G; Weaver, Donald L

2016-12-01

This study examined the case-specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast. Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histological features, which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists' perceptions of case difficulty, borderline features or whether they would obtain a second opinion were also examined for associations with agreement. Of the 2070 participant interpretations of the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (P < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (P < 0.001). Diagnostic agreement ranged from 10% to 89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytological monotony were associated with higher agreement. Lower agreement rates were associated with solid or micropapillary architecture, borderline cytological monotony, or cases without a diagnostic area that was obvious on low power. The results of this study suggest that pathologists frequently recognize the challenge of ADH cases, with some cases being more prone to diagnostic variability. In addition, there are specific histological features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. © 2016 John Wiley & Sons Ltd.

Histologic Features associated with Diagnostic Agreement in Atypical Ductal Hyperplasia of the Breast: Illustrative Cases from the B-Path Study

PubMed Central

Allison, Kimberly H.; Rendi, Mara H.; Peacock, Sue; Morgan, Tom; Elmore, Joann G.; Weaver, Donald L.

2016-01-01

Background Case specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast are poorly understood. Methods Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histologic features which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists’ perceptions of case difficulty, borderline features, or if they would obtain a second opinion were also examined for associations with agreement. Results Of the 2,070 participant interpretations on the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (p < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (p < 0.001). Diagnostic agreement ranged from 10–89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytologic monotony were associated with higher agreement. Lower agreement rates were associated with solid or micro-papillary architecture, borderline cytologic monotony or cases without a diagnostic area that was obvious on low power. Conclusions The results of this study suggest that pathologists frequently recognize the challenge of ADH cases with some cases more prone to diagnostic variability. In addition, there are specific histologic features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. PMID:27398812

Shifting Diagnostic Systems for Defining Intellectual Disability in Death Penalty Cases: Hall vs. Florida.

PubMed

Mukherjee, Mina; Westphal, Alexander

2015-07-01

The case of Hall vs. Florida tested Florida's so called "bright line rule" in determining intellectual disability in capital cases. The Supreme Court Decision reflects a more general trend from categorical to dimensional approaches in psychiatric diagnostic systems.

Shifting Diagnostic Systems for Defining Intellectual Disability in Death Penalty Cases: Hall vs. Florida

ERIC Educational Resources Information Center

Mukherjee, Mina; Westphal, Alexander

2015-01-01

The case of Hall vs. Florida tested Florida's so called "bright line rule" in determining intellectual disability in capital cases. The Supreme Court Decision reflects a more general trend from categorical to dimensional approaches in psychiatric diagnostic systems.

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.

Surgical implications and variability in the use of the flat epithelial atypia diagnosis on breast biopsy specimens.

PubMed

Samples, Laura S; Rendi, Mara H; Frederick, Paul D; Allison, Kimberly H; Nelson, Heidi D; Morgan, Thomas R; Weaver, Donald L; Elmore, Joann G

2017-08-01

Flat epithelial atypia (FEA) is a relatively new diagnostic term with uncertain clinical significance for surgical management. Any implied risk of invasive breast cancer associated with FEA is contingent upon diagnostic reproducibility, yet little is known regarding its use. Pathologists in the Breast Pathology Study interpreted one of four 60-case test sets, one slide per case, constructed from 240 breast biopsy specimens. An electronic data form with standardized diagnostic categories was used; participants were instructed to indicate all diagnoses present. We assessed participants' use of FEA as a diagnostic term within: 1) each test set; 2) 72 cases classified by reference as benign without FEA; and 3) six cases classified by reference as FEA. 115 pathologists participated, providing 6900 total independent assessments. Notation of FEA ranged from 0% to 35% of the cases interpreted, with most pathologists noting FEA on 4 or more test cases. At least one participant noted FEA in 34 of the 72 benign non-FEA cases. For the 6 reference FEA cases, participant agreement with the case reference FEA diagnosis ranged from 17% to 52%; diagnoses noted by participating pathologists for these FEA cases included columnar cell hyperplasia, usual ductal hyperplasia, atypical lobular hyperplasia, and atypical ductal hyperplasia. We observed wide variation in the diagnosis of FEA among U.S. pathologists. This suggests that perceptions of diagnostic criteria and any implied risk associated with FEA may also vary. Surgical excision following a core biopsy diagnosis of FEA should be reconsidered and studied further. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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

New method for detection of gastric cancer by hyperspectral imaging: a pilot study

NASA Astrophysics Data System (ADS)

Kiyotoki, Shu; Nishikawa, Jun; Okamoto, Takeshi; Hamabe, Kouichi; Saito, Mari; Goto, Atsushi; Fujita, Yusuke; Hamamoto, Yoshihiko; Takeuchi, Yusuke; Satori, Shin; Sakaida, Isao

2013-02-01

We developed a new, easy, and objective method to detect gastric cancer using hyperspectral imaging (HSI) technology combining spectroscopy and imaging A total of 16 gastroduodenal tumors removed by endoscopic resection or surgery from 14 patients at Yamaguchi University Hospital, Japan, were recorded using a hyperspectral camera (HSC) equipped with HSI technology Corrected spectral reflectance was obtained from 10 samples of normal mucosa and 10 samples of tumors for each case The 16 cases were divided into eight training cases (160 training samples) and eight test cases (160 test samples) We established a diagnostic algorithm with training samples and evaluated it with test samples Diagnostic capability of the algorithm for each tumor was validated, and enhancement of tumors by image processing using the HSC was evaluated The diagnostic algorithm used the 726-nm wavelength, with a cutoff point established from training samples The sensitivity, specificity, and accuracy rates of the algorithm's diagnostic capability in the test samples were 78.8% (63/80), 92.5% (74/80), and 85.6% (137/160), respectively Tumors in HSC images of 13 (81.3%) cases were well enhanced by image processing Differences in spectral reflectance between tumors and normal mucosa suggested that tumors can be clearly distinguished from background mucosa with HSI technology.

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.

Component-resolved diagnostics in vernal conjunctivitis.

PubMed

Armentia, Alicia; Sanchís, Eugenia; Montero, Javier A

2016-10-01

Conventional diagnostic tests in allergy are insufficient to clarify the cause of vernal conjunctivitis. Component-resolved diagnostic (CRD) by microarray allergen assay may be useful in detecting allergens that might be involved in the inflammatory process. In a recent trial in patients suffered from eosinophilic esophagitis, after 2 years of the CRD-guided exclusion diet and specific immunotherapy, significant clinical improvement was observed, and 68% of patients were discharged (cure based on negative biopsy, no symptoms, and no medication intake). Our new objective was to evaluate IgE-mediated hypersensitivity by CRD in tears and serum from patients with vernal conjunctivitis and treat patients with identified triggering allergens by specific immunotherapy. Twenty-five patients with vernal conjunctivitis were evaluated. The identified triggering allergens were n Lol p 1 (11 cases), n Cyn d 1 (eight cases), group 4 and 6 grasses (six cases) and group 5 of grasses (five cases). Prick test and pollen IgE were positive in one case. Clinical improvement was observed in 13/25 vernal conjunctivitis patients after 1-year specific immunotherapy. CRD seems to be a more sensitive diagnostic tool compared with prick test and IgE detection. Specific CRD-led immunotherapy may achieve clinical improvements in vernal conjunctivitis patients.

Diagnostic Tools for Acute Anterior Cruciate Ligament Injury: GNRB, Lachman Test, and Telos.

PubMed

Ryu, Seung Min; Na, Ho Dong; Shon, Oog Jin

2018-06-01

The purpose of this study is to compare the accuracy of the GNRB arthrometer (Genourob), Lachman test, and Telos device (GmbH) in acute anterior cruciate ligament (ACL) injuries and to evaluate the accuracy of each diagnostic tool according to the length of time from injury to examination. From September 2015 to September 2016, 40 cases of complete ACL rupture were reviewed. We divided the time from injury to examination into three periods of 10 days each and analyzed the diagnostic tools according to the time frame. An analysis of the area under the curve (AUC) of a receiver operating characteristic curve showed that all diagnostic tools were fairly informative. The GNRB showed a higher AUC than other diagnostic tools. In 10 cases assessed within 10 days after injury, the GNRB showed statistically significant side-to-side difference in laxity (p＜0.001), whereas the Telos test and Lachman test did not show significantly different laxity (p=0.541 and p=0.413, respectively). All diagnostic values of the GNRB were better than other diagnostic tools in acute ACL injuries. The GNRB was more effective in acute ACL injuries examined within 10 days of injury. The GNRB arthrometer can be a useful diagnostic tool for acute ACL injuries.

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.

A review of the public health management of shigellosis in Australia in the era of culture-independent diagnostic testing.

PubMed

Tai, Alex Y C; Easton, Marion; Encena, Jess; Rotty, Jessica; Valcanis, Mary; Howden, Benjamin P; Slota-Kan, Simon; Gregory, Joy

2016-12-01

To review the national case definition for shigellosis following the introduction of culture independent diagnostic testing by clinical laboratories and provide evidence to reform jurisdictional public health practices for the management shigellosis., . A review of all Australian jurisdictional public health guidelines for shigellosis was conducted. Victorian 2014 shigellosis data were analysed: demographics and risk factors for cases identified by conventional culture or culture-independent diagnostic methods were described. There was considerable variation in reporting of cases to the National Notifiable Disease Surveillance System (NNDSS) by the eight Australian jurisdictions, with an array of classifications based on diagnostic testing methodologies. Analysis of Victorian 2014 shigellosis data found that culture positive cases were more likely to have reported men who have sex with men (MSM) as a risk factor than PCR positive only cases (p<0.0001) and less likely to have reported overseas travel during their incubation period (p<0.0001). Over a 10-year period (2005 to 2014), only two of 86 cases who were employed in high-risk occupations had ongoing positive faecal cultures after appropriate treatment. The national surveillance case definition for shigellosis should be reviewed to facilitate standardised reporting across Australia. All jurisdictions must consider the public health significance of PCR positive only results in their surveillance risk assessments to inform management of shigellosis cases. © 2016 Public Health Association of Australia.

[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.

Paraneoplastic autoantibody panels: sensitivity and specificity, a retrospective cohort.

PubMed

Albadareen, Rawan; Gronseth, Gary; Goeden, Marcie; Sharrock, Matthew; Lechtenberg, Colleen; Wang, Yunxia

2017-06-01

Experts in the autoimmune paraneoplastic field recommend autoantibody testing as "panels" to improve the poor sensitivity of individual autoantibodies in detecting paraneoplastic neurological syndromes (PNS). The sensitivity of those panels was not reported to date in a fashion devoid of incorporation bias. We aimed to assess the collective sensitivity and specificity of one of the commonly used panels in detecting PNS. A single-centered retrospective cohort of all patients tested for paraneoplastic evaluation panel (PAVAL; test ID: 83380) over one year for the suspicion of PNS. Case adjudication was based on newly proposed diagnostic criteria in line with previously published literature, but modified to exclude serological status to avoid incorporation bias. Measures of diagnostic accuracy were subsequently calculated. Cases that failed to show association with malignancy within the follow-up time studied, reflecting a possibly pure autoimmune process was considered paraneoplastic-like syndromes. Out of 321 patients tested, 51 patients tested positive. Thirty-two patients met diagnostic criteria for paraneoplastic/paraneoplastic-like syndromes. The calculated collective sensitivity was 34% (95% CI: 17-53), specificity was 86% (95% CI: 81-90), Youden's index 0.2 and a positive clinical utility index 0.07 suggesting poor utility for case-detection. This is the first reported diagnostic accuracy measures of paraneoplastic panels without incorporation bias. Despite recommended panel testing to improve detection of PNS, sensitivity remains low with poor utility for case-detection. The high-calculated specificity suggests a possible role in confirming the condition in difficult cases suspicious for PNS, when enough supportive evidence is lacking on ancillary testing.

Sharing the Diagnostic Process in the Clinical Teaching Environment: A Case Study

ERIC Educational Resources Information Center

Cuello-Garcia; Carlos

2005-01-01

Revealing or visualizing the thinking involved in making clinical decisions is a challenge. A case study is presented with a visual implement for sharing the diagnostic process. This technique adapts the Bayesian approach to the case presentation. Pretest probabilities and likelihood ratios are gathered to obtain post-test probabilities of every…

Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening

PubMed Central

Condell, Orla; Wasunna, Christine; Kpaka, Jonathan; Zwizwai, Ruth; Nuha, Mahmood; Fallah, Mosoka; Freeman, Maxwell; Harris, Victoria; Miller, Mark; Baller, April; Massaquoi, Moses; Katawera, Victoria; Saindon, John; Bemah, Philip; Hamblion, Esther; Castle, Evelyn; Williams, Desmond; Gasasira, Alex; Nyenswah, Tolbert

2018-01-01

The 2014–16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64–100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region. PMID:29304039

Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening.

PubMed

Raftery, Philomena; Condell, Orla; Wasunna, Christine; Kpaka, Jonathan; Zwizwai, Ruth; Nuha, Mahmood; Fallah, Mosoka; Freeman, Maxwell; Harris, Victoria; Miller, Mark; Baller, April; Massaquoi, Moses; Katawera, Victoria; Saindon, John; Bemah, Philip; Hamblion, Esther; Castle, Evelyn; Williams, Desmond; Gasasira, Alex; Nyenswah, Tolbert

2018-01-01

The 2014-16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64-100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region.

A Next Generation Sequencing custom gene panel as first line diagnostic tool for atypical cases of syndromic obesity: Application in a case of Alström syndrome.

PubMed

Maltese, Paolo E; Iarossi, Giancarlo; Ziccardi, Lucia; Colombo, Leonardo; Buzzonetti, Luca; Crinò, Antonino; Tezzele, Silvia; Bertelli, Matteo

2018-02-01

Obesity phenotype can be manifested as an isolated trait or accompanied by multisystem disorders as part of a syndromic picture. In both situations, same molecular pathways may be involved to different degrees. This evidence is stronger in syndromic obesity, in which phenotypes of different syndromes may overlap. In these cases, genetic testing can unequivocally provide a final diagnosis. Here we describe a patient who met the diagnostic criteria for Alström syndrome only during adolescence. Genetic testing was requested at 25 years of age for a final confirmation of the diagnosis. The genetic diagnosis of Alström syndrome was obtained through a Next Generation Sequencing genetic test approach using a custom-designed gene panel of 47 genes associated with syndromic and non-syndromic obesity. Genetic analysis revealed a novel homozygous frameshift variant p.(Arg1550Lysfs*10) on exon 8 of the ALMS1 gene. This case shows the need for a revision of the diagnostic criteria guidelines, as a consequence of the recent advent of massive parallel sequencing technology. Indications for genetic testing reported in these currently accepted diagnostic criteria for Alström syndrome, were drafted when sequencing was expensive and time consuming. Nowadays, Next Generation Sequencing testing could be considered as first line diagnostic tool not only for Alström syndrome but, more generally, for all those atypical or not clearly distinguishable cases of syndromic obesity, thus avoiding delayed diagnosis and treatments. Early diagnosis permits a better follow-up and pre-symptomatic interventions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

A multimedia patient simulation for teaching and assessing endodontic diagnosis.

PubMed

Littlefield, John H; Demps, Elaine L; Keiser, Karl; Chatterjee, Lipika; Yuan, Cheng H; Hargreaves, Kenneth M

2003-06-01

Teaching and assessing diagnostic skills are difficult due to relatively small numbers of total clinical experiences and a shortage of clinical faculty. Patient simulations could help teach and assess diagnosis by displaying a well-defined diagnostic task, then providing informative feedback and opportunities for repetition and correction of errors. This report describes the development and initial evaluation of SimEndo I, a multimedia patient simulation program that could be used for teaching or assessing endodontic diagnosis. Students interact with a graphical interface that has four pull-down menus and related submenus. In response to student requests, the program presents patient information. Scoring is based on diagnosis of each case by endodontists. Pilot testing with seventy-four junior dental students identified numerous needed improvements to the user interface program. A multi-school field test of the interface program using three patient cases addressed three research questions: 1) How did the field test students evaluate SimEndo I? Overall mean evaluation was 8.1 on a 0 to 10 scale; 2) How many cases are needed to generate a reproducible diagnostic proficiency score for an individual student using the Rimoldi scoring procedure? Mean diagnostic proficiency scores by case ranged from .27 to .40 on a 0 to 1 scale; five cases would produce a score with a 0.80 reliability coefficient; and 3) Did students accurately diagnose each case? Mean correct diagnosis scores by case ranged from .54 to .78 on a 0 to 1 scale. We conclude that multimedia patient simulations offer a promising alternative for teaching and assessing student diagnostic skills.

The Leukocyte Esterase Strip Test has Practical Value for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Multicenter Study.

PubMed

Koh, In J; Han, Seung B; In, Yong; Oh, Kwang J; Lee, Dae H; Kim, Tae K

2017-11-01

Leukocyte esterase (LE) was recently reported to be an accurate marker for diagnosing periprosthetic joint infection (PJI) as defined by the Musculoskeletal Infection Society (MSIS) criteria. However, the diagnostic value of the LE test for PJI after total knee arthroplasty (TKA), the reliability of the subjective visual interpretation of the LE test, and the correlation between the LE test results and the current MSIS criteria remain unclear. This study prospectively enrolled 60 patients undergoing revision TKA for either PJI or aseptic failure. Serological marker, synovial fluid, and histological analyses were performed in all cases. The PJI group comprised 38 cases that met the MSIS criteria and the other 22 cases formed the aseptic group. All the LE tests were interpreted using both visual judgment and automated colorimetric reader. When "++" results were considered to indicate a positive PJI, the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were 84, 100, 100, 79, and 90%, respectively. The visual interpretation agreed with the automated colorimetric reader in 90% of cases (Cronbach α = 0.894). The grade of the LE test was strongly correlated with the synovial white blood cell count (ρ = 0.695) and polymorphonuclear leukocyte percentage (ρ = 0.638) and moderately correlated with the serum C-reactive protein and erythrocyte sedimentation rate. The LE test has high diagnostic value for diagnosing PJI after TKA. Subjective visual interpretation of the LE test was reliable and valid for the current battery of PJI diagnostic tests according to the MSIS criteria. Copyright © 2017. Published by Elsevier Inc.

The role of strategy and redundancy in diagnostic reasoning.

PubMed

Bloch, Ralph F; Hofer, Daniel; Feller, Sabine; Hodel, Maria

2003-01-24

Diagnostic reasoning is a key competence of physicians. We explored the effects of knowledge, practice and additional clinical information on strategy, redundancy and accuracy of diagnosing a peripheral neurological defect in the hand based on sensory examination. Using an interactive computer simulation that includes 21 unique cases with seven sensory loss patterns and either concordant, neutral or discordant textual information, 21 3rd year medical students, 21 6th year and 21 senior neurology residents each examined 15 cases over the course of one session. An additional 23 psychology students examined 24 cases over two sessions, 12 cases per session. Subjects also took a seven-item MCQ exam of seven classical patterns presented visually. Knowledge of sensory patterns and diagnostic accuracy are highly correlated within groups (R2 = 0.64). The total amount of information gathered for incorrect diagnoses is no lower than that for correct diagnoses. Residents require significantly fewer tests than either psychology or 6th year students, who in turn require fewer than the 3rd year students (p < 0.001). The diagnostic accuracy of subjects is affected both by level of training (p < 0.001) and concordance of clinical information (p < 0.001). For discordant cases, refutation testing occurs significantly in 6th year students (p < 0.001) and residents (p < 0.01), but not in psychology or 3rd year students. Conversely, there is a stable 55% excess of confirmatory testing, independent of training or concordance. Knowledge and practice are both important for diagnostic success. For complex diagnostic situations reasoning components employing redundancy seem more essential than those using strategy.

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.

Advances in malaria elimination in Botswana: a dramatic shift to parasitological diagnosis, 2008–2014

PubMed Central

Edwards, J. K.; Motlaleng, M.; Namboze, J.; Butt, W.; Obopile, M.; Mosweunyane, T.; Manzi, M.; Takarinda, K. C.; Owiti, P.

2018-01-01

Background: Malaria elimination requires infection detection using quality assured diagnostics and appropriate treatment regimens. Although Botswana is moving towards malaria elimination, reports of unconfirmed cases may jeopardise this effort. This study aimed to determine the proportion of cases treated for malaria that were confirmed by rapid diagnostic testing (RDT) and/or microscopy. Methods: This was a retrospective descriptive study using routine national data from the integrated disease surveillance and case-based surveillance systems from 2008 to 2014. The data were categorised into clinical and confirmed cases each year. An analysis of the data on cases registered in three districts that reported approximately 70% of all malaria cases was performed, stratified by year, type of reporting health facilities and diagnostic method. Results: During 2008–2014, 50 487 cases of malaria were reported in Botswana, and the proportion of RDT and/or blood microscopy confirmed cases improved from 6% in 2008 to 89% in 2013. The total number of malaria cases decreased by 97% in the same period, then increased by 41% in 2013. Conclusion: This study shows that malaria diagnostic tests dramatically improved malaria diagnosis and consequently reduced the malaria burden in Botswana. The study identified a need to build capacity on microscopy for species identification, parasite quantification and guiding treatment choices. PMID:29713592

Advances in malaria elimination in Botswana: a dramatic shift to parasitological diagnosis, 2008-2014.

PubMed

Moakofhi, K; Edwards, J K; Motlaleng, M; Namboze, J; Butt, W; Obopile, M; Mosweunyane, T; Manzi, M; Takarinda, K C; Owiti, P

2018-04-25

Background: Malaria elimination requires infection detection using quality assured diagnostics and appropriate treatment regimens. Although Botswana is moving towards malaria elimination, reports of unconfirmed cases may jeopardise this effort. This study aimed to determine the proportion of cases treated for malaria that were confirmed by rapid diagnostic testing (RDT) and/or microscopy. Methods: This was a retrospective descriptive study using routine national data from the integrated disease surveillance and case-based surveillance systems from 2008 to 2014. The data were categorised into clinical and confirmed cases each year. An analysis of the data on cases registered in three districts that reported approximately 70% of all malaria cases was performed, stratified by year, type of reporting health facilities and diagnostic method. Results: During 2008-2014, 50 487 cases of malaria were reported in Botswana, and the proportion of RDT and/or blood microscopy confirmed cases improved from 6% in 2008 to 89% in 2013. The total number of malaria cases decreased by 97% in the same period, then increased by 41% in 2013. Conclusion: This study shows that malaria diagnostic tests dramatically improved malaria diagnosis and consequently reduced the malaria burden in Botswana. The study identified a need to build capacity on microscopy for species identification, parasite quantification and guiding treatment choices.

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.

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.

Lichtheimia Infection in a Lymphoma Patient: Case Report and a Brief Review of the Available Diagnostic Tools.

PubMed

Zimmerli, Stefan; Bialek, Ralf; Blau, Igor W; Christe, Andreas; Lass-Flörl, Cornelia; Presterl, Elisabeth

2016-08-01

We describe the case of a patient with a T-lymphoblastic lymphoma whose disseminated mucormycosis was diagnosed with delay, and we address the diagnostic and therapeutic decision-making process and review the diagnostic workup of patients with potential IFD. The diagnosis was delayed despite a suggestive radiological presentation of the patient's pulmonary lesion. The uncommon risk profile (T-lymphoblastic lymphoma, short neutropenic phases) wrongly led to a low level of suspicion. The diagnosis was also hampered by the lack of indirect markers for infections caused by Mucorales, the low sensitivity of both fungal culture and panfungal PCR, and the limited availability of species-specific PCR. A high level of suspicion of IFD is needed, and aggressive diagnostic procedures should be promptly initiated even in apparently low-risk patients with uncommon presentations. The extent of the analytical workup should be decided on a case-by-case base. Diagnostic tests such as the galactomannan and β-D-glucan test and/or PCR on biological material followed by sequencing should be chosen according to their availability and after evaluation of their specificity and sensitivity. In high-risk patients, preemptive therapy with a broad-spectrum mould-active antifungal agent should be started before definitive diagnostic findings become available.

Comparing the diagnostic properties of skin scraping, adhesive tape, and dermoscopy in diagnosing scabies.

PubMed

Abdel-Latif, Azmy A; Elshahed, Ahmad R; Salama, Omar A; Elsaie, Mohamed L

2018-06-01

Scabies is a contagious skin infestation that mainly presents with itching at night and skin burrows that are visible to the naked eye. Diagnosing scabies with dermoscopy is still a matter of controversy. The aim of our study was to compare the diagnostic properties of adhesive tape, skin scraping, and dermoscopy in diagnosing scabies. One hundred patients with clinical presumptive diagnoses of scabies underwent skin scraping, adhesive tape testing, and dermoscopic examination. Each diagnostic procedure was performed on three different areas. Comparing the diagnostic properties of the three methods, the adhesive tape test was the most sensitive method for diagnosing scabies. Sixteen cases (16.0%) were definitely diagnosed as scabies using the adhesive tape test detecting the presence of mites or their eggs. Only 10 cases (10.0%) were definitely diagnosed as scabies using the skin scraping test detecting mites or their eggs. Dermoscopic examination suggested a diagnosis of scabies in 22 cases (22.0%), of which only 10 were definitely diagnosed as scabies by detecting mites using the adhesive tape test, skin scraping, or both. The diagnosis of scabies can only be confirmed by seeing mites. The adhesive tape test and skin scraping procedure have high specificity in diagnosing scabies, but their low sensitivity cannot exclude the possibility of scabies. Dermoscopy-guided tape testing can be a helpful tool for better diagnosis of scabies.

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012–2013

PubMed Central

Zucker, Jane R.; Giancotti, Francesca R.; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L.; Rosen, Jennifer B.

2017-01-01

ABSTRACT The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. PMID:28701468

Rapid diagnostic tests for malaria

PubMed Central

Daily, Jennifer; Hotte, Nora; Dolkart, Caitlin; Cunningham, Jane; Yadav, Prashant

2015-01-01

Abstract Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them. PMID:26668438

Diagnostic Yield of Laboratory Methods and Value of Viral Genotyping during an Outbreak of Mumps in a Partially Vaccinated Population in British Columbia, Canada.

PubMed

Nunn, Alexandra; Masud, Shazia; Krajden, Mel; Naus, Monika; Jassem, Agatha N

2018-05-01

Mumps remains endemic in North America despite routine use of the measles, mumps, and rubella (MMR) vaccine. In 2016, an outbreak of mumps in British Columbia, Canada, provided an opportunity to determine the diagnostic utility of laboratory testing methods. Specimens from patients with clinical mumps were tested for infection using a commercial enzyme-linked immunosorbent assay (ELISA) for antibody detection and an in-house reverse transcriptase PCR (RT-PCR) targeting viral fusion and small hydrophobic (SH) genes. Viral genotyping was performed by SH gene sequencing. Laboratory data was linked with epidemiologic case data. Of the 139 confirmed cases, 94 (68%) had reported or documented history of MMR vaccination. Specimens were typically collected 1 day (for buccal and IgM tests) or 2 days (for urine tests) after symptom onset. Most confirmed cases (69%) were confirmed by buccal swab RT-PCR. Among cases tested by multiple methods, the percent positivity for buccal swab RT-PCR was 90% (96/107) compared to 43% (30/69) for both IgM ELISA and urine RT-PCR. Mumps IgM detection was higher in confirmed cases with no history of vaccination than in those with history (64% versus 34%, P = 0.02). The outbreak strain was identified as genotype G related to MuVi/Sheffield.GBR/1.05 but with conserved variations in five nucleotides within the SH gene that allowed linkage of geographically distinct cases. In conclusion, RT-PCR of buccal specimens had the highest diagnostic yield during a mumps outbreak in a partially vaccinated population. To optimize mumps diagnostic potential, clinicians should collect specimens depending on when the patient presents for care and their immunization history. © Crown copyright 2018.

Triple Test in Carcinoma Breast

PubMed Central

Sameer; Mukherjee, Arindam

2014-01-01

Introduction: The commonest clinical presentation in majority of breast pathology is a lump. A definite diagnosis of breast lump is very important for the surgeon to decide on the final course of treatment and also saves the patient from unnecessary physical, emotional and psychological trauma if there is a definite preoperative diagnosis of benign lesion. The present study was done to evaluate the effectiveness and relevance of “TRIPLE TEST”in diagnosis of carcinoma breast in rural labour class population. Materials and Methods: The present study was a prospective study conducted on patients over 35 years of age having palpable breast lumps presenting in the out patient department of general surgery, ESI Hospital Basaidarapur New Delhi, India. The duration of study was from May 2007 to June 2009 and a total of 100 cases were studied. Each patient was subjected to a detailed history, clinical breast examination ,diagnostic mammography and FNAC. In this study, the results of each modality was divided in three groups: benign, suspicious and malignant. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of each test was calculated individually and as combined. Result: Out of 100 patients enrolled in this study, 60 cases were benign and 40 cases were of malignant breast disease. The age of patients with carcinoma breast in the series varied from 35 years to 70 years. The highest incidence of malignancy noted was 30% in 41-50 years age group (4th decade) followed by 27.5% in 51-60 years age group (5th decade). The sensitivity of clinical examination was found to be 75%, specificity was 83.3%, positive predictive value (PPV) of 75% and diagnostic accuracy of 80%. The sensitivity, specificity, positive predictive value and diagnostic accuracy of mammography was calculated and was found to be 94.9% , 90% , 86% and 92% respectively. The sensitivity, specificity, positive predictive value and diagnostic accuracy of FNAC was 94.7%, 98.3%, 97.3% and 96.6% respectively. Out of 100 cases triple test was concordant (all three test either benign or malignant) in 80 cases, all the benign cases detected by triple test were benign on final biopsy i.e. 100% specificity and 100% negative predictive value. Conclusion: TTS is an accurate and least invasive diagnostic test based on which definitive treatment can be initiated. PMID:25478391

Diagnostic Strategy Used To Establish Etiologies of Encephalitis in a Prospective Cohort of Patients in England▿

PubMed Central

Ambrose, H. E.; Granerod, J.; Clewley, J. P.; Davies, N. W. S.; Keir, G.; Cunningham, R.; Zuckerman, M.; Mutton, K. J.; Ward, K. N.; Ijaz, S.; Crowcroft, N. S.; Brown, D. W. G.

2011-01-01

The laboratory diagnostic strategy used to determine the etiology of encephalitis in 203 patients is reported. An etiological diagnosis was made by first-line laboratory testing for 111 (55%) patients. Subsequent testing, based on individual case reviews, resulted in 17 (8%) further diagnoses, of which 12 (71%) were immune-mediated and 5 (29%) were due to infection. Seventy-five cases were of unknown etiology. Sixteen (8%) of 203 samples were found to be associated with either N-methyl-d-aspartate receptor or voltage-gated potassium channel complex antibodies. The most common viral causes identified were herpes simplex virus (HSV) (19%) and varicella-zoster virus (5%), while the most important bacterial cause was Mycobacterium tuberculosis (5%). The diagnostic value of testing cerebrospinal fluid (CSF) for antibody was assessed using 139 samples from 99 patients, and antibody was detected in 46 samples from 37 patients. Samples collected at 14 to 28 days were more likely to be positive than samples taken 0 to 6 days postadmission. Three PCR-negative HSV cases were diagnosed by the presence of virus-specific antibody in the central nervous system (CNS). It was not possible to make an etiological diagnosis for one-third of the cases; these were therefore considered to be due to unknown causes. Delayed sampling did not contribute to these cases. Twenty percent of the patients with infections with an unknown etiology showed evidence of localized immune activation within the CNS, but no novel viral DNA or RNA sequences were found. We conclude that a good standard of clinical investigation and thorough first-line laboratory testing allows the diagnosis of most cases of infectious encephalitis; testing for CSF antibodies allows further cases to be diagnosed. It is important that testing for immune-mediated causes also be included in a diagnostic algorithm. PMID:21865429

Development of a diagnostic test set to assess agreement in breast pathology: practical application of the Guidelines for Reporting Reliability and Agreement Studies (GRRAS).

PubMed

Oster, Natalia V; Carney, Patricia A; Allison, Kimberly H; Weaver, Donald L; Reisch, Lisa M; Longton, Gary; Onega, Tracy; Pepe, Margaret; Geller, Berta M; Nelson, Heidi D; Ross, Tyler R; Tosteson, Aanna N A; Elmore, Joann G

2013-02-05

Diagnostic test sets are a valuable research tool that contributes importantly to the validity and reliability of studies that assess agreement in breast pathology. In order to fully understand the strengths and weaknesses of any agreement and reliability study, however, the methods should be fully reported. In this paper we provide a step-by-step description of the methods used to create four complex test sets for a study of diagnostic agreement among pathologists interpreting breast biopsy specimens. We use the newly developed Guidelines for Reporting Reliability and Agreement Studies (GRRAS) as a basis to report these methods. Breast tissue biopsies were selected from the National Cancer Institute-funded Breast Cancer Surveillance Consortium sites. We used a random sampling stratified according to woman's age (40-49 vs. ≥50), parenchymal breast density (low vs. high) and interpretation of the original pathologist. A 3-member panel of expert breast pathologists first independently interpreted each case using five primary diagnostic categories (non-proliferative changes, proliferative changes without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma). When the experts did not unanimously agree on a case diagnosis a modified Delphi method was used to determine the reference standard consensus diagnosis. The final test cases were stratified and randomly assigned into one of four unique test sets. We found GRRAS recommendations to be very useful in reporting diagnostic test set development and recommend inclusion of two additional criteria: 1) characterizing the study population and 2) describing the methods for reference diagnosis, when applicable.

Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure.

PubMed

Shapiro, Adam J; Leigh, Margaret W

2017-01-01

Primary ciliary dyskinesia (PCD) is a genetic disorder causing chronic oto-sino-pulmonary disease. No single diagnostic test will detect all PCD cases. Transmission electron microscopy (TEM) of respiratory cilia was previously considered the gold standard diagnostic test for PCD, but 30% of all PCD cases have either normal ciliary ultrastructure or subtle changes which are non-diagnostic. These cases are identified through alternate diagnostic tests, including nasal nitric oxide measurement, high-speed videomicroscopy analysis, immunofluorescent staining of axonemal proteins, and/or mutation analysis of various PCD causing genes. Autosomal recessive mutations in DNAH11 and HYDIN produce normal TEM ciliary ultrastructure, while mutations in genes encoding for radial spoke head proteins result in some cross-sections with non-diagnostic alterations in the central apparatus interspersed with normal ciliary cross-sections. Mutations in nexin link and dynein regulatory complex genes lead to a collection of different ciliary ultrastructures; mutations in CCDC65, CCDC164, and GAS8 produce normal ciliary ultrastructure, while mutations in CCDC39 and CCDC40 cause absent inner dynein arms and microtubule disorganization in some ciliary cross-sections. Mutations in CCNO and MCIDAS cause near complete absence of respiratory cilia due to defects in generation of multiple cellular basal bodies; however, the scant cilia generated may have normal ultrastructure. Lastly, a syndromic form of PCD with retinal degeneration results in normal ciliary ultrastructure through mutations in the RPGR gene. Clinicians must be aware of these genetic causes of PCD resulting in non-diagnostic TEM ciliary ultrastructure and refrain from using TEM of respiratory cilia as a test to rule out PCD.

Preliminary consideration of CFETR ITER-like case diagnostic system.

PubMed

Li, G S; Yang, Y; Wang, Y M; Ming, T F; Han, X; Liu, S C; Wang, E H; Liu, Y K; Yang, W J; Li, G Q; Hu, Q S; Gao, X

2016-11-01

Chinese Fusion Engineering Test Reactor (CFETR) is a new superconducting tokamak device being designed in China, which aims at bridging the gap between ITER and DEMO, where DEMO is a tokamak demonstration fusion reactor. Two diagnostic cases, ITER-like case and towards DEMO case, have been considered for CFETR early and later operating phases, respectively. In this paper, some preliminary consideration of ITER-like case will be presented. Based on ITER diagnostic system, three versions of increased complexity and coverage of the ITER-like case diagnostic system have been developed with different goals and functions. Version A aims only machine protection and basic control. Both of version B and version C are mainly for machine protection, basic and advanced control, but version C has an increased level of redundancy necessary for improved measurements capability. The performance of these versions and needed R&D work are outlined.

Preliminary consideration of CFETR ITER-like case diagnostic system

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

Li, G. S.; Liu, Y. K.; Gao, X.

2016-11-15

Chinese Fusion Engineering Test Reactor (CFETR) is a new superconducting tokamak device being designed in China, which aims at bridging the gap between ITER and DEMO, where DEMO is a tokamak demonstration fusion reactor. Two diagnostic cases, ITER-like case and towards DEMO case, have been considered for CFETR early and later operating phases, respectively. In this paper, some preliminary consideration of ITER-like case will be presented. Based on ITER diagnostic system, three versions of increased complexity and coverage of the ITER-like case diagnostic system have been developed with different goals and functions. Version A aims only machine protection and basicmore » control. Both of version B and version C are mainly for machine protection, basic and advanced control, but version C has an increased level of redundancy necessary for improved measurements capability. The performance of these versions and needed R&D work are outlined.« less

Effect of patient age awareness on diagnostic agreement of chronic or aggressive periodontitis between clinicians; a pilot study.

PubMed

Oshman, Sarah; El Chaar, Edgard; Lee, Yoonjung Nicole; Engebretson, Steven

2016-07-25

The aim of this pilot study was to test whether diagnostic agreement of aggressive and chronic periodontitis amongst Board Certified Periodontists, is influenced by knowledge of a patient's age. In 1999 at the International World Workshop age was removed as a diagnostic criteria for aggressive periodontitis. The impact of this change on the diagnostic reliability amongst clinicians has not yet been assessed. Nine periodontal case reports were twice presented to sixteen board certified periodontists, once with age withheld and again with patient age provided. Participants were instructed to choose a diagnosis of Chronic Periodontitis or Aggressive Periodontitis. Diagnostic agreement was calculated using the Fleiss Kappa test. Including the patients' age in case report information increased diagnostic agreement (the kappa statistic) from 0.49 (moderate agreement) to 0.61 (substantial agreement). These results suggest that knowledge of a patients' age influenced clinical diagnosis, when distinguishing between aggressive periodontitis and chronic periodontitis, which may in turn impact treatment decision-making.

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.

[Cost-benefit analysis of the active screening of pulmonary tuberculosis in a recluse population entering prison].

PubMed

Martín, V; Domínguez, A; Alcaide, J

1997-01-01

In spanish prisons, tuberculosis is a serious problem of public health and health authorities don't take it seriously. To prove the efficiency of pulmonary tuberculosis case-finding on arrival at prison in order to get location resources in this activity. Cost-benefit analysis of a case-finding program compared with to wait for diagnostic to illness. The sensitivity of test was fixed in 80% and the specificity in 99.99%. The cost was based on market prices. Sensitivity analysis was done in every variables as well as tridimensional analysis in those one of more influence. The case-finding was efficient on prevalences of tuberculosis over 5 per mil. Its efficiency was hardly affected by discount social rates or the sensitivity of diagnostic tests. The prevalence of illness, the cost of diagnostic activities as well as the success of treatment and the specificity of diagnostic tests used had as influence on the efficiency model. The tridimensional analysis proved that the case-finding of pulmonary tuberculosis has efficiency on low prevalences (1 per thousand), provided the number of people cured is a 5% higher than the alternative one and the costs of case-finding less than 1,000 pesetas per subject. The case-finding pulmonary tuberculosis on arrival at prisons is of high efficiency. In a cost-opportunity situation (location of available resources, penitentiary and extrapenitentiary) the program is very efficacious taking into account the fact of higher prevalence of pulmonary tuberculosis in this people.

The role of neurologists and diagnostic tests in the management of distal symmetric polyneuropathy

PubMed Central

Callaghan, Brian C.; Kerber, Kevin A.; Lisabeth, Lynda L.; Morgenstern, Lewis B.; Longoria, Ruth; Rodgers, Ann; Longwell, Paxton; Feldman, Eva L.

2014-01-01

Importance Distal symmetric polyneuropathy (DSP) is a prevalent condition resulting in high costs from diagnostic testing. However, the role of neurologists and diagnostic tests on patient care is unknown. Objective To determine how often neurologists and diagnostic tests influence the diagnosis and management of DSP patients in a community setting. Design We utilized a validated case-capture method (ICD-9 screening technique with subsequent medical chart abstraction) to identify patients with a new DSP diagnosis (retrospective cohort). Using a structured data abstraction process, diagnostic testing, diagnoses rendered (before and after testing), and subsequent management were recorded. Setting Community neurologist’s outpatient offices in Corpus Christi, Texas. Participants Patients meeting the Toronto consensus criteria for probable DSP. Main Outcome Measure Changes in etiology and management after diagnostic testing by neurologists. Results Between 1/1/2010–3/31/2011, we identified 458 DSP patients followed for mean (SD) 435.3 (44.1) days. Neurologists identified a cause of DSP in 63.5% of cases prior to their diagnostic testing. Seventy-one patients (15.5%) had a new DSP cause discovered after testing by neurologists. The most common new diagnoses were pre-diabetes (N=28), B12 deficiency (N=20), diabetes (N=8), and thyroid disease (N=8). Management changes were common (63.1%), usually related to neuropathic pain management (77.5%). Disease modifying management changes occurred in 24.7% with diabetes management (N=45), starting vitamins (N=39), advising diet/exercise (N=33), and adjusting thyroid medications (N=10) the most common. Electrodiagnostic testing and MRIs of the neuroaxis rarely led to management changes. Conclusions and Relevance Neurologists diagnosed the cause of DSP in almost two-thirds of patients prior to their diagnostic testing. Inexpensive blood tests for diabetes, thyroid dysfunction, and B12 deficiency, allowed neurologists to identify a new etiology in 15.5% of patients. In contrast, expensive electrodiagnostic tests and MRIs rarely changed patient care. Neurologists also frequently made pain medication changes utilizing best evidence medications. PMID:25048157

Rapid molecular diagnostics for multi-drug resistant tuberculosis in India.

PubMed

Ramachandran, Rajeswari; Muniyandi, M

2018-03-01

Rapid molecular diagnostic methods help in the detection of TB and Rifampicin resistance. These methods detect TB early, are accurate and play a crucial role in reducing the burden of drug resistant tuberculosis. Areas covered: This review analyses rapid molecular diagnostic tools used in the diagnosis of MDR-TB in India, such as the Line Probe Assay and GeneXpert. We have discussed the burden of MDR-TB and the impact of recent diagnostic tools on case detection and treatment outcomes. This review also discusses the costs involved in establishing these new techniques in India. Expert commentary: Molecular methods have considerable advantages for the programmatic management of drug resistant TB. These include speed, standardization of testing, potentially high throughput and reduced laboratory biosafety requirements. There is a desperate need for India to adopt modern, rapid, molecular tools with point-of-care tests being currently evaluated. New molecular diagnostic tests appear to be cost effective and also help in detecting missing cases. There is enough evidence to support the scaling up of these new tools in India.

Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever)

DTIC Science & Technology

1990-06-29

particles were used for a rapid serologic diagnostic test for HFRS. ’te-re were 430 cases of HFRS in Korea in 1989 and large outbreaks of scrub typhus...almost same as in 1988. A simple and rapid serologic diagnostic test for hantavirus infection was developed by high density particle agglutination...infection and HFRS b) serologic relation cif hantaviruses isolated from the different parts of the world c) development of a simple serologic diagnostic

Meta-analysis for the comparison of two diagnostic tests to a common gold standard: A generalized linear mixed model approach.

PubMed

Hoyer, Annika; Kuss, Oliver

2018-05-01

Meta-analysis of diagnostic studies is still a rapidly developing area of biostatistical research. Especially, there is an increasing interest in methods to compare different diagnostic tests to a common gold standard. Restricting to the case of two diagnostic tests, in these meta-analyses the parameters of interest are the differences of sensitivities and specificities (with their corresponding confidence intervals) between the two diagnostic tests while accounting for the various associations across single studies and between the two tests. We propose statistical models with a quadrivariate response (where sensitivity of test 1, specificity of test 1, sensitivity of test 2, and specificity of test 2 are the four responses) as a sensible approach to this task. Using a quadrivariate generalized linear mixed model naturally generalizes the common standard bivariate model of meta-analysis for a single diagnostic test. If information on several thresholds of the tests is available, the quadrivariate model can be further generalized to yield a comparison of full receiver operating characteristic (ROC) curves. We illustrate our model by an example where two screening methods for the diagnosis of type 2 diabetes are compared.

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012-2013.

PubMed

Isaac, Beth M; Zucker, Jane R; Giancotti, Francesca R; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L; Rosen, Jennifer B

2017-09-01

The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. Copyright © 2017 American Society for Microbiology.

Attribution of horizontal and vertical contributions to spurious mixing in an Arbitrary Lagrangian-Eulerian ocean model

NASA Astrophysics Data System (ADS)

Gibson, Angus H.; Hogg, Andrew McC.; Kiss, Andrew E.; Shakespeare, Callum J.; Adcroft, Alistair

2017-11-01

We examine the separate contributions to spurious mixing from horizontal and vertical processes in an ALE ocean model, MOM6, using reference potential energy (RPE). The RPE is a global diagnostic which changes only due to mixing between density classes. We extend this diagnostic to a sub-timestep timescale in order to individually separate contributions to spurious mixing through horizontal (tracer advection) and vertical (regridding/remapping) processes within the model. We both evaluate the overall spurious mixing in MOM6 against previously published output from other models (MOM5, MITGCM and MPAS-O), and investigate impacts on the components of spurious mixing in MOM6 across a suite of test cases: a lock exchange, internal wave propagation, and a baroclinically-unstable eddying channel. The split RPE diagnostic demonstrates that the spurious mixing in a lock exchange test case is dominated by horizontal tracer advection, due to the spatial variability in the velocity field. In contrast, the vertical component of spurious mixing dominates in an internal waves test case. MOM6 performs well in this test case owing to its quasi-Lagrangian implementation of ALE. Finally, the effects of model resolution are examined in a baroclinic eddies test case. In particular, the vertical component of spurious mixing dominates as horizontal resolution increases, an important consideration as global models evolve towards higher horizontal resolutions.

The Relationship of Comorbidities and Patient Navigation to Time to Diagnostic Resolution after Abnormal Cancer Screening

PubMed Central

Whitley, Elizabeth M; Raich, Peter C; Dudley, Donald J; Freund, Karen M; Paskett, Electra D; Patierno, Steven R; Simon, Melissa; Warren-Mears, Victoria; Snyder, Frederick R

2016-01-01

Background Whether patient navigation improves outcomes in patients with comorbidities is unknown. Study aims were to determine the effect of comorbidities on time to diagnostic resolution following an abnormal cancer screening test, and to examine for patients with comorbidities, if patient navigation improves timeliness and likelihood of diagnostic resolution compared to patients without navigation. Methods A secondary analysis from the Patient Navigation Research Program sites that collected comorbidity data using the Charlson Comorbidity Index (CCI) was conducted. Participants were 6,349 patients with abnormal breast, cervical, colon or prostate cancer screening tests between 2007 and 2011. The intervention was patient navigation or usual care. CCI data were highly skewed across projects and cancer sites and were categorized as 0, no comorbidities identified, CCI score of 0 (76% of cases); 1, CCI score of 1 (16% of cases); or 2, CCI score of ≥2 (8% of cases). A separate adjusted hazards ratio for each site and cancer type was obtained, and then pooled using meta-analysis random effects methodology. Results Having a CCI score of ≥2 delayed the time to diagnostic resolution following an abnormal cancer screening test compared with those with fewer than one comorbidity. Patient Navigation reduced delays in diagnostic resolution with the greatest benefit seen in those with a CCI score of ≥2. Conclusions Persons with a CCI score of ≥2 experienced significant delays in timely diagnostic care compared to patients without comorbidities. Patient navigation was effective in reducing delays in diagnostic resolution among those with CCI scores > 1. PMID:27648520

False positive malaria rapid diagnostic test in returning traveler with typhoid fever.

PubMed

Meatherall, Bonnie; Preston, Keith; Pillai, Dylan R

2014-07-09

Rapid diagnostic tests play a pivotal role in the early diagnosis of malaria where microscopy or polymerase chain reaction are not immediately available. We report the case of a 39 year old traveler to Canada who presented with fever, headache, and abdominal pain after visiting friends and relatives in India. While in India, the individual was not ill and had no signs or symptoms of malaria. Laboratory testing upon his return to Canada identified a false positive malaria rapid diagnostic (BinaxNOW® malaria) result for P. falciparum with coincident Salmonella Typhi bacteraemia without rheumatoid or autoimmune factors. Rapid diagnostic test false positivity for malaria coincided with the presence or absence of Salmonella Typhi in the blood. Clinicians should be aware that Salmonella Typhi infection may result in a false positive malaria rapid diagnostic test. The mechanism of this cross-reactivity is not clear.

Performance of Dengue Diagnostic Tests in a Single-Specimen Diagnostic Algorithm.

PubMed

Hunsperger, Elizabeth A; Muñoz-Jordán, Jorge; Beltran, Manuela; Colón, Candimar; Carrión, Jessica; Vazquez, Jesus; Acosta, Luz Nereida; Medina-Izquierdo, Juan F; Horiuchi, Kalanthe; Biggerstaff, Brad J; Margolis, Harold S

2016-09-15

Anti-dengue virus (DENV) immunoglobulin M (IgM) seroconversion has been the reference standard for dengue diagnosis. However, paired specimens are rarely obtained, and the interval for this testing negates its usefulness in guiding clinical case management. The presence of DENV viremia and appearance of IgM during the febrile phase of dengue provides the framework for dengue laboratory diagnosis by using a single serum specimen. Archived paired serum specimens (n = 1234) from patients with laboratory-confirmed dengue from 2005 through 2011 were used to determine the diagnostic performance of real-time reverse transcription polymerase chain reaction (RT-PCR), for detection of DENV serotypes 1-4, and enzyme-linked immunosorbent assays (ELISAs), for detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM. During 1-3 days after illness onset, real-time RT-PCR and NS1 antigen testing detected 82%-69% and 90%-84% of cases, respectively, as viremia levels declined, while anti-DENV IgM ELISA detected 5%-41% of cases as antibody appeared. Over the 10-day period of the febrile phase of dengue, the cumulative effect of using these 3 types of tests in a diagnostic algorithm confirmed ≥90% of dengue cases. The use of molecular or NS1 antigen tests to detect DENV and one to detect anti-DENV IgM in a single serum specimen collected during the first 10 days of illness accurately identified ≥90% of dengue primary and secondary cases. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

PubMed

Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

2016-10-07

Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

Current approach in the diagnosis and management of posterior uveitis

PubMed Central

Sudharshan, S; Ganesh, Sudha K; Biswas, Jyotrimay

2010-01-01

Posterior uveitic entities are varied entities that are infective or non-infective in etiology. They can affect the adjacent structures such as the retina, vitreous, optic nerve head and retinal blood vessels. Thorough clinical evaluation gives a clue to the diagnosis while ancillary investigations and laboratory tests assist in confirming the diagnosis. Newer evolving techniques in the investigations and management have increased the diagnostic yield. In case of diagnostic dilemma, intraocular fluid evaluation for polymerase chain testing for the genome and antibody testing against the causative agent provide greater diagnostic ability. PMID:20029144

The Log-Linear Cognitive Diagnostic Model (LCDM) as a Special Case of The General Diagnostic Model (GDM). Research Report. ETS RR-14-40

ERIC Educational Resources Information Center

von Davier, Matthias

2014-01-01

Diagnostic models combine multiple binary latent variables in an attempt to produce a latent structure that provides more information about test takers' performance than do unidimensional latent variable models. Recent developments in diagnostic modeling emphasize the possibility that multiple skills may interact in a conjunctive way within the…

Variability in the diagnostic performance of a bedside rapid diagnostic influenza test over four epidemic seasons in a pediatric emergency department.

PubMed

Avril, E; Lacroix, S; Vrignaud, B; Moreau-Klein, A; Coste-Burel, M; Launay, E; Gras-Le Guen, C

2016-07-01

We wanted to determine the diagnostic performance of a rapid influenza diagnostic test (RIDT) used bedside in a pediatric emergency department (PED). This was a prospective study over four consecutive winters (2009-2013), comparing the results of a RIDT (QuickVue®) with RT-PCR in children admitted to a PED. Among the 764 children included, we did not observe any significant differences in the diagnostic performance of RIDT except during the H1N1 pandemic. The overall sensitivity of the test was 0.82; the specificity 0.98; the positive and negative likelihood ratios 37.8 and 0.19. The positive and negative post-test probabilities of infection were 98% and 17%. The diagnostic performance was increased for influenza B cases (P = 0.03). RIDTs are suitable for use every winter with few differences in its diagnostic value, except during specific pandemic periods. This test could limit unnecessary complementary exams and guide the prescription of antivirals during influenza epidemic periods in PEDs. Copyright © 2016. Published by Elsevier Inc.

Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

PubMed Central

2011-01-01

Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT). The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85%) and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%), drug stores (14%), mobile providers (4%) and grocery stores (2%). Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61%) and private (42%) sectors. Conclusions While data on the anti-malarial market shows favourable progress towards replacing artemisinin monotherapies with ACT, the widespread use of drug cocktails to treat malaria is a barrier to effective case management. Significant achievements have been made in availability of diagnostic testing and effective treatment in the public and private sectors. However, interventions to improve case management are urgently required, particularly in the private sector. Evidence-based interventions that target provider and consumer behaviour are needed to support uptake of diagnostic testing and treatment with full-course first-line anti-malarials. PMID:22039922

Evaluation of case management of uncomplicated malaria in Haiti: a national health facility survey, 2012.

PubMed

Landman, Keren Z; Jean, Samuel E; Existe, Alexandre; Akom, Eniko E; Chang, Michelle A; Lemoine, Jean Frantz; Mace, Kimberly E

2015-10-09

Malaria is a public health concern in Haiti, although there are limited data on its burden and case management. National malaria guidelines updated in 2012 recommend treatment with chloroquine and primaquine. In December 2012, a nationally-representative cross-sectional survey of health facilities (HFs) was conducted to determine malaria prevalence among febrile outpatients and malaria case management quality at baseline before scale-up of diagnostics and case management training. Among all 833 HFs nationwide, 30 were selected randomly, in proportion to total HFs per region, for 2-day evaluations. Survey teams inventoried HF material and human resources. Outpatients of all ages were screened for temperature >37.5 °C or history of fever; those without severe symptoms were consented and enrolled. Providers evaluated and treated enrolled patients according to HF standards; the survey teams documented provider-ordered diagnostic tests and treatment decisions. Facility-based test results [microscopy and malaria rapid diagnostic tests (RDTs)] were collected from HF laboratories. Blood smears for gold-standard microscopy, and dried blood spots for polymerase chain reaction (PCR) were obtained. Malaria diagnostic capacity, defined as completing a test for an enrolled patient or having adequate resources for RDTs or microscopy, was present in 11 (37 %) HFs. Among 459 outpatients screened, 257 (56 %) were febrile, of which 193 (75 %) were eligible, and 153 (80 %) were enrolled. Among 39 patients with facility-level malaria test results available on the survey day, 11 (28 %) were positive, of whom 6 (55 %) were treated with an anti-malarial. Twenty-seven (95 %) of the 28 patients testing negative were not treated with an anti-malarial. Of 114 patients without test results available, 35 (31 %) were presumptively treated for malaria. Altogether, 42 patients were treated with an anti-malarial, one (2 %) according to Haiti's 2012 guidelines. Of 140 gold-standard smears, none were positive, although one patient tested positive by PCR, a more sensitive technique. The national prevalence of malaria among febrile outpatients is estimated to be 0.5 % (95 % confidence interval 0-1.7 %). Malaria is an uncommon cause of fever in Haitian outpatients, and limited, often inaccurate, diagnostic capacity at baseline contributes to over diagnosis. Scale-up of diagnostics and training on new guidelines should improve malaria diagnosis and treatment in Haiti.

Emergency coronary angioplasty with stenting using Cordis® diagnostic coronary catheters when there is difficulty in engaging guide catheters and bench evaluation of diagnostic and guide catheters.

PubMed

Arokiaraj, Mark Christopher

2018-02-01

Difficulty in engaging with guide catheters is not uncommon in acute emergencies. We aimed to evaluate the use of Cordis ® INFINITI diagnostic catheters to perform angioplasty in patients in whom the coronaries cannot be engaged using standard guide catheters. In 34 cases of acute coronary syndrome, when difficulty in engagement with two standard guide catheters was encountered with reasonable manipulations, angioplasty was performed using diagnostic catheters. In total, 40 stents were placed by this technique. Pushability and trackability, distal tip flexion and three-point bending tests were performed to evaluate the performance of the guide and diagnostic catheters. Angioplasty was performed easily in a setting where it would have been very difficult to perform. Coronary dissection occurred in one patient, treated by a stent. The stent and dilatation balloons were easily passed through the diagnostic catheters. Pressure tracings were clearly preserved with certain stent delivery systems, and at angioplasty, although there was slightly reduced opacification of the respective artery, the coronary anatomy was sufficiently visualized to perform angioplasty. No periprocedural target lesion complications were seen in any cases. Pushability and trackability tests showed good force transmission along a tortuous path with diagnostic catheters, and balanced force-displacement curves from three-point bending tests and distal tip softness tests. Angioplasty with stenting can be performed safely through 6F Cordis ® infiniti diagnostic catheters when difficulty in engaging guide catheters is encountered. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Intelligent Engine Systems

NASA Technical Reports Server (NTRS)

Xie, Ming

2008-01-01

A high bypass jet engine fan case represents one of the largest, heaviest single components in an engine. In addition to supporting the inlet and providing the fan flowpath, the most critical function is the containment of a failed fan blade. In this development program, a lightweight, low-cost composite containment case with diagnostic capabilities was developed, fabricated, and tested. The fan case design, containment methods, and diagnostic concepts evaluated in the initial Propulsion 21 program were improved and scaled up to a full case design.

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.

Using Informatics and the Electronic Medical Record to Describe Antimicrobial Use in the Clinical Management of Diarrhea Cases at 12 Companion Animal Practices

PubMed Central

Anholt, R. Michele; Berezowski, John; Ribble, Carl S.; Russell, Margaret L.; Stephen, Craig

2014-01-01

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%–95.4%) and specificity (85%, 95% confidence interval, 80.2%–89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use. PMID:25057893

Using informatics and the electronic medical record to describe antimicrobial use in the clinical management of diarrhea cases at 12 companion animal practices.

PubMed

Anholt, R Michele; Berezowski, John; Ribble, Carl S; Russell, Margaret L; Stephen, Craig

2014-01-01

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%-95.4%) and specificity (85%, 95% confidence interval, 80.2%-89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use.

30 CFR 250.524 - When am I required to take action from my casing diagnostic test?

Code of Federal Regulations, 2011 CFR

2011-07-01

.../casing, tubing/riser, casing/casing, riser/casing, or riser/riser communication; (d) Any well that has... initial startup operations described in § 250.521; (e) Any hybrid well with casing or riser pressure...

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

Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.

PubMed

Foutz, Aaron; Appleby, Brian S; Hamlin, Clive; Liu, Xiaoqin; Yang, Sheng; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Fausett, Cameron; Wang, Han; Gambetti, Pierluigi; Zhang, Shulin; Hughson, Andrew; Tatsuoka, Curtis; Schonberger, Lawrence B; Cohen, Mark L; Caughey, Byron; Safar, Jiri G

2017-01-01

Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases that were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and type 1 or type 2 human prions on diagnostic performance. The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1-2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, whereas genetic prion diseases revealed distinct profiles for each PRNP gene mutation. The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and tau proteins, and together with PRNP gene sequencing the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease-two important considerations for envisioned therapeutic interventions. ANN NEUROL 2017;81:79-92. © 2016 American Neurological Association.

Diagnostic and Prognostic Value of Human Prion Detection in Cerebrospinal Fluid

PubMed Central

Foutz, Aaron; Appleby, Brian S.; Hamlin, Clive; Liu, Xiaoqin; Yang, Sheng; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Fausett, Cameron; Wang, Han; Gambetti, Pierluigi; Zhang, Shulin; Hughson, Andrew; Tatsuoka, Curtis; Schonberger, Lawrence B.; Cohen, Mark L.; Caughey, Byron; Safar, Jiri G.

2016-01-01

Objective Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. Methods We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases which were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and Type 1 or Type 2 of human prions on diagnostic performance. Results The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1–2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, while genetic prion diseases revealed distinct profiles for each PRNP gene mutation. Interpretation The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and Tau proteins and together with PRNP gene sequencing, the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease—two important considerations for envisioned therapeutic interventions. PMID:27893164

Learning Machine Learning: A Case Study

ERIC Educational Resources Information Center

Lavesson, N.

2010-01-01

This correspondence reports on a case study conducted in the Master's-level Machine Learning (ML) course at Blekinge Institute of Technology, Sweden. The students participated in a self-assessment test and a diagnostic test of prerequisite subjects, and their results on these tests are correlated with their achievement of the course's learning…

Teaching clinical reasoning: case-based and coached.

PubMed

Kassirer, Jerome P

2010-07-01

Optimal medical care is critically dependent on clinicians' skills to make the right diagnosis and to recommend the most appropriate therapy, and acquiring such reasoning skills is a key requirement at every level of medical education. Teaching clinical reasoning is grounded in several fundamental principles of educational theory. Adult learning theory posits that learning is best accomplished by repeated, deliberate exposure to real cases, that case examples should be selected for their reflection of multiple aspects of clinical reasoning, and that the participation of a coach augments the value of an educational experience. The theory proposes that memory of clinical medicine and clinical reasoning strategies is enhanced when errors in information, judgment, and reasoning are immediately pointed out and discussed. Rather than using cases artificially constructed from memory, real cases are greatly preferred because they often reflect the false leads, the polymorphisms of actual clinical material, and the misleading test results encountered in everyday practice. These concepts foster the teaching and learning of the diagnostic process, the complex trade-offs between the benefits and risks of diagnostic tests and treatments, and cognitive errors in clinical reasoning. The teaching of clinical reasoning need not and should not be delayed until students gain a full understanding of anatomy and pathophysiology. Concepts such as hypothesis generation, pattern recognition, context formulation, diagnostic test interpretation, differential diagnosis, and diagnostic verification provide both the language and the methods of clinical problem solving. Expertise is attainable even though the precise mechanisms of achieving it are not known.

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.

Mixed Methods Survey of Zoonotic Disease Awareness and Practice among Animal and Human Healthcare Providers in Moshi, Tanzania

PubMed Central

Zhang, Helen L.; Mnzava, Kunda W.; Mitchell, Sarah T.; Melubo, Matayo L.; Kibona, Tito J.; Cleaveland, Sarah; Kazwala, Rudovick R.; Crump, John A.; Sharp, Joanne P.; Halliday, Jo E. B.

2016-01-01

Background Zoonoses are common causes of human and livestock illness in Tanzania. Previous studies have shown that brucellosis, leptospirosis, and Q fever account for a large proportion of human febrile illness in northern Tanzania, yet they are infrequently diagnosed. We conducted this study to assess awareness and knowledge regarding selected zoonoses among healthcare providers in Moshi, Tanzania; to determine what diagnostic and treatment protocols are utilized; and obtain insights into contextual factors contributing to the apparent under-diagnosis of zoonoses. Methodology/Results We conducted a questionnaire about zoonoses knowledge, case reporting, and testing with 52 human health practitioners and 10 livestock health providers. Immediately following questionnaire administration, we conducted semi-structured interviews with 60 of these respondents, using the findings of a previous fever etiology study to prompt conversation. Sixty respondents (97%) had heard of brucellosis, 26 (42%) leptospirosis, and 20 (32%) Q fever. Animal sector respondents reported seeing cases of animal brucellosis (4), rabies (4), and anthrax (3) in the previous 12 months. Human sector respondents reported cases of human brucellosis (15, 29%), rabies (9, 18%) and anthrax (6, 12%). None reported leptospirosis or Q fever cases. Nineteen respondents were aware of a local diagnostic test for human brucellosis. Reports of tests for human leptospirosis or Q fever, or for any of the study pathogens in animals, were rare. Many respondents expressed awareness of malaria over-diagnosis and zoonoses under-diagnosis, and many identified low knowledge and testing capacity as reasons for zoonoses under-diagnosis. Conclusions This study revealed differences in knowledge of different zoonoses and low case report frequencies of brucellosis, leptospirosis, and Q fever. There was a lack of known diagnostic services for leptospirosis and Q fever. These findings emphasize a need for improved diagnostic capacity alongside healthcare provider education and improved clinical guidelines for syndrome-based disease management to provoke diagnostic consideration of locally relevant zoonoses in the absence of laboratory confirmation. PMID:26943334

Script-theory virtual case: A novel tool for education and research.

PubMed

Hayward, Jake; Cheung, Amandy; Velji, Alkarim; Altarejos, Jenny; Gill, Peter; Scarfe, Andrew; Lewis, Melanie

2016-11-01

Context/Setting: The script theory of diagnostic reasoning proposes that clinicians evaluate cases in the context of an "illness script," iteratively testing internal hypotheses against new information eventually reaching a diagnosis. We present a novel tool for teaching diagnostic reasoning to undergraduate medical students based on an adaptation of script theory. We developed a virtual patient case that used clinically authentic audio and video, interactive three-dimensional (3D) body images, and a simulated electronic medical record. Next, we used interactive slide bars to record respondents' likelihood estimates of diagnostic possibilities at various stages of the case. Responses were dynamically compared to data from expert clinicians and peers. Comparative frequency distributions were presented to the learner and final diagnostic likelihood estimates were analyzed. Detailed student feedback was collected. Over two academic years, 322 students participated. Student diagnostic likelihood estimates were similar year to year, but were consistently different from expert clinician estimates. Student feedback was overwhelmingly positive: students found the case was novel, innovative, clinically authentic, and a valuable learning experience. We demonstrate the successful implementation of a novel approach to teaching diagnostic reasoning. Future study may delineate reasoning processes associated with differences between novice and expert responses.

Market surveillance of in vitro diagnostics by the BfArM until end 2010: how safe are products for tumor diagnostics?

PubMed

Siekmeier, R; Wetzel, D

2013-01-01

The European Directive 98/79/EC on in vitro diagnostic medical devices (IVD) regulates the marketing and post market surveillance of IVD in the European Economic Area. In cases of incidents and field corrective actions the manufacturers have to inform the responsible Competent Authorities (CA). In Germany, the Federal Institute for Drugs and Medical Devices (BfArM) is the responsible CA for most IVD. In this study all notifications regarding IVD (tests, calibrators, kits, and control materials, except laboratory analyzers) for tumor diagnostics received by the BfArM between begin 1999 until end of 2010 were analyzed. All notifications were analyzed in respect to the type of product, the source of notification, the underlying product defects and the corrective actions performed. In the observation period, a total of 2,851 notifications were received of which 84 were related to IVD for tumor diagnostics included in this study (clinical chemistry - 63, histology - 6, molecular biology - 3, rapid tests - 12). Reports were received from manufacturers (68 cases), CA (8 cases), users (4 cases) and other sources (4 cases). In the group of IVD based on clinical chemistry means, the affected products were mostly those for the measurement of prostate specific antigen (PSA, 14 cases), human chorion gonadotropine (13 cases), carcino embryonic antigen (6 cases), CA 19-9 (6 cases), α(1)-fetoprotein (6 cases) and CA 125 (5 cases), whereas in test strips 9 out of the 12 notifications were related to PSA. Investigations of the manufacturers were able to identify the underlying root causes of product failures in 66 cases (78.6%). In 10 cases (11.9%) the root cause remained unclear and in 6 cases and 2 cases (7.1% and 2.4%) a product failure was excluded or a user error was the underlying cause. Most common root causes of product failures were material defects (24 cases) and manufacturing errors (15 cases). Corrective actions were performed by the manufacturers in 64 cases (76.2%) and were predominantly (multiple entries possible) customer information (62 cases, mandatory in case of a recall), recalls (45 cases), modifications in production or quality management (45 cases) and design changes (14 cases). The obtained results suggest that the system for post marketing surveillance of IVD is an established tool to enhance product safety and provides valuable information on product specific problems serving for improvement of product safety.

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

The hypersensitivity pneumonitis diagnostic index: use of non-invasive testing to diagnose hypersensitivity pneumonitis in metalworkers.

PubMed

Dangman, Kenneth H; Cole, Solon R; Hodgson, Michael J; Kuhn, Charles; Metersky, Mark L; Schenck, Paula; Storey, Eileen

2002-08-01

Since 1993, several outbreaks of hypersensitivity pneumonitis (HP) have been reported in metalworkers. We report the largest outbreak of HP in metalworkers yet known. It occurred in a Connecticut factory that produces precision parts for the aerospace industry. The workers typically presented with systemic and respiratory problems ("sick fatigue," myalgias, cough, dyspnea, wheezing, and chest tightness). They had variable findings on clinical tests, which complicated diagnosis. An HP diagnostic index was developed to help reduce the uncertainties in case identification. Data from 16 biopsy-confirmed cases and 14 non-HP patients were compared, and the HP diagnostic index was derived using variables that best discriminated between the two groups. The index is based on (a) work-related symptoms, (b) dry crackles on auscultation, (c) restrictive spirometry, (d) decreased diffusion capacity and/or increased A-a oxygen gradient, (e) elevated erythrocyte sedimentation rate, (f) abnormal radiographic images, and (g) abnormal gallium scans. We then applied the HP diagnostic index and, for comparison, the "Kenosha epidemiological case criteria" (developed during a recent HP outbreak in an automobile factory) to our data set. The HP diagnostic index and the Kenosha criteria confirmed HP in overlapping sets of 36 and 34 patients, respectively, that were both in good agreement with the clinical diagnoses. The HP diagnostic index relies less heavily on symptoms, subjective evaluations, and invasive tests than the Kenosha criteria, but both identified similar subsets of the 61 patients as having HP. The HP diagnostic index could provide a useful tool in future HP outbreaks, which are increasingly being recognized in metalworking facilities. Copyright 2002 Wiley-Liss, Inc.

Relation of comorbidities and patient navigation with the time to diagnostic resolution after abnormal cancer screening.

PubMed

Whitley, Elizabeth M; Raich, Peter C; Dudley, Donald J; Freund, Karen M; Paskett, Electra D; Patierno, Steven R; Simon, Melissa; Warren-Mears, Victoria; Snyder, Frederick R

2017-01-01

Whether patient navigation improves outcomes for patients with comorbidities is unknown. The aims of this study were to determine the effect of comorbidities on the time to diagnostic resolution after an abnormal cancer screening test and to examine whether patient navigation improves the timeliness and likelihood of diagnostic resolution for patients with comorbidities in comparison with no navigation. A secondary analysis of comorbidity data collected by Patient Navigation Research Program sites using the Charlson Comorbidity Index (CCI) was conducted. The participants were 6,349 patients with abnormal breast, cervical, colon, or prostate cancer screening tests between 2007 and 2011. The intervention was patient navigation or usual care. The CCI data were highly skewed across projects and cancer sites, and the CCI scores were categorized as 0 (CCI score of 0 or no comorbidities identified; 76% of cases); 1 (CCI score of 1; 16% of cases), or 2 (CCI score ≥ 2; 8% of cases). Separate adjusted hazard ratios for each site and cancer type were obtained, and then they were pooled with a meta-analysis random effects methodology. Patients with a CCI score ≥ 2 had delayed diagnostic resolution after an abnormal cancer screening test in comparison with those with no comorbidities. Patient navigation reduced delays in diagnostic resolution, with the greatest benefits seen for those with a CCI score ≥ 2. Persons with a CCI score ≥ 2 experienced significant delays in timely diagnostic care in comparison with patients without comorbidities. Patient navigation was effective in reducing delays in diagnostic resolution among those with CCI scores > 1. Cancer 2017;123:312-318. © 2016 American Cancer Society. © 2016 American Cancer Society.

Case Report: A Case of Plasmodium falciparum hrp2 and hrp3 Gene Mutation in Bangladesh.

PubMed

Nima, Maisha Khair; Hougard, Thomas; Hossain, Mohammad Enayet; Kibria, Mohammad Golam; Mohon, Abu Naser; Johora, Fatema Tuj; Rahman, Rajibur; Haque, Rashidul; Alam, Mohammad Shafiul

2017-10-01

Several species of Plasmodium are responsible for causing malaria in humans. Proper diagnoses are crucial to case management, because severity and treatment varies between species. Diagnoses can be made using rapid diagnostic tests (RDTs), which detect Plasmodium proteins. Plasmodium falciparum causes the most virulent cases of malaria, and P. falciparum histidine-rich protein 2 (PfHRP2) is a common target of falciparum malaria RDTs. Here we report a case in which a falciparum malaria patient in Bangladesh tested negative on PfHRP2-based RDTs. The negative results can be attributed to a deletion of part of the pfhrp2 gene and frameshift mutations in both pfhrp2 and pfhrp3 gene. This finding may have implications for malaria diagnostics and case management in Bangladesh and other regions of South Asia.

30 CFR 250.527 - What must I include in my casing pressure request?

Code of Federal Regulations, 2011 CFR

2011-07-01

... casing/riser calculated MAWOPs; (h) All casing/riser pre-bleed down pressures; (i) Shut-in tubing... test (oil, gas, basic sediment, and water); (l) Well status (shut-in, temporarily abandoned, producing, injecting, or gas lift); (m) Well type (dry tree, hybrid, or subsea); (n) Date of diagnostic test; (o) Well...

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

PubMed

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

Initial impact and cost of a nationwide population screening campaign for diabetes in Brazil: A follow up study

PubMed Central

Toscano, Cristiana M; Duncan, Bruce B; Mengue, Sotero S; Polanczyk, Carísi Anne; Nucci, Luciana B; Costa e Forti, Adriana; Fonseca, Cláudio D; Schmidt, Maria Inês

2008-01-01

Background In 2001 Brazilian citizens aged 40 or older were invited to participate in a nationwide population screening program for diabetes. Capillary glucose screening tests and procedures for diagnostic confirmation were offered through the national healthcare system, diagnostic priority being given according to the severity of screening results. The objective of this study is to evaluate the initial impact of the program. Methods Positive testing was defined by a fasting capillary glucose ≥ 100 mg/dL or casual glucose ≥ 140 mg/dL. All test results were tabulated locally and aggregate data by gender and clinical categories were sent to the Ministry of Health. To analyze individual characteristics of screening tests performed, a stratified random sample of 90,106 tests was drawn. To describe the actions taken for positive screenees, a random sub-sample of 4,906 positive screenees was actively followed up through home interviews. Main outcome measures considered were the number of diabetes cases diagnosed and cost per case detected and incorporated into healthcare. Results Of 22,069,905 screening tests performed, we estimate that 3,417,106 (95% CI 3.1 – 3.7 million) were positive and that 346,168 (290,454 – 401,852) new cases were diagnosed (10.1% of positives), 319,157 (92.2%) of these being incorporated into healthcare. The number of screening tests needed to detect one case of diabetes was 64. As many cases of untreated but previously known diabetes were also linked to healthcare providers during the Campaign, the estimated number needed screen to incorporate one case into the healthcare system was 58. Total screening and diagnostic costs were US$ 26.19 million, the cost per diabetes case diagnosed being US$ 76. Results were especially sensitive to proportion of individuals returning for diagnostic confirmation. Conclusion This nationwide population-based screening program, conducted through primary healthcare services, demonstrates the feasibility, within the context of an organized national healthcare system, of screening campaigns for chronic diseases. Although overall costs were significant, cost per new case diagnosed was lower than previously reported. However, cost-effectiveness analysis based on more clinically significant outcomes needs to be conducted before this screening approach can be recommended in other settings. PMID:18808662

Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children.

PubMed

Santos, Alexandra F; Douiri, Abdel; Bécares, Natalia; Wu, Shih-Ying; Stephens, Alick; Radulovic, Suzana; Chan, Susan M H; Fox, Adam T; Du Toit, George; Turcanu, Victor; Lack, Gideon

2014-09-01

Most of the peanut-sensitized children do not have clinical peanut allergy. In equivocal cases, oral food challenges (OFCs) are required. However, OFCs are laborious and not without risk; thus, a test that could accurately diagnose peanut allergy and reduce the need for OFCs is desirable. To assess the performance of basophil activation test (BAT) as a diagnostic marker for peanut allergy. Peanut-allergic (n = 43), peanut-sensitized but tolerant (n = 36) and non-peanut-sensitized nonallergic (n = 25) children underwent skin prick test (SPT) and specific IgE (sIgE) to peanut and its components. BAT was performed using flow cytometry, and its diagnostic performance was evaluated in relation to allergy versus tolerance to peanut and validated in an independent population (n = 65). BAT in peanut-allergic children showed a peanut dose-dependent upregulation of CD63 and CD203c while there was no significant response to peanut in peanut-sensitized but tolerant (P < .001) and non-peanut-sensitized nonallergic children (P < .001). BAT optimal diagnostic cutoffs showed 97% accuracy, 95% positive predictive value, and 98% negative predictive value. BAT allowed reducing the number of required OFCs by two-thirds. BAT proved particularly useful in cases in which specialists could not accurately diagnose peanut allergy with SPT and sIgE to peanut and to Arah2. Using a 2-step diagnostic approach in which BAT was performed only after equivocal SPT or Arah2-sIgE, BAT had a major effect (97% reduction) on the number of OFCs required. BAT proved to be superior to other diagnostic tests in discriminating between peanut allergy and tolerance, particularly in difficult cases, and reduced the need for OFCs. Copyright © 2014. Published by Elsevier Inc.

Utilization of flow cytometry for diagnosis of hematologic malignancies in Thailand: increasing trends and diagnostic yields in 7,982 samples.

PubMed

Promsuwicha, Orathai; Kankhao, Supattra; Songmuang, Wayuree; Auewarakul, Chirayu U

2014-12-01

Diagnosis of hematologic malignancies requires a multidisciplinary approach. Flow cytometry (FCM) has become an essential tool for immunophenotypic studies of malignant hematopoietic cells. To evaluate the utilization trend of FCM and its diagnostic yields for hematologic malignancy at a major teaching hospital in Thailand. FCM results of bone marrow (BM) and peripheral blood (PB) specimens during 2000-2013 were analyzed and compared to clinical diagnosis. Overall, 7,982 specimens were submitted for diagnostic FCM including 6,561 BM and 1,421 PB. The number of specimens analyzedwas 121, 142, 164, 299, 491, 431, 690, 611, 719, 744, 725, 863, 955 and 1,027, respectively, from 2000 to 2013. The most common clinical diagnoses requested for FCM were acute leukemia (5,911 cases, 74%) followed by lymphoma (1,419 cases, 17.8%), and chronic lymphocytic leukemia (CLL) (634 cases, 7.94%). The highest diagnostic yield of FCM was found in acute leukemia cases (69.71%) followed by CLL (35.33%). Only 15.43% of clinically suspected lymphoma cases were positive by FCM. Overutilization of PB (35.6% of cases) instead of BM for lymphoma staging significantly contributed to low diagnostic yields of lymphoma by FCM as circulating tumor cells may not be present in such cases. FCM has an increasing role in the diagnosis of hematologic malignancies in Thai patients over the past 14 years with the highest diagnostic yield in acute leukemia. Appropriate specimen types and study indications are required in order to reduce futility of costly diagnostic tests and improve diagnostic yields.

Cost analysis of breast cancer diagnostic assessment programs.

PubMed

Honein-AbouHaidar, G N; Hoch, J S; Dobrow, M J; Stuart-McEwan, T; McCready, D R; Gagliardi, A R

2017-10-01

Diagnostic assessment programs (daps) appear to improve the diagnosis of cancer, but evidence of their cost-effectiveness is lacking. Given that no earlier study used secondary financial data to estimate the cost of diagnostic tests in the province of Ontario, we explored how to use secondary financial data to retrieve the cost of key diagnostic test services in daps, and we tested the reliability of that cost-retrieving method with hospital-reported costs in preparation for future cost-effectiveness studies. We powered our sample at an alpha of 0.05, a power of 80%, and a margin of error of ±5%, and randomly selected a sample of eligible patients referred to a dap for suspected breast cancer during 1 January-31 December 2012. Confirmatory diagnostic tests received by each patient were identified in medical records. Canadian Classification of Health Intervention procedure codes were used to search the secondary financial data Web portal at the Ontario Case Costing Initiative for an estimate of the direct, indirect, and total costs of each test. The hospital-reported cost of each test received was obtained from the host-hospital's finance department. Descriptive statistics were used to calculate the cost of individual or group confirmatory diagnostic tests, and the Wilcoxon signed-rank test or the paired t-test was used to compare the Ontario Case Costing Initiative and hospital-reported costs. For the 191 identified patients with suspected breast cancer, the estimated total cost of $72,195.50 was not significantly different from the hospital-reported total cost of $72,035.52 ( p = 0.24). Costs differed significantly when multiple tests to confirm the diagnosis were completed during one patient visit and when confirmatory tests reported in hospital data and in medical records were discrepant. The additional estimated cost for non-salaried physicians delivering diagnostic services was $28,387.50. It was feasible to use secondary financial data to retrieve the cost of key diagnostic tests in a breast cancer dap and to compare the reliability of the costs obtained by that estimation method with hospital-reported costs. We identified the strengths and challenges of each approach. Lessons learned from this study have to be taken into consideration in future cost-effectiveness studies.

Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics.

PubMed

Steyer, Andrej; Jevšnik, Monika; Petrovec, Miroslav; Pokorn, Marko; Grosek, Štefan; Fratnik Steyer, Adela; Šoba, Barbara; Uršič, Tina; Cerar Kišek, Tjaša; Kolenc, Marko; Trkov, Marija; Šparl, Petra; Duraisamy, Raja; Lipkin, W Ian; Terzić, Sara; Kolnik, Mojca; Mrvič, Tatjana; Kapoor, Amit; Strle, Franc

2016-09-01

Twenty-five percent to 50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. Two hundred ninety seven children ≤6 years of age, admitted to hospital in Slovenia, October 2011 to October 2012, with AGE, and 88 ≤6 years old healthy children were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing, and a potential viral pathogen was detected in 17 additional samples (5.8%). Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens.

Prenatal diagnostic procedures used in pregnancies with congenital malformations in 14 regions of Europe.

PubMed

Garne, Ester; Loane, Maria; de Vigan, Catherine; Scarano, Gioacchino; de Walle, Hermien; Gillerot, Yves; Stoll, Claude; Addor, Marie-Claude; Stone, David; Gener, Blanca; Feijoo, Maria; Mosquera-Tenreiro, Carmen; Gatt, Miriam; Queisser-Luft, Annette; Baena, Neus; Dolk, Helen

2004-11-01

To investigate outcomes of ultrasound investigations (US) and invasive diagnostic procedures in cases of congenital malformations (CM), and to compare the use of invasive prenatal test techniques (amniocentesis (AC) versus chorionic villus sampling (CVS)) among European populations. Analysis of data from population-based registries of CM. 25 400 cases of CM recorded by 14 EUROCAT registries covering a total population of 1,013,352 births 1995-99. US were performed in 91% of cases, and positively detected CM in 35% of cases. AC was performed in 24% of the cases and CVS in 3% of cases. Thirty-eight percent of invasive tests gave positive results. Fifty-two percent of cases with maternal age > or = 35 years had an invasive test performed compared to 20% of cases with younger mothers. Considerable variation was found between registries in the uptake rate of invasive tests in cases with older maternal age and on the use of invasive tests with only four regions employing CVS techniques in at least a third of the cases having invasive tests. For chromosomal anomalies US gave positive results in 46% of cases with maternal age < 35 years with US performed and in 36% of cases with maternal age > or = 35 years with US performed. Prenatal US was performed in 91% of all pregnancies with CM but the test was only positive in a third of the cases. There was large regional variation in the uptake rate of invasive tests with maternal age of 35 years or more. For every CVS carried out there were nine AC tests. US is an important tool in the prenatal diagnosis of chromosomal anomalies in Europe. Copyright 2004 John Wiley & Sons, Ltd.

Outcome of Whole Exome Sequencing for Diagnostic Odyssey Cases of an Individualized Medicine Clinic: The Mayo Clinic Experience.

PubMed

Lazaridis, Konstantinos N; Schahl, Kimberly A; Cousin, Margot A; Babovic-Vuksanovic, Dusica; Riegert-Johnson, Douglas L; Gavrilova, Ralitza H; McAllister, Tammy M; Lindor, Noralane M; Abraham, Roshini S; Ackerman, Michael J; Pichurin, Pavel N; Deyle, David R; Gavrilov, Dimitar K; Hand, Jennifer L; Klee, Eric W; Stephens, Michael C; Wick, Myra J; Atkinson, Elizabeth J; Linden, David R; Ferber, Matthew J; Wieben, Eric D; Farrugia, Gianrico

2016-03-01

To describe the experience and outcome of performing whole-exome sequencing (WES) for resolution of patients on a diagnostic odyssey in the first 18 months of an individualized medicine clinic (IMC). The IMC offered WES to physicians of Mayo Clinic practice for patients with suspected genetic disease. DNA specimens of the proband and relatives were submitted to WES laboratories. We developed the Genomic Odyssey Board with multidisciplinary expertise to determine the appropriateness for IMC services, review WES reports, and make the final decision about whether the exome findings explain the disease. This study took place from September 30, 2012, to March 30, 2014. In the first 18 consecutive months, the IMC received 82 consultation requests for patients on a diagnostic odyssey. The Genomic Odyssey Board deferred 7 cases and approved 75 cases to proceed with WES. Seventy-one patients met with an IMC genomic counselor. Fifty-one patients submitted specimens for WES testing, and the results have been received for all. There were 15 cases in which a diagnosis was made on the basis of WES findings; thus, the positive diagnostic yield of this practice was 29%. The mean cost per patient for this service was approximately $8000. Medicaid supported 27% of the patients, and 38% of patients received complete or partial insurance coverage. The significant diagnostic yield, moderate cost, and notable health marketplace acceptance for WES compared with conventional genetic testing make the former method a rational diagnostic approach for patients on a diagnostic odyssey. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Diagnostic reasoning by hospital pharmacists: assessment of attitudes, knowledge, and skills.

PubMed

Chernushkin, Kseniya; Loewen, Peter; de Lemos, Jane; Aulakh, Amneet; Jung, Joanne; Dahri, Karen

2012-07-01

Hospital pharmacists participate in activities that may be considered diagnostic. Two reasoning approaches to diagnosis have been described: non-analytic and analytic. Of the 6 analytic traditions, the probabilistic tradition has been shown to improve diagnostic accuracy and reduce unnecessary testing. To the authors' knowledge, pharmacists' attitudes toward having a diagnostic role and their diagnostic knowledge and skills have never been studied. To describe pharmacists' attitudes toward the role of diagnosis in pharmacotherapeutic problem-solving and to characterize the extent of pharmacists' knowledge and skills related to diagnostic literacy. Pharmacists working within Lower Mainland Pharmacy Services (British Columbia) who spent at least 33% of their time in direct patient care were invited to participate in a prospective observational survey. The survey sought information about demographic characteristics and attitudes toward diagnosis. Diagnostic knowledge and skills were tested by means of 3 case scenarios. The analysis included simple descriptive statistics and inferential statistics to evaluate relationships between responses and experience and training. Of 266 pharmacists invited to participate, 94 responded. The attitudes section of the survey was completed by 90 pharmacists; of these, 80 (89%) agreed with the definition of "diagnosis" proposed in the survey, and 83 (92%) agreed that it is important for pharmacists to have diagnosis-related skills. Respondents preferred an analytic to a non-analytic approach to diagnostic decision-making. The probabilistic tradition was not the preferred method in any of the 3 cases. In evaluating 5 clinical scenarios that might require diagnostic skills, on average 84% of respondents agreed that they should be involved in assessing such problems. Respondents' knowledge of and ability to apply probabilistic diagnostic tools were highest for test sensitivity (average of 61% of respondents with the correct answers) and lower for test specificity (average of 48% with correct answers) and likelihood ratios (average of 39% with correct answers). Respondents to this survey strongly believed that diagnostic skills were important for solving drug-related problems, but they demonstrated low levels of knowledge and ability to apply concepts of probabilistic diagnostic reasoning. Opportunities to expand pharmacists' knowledge of diagnostic reasoning exist, and the findings reported here indicate that pharmacists would consider such professional development valuable.

Protein and genetic diagnosis of limb girdle muscular dystrophy type 2A: The yield and the pitfalls.

PubMed

Fanin, Marina; Angelini, Corrado

2015-08-01

Limb girdle muscular dystrophy type 2A (LGMD2A) is the most frequent form of LGMD worldwide. Comprehensive clinical assessment and laboratory testing is essential for diagnosis of LGMD2A. Muscle immunoblot analysis of calpain-3 is the most useful tool to direct genetic testing, as detection of calpain-3 deficiency has high diagnostic value. However, calpain-3 immunoblot testing lacks sensitivity in about 30% of cases due to gene mutations that inactivate the enzyme. The best diagnostic strategy should be determined on a case-by-case basis, depending on which tissues are available, and which molecular and/or genetic methods are adopted. In this work we survey the current knowledge, advantages, limitations, and pitfalls of protein testing and mutation detection in LGMD2A and provide an update of genetic epidemiology. © 2015 Wiley Periodicals, Inc.

Repaglinide-induced factitious hypoglycemia.

PubMed

Hirshberg, B; Skarulis, M C; Pucino, F; Csako, G; Brennan, R; Gorden, P

2001-02-01

We report the first case of repaglinide-induced factitious hypoglycemia in a young male. This case posed a challenging diagnostic dilemma because commercial assays for repaglinide are not available. Furthermore, the patient had a series of positive diagnostic tests such as high proinsulin and localizing intra-arterial calcium stimulation suggestive of insulinoma. This case, again, demonstrates the importance of pure clinical judgment in the face of often-conflicting laboratory data in making a correct diagnosis and the requirement of definitive data for an appropriate therapeutic resolution.

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

PubMed

Raizada, Neeraj; Khaparde, Sunil D; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M; Singh, Varinder; Umadevi, K R; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C H Surya; Mall, Shalini; Singh, Pooja; Saha, B K; Denkinger, Claudia M; Boehme, Catharina; Sarin, Sanjay

2018-01-01

Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population.

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India

PubMed Central

Raizada, Neeraj; Khaparde, Sunil D.; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M.; Singh, Varinder; Umadevi, K. R.; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C. H. Surya; Mall, Shalini; Singh, Pooja; Saha, B. K.; Denkinger, Claudia M.; Boehme, Catharina

2018-01-01

Background Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. Methods A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. Results The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65–8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9–9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. Conclusion The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population. PMID:29489887

Diagnostic methods for insect sting allergy.

PubMed

Hamilton, Robert G

2004-08-01

This review overviews advances from mid-2002 to the present in the validation and performance methods used in the diagnosis of Hymenoptera venom-induced immediate-type hypersensitivity. The general diagnostic algorithm for insect sting allergy is initially discussed with an examination of the AAAAI's 2003 revised practice parameter guidelines. Changes as a result of a greater recognition of skin test negative systemic reactors include repeat analysis of all testing and acceptance of serology as a complementary diagnostic test to the skin test. Original data examining concordance of venom-specific IgE results produced by the second-generation Pharmacia CAP System with the Johns Hopkins University radioallergosorbent test are presented. Diagnostic performance of honeybee venom-specific IgE assays used in clinical laboratories in North America is discussed using data from the Diagnostic Allergy Proficiency Survey conducted by the College of American Pathologists. Validity of venom-specific IgE antibody in postmortem blood specimens is demonstrated. The utility of alternative in-vivo (provocation) and in-vitro (basophil-based) diagnostic testing methods is critiqued. This overview supports the following conclusions. Improved practice parameter guidelines include serology and skin test as complementary in supporting a positive clinical history during the diagnostic process. Data are provided which support the analytical performance of commercially available venom-specific IgE antibody serology-based assays. Intentional sting challenge in-vivo provocation, in-vitro basophil flow cytometry (CD63, CD203c) based assays, and in-vitro basophil histamine and sulfidoleukotriene release assays have their utility in the study of difficult diagnostic cases, but their use will remain as supplementary, secondary diagnostic tests.

Diagnostic grand rounds: a new teaching concept to train diagnostic reasoning.

PubMed

Stieger, Stefan; Praschinger, Andrea; Kletter, Kurt; Kainberger, Franz

2011-06-01

Diagnostic reasoning is a core skill in teaching and learning in undergraduate curricula. Diagnostic grand rounds (DGRs) as a subform of grand rounds are intended to train the students' skills in the selection of appropriate tests and in the interpretation of test results. The aim of this study was to test DGRs for their ability to improve diagnostic reasoning by using a pre-post-test design. During one winter term, all 398 fifth-year students (36.1% male, 63.9% female) solved 23 clinical cases presented in 8 DGRs. In an online questionnaire, a Diagnostic Thinking Inventory (DTI) with 41 items was evaluated for flexibility in thinking and structure of knowledge in memory. Results were correlated with those from a summative multiple-choice knowledge test and of the learning objectives in a logbook. The students' DTI scores in the post-test were significantly higher than those reported in the pre-test. DTI scores at either testing time did not correlate with medical knowledge as assessed by a multiple-choice knowledge test. Abilities acquired during clinical clerkships as documented in a logbook could only account for a small proportion of the increase in the flexibility subscale score. This effect still remained significant after accounting for potential confounders. Establishing DGRs proofed to be an effective way of successfully improving both students' diagnostic reasoning and the ability to select the appropriate test method in routine clinical practice. Copyright © 2009 Elsevier Ireland Ltd. 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 Central

Cassiday, Pamela K.; Pawloski, Lucia C.; Tatti, Kathleen M.; Martin, Monte D.; Briere, Elizabeth C.; Tondella, M. Lucia; Martin, Stacey W.

2018-01-01

Introduction 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. Methods 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). Results 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. Conclusions 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. PMID:29652945

Health Technology Assessment for Molecular Diagnostics: Practices, Challenges, and Recommendations from the Medical Devices and Diagnostics Special Interest Group.

PubMed

Garfield, Susan; Polisena, Julie; S Spinner, Daryl; Postulka, Anne; Y Lu, Christine; Tiwana, Simrandeep K; Faulkner, Eric; Poulios, Nick; Zah, Vladimir; Longacre, Michael

2016-01-01

Health technology assessments (HTAs) are increasingly used to inform coverage, access, and utilization of medical technologies including molecular diagnostics (MDx). Although MDx are used to screen patients and inform disease management and treatment decisions, there is no uniform approach to their evaluation by HTA organizations. The International Society for Pharmacoeconomics and Outcomes Research Devices and Diagnostics Special Interest Group reviewed diagnostic-specific HTA programs and identified elements representing common and best practices. MDx-specific HTA programs in Europe, Australia, and North America were characterized by methodology, evaluation framework, and impact. Published MDx HTAs were reviewed, and five representative case studies of test evaluations were developed: United Kingdom (National Institute for Health and Care Excellence's Diagnostics Assessment Programme, epidermal growth factor receptor tyrosine kinase mutation), United States (Palmetto's Molecular Diagnostic Services Program, OncotypeDx prostate cancer test), Germany (Institute for Quality and Efficiency in Healthcare, human papillomavirus testing), Australia (Medical Services Advisory Committee, anaplastic lymphoma kinase testing for non-small cell lung cancer), and Canada (Canadian Agency for Drugs and Technologies in Health, Rapid Response: Non-invasive Prenatal Testing). Overall, the few HTA programs that have MDx-specific methods do not provide clear parameters of acceptability related to clinical and analytic performance, clinical utility, and economic impact. The case studies highlight similarities and differences in evaluation approaches across HTAs in the performance metrics used (analytic and clinical validity, clinical utility), evidence requirements, and how value is measured. Not all HTAs are directly linked to reimbursement outcomes. To improve MDx HTAs, organizations should provide greater transparency, better communication and collaboration between industry and HTA stakeholders, clearer links between HTA and funding decisions, explicit recognition of and rationale for differential approaches to laboratory-developed versus regulatory-approved test, and clear evidence requirements. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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.

Powassan Virus-A New Reemerging Tick-Borne Disease.

PubMed

Fatmi, Syed Soheb; Zehra, Rija; Carpenter, David O

2017-01-01

Powassan virus is a neurovirulent flavivirus consisting of two lineages causing meningoencephalitis. It is the only member of the tick-borne encephalitis serogroup which is present in mainland North America. With a total number of 27 cases from 1958 to 1998 and 98 cases from 1999 to 2016, reported cases have increased by 671% over the last 18 years. Powassan infection is transmitted by different tick species in different geographical regions. Ixodes scapularis is the primary vector that transmits the virus on the East Coast of US and Ixodes cookei in the Midwest and Canada, while Hemaphysalis longicornis is the vector in Russia. Powassan has no singular pathognomonic finding and presents with a wide spectrum of symptoms including severe neurological symptoms. The clinical challenge lies within the management of the disease as there is no standard diagnostic protocol and most cases are only diagnosed after a patient goes through an extensive workup for other infectious disease. The diagnosis is established by a combination of imaging and serologic tests. In case of Powassan meningoencephalitis, computed tomography scan and magnetic resonance imaging show vascular insults, which are also seen in cases of tick-borne encephalitis virus, another flavivirus of medical importance. Serologic tests are the gold standard for diagnosis, although testing is not widely available and only state health departments and Center for Disease Control and Prevention can perform Powassan-specific IgM antibody testing utilizing enzyme-linked immunosorbent assay and immunofluorescence antibody. Powassan is also of veterinary medical importance. Wildlife animals act as a reservoir to the pathogens, hence possessing threat to humans and domestic animals. This review highlights Powassan's neurotropic presentation, epidemiology, diagnostic challenges, and prevalence. Strong emphasis is placed on establishing diagnostic protocols, widespread Powassan-specific IgM testing, role of the vector in disease presentation, and necessary preventive research.

Evidence of the preferential use of disease prototypes over case exemplars among early year one medical students prior to and following diagnostic training.

PubMed

Papa, Frank J; Li, Feiming

2015-12-01

Two core dual processing theory (DPT) System I constructs (Exemplars and Prototypes) were used to: 1) formulate a training exercise designed to improve diagnostic performance in year one medical students, and 2) explore whether any observed performance improvements were associated with preferential use of exemplars or prototypes. With IRB approval, 117 year one medical students participated in an acute chest pain diagnostic training exercise. A pre- and post-training test containing the same 27 case vignettes was used to determine if the subjects' diagnostic performance improved via training in both exemplars and prototypes. Exemplar and Prototype theory was also used to generate a unique typicality estimate for each case vignette. Because these estimates produce different performance predictions, differences in the subjects' observed performance would make it possible to infer whether subjects were preferentially using Exemplars or Prototypes. Pre- vs. post-training comparison revealed a significant performance improvement; t=14.04, p<0.001, Cohen's d=1.32. Pre-training, paired t-testing demonstrated that performance against the most typical vignettes>mid typical vignettes: t=4.94, p<0.001; and mid typical>least typical: t=5.16, p<0.001. Post-training, paired t-testing again demonstrated that performance against the most typical vignettes>mid typical: t=2.94, p<0.01; and mid typical>least typical: t=6.64, p<0.001. These findings are more consistent with the performance predictions generated via Prototype theory than Exemplar theory. DPT is useful in designing and evaluating the utility of new approaches to diagnostic training, and, investigating the cognitive factors driving diagnostic capabilities among early medical students.

"The Hole in the Sky Causes Global Warming": A Case Study of Secondary School Students' Climate Change Alternative Conceptions

ERIC Educational Resources Information Center

Chang, Chew-Hung; Pascua, Liberty

2015-01-01

This study identified secondary school students' alternative conceptions (ACs) of climate change and their resistance to instruction. Using a case-based approach, a diagnostic test was administered to Secondary 3 male students in a pre-test and post-test. The ACs identified in the pre-test were on the causes of climate change, the natural…

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer's Disease.

PubMed

Fantoni, Enrico R; Chalkidou, Anastasia; O' Brien, John T; Farrar, Gill; Hammers, Alexander

2018-01-01

Amyloid PET (aPET) imaging could improve patient outcomes in clinical practice, but the extent of impact needs quantification. To provide an aggregated quantitative analysis of the value added by aPET in cognitively impaired subjects. Systematic literature searches were performed in Embase and Medline until January 2017. 1,531 cases over 12 studies were included (1,142 cases over seven studies in the primary analysis where aPET was the key biomarker; the remaining cases included as defined groups in the secondary analysis). Data was abstracted by consensus among two observers and assessed for bias. Clinical utility was measured by diagnostic change, diagnostic confidence, and patient management before and after aPET. Three groups were further analyzed: control patients for whom feedback of aPET scan results was delayed; aPET Appropriate Use Criteria (AUC+) cases; and patients undergoing additional FDG/CSF testing. For 1,142 cases with only aPET, 31.3% of diagnoses were revised, whereas 3.2% of diagnoses changed in the delayed aPET control group (p < 0.0001). Increased diagnostic confidence following aPET was found for 62.1% of 870 patients. Management changes with aPET were found in 72.2% of 740 cases and in 55.5% of 299 cases in the control group (p < 0.0001). The diagnostic value of aPET in AUC+ patients or when FDG/CSF were additionally available did not substantially differ from the value of aPET alone in the wider population. Amyloid PET contributed to diagnostic revision in almost a third of cases and demonstrated value in increasing diagnostic confidence and refining management plans.

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer’s Disease

PubMed Central

Fantoni, Enrico R.; Chalkidou, Anastasia; O’ Brien, John T.; Farrar, Gill; Hammers, Alexander

2018-01-01

Background: Amyloid PET (aPET) imaging could improve patient outcomes in clinical practice, but the extent of impact needs quantification. Objective: To provide an aggregated quantitative analysis of the value added by aPET in cognitively impaired subjects. Methods: Systematic literature searches were performed in Embase and Medline until January 2017. 1,531 cases over 12 studies were included (1,142 cases over seven studies in the primary analysis where aPET was the key biomarker; the remaining cases included as defined groups in the secondary analysis). Data was abstracted by consensus among two observers and assessed for bias. Clinical utility was measured by diagnostic change, diagnostic confidence, and patient management before and after aPET. Three groups were further analyzed: control patients for whom feedback of aPET scan results was delayed; aPET Appropriate Use Criteria (AUC+) cases; and patients undergoing additional FDG/CSF testing. Results: For 1,142 cases with only aPET, 31.3% of diagnoses were revised, whereas 3.2% of diagnoses changed in the delayed aPET control group (p < 0.0001). Increased diagnostic confidence following aPET was found for 62.1% of 870 patients. Management changes with aPET were found in 72.2% of 740 cases and in 55.5% of 299 cases in the control group (p < 0.0001). The diagnostic value of aPET in AUC+ patients or when FDG/CSF were additionally available did not substantially differ from the value of aPET alone in the wider population. Conclusions: Amyloid PET contributed to diagnostic revision in almost a third of cases and demonstrated value in increasing diagnostic confidence and refining management plans. PMID:29689725

Vesical schistosomiasis with terminal hematuria in sub-Saharan patients.

PubMed

Pereira, J; Calleja, E; Marne, C; Borque, A

2014-03-01

To know the characteristics of vesical schistosomiasis caused by schistosoma hematobium in immigrant patients. The retrospective study of 41 cases microbiologically diagnosed in our hospital over the last 16 years is presented. Data was collected on origin, age, presentation form, diagnostic tests and treatment. All were African patients whose ages ranged from 4 to 32 years and who had terminal macroscopic hematuria. Most of the patients (85%) were men. In all of the cases, diagnosis was by a urinary microbiological study and in one case, cystoscopy with a biopsy of a typical vesical lesion. Terminal hematuria is the most representative clinical sign. They were treated with praziquantel. The epidemiology and intermittent terminal hematuria in African patients should lead to the suspicion of vesical schistosomiasis as the first diagnostic option. Urinary microbiological study is a rapid, non-invasive, test with high diagnostic yield that would avoid performing invasive studies. Its simple treatment assures high level of compliance and consequent efficacy. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Benign paroxysmal vertigo of childhood: diagnostic value of vestibular test and high stimulus rate auditory brainstem response test.

PubMed

Zhang, Daogong; Fan, Zhaomin; Han, Yuechen; Wang, Mingming; Xu, Lei; Luo, Jianfen; Ai, Yu; Wang, Haibo

2012-01-01

To investigate the diagnostic value of vestibular test and high stimulus rate auditory brainstem response (ABR) test and the possible mechanism responsible for benign paroxysmal vertigo of childhood (BPVC). Data of 56 patients with BPVC in vertigo clinic of our hospital from May 2007 to September 2008 were retrospectively analyzed in this study. Patients with BPVC were tested with pure tone audiometry, high stimulus rate auditory brainstem response test (ABR), transcranial Doppler sonography (TCD), bithermal caloric test, and VEMP. The results of the hearing and vestibular function test were compared and analyzed. There were 56 patients with BPVC, including 32 men, 24 women, aged 3-12 years old, with an average of 6.5 years. Among 56 cases of BPVC patients, the results of pure tone audiometry were all normal. High stimulus rate ABR was abnormal in 66.1% (37/56) of cases. TCD showed 57.1% abnormality in 56 cases, including faster flow rate in 28 cases and slower flow rate in 4 cases. High stimulus rate ABR and TCD were both abnormal in 48.2% (27/56) of cases. Bithermal caloric test was abnormal in 14.3% (8/56) of cases. VEMP showed 32.1% abnormality, including amplitude abnormality in 16 cases and latency abnormality in 2 cases. The abnormal rate of VEMP was much higher than that of caloric test. Vascular mechanisms might be involved in the pathogenesis of BPVC and there is strong evidence for close relationship between BPVC and migraine. High stimulus rate ABR is helpful in the diagnosis of BPVC. The inferior vestibular pathway is much more impaired than the superior vestibular pathway in BPVC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: a comparative diagnostic and clinical utility study.

PubMed

Halligan, E; Edgeworth, J; Bisnauthsing, K; Bible, J; Cliff, P; Aarons, E; Klein, J; Patel, A; Goldenberg, S

2014-08-01

Laboratory diagnosis and clinical management of inpatients with diarrhoea is complex and time consuming. Tests are often requested sequentially and undertaken in different laboratories. This causes prolonged unnecessary presumptive isolation of patients, because most cases are non-infectious. A molecular multiplex test (Luminex(®) Gastrointestinal Pathogen Panel (GPP)) was compared with conventional testing over 8 months to determine diagnostic accuracy, turnaround times, laboratory costs, use of isolation facilities and user acceptability. A total of 262 (12%) patients had a pathogen detected by conventional methods compared with 483 (22.1%) by GPP. Most additional cases were detected in patients developing symptoms in the first 4 days of admission. Additional cases were detected because of presumed improved diagnostic sensitivity but also because clinicians had not requested the correct pathogen. Turnaround time (41.8 h) was faster than bacterial culture (66.5 h) and parasite investigation (66.5 h) but slower than conventional testing for Clostridium difficile (17.3 h) and viruses (27 h). The test could allow simplified requesting by clinicians and a consolidated laboratory workflow, reducing the overall number of specimens received by the laboratory. A total of 154 isolation days were saved at an estimated cost of £30 800. Consumables and labour were estimated at £150 641 compared with £63 431 for conventional testing. Multiplex molecular testing using a panel of targets allowed enhanced detection and a consolidated laboratory workflow. This is likely to be of greater benefit to cases that present within the first 4 days of hospital admission. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Whole-genome sequencing expands diagnostic utility and improves clinical management in paediatric medicine

PubMed Central

Stavropoulos, Dimitri J; Merico, Daniele; Jobling, Rebekah; Bowdin, Sarah; Monfared, Nasim; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Yuen, Ryan K C; Szego, Michael J; Hayeems, Robin Z; Shaul, Randi Zlotnik; Brudno, Michael; Girdea, Marta; Frey, Brendan; Alipanahi, Babak; Ahmed, Sohnee; Babul-Hirji, Riyana; Porras, Ramses Badilla; Carter, Melissa T; Chad, Lauren; Chaudhry, Ayeshah; Chitayat, David; Doust, Soghra Jougheh; Cytrynbaum, Cheryl; Dupuis, Lucie; Ejaz, Resham; Fishman, Leona; Guerin, Andrea; Hashemi, Bita; Helal, Mayada; Hewson, Stacy; Inbar-Feigenberg, Michal; Kannu, Peter; Karp, Natalya; Kim, Raymond H; Kronick, Jonathan; Liston, Eriskay; MacDonald, Heather; Mercimek-Mahmutoglu, Saadet; Mendoza-Londono, Roberto; Nasr, Enas; Nimmo, Graeme; Parkinson, Nicole; Quercia, Nada; Raiman, Julian; Roifman, Maian; Schulze, Andreas; Shugar, Andrea; Shuman, Cheryl; Sinajon, Pierre; Siriwardena, Komudi; Weksberg, Rosanna; Yoon, Grace; Carew, Chris; Erickson, Raith; Leach, Richard A; Klein, Robert; Ray, Peter N; Meyn, M Stephen; Scherer, Stephen W; Cohn, Ronald D; Marshall, Christian R

2016-01-01

The standard of care for first-tier clinical investigation of the aetiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy-number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion–deletions (indels) and single-nucleotide variant (SNV) mutations. Whole-genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilised WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a fourfold increase in diagnostic rate over CMA (8%; P value=1.42E−05) alone and more than twofold increase in CMA plus targeted gene sequencing (13%; P value=0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harbouring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis. PMID:28567303

Whole Genome Sequencing Expands Diagnostic Utility and Improves Clinical Management in Pediatric Medicine.

PubMed

Stavropoulos, Dimitri J; Merico, Daniele; Jobling, Rebekah; Bowdin, Sarah; Monfared, Nasim; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Yuen, Ryan K C; Szego, Michael J; Hayeems, Robin Z; Shaul, Randi Zlotnik; Brudno, Michael; Girdea, Marta; Frey, Brendan; Alipanahi, Babak; Ahmed, Sohnee; Babul-Hirji, Riyana; Porras, Ramses Badilla; Carter, Melissa T; Chad, Lauren; Chaudhry, Ayeshah; Chitayat, David; Doust, Soghra Jougheh; Cytrynbaum, Cheryl; Dupuis, Lucie; Ejaz, Resham; Fishman, Leona; Guerin, Andrea; Hashemi, Bita; Helal, Mayada; Hewson, Stacy; Inbar-Feigenberg, Michal; Kannu, Peter; Karp, Natalya; Kim, Raymond; Kronick, Jonathan; Liston, Eriskay; MacDonald, Heather; Mercimek-Mahmutoglu, Saadet; Mendoza-Londono, Roberto; Nasr, Enas; Nimmo, Graeme; Parkinson, Nicole; Quercia, Nada; Raiman, Julian; Roifman, Maian; Schulze, Andreas; Shugar, Andrea; Shuman, Cheryl; Sinajon, Pierre; Siriwardena, Komudi; Weksberg, Rosanna; Yoon, Grace; Carew, Chris; Erickson, Raith; Leach, Richard A; Klein, Robert; Ray, Peter N; Meyn, M Stephen; Scherer, Stephen W; Cohn, Ronald D; Marshall, Christian R

2016-01-13

The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. Whole genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilized WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and >2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counseling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis.

Testing Pneumonia Vaccines in the Elderly: Determining a Case Definition for Pneumococcal Pneumonia in the Absence of a Gold Standard.

PubMed

Jokinen, Jukka; Snellman, Marja; Palmu, Arto A; Saukkoriipi, Annika; Verlant, Vincent; Pascal, Thierry; Devaster, Jeanne-Marie; Hausdorff, William P; Kilpi, Terhi M

2018-06-01

Clinical assessments of vaccines to prevent pneumococcal community-acquired pneumonia (CAP) require sensitive and specific case definitions, but there is no gold standard diagnostic test. To develop a new case definition suitable for vaccine efficacy studies, we applied latent class analysis (LCA) to the results from 7 diagnostic tests for pneumococcal etiology on clinical specimens from 323 elderly persons with radiologically confirmed pneumonia enrolled in the Finnish Community-Acquired Pneumonia Epidemiology study during 2005-2007. Compared with the conventional use of LCA, which is mainly to determine sensitivities and specificities of different tests, we instead used LCA as an appropriate instrument to predict the probability of pneumococcal etiology for each CAP case based on individual test profiles, and we used the predictions to minimize the sample size that would be needed for a vaccine efficacy trial. When compared with the conventional laboratory criteria of encapsulated pneumococci in culture, in blood culture or high-quality sputum culture, or urine antigen positivity, our optimized case definition for pneumococcal CAP resulted in a trial sample size that was almost 20,000 subjects smaller. We believe that the novel application of LCA detailed here to determine a case definition for pneumococcal CAP could also be similarly applied to other diseases without a gold standard.

Clinical and Genetic Diagnosis of Nonischemic Sudden Cardiac Death.

PubMed

Jiménez-Jáimez, Juan; Alcalde Martínez, Vicente; Jiménez Fernández, Miriam; Bermúdez Jiménez, Francisco; Rodríguez Vázquez Del Rey, María Del Mar; Perin, Francesca; Oyonarte Ramírez, José Manuel; López Fernández, Silvia; de la Torre, Inmaculada; García Orta, Rocío; González Molina, Mercedes; Cabrerizo, Elisa María; Álvarez Abril, Beatriz; Álvarez, Miguel; Macías Ruiz, Rosa; Correa, Concepción; Tercedor, Luis

2017-10-01

Nonischemic sudden cardiac death (SCD) is predominantly caused by cardiomyopathies and channelopathies. There are many diagnostic tests, including some complex techniques. Our aim was to analyze the diagnostic yield of a systematic diagnostic protocol in a specialized unit. The study included 56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with electrocardiogram, advanced cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the postmortem findings, familial evaluation, and molecular autopsy with next-generation sequencing (NGS). A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and nonsurvivors (P=.53). Cardiac channelopathies were more prevalent among survivors than nonsurvivors (66.6% vs 40%, P=.03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and nonsurvivors (P=.21). There is a strong likelihood of reaching a diagnosis in SCD after a rigorous protocol, with a more prevalent diagnosis of channelopathy among survivors and a worse familial prognosis in cardiomyopathies. Genetic testing with NGS is useful and its value is increasing with respect to the Sanger method. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

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.

Hotspot mutations in cancer genes may be missed in routine diagnostics due to neighbouring sequence variants.

PubMed

Bartels, Stephan; Schipper, Elisa; Hasemeier, Britta; Kreipe, Hans; Lehmann, Ulrich

2018-05-27

The detection of hotspot mutations in key cancer genes is now an essential part of the diagnostic work-up in molecular pathology. Nearly all assays for mutation detection involve an amplification step. A second single nucleotide variant (SNV) on the same allele adjacent to a mutational hotspot can interfere with primer binding, leading to unnoticed allele-specific amplification of the wild type allele and thereby false-negative mutation testing. We present two diagnostic cases with false negative sequence results for JAK2 and SRSF2. In both cases mutations would have escaped detection if only one strand of DNA had been analysed. Because many commercially available diagnostic kits rely on the analysis of only one DNA strand they are prone to fail in cases like these. Detailed protocols and quality control measures to prevent corresponding pitfalls are presented. Copyright © 2017. Published by Elsevier Inc.

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.

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.

Exploring Situational Awareness in Diagnostic Errors in Primary Care

PubMed Central

Singh, Hardeep; Giardina, Traber Davis; Petersen, Laura A.; Smith, Michael; Wilson, Lindsey; Dismukes, Key; Bhagwath, Gayathri; Thomas, Eric J.

2013-01-01

Objective Diagnostic errors in primary care are harmful but poorly studied. To facilitate understanding of diagnostic errors in real-world primary care settings using electronic health records (EHRs), this study explored the use of the Situational Awareness (SA) framework from aviation human factors research. Methods A mixed-methods study was conducted involving reviews of EHR data followed by semi-structured interviews of selected providers from two institutions in the US. The study population included 380 consecutive patients with colorectal and lung cancers diagnosed between February 2008 and January 2009. Using a pre-tested data collection instrument, trained physicians identified diagnostic errors, defined as lack of timely action on one or more established indications for diagnostic work-up for lung and colorectal cancers. Twenty-six providers involved in cases with and without errors were interviewed. Interviews probed for providers' lack of SA and how this may have influenced the diagnostic process. Results Of 254 cases meeting inclusion criteria, errors were found in 30 (32.6%) of 92 lung cancer cases and 56 (33.5%) of 167 colorectal cancer cases. Analysis of interviews related to error cases revealed evidence of lack of one of four levels of SA applicable to primary care practice: information perception, information comprehension, forecasting future events, and choosing appropriate action based on the first three levels. In cases without error, the application of the SA framework provided insight into processes involved in attention management. Conclusions A framework of SA can help analyze and understand diagnostic errors in primary care settings that use EHRs. PMID:21890757

Laboratory diagnosis of Ebola virus disease and corresponding biosafety considerations in the China Ebola Treatment Center.

PubMed

Huang, Qing; Fu, Wei-Ling; You, Jian-Ping; Mao, Qing

2016-10-01

Ebola virus disease (EVD), caused by Ebola virus (EBOV), is a potent acute infectious disease with a high case-fatality rate. Etiological and serological EBOV detection methods, including techniques that involve the detection of the viral genome, virus-specific antigens and anti-virus antibodies, are standard laboratory diagnostic tests that facilitate confirmation or exclusion of EBOV infection. In addition, routine blood tests, liver and kidney function tests, electrolytes and coagulation tests and other diagnostic examinations are important for the clinical diagnosis and treatment of EVD. Because of the viral load in body fluids and secretions from EVD patients, all body fluids are highly contagious. As a result, biosafety control measures during the collection, transport and testing of clinical specimens obtained from individuals scheduled to undergo EBOV infection testing (including suspected, probable and confirmed cases) are crucial. This report has been generated following extensive work experience in the China Ebola Treatment Center (ETC) in Liberia and incorporates important information pertaining to relevant diagnostic standards, clinical significance, operational procedures, safety controls and other issues related to laboratory testing of EVD. Relevant opinions and suggestions are presented in this report to provide contextual awareness associated with the development of standards and/or guidelines related to EVD laboratory testing.

A genetic study of autism in Costa Rica: multiple variables affecting IQ scores observed in a preliminary sample of autistic cases.

PubMed

McInnes, L Alison; González, Patricia Jiménez; Manghi, Elina R; Esquivel, Marcela; Monge, Silvia; Delgado, Marietha Fallas; Fournier, Eduardo; Bondy, Pamela; Castelle, Kathryn

2005-03-21

Autism is a heritable developmental disorder of communication and socialization that has not been well studied in Hispanic populations. Therefore, we are collecting and evaluating all possible cases of autism from a population isolate in the Central Valley of Costa Rica (CVCR) for a clinical and genetic study. We are assessing all subjects and parents, as appropriate, using the newly translated Spanish versions of the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) as well as tests of intelligence and adaptive behavior. Detailed obstetric and family medical/psychiatric histories are taken. All cases are tested for Fragile X and will be extensively evaluated for cytogenetic abnormalities. To date we have obtained clinical evaluations on over 76 cases of possible autism referred to our study and report data for the initial 35 complete cases. The mean age of the probands is 6.7 years, and 31 of the 35 cases are male. Twenty-one of the cases have IQs <50 and only 6 cases have IQs > or = 70. Over half of the mothers had complications during pregnancy and/or delivery. No cases have tested positively for Fragile X or PKU. Chromosomal G-banding is not yet complete for all cases. Diagnostic data gathered on cases of autism in the CVCR using Spanish versions of the ADI-R and ADOS look similar to that generated by studies of English-speaking cases. However, only 17% of our cases have IQs within the normal range, compared to the figure of 25% seen in most studies. This result reflects an ascertainment bias in that only severe cases of autism come to treatment in the CVCR because there are no government-sponsored support programs or early intervention programs providing an incentive to diagnose autism. The severity of mental retardation seen in most of our cases may also be exaggerated by the lack of early intervention programs and the use of IQ tests without Costa Rican norms. Still, we must formally train healthcare providers and teachers to recognize and refer autistic cases with normal or near normal IQs that are not seen in treatment.

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.

How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

PubMed

La Cesa, S; Tamburin, S; Tugnoli, V; Sandrini, G; Paolucci, S; Lacerenza, M; Marchettini, P; Cruccu, G; Truini, A

2015-12-01

Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Chey, William D; Talley, Nicholas J; Malhotra, Ashish; Spiegel, Brennan M R; Moayyedi, Paul

2009-04-13

Individuals with irritable bowel syndrome (IBS) report abdominal pain, bloating, and diarrhea, symptoms similar to those in celiac disease. Studies suggest that the prevalence of celiac disease is increased in individuals with IBS; however, evidence is conflicting, and current guidelines do not always recommend screening for celiac disease in these individuals. We conducted a systematic review and meta-analysis to estimate prevalence of celiac disease in unselected adults who met diagnostic criteria for IBS. MEDLINE (1950 to May 31, 2008) and EMBASE (1980 to May 31, 2008) were searched. Case series and case-control studies that used serologic tests for celiac disease were eligible for inclusion. Prevalence of positive serologic indications of celiac disease and biopsy-proved celiac disease were extracted and pooled for all studies and were compared between cases and controls using an odds ratio and 95% confidence interval. Fourteen studies were identified comprising 4204 individuals, of whom 2278 (54%) met diagnostic criteria for IBS. Pooled prevalence of positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease were 4.0% (95% confidence interval, 1.7-7.2), 1.63% (0.7-3.0), and 4.1% (1.9-7.0), respectively. Pooled odds ratios (95% confidence intervals) for positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS compared with controls without IBS were 3.40 (1.62-7.13), 2.94 (1.36-6.35), and 4.34 (1.78-10.6). Prevalence of biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS was more than 4-fold that in controls without IBS.

Epidemiological and Clinical Features of Brucellosis in the Country of Georgia

PubMed Central

Akhvlediani, Tamar; Bautista, Christian T.; Garuchava, Natalia; Sanodze, Lia; Kokaia, Nora; Malania, Lile; Chitadze, Nazibrola; Sidamonidze, Ketevan; Rivard, Robert G.; Hepburn, Matthew J.; Nikolich, Mikeljon P.; Imnadze, Paata; Trapaidze, Nino

2017-01-01

Background Brucellosis is an endemic disease in the country of Georgia. According to the National Center for Disease Control and Public Health of Georgia (NCDC), the average annual number of brucellosis cases was 161 during 2008–2012. However, the true number of cases is thought to be higher due to underreporting. The aim of this study was to provide current epidemiological and clinical information and evaluate diagnostic methods used for brucellosis in Georgia. Methodology Adult patients were eligible for participation if they met the suspected or probable case definition for brucellosis. After consent participants were interviewed using a standardized questionnaire to collect information on socio-demographic characteristics, epidemiology, history of present illness, and clinical manifestation. For the diagnosis of brucellosis, culture and serological tests were used. Results A total of 81 participants were enrolled, of which 70 (86%) were from rural areas. Seventy-four percent of participants reported consuming unpasteurized milk products and 62% consuming undercooked meat products before symptom onset. Forty-one participants were positive by the Wright test and 33 (41%) were positive by blood culture. There was perfect agreement between the Huddelston and Wright tests (k = 1.0). Compared with blood culture (the diagnostic gold standard), ELISA IgG and total ELISA (IgG + IgM), the Wright test had fair (k = 0.12), fair (k = 0.24), and moderate (k = 0.52) agreement, respectively. Conclusions Consumption of unpasteurized milk products and undercooked meat were among the most common risk factors in brucellosis cases. We found poor agreement between ELISA tests and culture results. This report also serves as an initial indication that the suspected case definition for brucellosis surveillance purposes needs revision. Further research is needed to characterize the epidemiology and evaluate the performance of the diagnostic methods for brucellosis in Georgia. PMID:28107444

Epidemiological and Clinical Features of Brucellosis in the Country of Georgia.

PubMed

Akhvlediani, Tamar; Bautista, Christian T; Garuchava, Natalia; Sanodze, Lia; Kokaia, Nora; Malania, Lile; Chitadze, Nazibrola; Sidamonidze, Ketevan; Rivard, Robert G; Hepburn, Matthew J; Nikolich, Mikeljon P; Imnadze, Paata; Trapaidze, Nino

2017-01-01

Brucellosis is an endemic disease in the country of Georgia. According to the National Center for Disease Control and Public Health of Georgia (NCDC), the average annual number of brucellosis cases was 161 during 2008-2012. However, the true number of cases is thought to be higher due to underreporting. The aim of this study was to provide current epidemiological and clinical information and evaluate diagnostic methods used for brucellosis in Georgia. Adult patients were eligible for participation if they met the suspected or probable case definition for brucellosis. After consent participants were interviewed using a standardized questionnaire to collect information on socio-demographic characteristics, epidemiology, history of present illness, and clinical manifestation. For the diagnosis of brucellosis, culture and serological tests were used. A total of 81 participants were enrolled, of which 70 (86%) were from rural areas. Seventy-four percent of participants reported consuming unpasteurized milk products and 62% consuming undercooked meat products before symptom onset. Forty-one participants were positive by the Wright test and 33 (41%) were positive by blood culture. There was perfect agreement between the Huddelston and Wright tests (k = 1.0). Compared with blood culture (the diagnostic gold standard), ELISA IgG and total ELISA (IgG + IgM), the Wright test had fair (k = 0.12), fair (k = 0.24), and moderate (k = 0.52) agreement, respectively. Consumption of unpasteurized milk products and undercooked meat were among the most common risk factors in brucellosis cases. We found poor agreement between ELISA tests and culture results. This report also serves as an initial indication that the suspected case definition for brucellosis surveillance purposes needs revision. Further research is needed to characterize the epidemiology and evaluate the performance of the diagnostic methods for brucellosis in Georgia.

Clinical, diagnostic and pathologic features of presumptive cases of Chlamydia pecorum-associated arthritis in Australian sheep flocks.

PubMed

Walker, Evelyn; Moore, Cecily; Shearer, Patrick; Jelocnik, Martina; Bommana, Sankhya; Timms, Peter; Polkinghorne, Adam

2016-09-08

Arthritis is an economically significant disease in lambs and is usually the result of a bacterial infection. One of the known agents of this disease is Chlamydia pecorum, a globally recognised livestock pathogen associated with several diseases in sheep, cattle and other hosts. Relatively little published information is available on the clinical, diagnostic and pathologic features of C. pecorum arthritis in sheep, hindering efforts to enhance our understanding of this economically significant disease. In this case series, a combination of standard diagnostic testing used routinely by veterinarians, such as the Chlamydia complement fixation text (CFT), veterinary clinical examinations, and additional screening via C. pecorum specific qPCR was used to describe putative chlamydial infections in five sheep flocks with suspected ovine arthritis. Five separate cases involving multiple lambs (aged six to ten months) of different breeds with suspected C. pecorum arthritis are presented. In two of the five cases, arthritic lambs exhibited marked depression and lethargy. Arthritis with concurrent conjunctivitis was present in four out of five lamb flocks examined. Chlamydia CFT demonstrated medium to high positive antibody titres in all flocks examined. C. pecorum shedding was evident at multiple sites including the conjunctiva, rectum and vagina, as determined via qPCR. Two of the five flocks received antimicrobials and all flocks recovered uneventfully regardless of treatment. This case series highlights the features a field veterinarian may encounter in cases of suspected ovine chlamydial arthritis. Our analysis suggests a presumptive diagnosis of chlamydial arthritis in lambs can be made when there is evidence of joint stiffness with or without synovial effusion and elevated chlamydia antibody titres. C. pecorum-specific qPCR was found to be a useful ancillary diagnostic tool, detecting Chlamydia positivity in low or negative CFT titre animals. Variables such as symptom duration relative to sampling, sheep breed and farm management practices were all factors recorded that paint a complex epidemiological and diagnostic picture for this disease. These case studies serve to provide a platform for further research to improve diagnostic testing and new treatment and control strategies for C. pecorum infections in sheep.

Airside HVAC BESTEST. Adaptation of ASHRAE RP 865 Airside HVAC Equipment Modeling Test Cases for ASHRAE Standard 140. Volume 1, Cases AE101-AE445

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

Neymark, J.; Kennedy, M.; Judkoff, R.

This report documents a set of diagnostic analytical verification cases for testing the ability of whole building simulation software to model the air distribution side of typical heating, ventilating and air conditioning (HVAC) equipment. These cases complement the unitary equipment cases included in American National Standards Institute (ANSI)/American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) Standard 140, Standard Method of Test for the Evaluation of Building Energy Analysis Computer Programs, which test the ability to model the heat-transfer fluid side of HVAC equipment.

Diagnostic accuracy of physical examination for anterior knee instability: a systematic review.

PubMed

Leblanc, Marie-Claude; Kowalczuk, Marcin; Andruszkiewicz, Nicole; Simunovic, Nicole; Farrokhyar, Forough; Turnbull, Travis Lee; Debski, Richard E; Ayeni, Olufemi R

2015-10-01

Determining diagnostic accuracy of Lachman, pivot shift and anterior drawer tests versus gold standard diagnosis (magnetic resonance imaging or arthroscopy) for anterior cruciate ligament (ACL) insufficiency cases. Secondarily, evaluating effects of: chronicity, partial rupture, awake versus anaesthetized evaluation. Searching MEDLINE, EMBASE and PubMed identified studies on diagnostic accuracy for ACL insufficiency. Studies identification and data extraction were performed in duplicate. Quality assessment used QUADAS tool, and statistical analyses were completed for pooled sensitivity and specificity. Eight studies were included. Given insufficient data, pooled analysis was only possible for sensitivity on Lachman and pivot shift test. During awake evaluation, sensitivity for the Lachman test was 89 % (95 % CI 0.76, 0.98) for all rupture types, 96 % (95 % CI 0.90, 1.00) for complete ruptures and 68 % (95 % CI 0.25, 0.98) for partial ruptures. For pivot shift in awake evaluation, results were 79 % (95 % CI 0.63, 0.91) for all rupture types, 86 % (95 % CI 0.68, 0.99) for complete ruptures and 67 % (95 % CI 0.47, 0.83) for partial ruptures. Decreased sensitivity of Lachman and pivot shift tests for partial rupture cases and for awake patients raised suspicions regarding the accuracy of these tests for diagnosis of ACL insufficiency. This may lead to further research aiming to improve the understanding of the true accuracy of these physical diagnostic tests and increase the reliability of clinical investigation for this pathology. IV.

Primary ciliary dyskinesia: improving the diagnostic approach

PubMed Central

Leigh, Margaret W.; Zariwala, Maimoona A.; Knowles, Michael R.

2009-01-01

Purpose of review The diagnosis of primary ciliary dyskinesia (PCD) has relied on analysis of ciliary motility and ultrastructure; however, these tests are not readily available and have not been standardized. Consequently, the diagnosis of PCD may be delayed or missed or made incorrectly. This review outlines the potential utility of new diagnostic tests, including measurement of nasal nitric oxide (NO) production and systematic analysis for mutations in gene encoding ciliary proteins. Recent findings Clinical manifestations of PCD have been expanded to include neonatal respiratory distress and heterotaxy. Measurement of nasal NO has emerged as a useful screening test for PCD based on the very low levels in PCD (approximately 1/10 of normal values). Genetic testing is emerging for PCD and demonstrates extensive genetic heterogeneity. Some genes and gene mutations involved in PCD have been defined. Approximately one third of PCD cases have identifiable gene mutations in one of 6 different genes. An international effort is focused on defining PCD-causing defects in other genes. Summary The incorporation of nasal NO measurement as a screening test to define probable PCD cases and gene mutation analysis to make a definitive diagnosis of PCD should enhance diagnostic evaluation of PCD. PMID:19300264

[Early congenital syphilis: a case report].

PubMed

Cavagnaro S M, Felipe; Pereira R, Teresita; Pérez P, Carla; Vargas Del V, Fernanda; Sandoval C, Carmen

2014-02-01

Congenital syphilis (CS) is a multisystemic infection of the newborn (NB) which can produce severe symptoms, and in some cases, even be fatal. In recent years, the incidence of syphilis has increased worldwide and similarly, the cases of CS in neonates have increased. To report two cases of early and severe presentation of CS, focusing on the importance of prevention of vertical transmission and monitoring of treated mothers. The diagnostic difficulties are discussed. Two premature newborns that were diagnosed with probable CS present in the newborn period are presented. In the first case, due to a high index of suspicion, but without confirmatory testing, treatment was started with good clinical response. In the second case, CS was confirmed through positive serology and the specific treatment was given. CS has significant diagnostic challenges as there is no test for early confirmation, therefore, a high index of suspicion might be key in the treatment and consequent prognosis. Due to the current epidemiology of the condition, it is also important to focus on preventive measures.

Decision Making for Borderline Cases in Pass/Fail Clinical Anatomy Courses: The Practical Value of the Standard Error of Measurement and Likelihood Ratio in a Diagnostic Test

ERIC Educational Resources Information Center

Severo, Milton; Silva-Pereira, Fernanda; Ferreira, Maria Amelia

2013-01-01

Several studies have shown that the standard error of measurement (SEM) can be used as an additional “safety net” to reduce the frequency of false-positive or false-negative student grading classifications. Practical examinations in clinical anatomy are often used as diagnostic tests to admit students to course final examinations. The aim of this…

Diagnostic and prognostic utility of an inexpensive rapid on site malaria diagnostic test (ParaHIT f) among ethnic tribal population in areas of high, low and no transmission in central India.

PubMed

Singh, Neeru; Mishra, A K; Shukla, M M; Chand, S K; Bharti, Praveen Kumar

2005-06-21

Malaria presents a diagnostic challenge in most tropical countries. Rapid detection of the malaria parasite and early treatment of infection still remain the most important goals of disease management. Therefore, performance characteristics of the new indigenous ParaHIT f test (Span diagnostic Ltd, Surat, India) was determined among ethnic tribal population in four districts of different transmission potential in central India to assess whether this rapid diagnostic test (RDT) could be widely applied as a diagnostic tool to control malaria. Beyond diagnosis, the logical utilization of RDTs is to monitor treatment outcome. A finger prick blood sample was collected from each clinically suspected case of malaria to prepare blood smear and for testing with the RDT after taking informed consent. The blood smears were read by an experienced technician blinded to the RDT results and clinical status of the subjects. The figures for specificity, sensitivity, accuracy and predictive values were calculated using microscopy as gold standard. The prevalence of malaria infection estimated by RDT in parallel with microscopy provide evidence of the type of high, low or no transmission in the study area. Analysis revealed (pooled data of all four epidemiological settings) that overall sensitivity, specificity and accuracy of the RDT were >90% in areas of different endemicity. While, RDT is useful to confirm the diagnosis of new symptomatic cases of suspected P. falciparum infection, the persistence of parasite antigen leading to false positives even after clearance of asexual parasitaemia has limited its utility as a prognostic tool. The study showed that the ParaHIT f test was easy to use, reliable and cheap. Thus this RDT is an appropriate test for the use in the field by paramedical staff when laboratory facilities are not available and thus likely to contribute greatly to an effective control of malaria in resource poor countries.

Diagnostic Accuracy and Cost-Effectiveness of Alternative Methods for Detection of Soil-Transmitted Helminths in a Post-Treatment Setting in Western Kenya

PubMed Central

Kepha, Stella; Kihara, Jimmy H.; Njenga, Sammy M.; Pullan, Rachel L.; Brooker, Simon J.

2014-01-01

Objectives This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys. Methods Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates. Results Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected. Conclusions The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings. PMID:24810593

Diagnostic accuracy and cost-effectiveness of alternative methods for detection of soil-transmitted helminths in a post-treatment setting in western Kenya.

PubMed

Assefa, Liya M; Crellen, Thomas; Kepha, Stella; Kihara, Jimmy H; Njenga, Sammy M; Pullan, Rachel L; Brooker, Simon J

2014-05-01

This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys. Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates. Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected. The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings.

An enhancement to the NA4 gear vibration diagnostic parameter

NASA Technical Reports Server (NTRS)

Decker, Harry J.; Handschuh, Robert F.; Zakrajsek, James J.

1994-01-01

A new vibration diagnostic parameter for health monitoring of gears, NA4*, is proposed and tested. A recently developed gear vibration diagnostic parameter NA4 outperformed other fault detection methods at indicating the start and initial progression of damage. However, in some cases, as the damage progressed, the sensitivity of the NA4 and FM4 parameters tended to decrease and no longer indicated damage. A new parameter, NA4* was developed by enhancing NA4 to improve the trending of the parameter. This allows for the indication of damage both at initiation and also as the damage progresses. The NA4* parameter was verified and compared to the NA4 and FM4 parameters using experimental data from single mesh spur and spiral bevel gear fatigue rigs. The primary failure mode for the test cases was naturally occurring tooth surface pitting. The NA4* parameter is shown to be a more robust indicator of damage.

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 Diagnostic Model for Dementia in Clinical Practice-Case Methodology Assisting Dementia Diagnosis.

PubMed

Londos, Elisabet

2015-04-02

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model's origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics.

A Diagnostic Model for Dementia in Clinical Practice—Case Methodology Assisting Dementia Diagnosis

PubMed Central

Londos, Elisabet

2015-01-01

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model’s origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics. PMID:26854146

The dilemma of diagnostic testing for Prader-Willi syndrome

PubMed Central

Hung, Dorothy

2017-01-01

Although Prader-Willi syndrome (PWS) is a well-described clinical dysmorphic syndrome, DNA testing is required for a definitive diagnosis. A definitive diagnosis can be made in approximately 99% of cases using DNA testing; there are a number of DNA tests that can be used for this purpose, although there is no set standard algorithm of testing. The dilemma arises because of the complex genetic mechanisms at the basis of PWS, which need to be elucidated. To establish the molecular mechanism with a complete work up, involves at least 2 tests. Here we discuss the commonly used tests currently available and suggest a cost—effective approach to diagnostic testing. PMID:28164030

30 CFR 250.528 - What must I include in my casing pressure request?

Code of Federal Regulations, 2013 CFR

2013-07-01

... calculated MAWOPs; (h) All casing/riser pre-bleed down pressures; (i) Shut-in tubing pressure; (j) Flowing tubing pressure; (k) Date and the calculated daily production rate during last well test (oil, gas, basic...); (m) Well type (dry tree, hybrid, or subsea); (n) Date of diagnostic test; (o) Well schematic; (p...

30 CFR 250.527 - What must I include in my casing pressure request?

Code of Federal Regulations, 2012 CFR

2012-07-01

... calculated MAWOPs; (h) All casing/riser pre-bleed down pressures; (i) Shut-in tubing pressure; (j) Flowing tubing pressure; (k) Date and the calculated daily production rate during last well test (oil, gas, basic...); (m) Well type (dry tree, hybrid, or subsea); (n) Date of diagnostic test; (o) Well schematic; (p...

30 CFR 250.528 - What must I include in my casing pressure request?

Code of Federal Regulations, 2014 CFR

2014-07-01

... calculated MAWOPs; (h) All casing/riser pre-bleed down pressures; (i) Shut-in tubing pressure; (j) Flowing tubing pressure; (k) Date and the calculated daily production rate during last well test (oil, gas, basic...); (m) Well type (dry tree, hybrid, or subsea); (n) Date of diagnostic test; (o) Well schematic; (p...

Tips and tricks in the dermoscopy of pigmented lesions

PubMed Central

2012-01-01

Dermoscopy is a useful, widely used tool for examining pigmented lesions, especially helpful in cases of an uncertain nature. Nevertheless, doctors may experience diagnostic difficulties while using this method. An example of this may be found in the examination of subcorneal hematoma, dark nevi with black lamella or lesions of acral volar skin. In such cases, a few diagnostic tricks have proven to be helpful in achieving diagnostic accuracy. This paper reviews various methods of performing dermoscopy, suggesting a number of simple, yet helpful tests. These include the adhesive tape test, the skin scraping test and the ink furrow test. The adhesive tape test is helpful in differentiating between dark melanocytic nevi and melanoma. Hematoma may be more easily differentiated with the use of the so-called skin scraping test. The confirmation of benign and melanocytic lesions of acral volar skin, on the other hand, is more accurate when using the ink furrow test. These methods have been discussed here based upon a series of literature reviews, the authors’ own experience and, also, iconography. The present article describes novel methods used in dermoscopy, helping to bring about a faster, more accurate diagnostics of those lesions which have proven to be more difficult to recognize. Helpful tricks, such as have been known to professional literature, as well as the authors’ own experience (for instance, applying urea cream to hyperkeratotic lesions or using photographs of skin lesions taken with the aid of a mobile phone camera – all prior to surgery) will surely be considered beneficial to the practitioner, be it dermatologist or any other physician. PMID:22916721

Diagnosis of a 64-year-old patient presenting with suspected lumbar spinal stenosis: an evidence-based case report

PubMed Central

Emary, Peter C.

2015-01-01

Objective: To present an evidence-based case report on the diagnosis of a patient with suspected lumbar spinal stenosis (LSS). Case: A 64-year-old man presented with signs and symptoms suggestive of LSS, but physical examination and diagnostic imaging findings were inconclusive. Other co-morbidities included diabetes, congestive heart failure, and left hip joint osteoarthritis. Outcome: PubMed was searched for systematic reviews of diagnostic studies on LSS. Two recent articles were found and appraised with respect to their validity, importance, and applicability in diagnosing the current patient. Copies of his magnetic resonance imaging were also obtained and used in combination with the appraised literature, including diagnostic test specificities and likelihood ratios, to confirm an LSS diagnosis. Summary: This case illustrates how research evidence can be used in clinical practice, particularly in the diagnosis of an individual patient. PMID:25729085

Use of an Additional 19-G EBUS-TBNA Needle Increases the Diagnostic Yield of EBUS-TBNA.

PubMed

Garrison, Garth; Leclair, Timothy; Balla, Agnes; Wagner, Sarah; Butnor, Kelly; Anderson, Scott R; Kinsey, C Matthew

2018-06-12

Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has an excellent diagnostic yield, there remain cases where the diagnosis is not obtained. We hypothesized that additional sampling with a 19-G EBUS-TBNA needle may increase diagnostic yield in a subset of cases where additional tissue sampling was required. Indications for use of the 19-G needle following 22-G sampling with rapid on-site cytologic examination were: (1) diagnostic uncertainty of the on-site cytopathologist (eg, nondiagnostic, probable lymphoma, etc.), (2) non-small cell lung cancer with probable need for molecular genetic and/or PD-L1 testing, or (3) need for a larger tissue sample for consideration of inclusion in a research protocol. A 19-G EBUS-TBNA needle was utilized following standard sampling with a 22-G needle in 48 patients (50 sites) during the same procedure. Although the diagnostic yield between the needles was equivalent, the concordance rate was only 83%. The 19-G determined a diagnosis in 4 additional patients (8%) and provided additional histopathologic information in 6 other cases (12%). Conversely, in 3 cases (6%) diagnostic information was provided only by the 22-G needle. Compared with 22-G EBUS-TBNA alone, sampling with both the 22- and 19-G EBUS needles resulted in an increase in diagnostic yield from 92% to 99% (P=0.045) and a number needed to sample of 13 patients to provide one additional diagnosis. There were no significant complications. In select cases where additional tissue may be needed, sampling with a 19-G EBUS needle following standard aspiration with a 22-G needle results in an increase in diagnostic yield.

Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison with culture and Xpert® MTB/RIF.

PubMed

Mulder, C; Mgode, G F; Ellis, H; Valverde, E; Beyene, N; Cox, C; Reid, S E; Van't Hoog, A H; Edwards, T L

2017-11-01

Enhanced tuberculosis (TB) case finding using detection rats in Tanzania. To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients. A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert. Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone. Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.

A standard test case suite for two-dimensional linear transport on the sphere: results from a collection of state-of-the-art schemes

NASA Astrophysics Data System (ADS)

Lauritzen, P. H.; Ullrich, P. A.; Jablonowski, C.; Bosler, P. A.; Calhoun, D.; Conley, A. J.; Enomoto, T.; Dong, L.; Dubey, S.; Guba, O.; Hansen, A. B.; Kaas, E.; Kent, J.; Lamarque, J.-F.; Prather, M. J.; Reinert, D.; Shashkin, V. V.; Skamarock, W. C.; Sørensen, B.; Taylor, M. A.; Tolstykh, M. A.

2013-09-01

Recently, a standard test case suite for 2-D linear transport on the sphere was proposed to assess important aspects of accuracy in geophysical fluid dynamics with a "minimal" set of idealized model configurations/runs/diagnostics. Here we present results from 19 state-of-the-art transport scheme formulations based on finite-difference/finite-volume methods as well as emerging (in the context of atmospheric/oceanographic sciences) Galerkin methods. Discretization grids range from traditional regular latitude-longitude grids to more isotropic domain discretizations such as icosahedral and cubed-sphere tessellations of the sphere. The schemes are evaluated using a wide range of diagnostics in idealized flow environments. Accuracy is assessed in single- and two-tracer configurations using conventional error norms as well as novel diagnostics designed for climate and climate-chemistry applications. In addition, algorithmic considerations that may be important for computational efficiency are reported on. The latter is inevitably computing platform dependent, The ensemble of results from a wide variety of schemes presented here helps shed light on the ability of the test case suite diagnostics and flow settings to discriminate between algorithms and provide insights into accuracy in the context of global atmospheric/ocean modeling. A library of benchmark results is provided to facilitate scheme intercomparison and model development. Simple software and data-sets are made available to facilitate the process of model evaluation and scheme intercomparison.

A standard test case suite for two-dimensional linear transport on the sphere: results from a collection of state-of-the-art schemes

NASA Astrophysics Data System (ADS)

Lauritzen, P. H.; Ullrich, P. A.; Jablonowski, C.; Bosler, P. A.; Calhoun, D.; Conley, A. J.; Enomoto, T.; Dong, L.; Dubey, S.; Guba, O.; Hansen, A. B.; Kaas, E.; Kent, J.; Lamarque, J.-F.; Prather, M. J.; Reinert, D.; Shashkin, V. V.; Skamarock, W. C.; Sørensen, B.; Taylor, M. A.; Tolstykh, M. A.

2014-01-01

Recently, a standard test case suite for 2-D linear transport on the sphere was proposed to assess important aspects of accuracy in geophysical fluid dynamics with a "minimal" set of idealized model configurations/runs/diagnostics. Here we present results from 19 state-of-the-art transport scheme formulations based on finite-difference/finite-volume methods as well as emerging (in the context of atmospheric/oceanographic sciences) Galerkin methods. Discretization grids range from traditional regular latitude-longitude grids to more isotropic domain discretizations such as icosahedral and cubed-sphere tessellations of the sphere. The schemes are evaluated using a wide range of diagnostics in idealized flow environments. Accuracy is assessed in single- and two-tracer configurations using conventional error norms as well as novel diagnostics designed for climate and climate-chemistry applications. In addition, algorithmic considerations that may be important for computational efficiency are reported on. The latter is inevitably computing platform dependent. The ensemble of results from a wide variety of schemes presented here helps shed light on the ability of the test case suite diagnostics and flow settings to discriminate between algorithms and provide insights into accuracy in the context of global atmospheric/ocean modeling. A library of benchmark results is provided to facilitate scheme intercomparison and model development. Simple software and data sets are made available to facilitate the process of model evaluation and scheme intercomparison.

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

Diagnostic sensitivity and specificity of in situ hybridization and immunohistochemistry for Eastern equine encephalitis virus and West Nile virus in formalin-fixed, paraffin-embedded brain tissue of horses.

PubMed

Pennick, Kate E; McKnight, Christy A; Patterson, Jon S; Latimer, Kenneth S; Maes, Roger K; Wise, Annabel G; Kiupel, Matti

2012-03-01

Immunohistochemistry (IHC) and in situ hybridization (ISH) can be used either to detect or to differentiate between Eastern equine encephalitis virus (EEEV) and West Nile virus (WNV) within formalin-fixed, paraffin-embedded (FFPE) brain tissue of horses. To compare the diagnostic sensitivity and specificity of ISH and IHC, FFPE brain tissue from 20 EEEV-positive horses and 16 WNV-positive horses were tested with both EEEV and WNV oligoprobes and EEEV- and WNV-specific antibodies. Reverse transcription polymerase chain reaction (RT-PCR) for detection of EEEV and WNV was used as the gold standard to confirm infection. All horses that tested positive for EEEV by RT-PCR also tested positive by IHC and ISH, except for 1 case that was false-negative by ISH. In contrast, all horses that tested positive for WNV by RT-PCR tested negative by IHC and only 2 horses tested positive by ISH. No false-positives were detected with either method for both viruses. Both IHC and ISH are highly specific and sensitive diagnostic methods to detect EEEV in equine FFPE brain tissues, although neither appear effective for the diagnosis of WNV in equine neurologic cases.

Diagnostic Challenges of Central Nervous System Tuberculosis

PubMed Central

Loeffler, Ann M.; Honarmand, Somayeh; Flood, Jennifer M.; Baxter, Roger; Jacobson, Susan; Alexander, Rick; Glaser, Carol A.

2008-01-01

Central nervous system tuberculosis (TB) was identified in 20 cases of unexplained encephalitis referred to the California Encephalitis Project. Atypical features (encephalitic symptoms, rapid onset, age) and diagnostic challenges (insensitive cerebrospinal fluid [CSF] TB PCR result, elevated CSF glucose levels in patients with diabetes, negative result for tuberculin skin test) complicated diagnosis. PMID:18760024

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.

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

PubMed

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Fetal Intelligent Navigation Echocardiography (FINE): a novel method for rapid, simple, and automatic examination of the fetal heart.

PubMed

Yeo, Lami; Romero, Roberto

2013-09-01

To describe a novel method (Fetal Intelligent Navigation Echocardiography (FINE)) for visualization of standard fetal echocardiography views from volume datasets obtained with spatiotemporal image correlation (STIC) and application of 'intelligent navigation' technology. We developed a method to: 1) demonstrate nine cardiac diagnostic planes; and 2) spontaneously navigate the anatomy surrounding each of the nine cardiac diagnostic planes (Virtual Intelligent Sonographer Assistance (VIS-Assistance®)). The method consists of marking seven anatomical structures of the fetal heart. The following echocardiography views are then automatically generated: 1) four chamber; 2) five chamber; 3) left ventricular outflow tract; 4) short-axis view of great vessels/right ventricular outflow tract; 5) three vessels and trachea; 6) abdomen/stomach; 7) ductal arch; 8) aortic arch; and 9) superior and inferior vena cava. The FINE method was tested in a separate set of 50 STIC volumes of normal hearts (18.6-37.2 weeks of gestation), and visualization rates for fetal echocardiography views using diagnostic planes and/or VIS-Assistance® were calculated. To examine the feasibility of identifying abnormal cardiac anatomy, we tested the method in four cases with proven congenital heart defects (coarctation of aorta, tetralogy of Fallot, transposition of great vessels and pulmonary atresia with intact ventricular septum). In normal cases, the FINE method was able to generate nine fetal echocardiography views using: 1) diagnostic planes in 78-100% of cases; 2) VIS-Assistance® in 98-100% of cases; and 3) a combination of diagnostic planes and/or VIS-Assistance® in 98-100% of cases. In all four abnormal cases, the FINE method demonstrated evidence of abnormal fetal cardiac anatomy. The FINE method can be used to visualize nine standard fetal echocardiography views in normal hearts by applying 'intelligent navigation' technology to STIC volume datasets. This method can simplify examination of the fetal heart and reduce operator dependency. The observation of abnormal echocardiography views in the diagnostic planes and/or VIS-Assistance® should raise the index of suspicion for congenital heart disease. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Iridology: A systematic review.

PubMed

Ernst, E

1999-02-01

Iridologists claim to be able to diagnose medical conditions through abnormalities of pigmentation in the iris. This technique is popular in many countries. Therefore it is relevant to ask whether it is valid. To systematically review all interpretable tests of the validity of iridology as a diagnostic tool. DATA SOURCE AND EXTRACTION: Three independent literature searches were performed to identify all blinded tests. Data were extracted in a predefined, standardized fashion. Four case control studies were found. The majority of these investigations suggests that iridology is not a valid diagnostic method. The validity of iridology as a diagnostic tool is not supported by scientific evaluations. Patients and therapists should be discouraged from using this method.

T cell lymphomatoid contact dermatitis: a challenging case and review of the literature.

PubMed

Knackstedt, Thomas J; Zug, Kathryn A

2015-02-01

Lymphomatoid contact dermatitis is a pseudolymphoma with clinical and histological features of allergic contact dermatitis and cutaneous T cell lymphoma. Incorrect diagnosis may lead to unnecessary testing, unnecessary treatment, or patient harm. The objective of this study is to present a case to demonstrate the diagnostic challenge and overlap between allergic contact dermatitis and cutaneous T cell lymphoma in a patient with lymphomatoid contact dermatitis caused by methylchoroisothiazolinone/methylisothiazolinone and paraben mix, and to review the existing literature in order to summarize the demographics, clinical features, allergens and treatments reported for lymphomatoid contact dermatitis. A search of major scientific databases was conducted for English-language articles reporting cases of lymphomatoid contact dermatitis or additional synonymous search headings. Nineteen articles with a total of 23 patients were analysed. Lymphomatoid contact dermatitis was more common in men, with an average age of 58.5 years. Fourteen unique allergens were identified and confirmed by patch testing. However, no single test or study was diagnostic of lymphomatoid contact dermatitis. Allergen avoidance was the most useful management tool, but selected patients required topical or systemic immunosuppression. In conclusion, without specific diagnostic features, evaluation for lymphomatoid contact dermatitis should include a thorough history and examination, patch testing, and biopsy with immunohistochemistry and clonality studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Powassan Virus—A New Reemerging Tick-Borne Disease

PubMed Central

Fatmi, Syed Soheb; Zehra, Rija; Carpenter, David O.

2017-01-01

Powassan virus is a neurovirulent flavivirus consisting of two lineages causing meningoencephalitis. It is the only member of the tick-borne encephalitis serogroup which is present in mainland North America. With a total number of 27 cases from 1958 to 1998 and 98 cases from 1999 to 2016, reported cases have increased by 671% over the last 18 years. Powassan infection is transmitted by different tick species in different geographical regions. Ixodes scapularis is the primary vector that transmits the virus on the East Coast of US and Ixodes cookei in the Midwest and Canada, while Hemaphysalis longicornis is the vector in Russia. Powassan has no singular pathognomonic finding and presents with a wide spectrum of symptoms including severe neurological symptoms. The clinical challenge lies within the management of the disease as there is no standard diagnostic protocol and most cases are only diagnosed after a patient goes through an extensive workup for other infectious disease. The diagnosis is established by a combination of imaging and serologic tests. In case of Powassan meningoencephalitis, computed tomography scan and magnetic resonance imaging show vascular insults, which are also seen in cases of tick-borne encephalitis virus, another flavivirus of medical importance. Serologic tests are the gold standard for diagnosis, although testing is not widely available and only state health departments and Center for Disease Control and Prevention can perform Powassan-specific IgM antibody testing utilizing enzyme-linked immunosorbent assay and immunofluorescence antibody. Powassan is also of veterinary medical importance. Wildlife animals act as a reservoir to the pathogens, hence possessing threat to humans and domestic animals. This review highlights Powassan’s neurotropic presentation, epidemiology, diagnostic challenges, and prevalence. Strong emphasis is placed on establishing diagnostic protocols, widespread Powassan-specific IgM testing, role of the vector in disease presentation, and necessary preventive research. PMID:29312918

Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): case definition in surveillance for childhood-onset Duchenne/Becker muscular dystrophy.

PubMed

Mathews, Katherine D; Cunniff, Chris; Kantamneni, Jiji R; Ciafaloni, Emma; Miller, Timothy; Matthews, Dennis; Cwik, Valerie; Druschel, Charlotte; Miller, Lisa; Meaney, F John; Sladky, John; Romitti, Paul A

2010-09-01

The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

Exploration of Analysis Methods for Diagnostic Imaging Tests: Problems with ROC AUC and Confidence Scores in CT Colonography

PubMed Central

Mallett, Susan; Halligan, Steve; Collins, Gary S.; Altman, Doug G.

2014-01-01

Background Different methods of evaluating diagnostic performance when comparing diagnostic tests may lead to different results. We compared two such approaches, sensitivity and specificity with area under the Receiver Operating Characteristic Curve (ROC AUC) for the evaluation of CT colonography for the detection of polyps, either with or without computer assisted detection. Methods In a multireader multicase study of 10 readers and 107 cases we compared sensitivity and specificity, using radiological reporting of the presence or absence of polyps, to ROC AUC calculated from confidence scores concerning the presence of polyps. Both methods were assessed against a reference standard. Here we focus on five readers, selected to illustrate issues in design and analysis. We compared diagnostic measures within readers, showing that differences in results are due to statistical methods. Results Reader performance varied widely depending on whether sensitivity and specificity or ROC AUC was used. There were problems using confidence scores; in assigning scores to all cases; in use of zero scores when no polyps were identified; the bimodal non-normal distribution of scores; fitting ROC curves due to extrapolation beyond the study data; and the undue influence of a few false positive results. Variation due to use of different ROC methods exceeded differences between test results for ROC AUC. Conclusions The confidence scores recorded in our study violated many assumptions of ROC AUC methods, rendering these methods inappropriate. The problems we identified will apply to other detection studies using confidence scores. We found sensitivity and specificity were a more reliable and clinically appropriate method to compare diagnostic tests. PMID:25353643

Exploration of analysis methods for diagnostic imaging tests: problems with ROC AUC and confidence scores in CT colonography.

PubMed

Mallett, Susan; Halligan, Steve; Collins, Gary S; Altman, Doug G

2014-01-01

Different methods of evaluating diagnostic performance when comparing diagnostic tests may lead to different results. We compared two such approaches, sensitivity and specificity with area under the Receiver Operating Characteristic Curve (ROC AUC) for the evaluation of CT colonography for the detection of polyps, either with or without computer assisted detection. In a multireader multicase study of 10 readers and 107 cases we compared sensitivity and specificity, using radiological reporting of the presence or absence of polyps, to ROC AUC calculated from confidence scores concerning the presence of polyps. Both methods were assessed against a reference standard. Here we focus on five readers, selected to illustrate issues in design and analysis. We compared diagnostic measures within readers, showing that differences in results are due to statistical methods. Reader performance varied widely depending on whether sensitivity and specificity or ROC AUC was used. There were problems using confidence scores; in assigning scores to all cases; in use of zero scores when no polyps were identified; the bimodal non-normal distribution of scores; fitting ROC curves due to extrapolation beyond the study data; and the undue influence of a few false positive results. Variation due to use of different ROC methods exceeded differences between test results for ROC AUC. The confidence scores recorded in our study violated many assumptions of ROC AUC methods, rendering these methods inappropriate. The problems we identified will apply to other detection studies using confidence scores. We found sensitivity and specificity were a more reliable and clinically appropriate method to compare diagnostic tests.

Rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in Tanzania: randomised trial.

PubMed

Reyburn, Hugh; Mbakilwa, Hilda; Mwangi, Rose; Mwerinde, Ombeni; Olomi, Raimos; Drakeley, Chris; Whitty, Christopher J M

2007-02-24

To compare rapid diagnostic tests (RDTs) for malaria with routine microscopy in guiding treatment decisions for febrile patients. Randomised trial. Outpatient departments in northeast Tanzania at varying levels of malaria transmission. 2416 patients for whom a malaria test was requested. Staff received training on rapid diagnostic tests; patients sent for malaria tests were randomised to rapid diagnostic test or routine microscopy Proportion of patients with a negative test prescribed an antimalarial drug. Of 7589 outpatient consultations, 2425 (32%) had a malaria test requested. Of 1204 patients randomised to microscopy, 1030 (86%) tested negative for malaria; 523 (51%) of these were treated with an antimalarial drug. Of 1193 patients randomised to rapid diagnostic test, 1005 (84%) tested negative; 540 (54%) of these were treated for malaria (odds ratio 1.13, 95% confidence interval 0.95 to 1.34; P=0.18). Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides (P=0.003). Patients with a negative test by any method were more likely to be prescribed an antibiotic (odds ratio 6.42, 4.72 to 8.75; P<0.001). More than 90% of prescriptions for antimalarial drugs in low-moderate transmission settings were for patients for whom a test requested by a clinician was negative for malaria. Although many cases of malaria are missed outside the formal sector, within it malaria is massively over-diagnosed. This threatens the sustainability of deployment of artemisinin combination treatment, and treatable bacterial diseases are likely to be missed. Use of rapid diagnostic tests, with basic training for clinical staff, did not in itself lead to any reduction in over-treatment for malaria. Interventions to improve clinicians' management of febrile illness are essential but will not be easy. Clinical trials NCT00146796 [ClinicalTrials.gov].

[Molecular diagnostics of ALK-positive lung cancer].

PubMed

Tímár, József; Lotz, Gábor; Rásó, Erzsébet; Moldvay, Judit

2017-09-20

ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH). In case of cytological samples FISH technique must be used as ALK diagnostics. In equivocal cases the genetic alteration of ALK can be confirmed by alternative molecular techniques such as next generation sequencing or RNAbased PCR methods. Upon administration of ALK inhibitors, acquired resistance is frequent which is mostly due to ALK amplification and/or mutation. It is evident that the diagnostics of these secondary ALK gene alterations must be done from recurrent tumors or circulating nucleic acids.

The risk of a second diagnostic window with 4th generation HIV assays: Two cases.

PubMed

Niederhauser, C; Ströhle, A; Stolz, M; Müller, F; Tinguely, C

2009-08-01

Despite the improved sensitivity of the 4th generation combined antigen/antibody HIV assays, detection of HIV in the early phase of an infection may still be ineffective. Description of two cases that highlight the existence of the "second diagnostic window phase" observed with commonly used sensitive 4th generation HIV assays. Samples were screened with different 4th generation HIV assays. HIV infection was confirmed with an HIV I/II antibody assay, a HIV-1 p24 antigen assay, the INNO-LIA HIV I/II Score Line immunoassay and HIV-1 PCR. In both investigated cases, the limitations of the 4th generation HIV assays within the second diagnostic window were apparent. The overall sensitivity of the commercial 4th generation HIV assays is currently higher than the 3rd generation HIV assays. Nevertheless, the rare occurrence of a second diagnostic window with 4th generation HIV assays strongly suggests that the following up testing algorithms need to be adjusted accordingly.

PUBLIC HEALTH ASPECTS OF LYMPHOGRANULOMA VENEREUM

PubMed Central

Koch, Richard A.; McDonald, Ruth S.; Marshall, Max S.

1949-01-01

The clinical symptoms of lymphogranuloma venereum with the serious pathologic changes often occurring in the late stages of the disease warrant greater attention to the disease. The reported ratio of cases of lymphogranuloma venereum to cases of syphilis and gonorrhea is much higher in San Francisco than in other metropolitan ports of western United States, apparently because of greater use of diagnostic tests for the disease. Tests of persons likely to be exposed and other persons not likely to be exposed to venereal diseases indicate that a positive reaction to a Frei test implies past or present infection with lymphogranuloma venereum. Positive reactions to complement fixation tests are notably more frequent than positive response to Frei tests. The complement fixation test appears to be an unreliable diagnostic aid. The frequency of positive reactions associated with other venereal diseases, and their infrequency otherwise, suggests that lymphogranuloma venereum may exist, unrecognized, in many persons, who may be, potentially at least, carriers of the disease. PMID:18147525

Comparison of species-level identification and antifungal susceptibility results from diagnostic and reference laboratories for bloodstream Candida surveillance isolates, South Africa, 2009-2010.

PubMed

Naicker, Serisha D; Govender, Nevashan; Patel, Jaymati; Zietsman, Inge L; Wadula, Jeannette; Coovadia, Yacoob; Kularatne, Ranmini; Seetharam, Sharona; Govender, Nelesh P

2016-11-01

From February 2009 through August 2010, we compared species-level identification of bloodstream Candida isolates and susceptibility to fluconazole, voriconazole, and caspofungin between diagnostic and reference South African laboratories during national surveillance for candidemia. Diagnostic laboratories identified isolates to genus/species level and performed antifungal susceptibility testing, as indicated. At a reference laboratory, viable Candida isolates were identified to species-level using automated systems, biochemical tests, or DNA sequencing; broth dilution susceptibility testing was performed. Categorical agreement (CA) was calculated for susceptibility results of isolates with concordant species identification. Overall, 2172 incident cases were detected, 773 (36%) by surveillance audit. The Vitek 2 YST system (bioMérieux Inc, Marcy l'Etoile, France) was used for identification (360/863, 42%) and susceptibility testing (198/473, 42%) of a large proportion of isolates. For the five most common species (n = 1181), species-level identification was identical in the majority of cases (Candida albicans: 98% (507/517); Candida parapsilosis: 92% (450/488); Candida glabrata: 89% (89/100); Candida tropicalis: 91% (49/54), and Candida krusei: 86% (19/22)). However, diagnostic laboratories were significantly less likely to correctly identify Candida species other than C. albicans versus C. albicans (607/664, 91% vs. 507/517, 98%; P < .001). Susceptibility data were compared for isolates belonging to the five most common species and fluconazole, voriconazole, and caspofungin in 860, 580, and 99 cases, respectively. Diagnostic laboratories significantly under-reported fluconazole resistance in C. parapsilosis (225/393, 57% vs. 239/393, 61%; P < .001) but over-reported fluconazole non-susceptibility in C. albicans (36/362, 10% vs. 3/362, 0.8%; P < .001). Diagnostic laboratories were less likely to correctly identify Candida species other than C. albicans, under-reported fluconazole resistance for C. parapsilosis and over-reported fluconazole resistance for C. albicans. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Primary hyperaldosteronism: problems of diagnostic approaches].

PubMed

Widimský, Jiří

2015-05-01

Primary hyperaldosteronism (PH) is common cause of endocrine/secondary hypertension with autonomous aldosterone overproduction by adrenal cortex. PH is typically characterized by hypertension, hypokalemia, high plasma aldosterone/renin ratio, high aldosterone, suppressed renin and nonsupressibilty of aldosterone during confirmatory tests. Diagnosis of PH can be difficult since hypokalemia is found only in 50 % of cases and measurement of the parameters of renin-angiotensin-aldosterone system can be influenced by several factors. Morphological dia-gnosis requires in majority of cases adrenal venous sampling. Early diagnostic and therapeutic measures are very important due to high prevalence of PH and potential cure. Patients with suspicion to PH should be investigated in experienced hypertensive centers due to relatively difficult laboratory and morphological diagnostic approaches.

Occupational rhinitis in the Slovak Republic--a long-term retrospective study.

PubMed

Perečinský, Slavomir; Legáth, L'ubomír; Varga, Marek; Javorský, Martin; Bátora, Igor; Klimentová, Gabriela

2014-12-01

Allergic and non-allergic rhinitis ranks among the common occupational health problems. However, data on the incidence of occupational rhinitis are lacking, since comprehensive studies are rare. The study includes a group of patients in the Slovak Republic who were reported as having occupational rhinitis in the years 1990-2011. The following parameters were tracked in the investigated sample: age, gender, number of cases by individual years, occupations, causative factors and the length of exposure to the given agent. Possible progression of rhinitis to bronchial asthma was evaluated as well. The diagnostic algorithm was also analysed retrospectively, which included skin tests, the examination of specific IgE antibodies and nasal provocation tests. A total of 70 cases of occupational rhinitis were reported. The disease most often occurred in food industry workers (50% of cases). The most common aetiological factor was flour. Among other relatively common allergens were synthetic textile, wool, cotton and different types of moulds. Significant agents were also different chemical factors causing allergic and irritant rhinitis. The average length of exposure was 14.8 years. Exposure was shorter in men than in women (11 years vs. 16 years) (p = 0.04). Bronchial asthma as a comorbidity was diagnosed in 13 patients (19.7%). The critical diagnostic method on the basis of which the causal association between rhinitis and work environments was confirmed in 59% of cases was skin test; confirmation of the occupational cause using nasal provocation test was less frequent (18%). Food industry, textile industry and agriculture were the most risky occupational environments. Workers in these sectors require preventive intervention. In case of showing rhinitis symptoms it is necessary to confirm the occupational aetiology of the disease by the objective diagnostic methods. Since occupational rhinitis mostly precedes the occupational asthma, the elimination from the workplace is necessary.

Malaria rapid diagnostic tests in tropical climates: the need for a cool chain.

PubMed

Jorgensen, Pernille; Chanthap, Lon; Rebueno, Antero; Tsuyuoka, Reiko; Bell, David

2006-05-01

Malaria control programs in endemic countries increasingly rely on early case detection and treatment at village level. The rapid diagnostic tests (RDTs) and accompanying drugs on which the success of these programs depends deteriorate to varying degrees at high temperatures. To assess the ability of health systems to maintain RDTs within manufacturers' specifications, we monitored temperatures in the delivery chain from manufacturer through to the village health worker in Cambodia and the Philippines. In both countries, storage temperatures regularly exceeded those recommended for most RDTs intended for field use, whereas temperatures during transport greatly exceeded the lower and upper limits. These results emphasize the need for good logistical planning during the introduction of point-of-care tests in tropical countries and the importance of considering the stability of diagnostic tests during procurement.

Veterinary Forensic Toxicology.

PubMed

Gwaltney-Brant, S M

2016-09-01

Veterinary pathologists working in diagnostic laboratories are sometimes presented with cases involving animal poisonings that become the object of criminal or civil litigation. Forensic veterinary toxicology cases can include cases involving animal cruelty (malicious poisoning), regulatory issues (eg, contamination of the food supply), insurance litigation, or poisoning of wildlife. An understanding of the appropriate approach to these types of cases, including proper sample collection, handling, and transport, is essential so that chain of custody rules are followed and proper samples are obtained for toxicological analysis. Consultation with veterinary toxicologists at the diagnostic laboratory that will be processing the samples before, during, and after the forensic necropsy can help to ensure that the analytical tests performed are appropriate for the circumstances and findings surrounding the individual case. © The Author(s) 2016.

Acute undifferentiated fever in India: a multicentre study of aetiology and diagnostic accuracy.

PubMed

Mørch, Kristine; Manoharan, Anand; Chandy, Sara; Chacko, Novin; Alvarez-Uria, Gerardo; Patil, Suvarna; Henry, Anil; Nesaraj, Joel; Kuriakose, Cijoy; Singh, Ashita; Kurian, Siby; Gill Haanshuus, Christel; Langeland, Nina; Blomberg, Bjørn; Vasanthan Antony, George; Mathai, Dilip

2017-10-04

The objectives of this study were to determine the proportion of malaria, bacteraemia, scrub typhus, leptospirosis, chikungunya and dengue among hospitalized patients with acute undifferentiated fever in India, and to describe the performance of standard diagnostic methods. During April 2011-November 2012, 1564 patients aged ≥5 years with febrile illness for 2-14 days were consecutively included in an observational study at seven community hospitals in six states in India. Malaria microscopy, blood culture, Dengue rapid NS1 antigen and IgM Combo test, Leptospira IgM ELISA, Scrub typhus IgM ELISA and Chikungunya IgM ELISA were routinely performed at the hospitals. Second line testing, Dengue IgM capture ELISA (MAC-ELISA), Scrub typhus immunofluorescence (IFA), Leptospira Microscopic Agglutination Test (MAT), malaria PCR and malaria immunochromatographic rapid diagnostic test (RDT) Parahit Total™ were performed at the coordinating centre. Convalescence samples were not available. Case definitions were as follows: Leptospirosis: Positive ELISA and positive MAT. Scrub typhus: Positive ELISA and positive IFA. Dengue: Positive RDT and/or positive MAC-ELISA. Chikungunya: Positive ELISA. Bacteraemia: Growth in blood culture excluding those defined as contaminants. Malaria: Positive genus-specific PCR. Malaria was diagnosed in 17% (268/1564) and among these 54% had P. falciparum. Dengue was diagnosed in 16% (244/1564). Bacteraemia was found in 8% (124/1564), and among these Salmonella typhi or S. paratyphi constituted 35%. Scrub typhus was diagnosed in 10%, leptospirosis in 7% and chikungunya in 6%. Fulfilling more than one case definition was common, most frequent in chikungunya where 26% (25/98) also had positive dengue test. Malaria and dengue were the most common causes of fever in this study. A high overlap between case definitions probably reflects high prevalence of prior infections, cross reactivity and subclinical infections, rather than high prevalence of coinfections. Low accuracy of routine diagnostic tests should be taken into consideration when approaching the patient with acute undifferentiated fever in India.

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

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.

Comparison of Diagnostic Yield of a FISH Panel Against Conventional Cytogenetic Studies for Hematological Malignancies: A South Indian Referral Laboratory Analysis Of 201 Cases

PubMed Central

Ashok, Vishal; Ranganathan, Ramya; Chander, Smitha; Damodar, Sharat; Bhat, Sunil; KS, Nataraj; A, Satish Kumar; Jadav, Sachin Suresh; Rajashekaraiah, Mahesh; TS, Sundareshan

2017-01-01

Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS. Results: Exhibited a greater diagnostic yield with a positive result in 39.8% of the cases, as compared to 17.9% of cases detected by CCS. Cases of chronic lymphocytic leukaemia (CLL) benefited the most by FISH testing, which identified chromosomal aberrations beyond the capacity of CCS. FISH was least beneficial in myelodysplastic syndrome (MDS) where the highest concordance with CCS was exhibited. Acute lymphocytic leukaemia (ALL) demonstrated greater benefit with CCS. In addition, we found the following abnormalities to be most prevalent in HMs by FISH panel testing: RUNX1 (21q22) amplification in ALL, deletion of D13S319/LAMP1 (13q14) in CLL, CKS1B (1q21) amplification in multiple myeloma and deletion of EGR1/RPS14 (5q31/5q32) in MDS, consistent with the literature. Conclusions: In conclusion, FISH was found to be advantageous in only a subset of HMs and cannot completely replace CCS. Utilization of the two modalities in conjunction or independently should depend on the indicated HM for an optimal approach to detecting chromosomal aberrations. PMID:29286619

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.

PubMed Central

Beaulieu, M. D.; Latulipe, L.; Ringuet, J.; Veilleux, J.

1983-01-01

For a random sample of 1029 visits occurring over a 1-year period in a family medicine service 1067 diagnostic tests were done within 1 week (or within 3 weeks in the case of nuclear medicine) following the visit; this represents a mean of 1.04 tests, costing $ 8.30, per visit. There was no test ordered in most (62.5%) of the visits. The results of 909 tests were recorded; 36.6% were abnormal. The pattern of use of diagnostic tests varied considerably among the physicians; however, no association was observed between this pattern and the status of the physician, the site of the encounter, or the age or sex of the patient. There was a weak and not statistically significant correlation between the number of problems identified and the number of tests with abnormal results per visit. These results suggest that the problem of overuse of diagnostic tests may not be as acute in a family medicine service as it has been observed to be in other settings. PMID:6671181

Clinical Diagnostic Utility of IP-10 and LAM Antigen Levels for the Diagnosis of Tuberculous Pleural Effusions in a High Burden Setting

PubMed Central

Dheda, Keertan; Van-Zyl Smit, Richard N.; Sechi, Leonardo A.; Badri, Motasim; Meldau, Richard; Symons, Gregory; Khalfey, Hoosein; Carr, Igshaan; Maredza, Alice; Dawson, Rodney; Wainright, Helen; Whitelaw, Andrew; Bateman, Eric D.; Zumla, Alimuddin

2009-01-01

Background Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid. Methods We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis. Principal Findings Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed ∼20% of TB cases and mis-diagnosed ∼20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful. Conclusion Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings. PMID:19277111

Economic evaluation of laboratory testing strategies for hospital-associated Clostridium difficile infection.

PubMed

Schroeder, Lee F; Robilotti, Elizabeth; Peterson, Lance R; Banaei, Niaz; Dowdy, David W

2014-02-01

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI.

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

PubMed Central

Robilotti, Elizabeth; Peterson, Lance R.; Banaei, Niaz; Dowdy, David W.

2014-01-01

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI. PMID:24478478

Acute bacterial and viral meningitis.

PubMed

Bartt, Russell

2012-12-01

Most cases of acute meningitis are infectious and result from a potentially wide range of bacterial and viral pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Acute meningitis is infectious in most cases and caused by a potentially wide range of bacterial and viral pathogens. Shifts in the epidemiology of bacterial pathogens have been influenced by changes in vaccines and their implementation. Seasonal and environmental changes influence the likely viral and rickettsial pathogens. The organized approach to the patient with suspected meningitis enables the prompt administration of antibiotics, possibly corticosteroids, and diagnostic testing with neuroimaging and spinal fluid analysis. Pertinent testing and treatment can vary with the clinical presentation, season, and possible exposures. This article reviews the epidemiology, clinical presentation, diagnosis, and treatment of acute meningitis.

[Diagnostic workup of fragrance allergy].

PubMed

Geier, J; Uter, W

2015-09-01

The diagnostic workup of contact allergy to fragrances must not be limited to patch testing with the two well-established fragrance mixes. False-positive reactions to these mixes occur in up to 50 % of the patch tested patients. For the diagnostic work-up of positive reactions, and in cases of suspected fragrance allergy, patch testing with the single mix components and additional fragrances is mandatory. Frequently sensitizing fragrance materials are the 14 components of the two fragrance mixes and tree moss (Evernia furfuracea), ylang ylang oil (I + II; Cananga odorata), lemongrass oil (Cymbopogon schoenanthus), sandalwood oil (Santalum album), jasmine absolute (Jasminum spp.), and, less frequently, clove oil (Eugenia caryophyllus), cedarwood oil (Cedrus atlantica/deodara, Juniperus virginiana), Neroli oil (Citrus aurantium amara flower oil), salicylaldehyde, narcissus absolute (Narcissus spp.), and patchouli oil (Pogostemon cablin).

Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

PubMed

Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

2016-10-01

Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age < 60 and/or Bethesda criteria). From 2012 to 2014, we screened all CRCs. Immunohistochemistry for the four mismatch repair proteins was done in all cases, followed by other diagnostic studies as indicated. We modeled the diagnostic costs of detecting Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

Clinical routine utility of basophil activation testing for diagnosis of hymenoptera-allergic patients with emphasis on individuals with negative venom-specific IgE antibodies.

PubMed

Korošec, Peter; Šilar, Mira; Eržen, Renato; Čelesnik, Nina; Bajrović, Nissera; Zidarn, Mihaela; Košnik, Mitja

2013-01-01

Previous reports suggest the usefulness of basophil activation testing (BAT) in Hymenoptera-allergic patients with negative venom-specific IgE antibodies. We sought to evaluate the diagnostic utility of this testing in a routine clinical laboratory setting. Twenty-one patients with anaphylactic reactions to Hymenoptera sting (median grade III) and negative venom-specific IgE were routinely and prospectively tested with BAT. We were able to diagnose 81% (17 of 21) of patients with BAT and 57% (12 of 21) with intradermal skin testing. Three wasp venom-allergic patients showed IgE positivity to rVes v 5. Four patients (19%) were negative for all tests. In the case of double-positive BAT, the culprit insect correlated with the venom that induced a significantly higher basophil response. BAT allows the identification of severe Hymenoptera-allergic patients with negative specific IgE and skin tests. The routine use of this cellular test should facilitate prescription of venom immunotherapy in complex cases with inconclusive diagnostic results. Copyright © 2013 S. Karger AG, Basel.

Laboratory Diagnosis of Infective Endocarditis

PubMed Central

Liesman, Rachael M.; Pritt, Bobbi S.; Maleszewski, Joseph J.

2017-01-01

ABSTRACT Infective endocarditis is life-threatening; identification of the underlying etiology informs optimized individual patient management. Changing epidemiology, advances in blood culture techniques, and new diagnostics guide the application of laboratory testing for diagnosis of endocarditis. Blood cultures remain the standard test for microbial diagnosis, with directed serological testing (i.e., Q fever serology, Bartonella serology) in culture-negative cases. Histopathology and molecular diagnostics (e.g., 16S rRNA gene PCR/sequencing, Tropheryma whipplei PCR) may be applied to resected valves to aid in diagnosis. Herein, we summarize recent knowledge in this area and propose a microbiologic and pathological algorithm for endocarditis diagnosis. PMID:28659319

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

PubMed

Lutterloh, Emily; Likaka, Andrew; Sejvar, James; Manda, Robert; Naiene, Jeremias; Monroe, Stephan S; Khaila, Tadala; Chilima, Benson; Mallewa, Macpherson; Kampondeni, Sam D; Lowther, Sara A; Capewell, Linda; Date, Kashmira; Townes, David; Redwood, Yanique; Schier, Joshua G; Nygren, Benjamin; Tippett Barr, Beth; Demby, Austin; Phiri, Abel; Lungu, Rudia; Kaphiyo, James; Humphrys, Michael; Talkington, Deborah; Joyce, Kevin; Stockman, Lauren J; Armstrong, Gregory L; Mintz, Eric

2012-04-01

Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

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.

Generalized likelihood ratios for quantitative diagnostic test scores.

PubMed

Tandberg, D; Deely, J J; O'Malley, A J

1997-11-01

The reduction of quantitative diagnostic test scores to the dichotomous case is a wasteful and unnecessary simplification in the era of high-speed computing. Physicians could make better use of the information embedded in quantitative test results if modern generalized curve estimation techniques were applied to the likelihood functions of Bayes' theorem. Hand calculations could be completely avoided and computed graphical summaries provided instead. Graphs showing posttest probability of disease as a function of pretest probability with confidence intervals (POD plots) would enhance acceptance of these techniques if they were immediately available at the computer terminal when test results were retrieved. Such constructs would also provide immediate feedback to physicians when a valueless test had been ordered.

Probability scores and diagnostic algorithms in pulmonary embolism: are they followed in clinical practice?

PubMed

Sanjuán, Pilar; Rodríguez-Núñez, Nuria; Rábade, Carlos; Lama, Adriana; Ferreiro, Lucía; González-Barcala, Francisco Javier; Alvarez-Dobaño, José Manuel; Toubes, María Elena; Golpe, Antonio; Valdés, Luis

2014-05-01

Clinical probability scores (CPS) determine the pre-test probability of pulmonary embolism (PE) and assess the need for the tests required in these patients. Our objective is to investigate if PE is diagnosed according to clinical practice guidelines. Retrospective study of clinically suspected PE in the emergency department between January 2010 and December 2012. A D-dimer value ≥ 500 ng/ml was considered positive. PE was diagnosed on the basis of the multislice computed tomography angiography and, to a lesser extent, with other imaging techniques. The CPS used was the revised Geneva scoring system. There was 3,924 cases of suspected PE (56% female). Diagnosis was determined in 360 patients (9.2%) and the incidence was 30.6 cases per 100,000 inhabitants/year. Sensitivity and the negative predictive value of the D-dimer test were 98.7% and 99.2% respectively. CPS was calculated in only 24 cases (0.6%) and diagnostic algorithms were not followed in 2,125 patients (54.2%): in 682 (17.4%) because clinical probability could not be estimated and in 482 (37.6%), 852 (46.4%) and 109 (87.9%) with low, intermediate and high clinical probability, respectively, because the diagnostic algorithms for these probabilities were not applied. CPS are rarely calculated in the diagnosis of PE and the diagnostic algorithm is rarely used in clinical practice. This may result in procedures with potential significant side effects being unnecessarily performed or to a high risk of underdiagnosis. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

[Economic evaluation of rapid diagnostic tests in malaria treatment].

PubMed

Faye, Adama; Ndiaye, Papa; Diagne-Camara, Maty; Badiane, Ousseynou; Wone, Issa; Diongue, Mayassine; Seck, Ibrahima; Dia, Anta Tal; Dia, Amadou Lamine

2010-01-01

This study aimed to evaluate the economic implications of rapid diagnostic tests (RDTs) on malaria management through the rational use of artemisinin-based combination therapy (ACT). The study was carried out in 2006 from November 10th to December 10th; it focused on patients who were seen and treated with ACT for suspicion of uncomplicated malaria in the health district of Ziguinchor, Senegal. The variables studied included age, sex, RDT results, and costs of care and RDT. The cost of care for malaria, estimated in CFA Francs, was evaluated both with and without the use of RDT. Among the 379 patients, 25,1% were aged 0-4 years, 12,7% of 5-14 years and 62,2% of at least 15 years; 51% were women. The result of the RDT was negative in 60% of cases. Without the use of diagnostic testing, the cost of care for all 379 cases was estimated at 299 957 CFA: patient contributions would cover 184 500 CFA and the State would cover the rest (115 457 CFA). With the use of RDTs, the overall cost of the RDT screening for 379 patients and the cost of treatment for the 150 positive cases amounted to 254 786 CFA, with patients bearing the cost of 205 550 CFA and the State subsidizing up to 49 236 CFA. RDT can help identify the positive cases of malaria, and avoid up to 60% of unnecessary treatments, corresponding to an estimated 27 297 cases at the district level and 584 630 cases nationally. The RDT also allow a more rational use of ACTs and a lower risk of emergence of Plasmodium resistance. The use of RDTs could result in savings of 45 171 CFA at the level of the district health centre and 111 240 136 CFA nationally.

Knowledge and Adherence to the National Guidelines for Malaria Diagnosis in Pregnancy among Health-Care Providers and Drug-Outlet Dispensers in Rural Western Kenya.

PubMed

Riley, Christina; Dellicour, Stephanie; Ouma, Peter; Kioko, Urbanus; Omar, Ahmeddin; Kariuki, Simon; Ng'ang'a, Zipporah; Desai, Meghna; Buff, Ann M; Gutman, Julie R

2018-05-01

Prompt diagnosis and effective treatment of acute malaria in pregnancy (MiP) is important for the mother and fetus; data on health-care provider adherence to diagnostic guidelines in pregnancy are limited. From September to November 2013, a cross-sectional survey was conducted in 51 health facilities and 39 drug outlets in Western Kenya. Provider knowledge of national diagnostic guidelines for uncomplicated MiP were assessed using standardized questionnaires. The use of parasitologic testing was assessed in health facilities via exit interviews with febrile women of childbearing age and in drug outlets via simulated-client scenarios, posing as pregnant women or their spouses. Overall, 93% of providers tested for malaria or accurately described signs and symptoms consistent with clinical malaria. Malaria was parasitologically confirmed in 77% of all patients presenting with febrile illness at health facilities and 5% of simulated clients at drug outlets. Parasitological testing was available in 80% of health facilities; 92% of patients evaluated at these facilities were tested. Only 23% of drug outlets had malaria rapid diagnostic tests (RDTs); at these outlets, RDTs were offered in 17% of client simulations. No differences were observed in testing rates by pregnancy trimester. The study highlights gaps among health providers in diagnostic knowledge and practice related to MiP, and the lack of malaria diagnostic capacity, particularly in drug outlets. The most important factor associated with malaria testing of pregnant women was the availability of diagnostics at the point of service. Interventions that increase the availability of malaria diagnostic services might improve malaria case management in pregnant women.

Does exposure to simulated patient cases improve accuracy of clinicians' predictive value estimates of diagnostic test results? A within-subjects experiment at St Michael's Hospital, Toronto, Canada.

PubMed

Armstrong, Bonnie; Spaniol, Julia; Persaud, Nav

2018-02-13

Clinicians often overestimate the probability of a disease given a positive test result (positive predictive value; PPV) and the probability of no disease given a negative test result (negative predictive value; NPV). The purpose of this study was to investigate whether experiencing simulated patient cases (ie, an 'experience format') would promote more accurate PPV and NPV estimates compared with a numerical format. Participants were presented with information about three diagnostic tests for the same fictitious disease and were asked to estimate the PPV and NPV of each test. Tests varied with respect to sensitivity and specificity. Information about each test was presented once in the numerical format and once in the experience format. The study used a 2 (format: numerical vs experience) × 3 (diagnostic test: gold standard vs low sensitivity vs low specificity) within-subjects design. The study was completed online, via Qualtrics (Provo, Utah, USA). 50 physicians (12 clinicians and 38 residents) from the Department of Family and Community Medicine at St Michael's Hospital in Toronto, Canada, completed the study. All participants had completed at least 1 year of residency. Estimation accuracy was quantified by the mean absolute error (MAE; absolute difference between estimate and true predictive value). PPV estimation errors were larger in the numerical format (MAE=32.6%, 95% CI 26.8% to 38.4%) compared with the experience format (MAE=15.9%, 95% CI 11.8% to 20.0%, d =0.697, P<0.001). Likewise, NPV estimation errors were larger in the numerical format (MAE=24.4%, 95% CI 14.5% to 34.3%) than in the experience format (MAE=11.0%, 95% CI 6.5% to 15.5%, d =0.303, P=0.015). Exposure to simulated patient cases promotes accurate estimation of predictive values in clinicians. This finding carries implications for diagnostic training and practice. © 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.

[Laboratory diagnostics and monitoring of virus circulation in surveillance system for rubella in Belarus].

PubMed

Samoĭlovich, E O; Semeĭko, G V; Ermolovich, M A; Svirchevskaia, E Iu

2010-01-01

To summarize data on laboratory diagnostics of prenatal and postnatal rubella and molecular monitoring of rubella virus circulation in Belarus obtained during implementation of rubella elimination program. Serum samples from 2314 persons were tested on the presence of IgM to rubella virus and measles virus (in case of negative result on rubella) using respective enzyme immunoassays. Virological testing using RT-PCR as well as genotyping on the basis of E1 gene fragment sequencing were also performed. Two viruses isolated in Belarus were set as reference strains of genotypes 1G and 1h. Implementation of laboratory diagnostics allowed to differentiate cases of rubella from other exanthematous infections, significantly increase the number of laboratory-confirmed cases among all reported cases, and show presence of endemic circulation of rubella virus strains of 3 different genotypes (1G, 1E, and 1h) in Belarus (2004-2006). In 2006, when relatively high incidence of rubella was reported in the country (24.39 per 100,000 population), the risk of congenital rubella syndrome was not less than 9 per 100,000 births. Conducted in October 2005-May 2006 additional rounds of immunization against rubella (>1 million people were vaccinated) decreased incidence to single cases. Obtained data show achievability of indigenous rubella elemination by 2010. Revealed genetic diversity of rubella virus strains allowed to update the International classification of wild rubella viruses.

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.

Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of Borrelia burgdorferi sensu lato-specific PCR in Lyme neuroborreliosis?

PubMed

Forselv, Kristine J N; Lorentzen, Åslaug R; Ljøstad, Unn; Mygland, Åse; Eikeland, Randi; Kjelland, Vivian; Noraas, Sølvi; Quarsten, Hanne

2018-04-01

Tests for direct detection of Borrelia burgdorferi sensu lato (Bb) in Lyme neuroborreliosis (LNB) are needed. Detection of Bb DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples. Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls. Bb DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were Bb antibody negative. No Bb DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases. We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without Bb antibodies due to short duration of symptoms.

Is D-dimer used according to clinical algorithms in the diagnostic work-up of patients with suspicion of venous thromboembolism? A study in six European countries.

PubMed

Kristoffersen, Ann Helen; Ajzner, Eva; Rogic, Dunja; Sozmen, Eser Y; Carraro, Paolo; Faria, Ana Paula; Watine, Joseph; Meijer, Piet; Sandberg, Sverre

2016-06-01

Clinical algorithms consisting of pre-test probability estimation and D-dimer testing are recommended in diagnostic work-up for suspected venous thromboembolism (VTE). The aim of this study was to explore how physicians working in emergency departments investigated patients suspected to have VTE. A questionnaire with two case histories related to the diagnosis of suspected pulmonary embolism (PE) (Case A) and deep venous thrombosis (DVT) (Case B) were sent to physicians in six European countries. The physicians were asked to estimate pre-test probability of VTE, and indicate their clinical actions. In total, 487 physicians were included. Sixty percent assessed pre-test probability of PE to be high in Case A, but 7% would still request only D-dimer and 11% would exclude PE if D-dimer was negative, which could be hazardous. Besides imaging, a D-dimer test was requested by 41%, which is a "waste of resources" (extra costs and efforts, no clinical benefit). For Case B, 92% assessed pre-test probability of DVT to be low. Correctly, only D-dimer was requested by 66% of the physicians, while 26% requested imaging, alone or in addition to D-dimer, which is a "waste of resources". These results should encourage scientific societies to improve the dissemination and knowledge of the current recommendations for the diagnosis of VTE. Copyright © 2016 Elsevier Ltd. All rights reserved.

A hybrid Bayesian hierarchical model combining cohort and case-control studies for meta-analysis of diagnostic tests: Accounting for partial verification bias.

PubMed

Ma, Xiaoye; Chen, Yong; Cole, Stephen R; Chu, Haitao

2016-12-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities, and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. © The Author(s) 2014.

A Hybrid Bayesian Hierarchical Model Combining Cohort and Case-control Studies for Meta-analysis of Diagnostic Tests: Accounting for Partial Verification Bias

PubMed Central

Ma, Xiaoye; Chen, Yong; Cole, Stephen R.; Chu, Haitao

2014-01-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. PMID:24862512

Genetic counseling in monogenic diabetes GCK MODY.

PubMed

Skała-Zamorowska, Eliza; Deja, Grażyna; Borowiec, Maciej; Fendler, Wojciech; Małachowska, Beata; Kamińska, Halla; Młynarski, Wojciech; Jarosz-Chobot, Przemysława

2016-01-01

Genetic testing in families with monogenic GCK MODY has predictive, diagnostic, and preventive utility. Predictive tests relate to people who have no features of the disorder themselves at the time of testing. Diagnostic tests relate to family members who have been previously diagnosed with diabetes mellitus or glucose metabolism disturbances. The preventive value of genetic testing for families is to raise awareness of the circumstances leading to glucose metabolism disorders. The detection of mutation carriers among family members of patients with GCK MODY and the determination of the clinical significance of the genetic test result. The study group included 27 families of adolescent patients with GCK MODY (39 (75%) of parents and 19 (73.08%) of siblings) monitored in the Department of Pediatrics, Endocrinology and Diabetes and in the Diabetes Clinic of John Paul II Upper Silesian Child Health Centre in Katowice in the years 2007-2012. Subjects underwent a blood sample drawing for genetic and biochemical testing. Through the genetic diagnostics we diagnosed GCK MODY in 14 (63.64%) mothers, 6 (35.29%) fathers and in 7 (36,84%) siblings. Genetic testing has contributed to the detection of 7 (26.92%) asymptomatic carriers of GCK gene mutation among parents and 3 (15,79%) asymptomatic carriers among siblings declaring no carbohydrate metabolism disturbances (before genetic testing there were no indications suggesting carbohydrate metabolism disturbances; OGTT were performed after positive genetic testing). Each case of mutation detection, which is the cause of monogenic diabetes in a patient, justifies the genetic testing in other members of his/her family. Awareness of the genetic status may allow sick family member to confirm the diagnosis, while asymptomatic mutation carriers could benefit from an early clinical observation. Consequently, in each case it gives an opportunity to take diagnostic and therapeutic measures in accordance with the current state of knowledge. © Polish Society for Pediatric Endocrinology and Diabetology.

Should all suspected tuberculosis cases in high income countries be tested with GeneXpert?

PubMed

Vella, Venanzio; Broda, Agnieszka; Drobniewski, Francis

2018-05-01

In countries with a low incidence of multidrug-resistant tuberculosis (MDR-TB), universal testing with GeneXpert might not be always cost-effective. This study provides hospital managers in low MDR-TB incidence countries with criteria on when decentralised universal GeneXpert testing would make sense. The alternatives taken into consideration include: universal microbiological culture and drug susceptibility testing (DST) only (comparator); as above but with concurrent centralized GeneXpert in a referral laboratory vs a decentralized GeneXpert system in every hospital to test smear-positive cases only; as above but testing all samples with GeneXpert regardless of smear status. The parameters were from the national TB statistics for England and from a systematic review. Decentralised GeneXpert to test any suspected TB case was the most cost-effective option when 6% or more TB patients belonged to the high-risk group, defined as previous TB diagnosis and or being born in countries with a high MDR-TB incidence. Hospital managers in England and other low MDR-TB incidence countries could use these findings to decide when to invest in GeneXpert or other molecular diagnostics with similar performance criteria for TB diagnostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical Assessment and Diagnostics of Patients With Hand Disorders: A Case Study Approach.

PubMed

Leow, Mabel Qi He; Lim, Rebecca Qian Ru; Tay, Shian Chao

Clinical assessment of the hand is important for diagnosing underlying hand disorders. Using a case study approach, the clinical assessment for three disorders of the hands is presented: trigger finger (stenosing tenosynovitis), carpal tunnel syndrome, and ulnar-sided wrist injury (styloid impingement). We assess the annular one pulley and finger range of motion for patients with trigger finger. To diagnose for carpal tunnel syndrome, assessment for Tinel's sign, Phalen's sign, abductor pollicis brevis muscle bulk, two-point discrimination, and obtaining a nerve conduction study are performed. Assessment for ulnar-sided wrist injury includes wrist range of motion, assessment of distal radial ulnar joint stability, provocation tests, grip strength, x-ray, and magnetic resonance imaging. This article begins with a description of the hand and wrist anatomy. For each case study, the clinical history is described, followed by a discussion of the pathophysiology, clinical assessments, and diagnostic tests.

Efficiency of Nested-PCR in Detecting Asymptomatic Cases toward Malaria Elimination Program in an Endemic Area of Iran.

PubMed

Turki, Habibollah; Raeisi, Ahmad; Malekzadeh, Kianoosh; Ghanbarnejad, Amin; Zoghi, Samaneh; Yeryan, Masoud; Abedi Nejad, Masoumeh; Mohseni, Fatemeh; Shekari, Mohammad

2015-01-01

The aim of this study was to detect low parasite and asymptomatic malaria infections by means of three malaria diagnostic tests, in a low transmission region of Minab district, Hormozgan Province, southern Iran. Blood samples of 200 healthy volunteers from Bagh-e-Malek area were evaluated using microscopic, rapid diagnostic tests (RDT) and nested-PCR to inspect malaria parasite. The results showed no Plasmodium parasite in subjects by means of microscopy and RDT. However, 3 P. vivax positive samples (1.5%) were discovered by Nested-PCR while microscopy and RDT missed the cases. Microscopy as the gold standard method and RDT correctly identified 98.5% of cases, and molecular analysis is sensitive and reliable, especially in the detection of "asymptomatic" infections for active case surveillance. Regarding the existence of asymptomatic malaria in endemic area of Hormozgan, Iran, nested-PCR could be considered as a sensitive tool to interrupt malaria transmission in the country, beside the microscopic and RDT methods.

[Giant paraovarian cyst in childhood - Case report].

PubMed

Torres, Janina P; Íñiguez, Rodrigo D

2015-01-01

Paraovarian cysts are very uncommon in children To present a case of giant paraovarian cyst case in a child and its management using a modified laparoscopic-assisted technique A 13-year-old patient with a 15 day-history of intermittent abdominal pain, located in the left hemiabdomen and associated with progressive increase in abdominal volume. Diagnostic imaging was inconclusive, describing a giant cystic formation that filled up the abdomen, but without specifying its origin. Laboratory tests and tumor markers were within normal range. Video-assisted transumbilical cystectomy, a modified laparoscopic procedure with diagnostic and therapeutic intent, was performed with a successful outcome. The histological study reported giant paraovarian cyst. Cytology results were negative for tumor cells. The patient remained asymptomatic during the postoperative follow-up. The video-assisted transumbilical cystectomy is a safe procedure and an excellent diagnostic and therapeutic alternative for the treatment of giant paraovarian cysts. Copyright © 2015. Publicado por Elsevier España, S.L.U.

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.

The role of IQSEC2 in syndromic intellectual disability: Narrowing the diagnostic odyssey.

PubMed

Helm, Benjamin M; Powis, Zoe; Prada, Carlos E; Casasbuenas-Alarcon, Olga L; Balmakund, Tonya; Schaefer, G B; Kahler, Stephen G; Kaylor, Julie; Winter, Susan; Zarate, Yuri A; Schrier Vergano, Samantha A

2017-10-01

While X-linked intellectual disability (XLID) syndromes pose a diagnostic challenge for clinicians, an increasing number of recognized disorders and their genetic etiologies are providing answers for patients and their families. The availability of clinical exome sequencing is broadening the ability to identify mutations in genes previously unrecognized as causing XLID. In recent years, the IQSEC2 gene, located at Xp11.22, has emerged as the cause of multiple cases of both nonsyndromic and syndromic XLID. Herein we present a case series of six individuals (five males, one female) with intellectual disability and seizures found to have alterations in IQSEC2. In all cases, the diagnostic odyssey was extensive and expensive, often including invasive testing such as muscle biopsies, before ultimately reaching the diagnosis. We report these cases to demonstrate the exhaustive work-up prior to finding the changes in IQSEC2 gene, recommend that this gene be considered earlier in the diagnostic evaluation of individuals with global developmental delay, microcephaly, and severe, intractable epilepsy, and support the use of intellectual disability panels including IQSEC2 in the first-line evaluation of these patients. © 2017 Wiley Periodicals, Inc.

Testing the validity and acceptability of the diagnostic criteria for Hoarding Disorder: a DSM-5 survey.

PubMed

Mataix-Cols, D; Fernández de la Cruz, L; Nakao, T; Pertusa, A

2011-12-01

The DSM-5 Obsessive-Compulsive Spectrum Sub-Workgroup is recommending the creation of a new diagnostic category named Hoarding Disorder (HD). The validity and acceptability of the proposed diagnostic criteria have yet to be formally tested. Obsessive-compulsive disorder/hoarding experts and random members of the American Psychiatric Association (APA) were shown eight brief clinical vignettes (four cases meeting criteria for HD, three with hoarding behaviour secondary to other mental disorders, and one with subclinical hoarding behaviour) and asked to decide the most appropriate diagnosis in each case. Participants were also asked about the perceived acceptability of the criteria and whether they supported the inclusion of HD in the main manual. Altogether, 211 experts and 48 APA members completed the survey (30% and 10% response rates, respectively). The sensitivity and specificity of the HD diagnosis and the individual criteria were high (80-90%) across various types of professionals, irrespective of their experience with hoarding cases. About 90% of participants in both samples thought the criteria would be very/somewhat acceptable for professionals and sufferers. Most experts (70%) supported the inclusion of HD in the main manual, whereas only 50% of the APA members did. The proposed criteria for HD have high sensitivity and specificity. The criteria are also deemed acceptable for professionals and sufferers alike. Training of professionals and the development and validation of semi-structured diagnostic instruments should improve diagnostic accuracy even further. A field trial is now needed to confirm these encouraging findings with real patients in real clinical settings.

Imaging in conjunction with physical therapy in management of a patient with history of thoracic tumour

PubMed Central

Rendeiro, Daniel G.; Deyle, Gail D.; Boissonnault, William G.

2015-01-01

Background: Physical therapy care for musculoskeletal conditions includes an ongoing process that systematically considers and prioritises diagnostic hypotheses. These diagnostic hypotheses include those that are typical for common musculoskeletal conditions, and must also include more rare conditions that would require care outside the scope of practice of the physical therapist. When additional screening is required, physical therapists collaborate with other providers or directly order the appropriate tests to rule out suspected pathology. Case Description: This article illustrates the use of musculoskeletal imaging ordered by a physical therapist to guide ongoing management of a patient with back pain and a history of cancer. Outcomes: The patient successfully returned to moderate-intensity sport activities after a course of physical therapy. Discussion: This case provides an example of how clinical diagnostic reasoning combined with clinical privileges to order musculoskeletal imaging can facilitate diagnostic accuracy in a timely and cost-efficient manner. PMID:26309382

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.

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.

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.

30 CFR 250.527 - What must I include in my casing pressure request?

Code of Federal Regulations, 2010 CFR

2010-07-01

... and the calculated daily production rate during last well test (oil, gas, basic sediment, and water... (dry tree, hybrid, or subsea); (n) Date of diagnostic test; (o) Well schematic; (p) Water depth; (q...: (1) Bleed down/buildup test; (2) Shut-in the well and monitor the pressure drop test; (3) Constant...

Estimating the Burden of Pneumococcal Pneumonia among Adults: A Systematic Review and Meta-Analysis of Diagnostic Techniques

PubMed Central

Said, Maria A.; Johnson, Hope L.; Nonyane, Bareng A. S.; Deloria-Knoll, Maria; O′Brien, Katherine L.

2013-01-01

Background Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay. Methods and Findings We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults. Conclusions Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia. PMID:23565216

Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP).

PubMed

Planté-Bordeneuve, V; Ferreira, A; Lalu, T; Zaros, C; Lacroix, C; Adams, D; Said, G

2007-08-14

Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when associated with autonomic dysfunction.

Recurrent fever of unknown origin (FUO): aseptic meningitis, hepatosplenomegaly, pericarditis and a double quotidian fever due to juvenile rheumatoid arthritis (JRA).

PubMed

Cunha, Burke A; Hage, Jean E; Nouri, Yelda

2012-01-01

Fever of unknown origin (FUO) has been defined as a fever of ≥101°F that persists for 3 weeks or more. It is not readily diagnosed after 1 week of intensive in-hospital testing or after intensive outpatient or inpatient testing. Fevers of unknown origin may be caused by infectious diseases, malignancies, collagen vascular diseases, or a variety of miscellaneous disorders. The relative distribution of causes of FUOs is partly age-related. In the elderly, the preponderance of FUOs is attributable to neoplastic and infectious etiologies, whereas in children, collagen vascular diseases, neoplasms, and viral infectious disease predominate. The diagnostic approach to FUOs depends on a careful analysis of the history, physical findings, and laboratory tests. Most patients with FUOs exhibit localizing findings that should direct the diagnostic workup and limit diagnostic possibilities. The most perplexing causes of FUOs involve those without specific diagnostic tests, e.g., juvenile rheumatoid arthritis (JRA) or adult Still's disease. In a young adult with FUO, if all of the cardinal symptoms are present, JRA may present either a straightforward or an elusive diagnosis, if key findings are absent or if the diagnosis goes unsuspected. We present a 19-year-old man with a recurrent FUO. His illness began 3 years before admission and has recurred twice since. In the past, he did not manifest arthralgias, arthritis, or a truncal rash. On admission, he presented with an FUO with hepatosplenomegaly, aseptic meningitis, and pericarditis. An extensive diagnostic workup ruled out lymphoma and leukemia. Moreover, a further extensive workup eliminated infectious causes of FUO appropriate to his clinical presentation, ie, tuberculosis, histoplasmosis, brucellosis, Q fever, typhoid fever, Epstein-Barr virus, infectious mononucleosis, cytomegalovirus, human herpes virus (HHV)-6, babesiosis, ehrlichiosis, viral hepatitis, and Whipple's disease. The diagnosis of JRA was based on the exclusion of infectious and neoplastic disorders in a young adult with hepatosplenomegaly, aseptic meningitis, pericarditis, and a double quotidian fever. With JRA, tests for rheumatic diseases are negative, as they were in this case. The only laboratory abnormalities in this patient included elevated serum transaminases, a mildly elevated erythrocyte sedimentation rate, and a moderately elevated level of serum ferritin. Diagnostic fever curves are most helpful in cases where the diagnosis is most elusive, as was the case here. Relatively few disorders are associated with a double quotidian fever, ie, visceral leishmaniasis, mixed malarial infections, right-sided gonococcal acute bacterial endocarditis, and JRA. Because the patient received antipyretics during the first week of admission, fever was not present. After infectious disease consultation during week 2 of hospitalization, antipyretics were discontinued, and a double quotidian fever was present, which provided the key diagnostic clue in this case. Copyright © 2012 Elsevier Inc. All rights reserved.

Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): Case Definition in Surveillance for Childhood-Onset Duchenne/Becker Muscular Dystrophy

PubMed Central

Mathews, Katherine D.; Cunniff, Chris; Kantamneni, Jiji R.; Ciafaloni, Emma; Miller, Timothy; Matthews, Dennis; Cwik, Valerie; Druschel, Charlotte; Miller, Lisa; Meaney, F. John; Sladky, John; Romitti, Paul A.

2013-01-01

The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in one of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by ≥4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either “definite” or “probable” Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982–1987) to 94% in the cohort born 2004–2009. PMID:20817884

Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles

PubMed Central

Ade, Maria Paz; Baird, J. Kevin; Cheng, Qin; Cunningham, Jane; Dhorda, Mehul; Drakeley, Chris; Felger, Ingrid; Gamboa, Dionicia; Harbers, Matthias; Herrera, Socrates; Lucchi, Naomi; Mayor, Alfredo; Mueller, Ivo; Sattabongkot, Jetsumon; Ratsimbason, Arsène; Richards, Jack; Tanner, Marcel; González, Iveth J.

2017-01-01

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria. PMID:28369085

[Effectiveness of heart tumor therapy in the cardiology department during 7 year follow-up].

PubMed

Dabek, Józefa; Twardowski, Romuald; Jakubowski, Daniel; Michniak, Barbara; Swiderski, Robert; Gasior, Zbigniew

2009-11-01

Neoplasms of the heart are rare. Usually asymptomatic on the early stage are diagnosed incidentally. Among primary heart neoplasms the most often benign tumors are diagnosed--mostly myxomas, whereas the majority of malignant heart tumors are sarcomas. The aim of this paper was to present heart tumors diagnosed in the cardiology department, their symptoms, used diagnostic tests and therapy and to show after therapy quality of life changes. There were 18 patients included to the study, whom during hospitalization in the cardiology department heart tumors were diagnosed. There were 11 women and 7 men, aged from 33- to 76-years-old (mean 60,5 years). To all of the patients medical interview, physical examination, EKG, UCG and laboratory test were performed. Additionally in some cases computed tomography or magnetic resonance imaging of the chest and coronary angiograms were done. Based on the diagnostic tests results the patients were qualified to conservative or surgical treatment. Among 18 heart tumor patients in 12 cases primary benign tumors were diagnosed (66,6%), 1 patient had primary malignant tumor (5,5%), there were 3 cases of metastatic tumors (16,6%) and 2 patients with non-neoplasmic tumors--clots (11,1%). From 18 subjects with heart tumor 3 patients died because of advanced stage of neoplasmic disease and presence of metastatic tumors in the heart. Results of the study show, that heart tumors, regardless of development of diagnostic tests, are still diagnosed too late. The study group follow-up proved, that early diagnosis and proper heart tumor treatment prevented complications and improved the quality of life. It is worth to emphasize, that coronary angiogram in some cases allowed to diagnose coronary artery disease, to treat heart tumor and to perform coronary artery by-pass grafting simultaneously.

Accuracy of Immunofluorescence in the Diagnosis of Primary Ciliary Dyskinesia

PubMed Central

Frost, Emily; Dixon, Mellisa; Ollosson, Sarah; Kilpin, Kate; Patel, Mitali; Scully, Juliet; Rogers, Andrew V.; Mitchison, Hannah M.; Bush, Andrew; Hogg, Claire

2017-01-01

Rationale: The standard approach to diagnosis of primary ciliary dyskinesia (PCD) in the United Kingdom consists of assessing ciliary function by high-speed microscopy and ultrastructure by election microscopy, but equipment and expertise is not widely available internationally. The identification of biallelic disease-causing mutations is also diagnostic, but many disease-causing genes are unknown, and testing is not widely available outside the United States. Fluorescent antibodies to ciliary proteins are used to validate research genetic studies, but diagnostic utility in this disease has not been systematically evaluated. Objectives: To determine utility of a panel of six fluorescent labeled antibodies as a diagnostic tool for PCD. Methods: The study used immunofluorescent labeling of nasal brushings from a discovery cohort of 35 patients diagnosed with PCD by ciliary ultrastructure, and a diagnostic accuracy cohort of 386 patients referred with symptoms suggestive of disease. The results were compared with diagnostic outcome. Measurements and Main Results: Immunofluorescence correctly identified mislocalized or absent staining in 100% of the discovery cohort. In the diagnostic cohort immunofluorescence successfully identified 22 of 25 patients with PCD and normal staining in all 252 in whom PCD was considered highly unlikely. In addition, immunofluorescence provided a result in 55% (39) of cases that were previously inconclusive. Immunofluorescence results were available within 14 days, costing $187 per sample compared with electron microscopy (27 days; cost $1,452). Conclusions: Immunofluorescence is a highly specific diagnostic test for PCD, and it improves the speed and availability of diagnostic testing. However, sensitivity is limited and immunofluorescence is not suitable as a stand-alone test. PMID:28199173

Proteomic Approach for Diagnostic Applications in Head and Neck Cancer — EDRN Public Portal

Cancer.gov

To evaluate the test characteristics of a panel of biomarkers for identifying patients with early stage head and neck squamous cell carcinoma (HNSCC). The primary endpoints are sensitivity, specificity and accuracy of the marker panel. This study of the test characteristics of a modeling strategy for diagnosing HNSCC uses a case-control design, with several types of cases and several types of controls.

Epidemiology and diagnostic testing for meningitis in adults as the meningococcal epidemic declined at Middlemore Hospital.

PubMed

McBride, Stephen; Fulke, Jennifer; Giles, Hannah; Hobbs, Mark; Suh, Jun; Sathyendran, Vani; Thompson, Emily; Taylor, Susan; Holland, David

2015-03-13

To describe changes in epidemiology and diagnostic techniques for adult meningitis at Middlemore Hospital following the decline of the meningococcal epidemic. Retrospective audit of cases of meningitis from 2000 to 2009. Microbiologically-confirmed diagnosis (MCD) was established in 296 of 743 episodes (40%), most commonly enterovirus (123/296, 42%), Neisseria meningitidis (43/296, 15%) and Streptococcus pneumoniae (34/296, 11%). N. meningitidis meningitis declined and herpes viruses increased over time, without significant change in overall meningitis case numbers. By 2009, S. pneumoniae constituted a greater proportion of cases than N. meningitidis. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) and pneumococcal immunochromatographic testing (PICT) increased over time as did the proportion of cases with MCD. CSF Gram stain was positive in 45% (53/118) and CSF culture made MCD in 37% (44/118) of confirmed bacterial episodes (CBE). PCR provided MCD in 59% (26/54) of CBE and 99% (168/170) of viral episodes. CSF PICT was tested in 76% (26/34) of S. pneumoniae meningitis (positive in 92% (24/26). As the epidemic waned, local incidence of meningococcal meningitis decreased without significant decreasing meningitis overall. Empiric treatment for meningitis in New Zealand adults should routinely include pneumococcal cover. Increased PCR testing increases MCD in meningitis.

Molecular Surveillance for Lymphoproliferative Disease Virus in Wild Turkeys (Meleagris gallopavo) from the Eastern United States.

PubMed

Thomas, Jesse M; Allison, Andrew B; Holmes, Edward C; Phillips, Jamie E; Bunting, Elizabeth M; Yabsley, Michael J; Brown, Justin D

2015-01-01

Lymphoproliferative disease virus (LPDV) is a poorly understood, oncogenic avian retrovirus of domestic turkeys that has historically been restricted to Europe and Israel. However, a recent study reported LPDV in multiple wild turkey diagnostic cases from throughout the eastern United States of America (USA). To better understand the distribution of LPDV in the eastern USA, we surveyed 1,164 reportedly asymptomatic hunter-harvested wild turkeys from 17 states for the presence of LPDV proviral DNA by PCR. In total, 564/1,164 (47%) turkeys were positive for LPDV. Wild turkeys from each state had a relatively high prevalence of LPDV, although statewide prevalence varied from 26 to 83%. Phylogenetic analysis revealed two major clades of LPDV in the USA, although one was at a low frequency suggesting restricted transmission, as well as significant clustering by state of isolation. To determine the best tissue to target for diagnostic purposes, liver, spleen, and bone marrow were tested from a subset of 15 hunter-harvested wild turkeys and 20 wild turkey diagnostic cases. Overall, bone marrow provided the highest level of detection for both hunter-harvested turkeys and diagnostic cases. The sensitivity of LPDV detection between tissues was not significantly different for diagnostic cases, but was for hunter-harvested birds. These results indicate that LPDV infection is common and widespread in wild turkey populations throughout the eastern USA, even without overt signs of disease.

Dengue Surveillance in Veterans Affairs Healthcare Facilities, 2007–2010

PubMed Central

Schirmer, Patricia L.; Lucero-Obusan, Cynthia A.; Benoit, Stephen R.; Santiago, Luis M.; Stanek, Danielle; Dey, Achintya; Martinez, Mirsonia; Oda, Gina; Holodniy, Mark

2013-01-01

Background Although dengue is endemic in Puerto Rico (PR), 2007 and 2010 were recognized as epidemic years. In the continental United States (US), outside of the Texas-Mexico border, there had not been a dengue outbreak since 1946 until dengue re-emerged in Key West, Florida (FL), in 2009–2010. The objective of this study was to use electronic and manual surveillance systems to identify dengue cases in Veterans Affairs (VA) healthcare facilities and then to clinically compare dengue cases in Veterans presenting for care in PR and in FL. Methodology Outpatient encounters from 1/2007–12/2010 and inpatient admissions (only available from 10/2009–12/2010) with dengue diagnostic codes at all VA facilities were identified using VA's Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE). Additional case sources included VA data from Centers for Disease Control and Prevention BioSense and VA infection preventionists. Case reviews were performed. Categorical data was compared using Mantel-Haenszel or Fisher Exact tests and continuous variables using t-tests. Dengue case residence was mapped. Findings Two hundred eighty-eight and 21 PR and FL dengue cases respectively were identified. Of 21 FL cases, 12 were exposed in Key West and 9 were imported. During epidemic years, FL cases had significantly increased dengue testing and intensive care admissions, but lower hospitalization rates and headache or eye pain symptoms compared to PR cases. There were no significant differences in clinical symptoms, laboratory abnormalities or outcomes between epidemic and non-epidemic year cases in FL and PR. Confirmed/probable cases were significantly more likely to be hospitalized and have thrombocytopenia or leukopenia compared to suspected cases. Conclusions Dengue re-introduction in the continental US warrants increased dengue surveillance and education in VA. Throughout VA, under-testing of suspected cases highlights the need to emphasize use of diagnostic testing to better understand the magnitude of dengue among Veterans. PMID:23516642

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.

Sample size for positive and negative predictive value in diagnostic research using case–control designs

PubMed Central

Steinberg, David M.; Fine, Jason; Chappell, Rick

2009-01-01

Important properties of diagnostic methods are their sensitivity, specificity, and positive and negative predictive values (PPV and NPV). These methods are typically assessed via case–control samples, which include one cohort of cases known to have the disease and a second control cohort of disease-free subjects. Such studies give direct estimates of sensitivity and specificity but only indirect estimates of PPV and NPV, which also depend on the disease prevalence in the tested population. The motivating example arises in assay testing, where usage is contemplated in populations with known prevalences. Further instances include biomarker development, where subjects are selected from a population with known prevalence and assessment of PPV and NPV is crucial, and the assessment of diagnostic imaging procedures for rare diseases, where case–control studies may be the only feasible designs. We develop formulas for optimal allocation of the sample between the case and control cohorts and for computing sample size when the goal of the study is to prove that the test procedure exceeds pre-stated bounds for PPV and/or NPV. Surprisingly, the optimal sampling schemes for many purposes are highly unbalanced, even when information is desired on both PPV and NPV. PMID:18556677

Inventions leading to the development of the diagnostic test kit industry--from the modern pregnancy test to the sandwich assays.

PubMed

Wide, Leif

2005-01-01

The universities are encouraged by the government nowadays to stimulate innovations and also to provide the proper machinery for assisting the protection and commercialisation of innovations. A better understanding of the innovation process may help to create an atmosphere suitable for inventions at the university. Examples can be taken from successful innovations previously made at the university. During the 1960's I made a series of inventions, which ultimately led to the development of the diagnostic test kit industry. The first, which I made as an undergraduate, was a simple and reliable test kit for diagnosis of pregnancy. This was followed by the solid phase radioimmunoassay and a solid phase assay for vitamin B12; next, the dual specific non-competitive sandwich assay and the in-vitro test for diagnosis of allergy, called RAST (Radioallergosorbent test). Organon in Holland with the pregnancy test kit, and Pharmacia in Sweden with test kits for radioimmunoassay, became pioneers among the diagnostic test kit industries. Pharmacia Diagnostics later became one of the leading diagnostic test kit companies in the world and has continued to be so in the field of allergy diagnosis. Each one of these inventions started with a few unique observations leading to a technical development. The pregnancy test as well as the allergy test emerged from the development of assay methods with unique qualities with the subsequent search for appropriate applications. The foreseeing of a commercial value on a future market was a very important step. This was followed by the search for a suitable industry interested to exploit the invention with its new business opportunity i.e. apply for a patent, produce and market the products, which in my case consisted of the necessary reagents and equipments for particular diagnostic tests. Finally, an agreement had to be settled between the entrepreneur and the inventors. This report describes these inventions and particularly discusses some crucial steps of the innovation processes.

Field performance of clinical case definitions for influenza screening during the 2009 pandemic.

PubMed

Chen, Shey-Ying; Chen, Yee-Chun; Chiang, Wen-Chu; Kung, Hsiang-Chi; King, Chwan-Chuen; Lai, Mei-Shu; Chie, Wei-Chu; Chen, Shyr-Chyr; Chen, Wen-Jone; Chang, Shan-Chwen

2012-11-01

The aim of this study was to assess the performance of 3 different influenza-like illness (ILI) case definitions, adopted by the European (European-CDC), USA (USA-CDC), and Taiwan Centers for Disease Prevention and Control (Taiwan-CDC), as screening tools for influenza during the 2009 H1N1 pandemic. From August 15 to 30, 2009, all emergency department patients with clinical symptoms or at epidemiologic risk for influenza were enrolled in an observational cohort study. Influenza diagnosis was established by positive rapid influenza diagnostic test or virus isolation. Sensitivity, specificity, positive predictive value, and negative predictive value of the European-, USA, and Taiwan-CDC ILI case definitions for screening were determined. A total of 870 patients were screened during the study period. Rapid influenza diagnostic test was positive in 315 patients, 273 (85.6%) of whom had fever duration less than 72 hours. Virus isolation identified 4 more patients with influenza A initially negative by rapid influenza diagnostic test. The mean (SD) age of these 319 patients was 24.3 (18.1) years. Of the 870 screened patients, 670 (77.0%), 476 (54.7%), and 325 (37.4%) met the European-, USA-, and Taiwan-CDC ILI case definition, respectively. Screening sensitivity was 95%, 77.7%, and 57.7% and specificity was 33.4%, 58.6%, and 74.4%, respectively. Differences in sensitivity and specificity between any 2 of the 3 groups were statistically significant (P < .05). First-line physicians should recognize the advantage and limitation of different ILI case definitions in influenza screening, especially confronted by pandemic or highly pathogenic avian influenza in the future. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

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.

Central nervous system Aspergillus infection after epidural analgesia: diagnosis, therapeutic challenges, and literature review

PubMed Central

Genzen, Jonathan R.; Kenney, Barton

2009-01-01

Aspergillus terreus was identified in an intra-dural spinal biopsy specimen from an African female with recurrent headache and hydrocephalus. Prior laboratory testing of cerebrospinal fluid (CSF) was non-diagnostic, despite extensive central nervous system (CNS) involvement. CNS Aspergillus infection presents a diagnostic and therapeutic challenge and is reviewed in the context of this particularly instructive and difficult case. PMID:19717262

[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.

Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

PubMed

Trautmann, A; Seitz, C S; Stoevesandt, J; Kerstan, A

2014-12-01

The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions. © 2014 John Wiley & Sons Ltd.

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.

Considerations of study design.

PubMed

Koretz, Ronald L

2007-12-01

Research projects attempt to answer specific questions. The particular study design that is selected will depend in large measure on the nature of the question and the time and resources available. There are 5 common categories of clinical questions; they relate to etiology, prognosis, utility of diagnostic tests, efficacy of proposed interventions, and cost of treatment in specific disease states. A number of study designs can be used. Case reports serve to memorialize unusual or novel aspects of diseases. Retrospective case series are useful for defining natural history. Case-control studies are used by epidemiologists to elucidate potential etiologies of diseases. Prospective cohort studies can be used to assess natural history or to assess potential disease etiologies. Controlled trials are designed to assess the efficacy of therapeutic interventions. Studies that define the sensitivity and specificity of diagnostic tests can be used to assess the utility of those tests. Economic analyses estimate the costs that particular diseases or therapies will require. Each of these study designs has limitations; with the exception of high-quality randomized trials, none of these study designs can establish a causative relationship between putative etiologic (or therapeutic) factors and disease (outcomes).

Educational case series: β-lactam allergy and cross-reactivity.

PubMed

Atanasković-Marković, Marina

2011-12-01

Penicillins and cephalosporins are the most widely used antibiotics for the treatment of common infections, and they are the two main classes of β-lactams. On the basis of the time of appearance of the reaction after drug intake and for diagnostic purposes, hypersensitivity reactions to β-lactams have been classified as immediate or non-immediate. The diagnostic evaluation of allergic reactions to β-lactams has changed over the last decade, for several reasons. In many countries, major and minor determinants for skin testing are not available. In immediate allergic reactions, the sensitivity of skin testing is decreasing. For non-immediate reactions, skin testing appears to be less sensitive than previously reported. The drug provocation test is still necessary for diagnosis. In this education review series, we described three cases of β-lactam allergy: first, a child with an IgE-mediated allergy to benzyl-penicillin; second, a child with a non-allergic hypersensitivity to amoxicillin; and in the third patient, we will discuss about cross-reactivity between penicillins and cephalosporins. These cases are correlated with the practical management of evaluating β-lactam allergy. © 2011 John Wiley & Sons A/S.

Pediatric colonic volvulus: A single-institution experience and review.

PubMed

Tannouri, Sami; Hendi, Aditi; Gilje, Elizabeth; Grissom, Leslie; Katz, Douglas

2017-06-01

Pediatric colonic volvulus is both rare and underreported. Existing literature consists only of case reports and small series. We present an analysis of cases (n=11) over 15 years at a single institution, focusing on workup and diagnosis. This was an institutional review board approved single-institution retrospective chart review of 11 cases of large bowel volvulus occurring over 15 years (2000-2015). In our series, the most common presenting symptoms were abdominal pain and distention. Afflicted patients often had prior abdominal surgery, a neurodevelopmental disorder or chronic constipation. Of the imaging modalities utilized in the 11 patients studied, colonic volvulus was correctly diagnosed by barium enema in 100% of both cases, CT in 55.6% of cases and by plain radiography of the abdomen in only 22.2%of cases. Colonic volvulus was confirmed by laparotomy in all cases. The cecum (n=5) was the most often affected colonic segment, followed by the sigmoid (n=3). Operative treatment mainly consisted of resection (63.6%) and ostomy creation (36.4%). Colopexy was performed in 18.2% of cases. Plain abdominal radiography may be performed as an initial diagnostic study, however, it should be followed CT or air or contrast enema in children where there is high clinical suspicion and who do not have indications for immediate laparotomy. CT may be the most specific and useful test in diagnosis of colonic volvulus and has the added advantage of detection of complications including bowel ischemia. We demonstrate a range of diagnostic and therapeutic modalities for pediatric colonic volvulus. This underscores the need for further study to draft standard best practices for this life-threatening condition. Prognosis Study: Level IV. Study of a Diagnostic Test: Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Fever case management at private health facilities and private pharmacies on the Kenyan coast: analysis of data from two rounds of client exit interviews and mystery client visits.

PubMed

Poyer, Stephen; Musuva, Anne; Njoki, Nancy; Okara, Robi; Cutherell, Andrea; Sievers, Dana; Lussiana, Cristina; Memusi, Dorothy; Kiptui, Rebecca; Ejersa, Waqo; Dolan, Stephanie; Charman, Nicole

2018-03-13

Private sector availability and use of malaria rapid diagnostic tests (RDTs) lags behind the public sector in Kenya. Increasing channels through which quality malaria diagnostic services are available can improve access to testing and help meet the target of universal diagnostic testing. Registered pharmacies are currently not permitted to perform blood tests, and evidence of whether malaria RDTs can be used by non-laboratory private providers in line with the national malaria control guidelines is required to inform ongoing policy discussions in Kenya. Two rounds of descriptive cross-sectional exit interviews and mystery client surveys were conducted at private health facilities and registered pharmacies in 2014 and 2015, 6 and 18 months into a multi-country project to prime the private sector market for the introduction of RDTs. Data were collected on reported RDT use, medicines received and prescribed, and case management of malaria test-negative mystery clients. Analysis compared outcomes at facilities and pharmacies independently for the two survey rounds. Across two rounds, 534 and 633 clients (including patients) from 130 and 120 outlets were interviewed, and 214 and 250 mystery client visits were completed. Reported testing by any malaria diagnostic test was higher in private health facilities than registered pharmacies in both rounds (2014: 85.6% vs. 60.8%, p < 0.001; 2015: 85.3% vs. 56.3%, p < 0.001). In registered pharmacies, testing by RDT was 52.1% in 2014 and 56.3% in 2015. At least 75% of test-positive patients received artemisinin-based combination therapy (ACT) in both rounds, with no significant difference between outlet types in either round. Provision of any anti-malarial for test-negative patients ranged from 0 to 13.9% across outlet types and rounds. In 2015, mystery clients received the correct (negative) diagnosis and did not receive an anti-malarial in 75.5% of visits to private health facilities and in 78.4% of visits to registered pharmacies. Non-laboratory staff working in registered pharmacies in Kenya can follow national guidelines for diagnosis with RDTs when provided with the same level of training and supervision as private health facility staff. Performance and compliance to treatment recommendations are comparable to diagnostic testing outcomes recorded in private health facilities.

Towards a precise test for malaria diagnosis in the Brazilian Amazon: comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks

PubMed Central

2010-01-01

Background Accurate malaria diagnosis is mandatory for the treatment and management of severe cases. Moreover, individuals with asymptomatic malaria are not usually screened by health care facilities, which further complicates disease control efforts. The present study compared the performances of a malaria rapid diagnosis test (RDT), the thick blood smear method and nested PCR for the diagnosis of symptomatic malaria in the Brazilian Amazon. In addition, an innovative computational approach was tested for the diagnosis of asymptomatic malaria. Methods The study was divided in two parts. For the first part, passive case detection was performed in 311 individuals with malaria-related symptoms from a recently urbanized community in the Brazilian Amazon. A cross-sectional investigation compared the diagnostic performance of the RDT Optimal-IT, nested PCR and light microscopy. The second part of the study involved active case detection of asymptomatic malaria in 380 individuals from riverine communities in Rondônia, Brazil. The performances of microscopy, nested PCR and an expert computational system based on artificial neural networks (MalDANN) using epidemiological data were compared. Results Nested PCR was shown to be the gold standard for diagnosis of both symptomatic and asymptomatic malaria because it detected the major number of cases and presented the maximum specificity. Surprisingly, the RDT was superior to microscopy in the diagnosis of cases with low parasitaemia. Nevertheless, RDT could not discriminate the Plasmodium species in 12 cases of mixed infections (Plasmodium vivax + Plasmodium falciparum). Moreover, the microscopy presented low performance in the detection of asymptomatic cases (61.25% of correct diagnoses). The MalDANN system using epidemiological data was worse that the light microscopy (56% of correct diagnoses). However, when information regarding plasma levels of interleukin-10 and interferon-gamma were inputted, the MalDANN performance sensibly increased (80% correct diagnoses). Conclusions An RDT for malaria diagnosis may find a promising use in the Brazilian Amazon integrating a rational diagnostic approach. Despite the low performance of the MalDANN test using solely epidemiological data, an approach based on neural networks may be feasible in cases where simpler methods for discriminating individuals below and above threshold cytokine levels are available. PMID:20459613

Towards a precise test for malaria diagnosis in the Brazilian Amazon: comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks.

PubMed

Andrade, Bruno B; Reis-Filho, Antonio; Barros, Austeclino M; Souza-Neto, Sebastião M; Nogueira, Lucas L; Fukutani, Kiyoshi F; Camargo, Erney P; Camargo, Luís M A; Barral, Aldina; Duarte, Angelo; Barral-Netto, Manoel

2010-05-06

Accurate malaria diagnosis is mandatory for the treatment and management of severe cases. Moreover, individuals with asymptomatic malaria are not usually screened by health care facilities, which further complicates disease control efforts. The present study compared the performances of a malaria rapid diagnosis test (RDT), the thick blood smear method and nested PCR for the diagnosis of symptomatic malaria in the Brazilian Amazon. In addition, an innovative computational approach was tested for the diagnosis of asymptomatic malaria. The study was divided in two parts. For the first part, passive case detection was performed in 311 individuals with malaria-related symptoms from a recently urbanized community in the Brazilian Amazon. A cross-sectional investigation compared the diagnostic performance of the RDT Optimal-IT, nested PCR and light microscopy. The second part of the study involved active case detection of asymptomatic malaria in 380 individuals from riverine communities in Rondônia, Brazil. The performances of microscopy, nested PCR and an expert computational system based on artificial neural networks (MalDANN) using epidemiological data were compared. Nested PCR was shown to be the gold standard for diagnosis of both symptomatic and asymptomatic malaria because it detected the major number of cases and presented the maximum specificity. Surprisingly, the RDT was superior to microscopy in the diagnosis of cases with low parasitaemia. Nevertheless, RDT could not discriminate the Plasmodium species in 12 cases of mixed infections (Plasmodium vivax + Plasmodium falciparum). Moreover, the microscopy presented low performance in the detection of asymptomatic cases (61.25% of correct diagnoses). The MalDANN system using epidemiological data was worse that the light microscopy (56% of correct diagnoses). However, when information regarding plasma levels of interleukin-10 and interferon-gamma were inputted, the MalDANN performance sensibly increased (80% correct diagnoses). An RDT for malaria diagnosis may find a promising use in the Brazilian Amazon integrating a rational diagnostic approach. Despite the low performance of the MalDANN test using solely epidemiological data, an approach based on neural networks may be feasible in cases where simpler methods for discriminating individuals below and above threshold cytokine levels are available.

Vitrectomy for the diagnosis and management of uveitis of unknown cause.

PubMed

Margolis, Ron; Brasil, Oswaldo F M; Lowder, Careen Y; Singh, Rishi P; Kaiser, Peter K; Smith, Scott D; Perez, Victor L; Sonnie, Christine; Sears, Jonathan E

2007-10-01

To determine the diagnostic yield of tests commonly used for vitreous fluid analysis in eyes with suspected intraocular infection or malignancy. Noncomparative interventional case series. Forty-four consecutive patients (45 eyes) treated from 1998 through 2006 with posterior segment inflammation who underwent pars plana vitrectomy for diagnostic purposes. Vitreous specimens obtained via pars plana vitrectomy were analyzed by microbiologic culture, cytologic analysis, and flow cytometry. Diagnostic yield and sensitivity of each test performed on vitreous specimens and visual outcomes of eyes that underwent diagnostic vitrectomy (DVx). Preoperative diagnoses were infection in 15 eyes and malignancy in 30 eyes. Overall, vitreous analysis identified a specific cause in 9 (20%) of 45 eyes. The overall sensitivity of DVx was 63.6%. The sensitivities of individual tests were: culture, 50%; cytologic analysis, 66.7%; and flow cytometry, 83.3%. The yields of diagnostic tests were: culture, 5.7%; cytologic analysis, 14.3%; and flow cytometry, 20.6%. Final diagnoses were infection in 6 eyes, malignancy in 9 eyes, and idiopathic in 30 eyes. Mean visual acuity improved significantly in the first 6 months after DVx. Visual acuity improved in 60% of eyes, with 37.8% of eyes improving by 3 lines or more. Analysis of vitreous fluid by widely available tests is useful in identifying intraocular infection or malignancy. Most patients experienced a substantial improvement in vision.

Adult encephalitis surveillance: experiences from an Australian prospective sentinel site study.

PubMed

Eastwood, K; Paterson, B J; Levi, C; Givney, R; Loewenthal, M; DE Malmanche, T; Lai, K; Granerod, J; Durrheim, D N

2015-11-01

Few countries routinely collect comprehensive encephalitis data, yet understanding the epidemiology of this condition has value for clinical management, detecting novel and emerging pathogens, and guiding timely public health interventions. When this study was conducted there was no standardized diagnostic algorithm to aid identification of encephalitis or systematic surveillance for adult encephalitis. In July 2012 we tested three pragmatic surveillance options aimed at identifying possible adult encephalitis cases admitted to a major Australian hospital: hospital admissions searches, clinician notifications and laboratory test alerts (CSF herpes simplex virus requests). Eligible cases underwent structured laboratory investigation and a specialist panel arbitrated on the final diagnosis. One hundred and thirteen patients were initially recruited into the 10-month study; 20/113 (18%) met the study case definition, seven were diagnosed with infectious or immune-mediated encephalitis and the remainder were assigned alternative diagnoses. The laboratory alert identified 90% (102/113) of recruited cases including six of the seven cases of confirmed encephalitis suggesting that this may be a practical data source for case ascertainment. The application of a standardized diagnostic algorithm and specialist review by an expert clinical panel aided diagnosis of patients with encephalitis.

Diagnostic performance of a rapid in-clinic test for the detection of Canine Parvovirus under different storage conditions and vaccination status.

PubMed

Kantere, Maria C; Athanasiou, Labrini V; Spyrou, Vassiliki; Kyriakis, Constantinos S; Kontos, Vassilios; Chatzopoulos, Dimitrios C; Tsokana, Constantina N; Billinis, Charalambos

2015-04-01

Canine parvovirus (CPV) is one of the most common causes of acute haemorrhagic enteritis in young dogs, while clinical diagnosis is often indecisive. The aim of our study was to evaluate the diagnostic accuracy of an in-clinic rapid test in the detection of CPV infection in dogs. To this end, we compared the Rapid Diagnostic Kit of Canine Parvovirus, Coronavirus and Rotavirus antigen (Quicking(®)) to PCR, which is considered as the most reliable diagnostic method. A total of 78 duplicated faecal samples were collected from diarrhoeic dogs. Vaccination history within a month prior to the onset of diarrhoea was reported for 12 of the sampled dogs. The rapid diagnostic test was performed in 23 of the faecal samples directly, while the rest were placed into a sterile cotton tipped swab suitable for collection and transportation of viruses (Sigma Σ-VCM(®)) and stored at -20 °C. The sensitivity of the Quicking rapid diagnostic test compared to PCR in the total number of samples, in samples from non-vaccinated dogs and in samples tested directly after collection were 22.22% (95% CI: 13.27-33.57%), 26.67% (95% CI: 16.08-39.66%) and 76.47% (95% CI: 50.10-93.04%) respectively, while the specificity of the test was 100% in any case. In conclusion, negative results do not exclude parvoenteritis from the differential diagnosis, especially in dogs with early vaccination history, but a positive result almost certainly indicates CPV infection. An improved sensitivity may be expected when the test is performed immediately. Copyright © 2015 Elsevier B.V. All rights reserved.

Transscrotal Near Infrared Spectroscopy as a Diagnostic Test for Testis Torsion in Pediatric Acute Scrotum: A Prospective Comparison to Gold Standard Diagnostic Test Study.

PubMed

Schlomer, Bruce J; Keays, Melise A; Grimsby, Gwen M; Granberg, Candace F; DaJusta, Daniel G; Menon, Vani S; Ostrov, Lauren; Sheth, Kunj R; Hill, Martinez; Sanchez, Emma J; Harrison, Clanton B; Jacobs, Micah A; Huang, Rong; Burgu, Berk; Hennes, Halim; Baker, Linda A

2017-09-01

A rapid test for testicular torsion in children may obviate the delay for testicular ultrasound. In this study we assessed testicular tissue percent oxygen saturation (%StO2) measured by transscrotal near infrared spectroscopy as a diagnostic test for pediatric testicular torsion. This was a prospective comparison to a gold standard diagnostic test study that evaluated near infrared spectroscopy %StO2 readings to diagnose testicular torsion. The gold standard for torsion diagnosis was standard clinical care. From 2013 to 2015 males with acute scrotum for more than 1 month and who were less than 18 years old were recruited. Near infrared spectroscopy %StO2 readings were obtained for affected and unaffected testes. Near infrared spectroscopy Δ%StO2 was calculated as unaffected minus affected reading. The utility of near infrared spectroscopy Δ%StO2 to diagnose testis torsion was described with ROC curves. Of 154 eligible patients 121 had near infrared spectroscopy readings. Median near infrared spectroscopy Δ%StO2 in the 36 patients with torsion was 2.0 (IQR -4.2 to 9.8) vs -1.7 (IQR -8.7 to 2.0) in the 85 without torsion (p=0.004). AUC for near infrared spectroscopy as a diagnostic test was 0.66 (95% CI 0.55-0.78). Near infrared spectroscopy Δ%StO2 of 20 or greater had a positive predictive value of 100% and a sensitivity of 22.2%. Tanner stage 3-5 cases without scrotal edema or with pain for 12 hours or less had an AUC of 0.91 (95% CI 0.86-1.0) and 0.80 (95% CI 0.62-0.99), respectively. In all children near infrared spectroscopy readings had limited utility in diagnosing torsion. However, in Tanner 3-5 cases without scrotal edema or with pain 12 hours or less, near infrared spectroscopy discriminated well between torsion and nontorsion. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. 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.

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.

Diagnostic strategies for urinary tract infections in French general practice.

PubMed

Kinouani, S; de Lary de Latour, H; Joseph, J-P; Letrilliart, L

2017-10-01

We aimed to describe the diagnostic management procedures for detection of urinary tract infections in general practice and their correlated factors. We analyzed data from the ECOGEN study on urinary tract infections, collected in France between November 2011 and April 2012. This national cross-sectional study was carried out in general practices. Data was coded according to the International Classification of Primary Care. A total of 340 consultations or home visits were held for urinary tract infections. The five most frequent diagnostic procedures were (in descending order) clinical examination (67.6%), urine cytobacteriological examination (UCBE) (47.9%), urine dipstick test (15.6%), blood test (8.5%), and imaging (6.5%). No urine dipstick test or UCBE was performed in 43% of cases. Factors correlated with diagnostic procedures were age and gender of patients, annual number of consultations held by family physicians, and duration of consultation. Family physicians did not comply with guidelines on diagnostic management for detection of urinary tract infections. We hypothesized that this non-compliance could be due to the family physicians' environment and characteristics, and to clinical practice guidelines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cochineal dye-induced immediate allergy: Review of Japanese cases and proposed new diagnostic chart.

PubMed

Takeo, Naoko; Nakamura, Masashi; Nakayama, Satoshi; Okamoto, Osamu; Sugimoto, Naoki; Sugiura, Shinichi; Sato, Nayu; Harada, Susumu; Yamaguchi, Masao; Mitsui, Naoya; Kubota, Yumiko; Suzuki, Kayoko; Terada, Makoto; Nagai, Akiyo; Sowa-Osako, Junko; Hatano, Yutaka; Akiyama, Hiroshi; Yagami, Akiko; Fujiwara, Sakuhei; Matsunaga, Kayoko

2018-04-25

Cochineal dye is used worldwide as a red coloring in foods, drinks, cosmetics, quasi-drugs, and drugs. The main component of the red color is carminic acid (CA). Carmine is an aluminum- or calcium-chelated product of CA. CA and carmine usually contain contaminating proteins, including a 38-kDa protein thought to be the primary allergen. Severe allergic reactions manifest as anaphylaxis. The aim of this study was to review all Japanese reported cases and propose useful diagnostic chart. All reported Japanese cases of cochineal dye-induced immediate allergy were reviewed, and newly registered cases were examined by skin prick test (SPT) with cochineal extract (CE) and measurement of CE and carmine-specific serum IgE test. Two-dimensional (2D) western blotting using patient serum was conducted to identify the antigen. Twenty-two Japanese cases have been reported. SPT and the level of specific IgE test indicated that six cases should be newly registered as cochineal dye allergy. All cases were adult females, and all cases except three involved anaphylaxis; 13 cases involved past history of local symptoms associated with cosmetics use. Japanese strawberry juice and fish-meat sausage, and European processed foods (especially macarons made in France) and drinks were recent major sources of allergen. 2D western blotting showed that patient IgE reacted to the 38-kDa protein and other proteins. Serum from healthy controls also weakly reacted with these proteins. SPT with CE and determination of the level of CE and carmine-specific IgE test are useful methods for the diagnosis of cochineal dye allergy. Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Cost-effectiveness of active case-finding of household contacts of pulmonary tuberculosis patients in a low HIV, tuberculosis-endemic urban area of Lima, Peru.

PubMed

Shah, L; Rojas, M; Mori, O; Zamudio, C; Kaufman, J S; Otero, L; Gotuzzo, E; Seas, C; Brewer, T F

2017-04-01

We compared the cost-effectiveness (CE) of an active case-finding (ACF) programme for household contacts of tuberculosis (TB) cases enrolled in first-line treatment to routine passive case-finding (PCF) within an established national TB programme in Peru. Decision analysis was used to model detection of TB in household contacts through: (1) self-report of symptomatic cases for evaluation (PCF), (2) a provider-initiated ACF programme, (3) addition of an Xpert MTB/RIF diagnostic test for a single sputum sample from household contacts, and (4) all strategies combined. CE was calculated as the incremental cost-effectiveness ratio (ICER) in terms of US dollars per disability-adjusted life years (DALYs) averted. Compared to PCF alone, ACF for household contacts resulted in an ICER of $2155 per DALY averted. The addition of the Xpert MTB/RIF diagnostic test resulted in an ICER of $3275 per DALY averted within a PCF programme and $3399 per DALY averted when an ACF programme was included. Provider-initiated ACF of household contacts in an urban setting of Lima, Peru can be highly cost-effective, even including costs to seek out contacts and perform an Xpert/MTB RIF test. ACF including Xpert MTB/RIF was not cost-effective if TB cases detected had high rates of default from treatment or poor outcomes.

Gonorrhoea Diagnostic and Treatment Uncertainties: Risk Factors for Culture Negative Confirmation after Positive Nucleic Acid Amplification Tests.

PubMed

Vyth, Rebecka; Leval, Amy; Eriksson, Björn; Ericson, Eva-Lena; Marions, Lena; Hergens, Maria-Pia

2016-01-01

Gonorrhoea incidence has increased substantially in Stockholm during the past years. These increases have coincided with changes in testing practice from solely culture-based to nucleic acid amplification tests (NAAT). Gonorrhoea NAAT is integrated with Chlamydia trachomatis testing and due to opportunistic screening for chlamydia, testing prevalence for gonorrhoea has increased substantially in the Stockholm population. The aim of this study was to examine epidemiological risk-factors for discordant case which are NAAT positive but culture negative. These discordant cases are especially problematic as they give rise to diagnostic and treatment uncertainties with risk for subsequent sequelae. All gonorrhoea cases from Stockholm county during 2011-2012 with at least one positive N. gonorrhoea NAAT test and follow-up cultures were included (N = 874). Data were analysed using multivariate and stratified logistic regression models. Results showed that women were 4-times more likely (OR 4.9; 95% CI 2.4-6.7) than men to have discordant cultures. Individuals tested for gonorrhoea without symptoms were 2.3 times more likely (95% CI 1.5-3.5) than those with symptoms to be discordant. NAAT method and having one week or more between NAAT and culture testing were also indicative of an increased likelihood for discordance. Using NAAT should be based on proper clinical or epidemiological indications and, when positive, followed-up with a culture-based test within one week if possible. Routine gonorrhoea testing is not recommended in low prevalence populations.

Gonorrhoea Diagnostic and Treatment Uncertainties: Risk Factors for Culture Negative Confirmation after Positive Nucleic Acid Amplification Tests

PubMed Central

Vyth, Rebecka; Leval, Amy; Eriksson, Björn; Ericson, Eva-Lena; Marions, Lena; Hergens, Maria-Pia

2016-01-01

Gonorrhoea incidence has increased substantially in Stockholm during the past years. These increases have coincided with changes in testing practice from solely culture-based to nucleic acid amplification tests (NAAT). Gonorrhoea NAAT is integrated with Chlamydia trachomatis testing and due to opportunistic screening for chlamydia, testing prevalence for gonorrhoea has increased substantially in the Stockholm population. The aim of this study was to examine epidemiological risk-factors for discordant case which are NAAT positive but culture negative. These discordant cases are especially problematic as they give rise to diagnostic and treatment uncertainties with risk for subsequent sequelae. All gonorrhoea cases from Stockholm county during 2011–2012 with at least one positive N. gonorrhoea NAAT test and follow-up cultures were included (N = 874). Data were analysed using multivariate and stratified logistic regression models. Results showed that women were 4-times more likely (OR 4.9; 95% CI 2.4–6.7) than men to have discordant cultures. Individuals tested for gonorrhoea without symptoms were 2.3 times more likely (95% CI 1.5–3.5) than those with symptoms to be discordant. NAAT method and having one week or more between NAAT and culture testing were also indicative of an increased likelihood for discordance. Using NAAT should be based on proper clinical or epidemiological indications and, when positive, followed-up with a culture-based test within one week if possible. Routine gonorrhoea testing is not recommended in low prevalence populations. PMID:27152704

Does the patient with chest pain have a coronary heart disease? Diagnostic value of single symptoms and signs--a meta-analysis.

PubMed

Haasenritter, Jorg; Stanze, Damaris; Widera, Grit; Wilimzig, Christian; Abu Hani, Maren; Sonnichsen, Andreas C; Bosner, Stefan; Rochon, Justine; Donner-Banzhoff, Norbert

2012-10-01

To determine the diagnostic value of single symptoms and signs for coronary heart disease (CHD) in patients with chest pain. Searches of two electronic databases (EMBASE 1980 to March 2008, PubMed 1966 to May 2009) and hand searching in seven journals were conducted. Eligible studies recruited patients presenting with acute or chronic chest pain. The target disease was CHD, with no restrictions regarding case definitions, eg, stable CHD, acute coronary syndrome (ACS), acute myocardial infarction (MI), or major cardiac event (MCE). Diagnostic tests of interest were items of medical history and physical examination. Bivariate random effects model was used to derive summary estimates of positive (pLR) and negative likelihood ratios (nLR). We included 172 studies providing data on the diagnostic value of 42 symptoms and signs. With respect to case definition of CHD, diagnostically most useful tests were history of CHD (pLR=3.59), known MI (pLR=3.21), typical angina (pLR=2.35), history of diabetes mellitus (pLR=2.16), exertional pain (pLR=2.13), history of angina pectoris (nLR=0.42), and male sex (nLR=0.49) for diagnosing stable CHD; pain radiation to right arm/shoulder (pLR=4.43) and palpitation (pLR=0.47) for diagnosing MI; visceral pain (pLR=2.05) for diagnosing ACS; and typical angina (pLR=2.60) and pain reproducible by palpation (pLR=0.13) for predicting MCE. We comprehensively reported the accuracy of a broad spectrum of single symptoms and signs for diagnosing myocardial ischemia. Our results suggested that the accuracy of several symptoms and signs varied in the published studies according to the case definition of CHD.

[Vestibulo-cochlear disturbances in the course of vaso-neural conflict of vestibule-cochlear nerve--diagnostic and therapeutic problems].

PubMed

Orendorz-Fraczkowska, Krystyna; Jaworska, Marzena; Gawron, Wojciech; Badowski, Roman; Nadolska, Beata

2007-01-01

Symptoms encompassing sensorineural hearing loss, tinnitus and vertigo occur in many diseases of various origin. The diagnostics in such cases is especially difficult and often requires interdisciplinary cooperation. Despite of that many cases remain unexplained. The two cases with above mentioned symptoms (52 year-old woman and 46 year-old man) with differentiated clinical course were presented. The woman for one year experienced left sided, extreme tinnitus with paroxysmal vertigo and dizziness. The man with sudden monolateral hearing loss and tinnitus that disappeared after corticosteroid therapy, complained about recurrence of fluctuating hearing loss and tinnitus accompanied by chronic instability. The diagnostics of hearing and balance organs was performed (pure tone audiometry, impedance audiometry, DPOAE, ABR, ENG) complemented with computed tomography and Nuclear Resonance. Female patient presented bilateral mild sensorineural hearing loss, more intensive on the left side, male patient right sided sensorineural hearing loss in the frequencies from 250 to 1500 Hz. The elongation of some peak values in ABR test (with bilaterally proper otoacoustic emissions) as well as partial canal paresis on the hearing loss side suggested primary diagnosis of neoplasmatic process. It was an indication to perform radiological diagnostics. The radiologic findings revealed the contact of vestibulo-cochlear nerve with the loop of cerebellar inferior anterior artery within the internal acoustic canal. The course of the disease and diagnostic tests do not provide characteristic data that let diagnose neuro-vascular conflict. One has to be aware of such possibility in patients with intensive vertigo and dizziness that do not improve after treatment when other causes do not justify the symptoms.

Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

PubMed

Llorens, Franc; Kruse, Niels; Karch, André; Schmitz, Matthias; Zafar, Saima; Gotzmann, Nadine; Sun, Ting; Köchy, Silja; Knipper, Tobias; Cramm, Maria; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel P; Sánchez-Valle, Raquel; Fischer, Andre; Mollenhauer, Brit; Zerr, Inga

2018-03-01

The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

[ERG diagnosis and differential diagnosis: results of examination over 6 years].

PubMed

Stemeyer, G; Stähli, P

1996-05-01

This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement in uveitis with opaque media, and incomplete CSNB.

Improved detection of Burkholderia pseudomallei from non-blood clinical specimens using enrichment culture and PCR: narrowing diagnostic gap in resource-constrained settings.

PubMed

Tellapragada, Chaitanya; Shaw, Tushar; D'Souza, Annet; Eshwara, Vandana Kalwaje; Mukhopadhyay, Chiranjay

2017-07-01

To evaluate the diagnostic utility of enrichment culture and PCR for improved case detection rates of non-bacteraemic form of melioidosis in limited resource settings. Clinical specimens (n = 525) obtained from patients presenting at a tertiary care hospital of South India with clinical symptoms suggestive of community-acquired pneumonia, lower respiratory tract infections, superficial or internal abscesses, chronic skin ulcers and bone or joint infections were tested for the presence of Burkholderia pseudomallei using conventional culture (CC), enrichment culture (EC) and PCR. Sensitivity, specificity, positive and negative predictive values of CC and PCR were initially deduced using EC as the gold standard method. Further, diagnostic accuracies of all the three methods were analysed using Bayesian latent class modelling (BLCM). Detection rates of B. pseudomallei using CC, EC and PCR were 3.8%, 5.3% and 6%, respectively. Diagnostic sensitivities and specificities of CC and PCR were 71.4, 98.4% and 100 and 99.4%, respectively in comparison with EC as the gold standard test. With Bayesian latent class modelling, EC and PCR demonstrated sensitivities of 98.7 and 99.3%, respectively, while CC showed a sensitivity of 70.3% for detection of B. pseudomallei. An increase of 1.6% (95% CI: 1.08-4.32%) in the case detection rate of melioidosis was observed in the study population when EC and/or PCR were used in adjunct to the conventional culture technique. Our study findings underscore the diagnostic superiority of enrichment culture and/or PCR over conventional microbiological culture for improved case detection of melioidosis from non-blood clinical specimens. © 2017 John Wiley & Sons Ltd.

Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China.

PubMed

Wang, Rongyue; Lei, Tingying; Fu, Fang; Li, Ru; Jing, Xiangyi; Yang, Xin; Liu, Juan; Li, Dongzhi; Liao, Can

2018-03-26

Chromosome microarray analysis (CMA) is currently the first-tier diagnostic assay for the evaluation of developmental delay (DD) and intellectual disability (ID) with unknown etiology. Here, we present our clinical experience in implementing whole-genome high-resolution single nucleotide polymorphism (SNP) arrays to investigate 489 patients with unexplained DD/ID in whom standard karyotyping analyses showed normal karyotypes. This study aimed to assess the usefulness of CMA for clinical diagnostic testing in the Chinese population. A total of 489 children were classified into three groups: isolated DD/ID (n = 358), DD/ID with epilepsy (n = 49), and DD/ID with other structural anomalies (n = 82). We identified 126 cases (25.8%, 126/489) of pathogenic copy number variants (CNVs) by CMA, including 89 (24.9%, 89/358) with isolated DD/ID, 13 (26.5%, 13/49) with DD/ID with epilepsy, and 24 (29.3%, 24/82) with DD/ID with other structural anomalies. Among the 126 cases of pathogenic CNVs, 79 cases were identified as microdeletion/microduplication syndromes, among which 76 cases were classified as common syndromes, and 3 cases were classified as rare syndromes, including 15q24 microdeletion syndrome, Xq28 microduplication syndrome and Lowe syndrome. Additionally, there were forty-seven cases of non-syndromic pathogenic CNVs. The ABAT, FTSJ1, DYNC1H1, and SETBP1 genes were identified as DD/ID candidate genes. Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD/ID in South China. Copyright © 2018. Published by Elsevier B.V.

The diagnostic value of late-night salivary cortisol for diagnosis of subclinical Cushing's syndrome.

PubMed

Kuzu, Idris; Zuhur, Sayid Shafi; Demir, Nazan; Aktas, Gokce; Yener Ozturk, Feyza; Altuntas, Yuksel

2016-01-01

Late-night salivary cortisol is a frequently used and easily implemented diagnostically valuable test for the diagnosis of overt Cushing's syndrome. The use of late-night salivary cortisol in the diagnosis of subclinical Cushing's syndrome is somewhat controversial. In this study, we aimed to determine the diagnostic value of late-night salivary cortisol in diagnosing subclinical Cushing's syndrome and compare it with 24-hour urinary free cortisol levels (UFC). The study consisted of 33 cases of subclinical Cushing's syndrome, 59 cases of non-functioning adrenal adenoma, and 41 control subjects. Late-night salivary cortisol and UFC were measured in all the cases. The diagnosis of subclinical Cushing's syndrome was based on combined results of 1 mg dexamethasone suppression test > 1.8 μg/dL and ACTH < 10 pg/mL. Mean late-night salivary cortisol levels in subjects with subclinical Cushing's syndrome were significantly higher than in subjects with non-functioning adrenal adenoma and the control group (p < 0.001). Using a cut-off value of 0.18 μg/dL, the sensitivity and specificity of late-night salivary cortisol for diagnosing subclinical Cushing's syndrome were determined as 82% and 60%, respectively. Using a cut-off value of 137 μg/day, the sensitivity and specificity of UFC was determined as 18% and 90%, respectively. Because the sensitivity of late-night salivary cortisol for the diagnosis of subclinical Cushing's syndrome is limited, using it as the sole screening test for subclinical Cushing's syndrome may lead to false negative results. However, using it as an adjunct test to other tests may be beneficial in the diagnosis of subclinical Cushing's syndrome. (Endokrynol Pol 2016; 67 (5): 487-492).

The Use of a Mobile Laboratory Unit in Support of Patient Management and Epidemiological Surveillance during the 2005 Marburg Outbreak in Angola

PubMed Central

Grolla, Allen; Jones, Steven M.; Fernando, Lisa; Strong, James E.; Ströher, Ute; Möller, Peggy; Paweska, Janusz T.; Burt, Felicity; Pablo Palma, Pedro; Sprecher, Armand; Formenty, Pierre; Roth, Cathy; Feldmann, Heinz

2011-01-01

Background Marburg virus (MARV), a zoonotic pathogen causing severe hemorrhagic fever in man, has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever (MHF) with the highest case fatality rate to date. Methodology/Principal Findings A mobile laboratory unit (MLU) was deployed as part of the World Health Organization outbreak response. Utilizing quantitative real-time PCR assays, this laboratory provided specific MARV diagnostics in Uige, the epicentre of the outbreak. The MLU operated over a period of 88 days and tested 620 specimens from 388 individuals. Specimens included mainly oral swabs and EDTA blood. Following establishing on site, the MLU operation allowed a diagnostic response in <4 hours from sample receiving. Most cases were found among females in the child-bearing age and in children less than five years of age. The outbreak had a high number of paediatric cases and breastfeeding may have been a factor in MARV transmission as indicated by the epidemiology and MARV positive breast milk specimens. Oral swabs were a useful alternative specimen source to whole blood/serum allowing testing of patients in circumstances of resistance to invasive procedures but limited diagnostic testing to molecular approaches. There was a high concordance in test results between the MLU and the reference laboratory in Luanda operated by the US Centers for Disease Control and Prevention. Conclusions/Significance The MLU was an important outbreak response asset providing support in patient management and epidemiological surveillance. Field laboratory capacity should be expanded and made an essential part of any future outbreak investigation. PMID:21629730

Statistical adjustment of culture-independent diagnostic tests for trend analysis in the Foodborne Diseases Active Surveillance Network (FoodNet), USA.

PubMed

Gu, Weidong; Dutta, Vikrant; Patrick, Mary; Bruce, Beau B; Geissler, Aimee; Huang, Jennifer; Fitzgerald, Collette; Henao, Olga

2018-03-19

Culture-independent diagnostic tests (CIDTs) are increasingly used to diagnose Campylobacter infection in the Foodborne Diseases Active Surveillance Network (FoodNet). Because CIDTs have different performance characteristics compared with culture, which has been used historically and is still used to diagnose campylobacteriosis, adjustment of cases diagnosed by CIDT is needed to compare with culture-confirmed cases for monitoring incidence trends. We identified the necessary parameters for CIDT adjustment using culture as the gold standard, and derived formulas to calculate positive predictive values (PPVs). We conducted a literature review and meta-analysis to examine the variability in CIDT performance and Campylobacter prevalence applicable to FoodNet sites. We then developed a Monte Carlo method to estimate test-type and site-specific PPVs with their associated uncertainties. The uncertainty in our estimated PPVs was largely derived from uncertainty about the specificity of CIDTs and low prevalence of Campylobacter in tested samples. Stable CIDT-adjusted incidences of Campylobacter cases from 2012 to 2015 were observed compared with a decline in culture-confirmed incidence. We highlight the lack of data on the total numbers of tested samples as one of main limitations for CIDT adjustment. Our results demonstrate the importance of adjusting CIDTs for understanding trends in Campylobacter incidence in FoodNet.

Impact of antepartum diagnostic amnioinfusion on targeted ultrasound imaging of pregnancies presenting with severe oligo- and anhydramnios: An analysis of 61 cases.

PubMed

Vikraman, Seneesh Kumar; Chandra, Vipin; Balakrishnan, Bijoy; Batra, Meenu; Sethumadhavan, Sreeja; Patil, Swapneel Neelkanth; Nair, Sabila; Kannoly, Gopinathan

2017-05-01

The primary objective our study was to assess the role of diagnostic antepartum amnioinfusion on the yield from targeted ultrasounds performed in pregnancies with severe oligo- and anhydramnios. This was a retrospective and descriptive study, conducted in the fetal medicine units of two private tertiary care referral centers in south India. The details of all the cases of diagnostic amnioinfusion performed at these two centers from January 2009 to June 2016 were collected and analyzed. Inclusion criteria were pregnancies between 17 and 26 weeks of gestational age with severe oligo- or anhydramnios. Pregnancies with obvious preterm premature rupture of membranes (PPROM) were excluded. The primary outcome measure was the improvement in diagnostic information pertaining to cause of severe oligo- and anhydramnios, and the nature of such anomalies. A total of 61 cases of were identified. The median gestational age at performance of the procedure was 22 weeks [IQR, 19.5-23]. The mean volume of normal saline infused was 314±54ml. A significant increase in the single vertical pocket (SVP) was observed following the procedure (pre-procedure SVP=0.6±0.9cm, post procedure SVP=3.4±1.7; paired t test, p<0.001). In 37 cases (37/61, 60.7%), there were no pre-procedure ultrasound findings. There was significant overall detection of abnormalities post procedure (mean pre-procedure findings=0.39±0.49, mean post procedure findings=1.59±1.24; paired t test, p<0.001). The most frequent group of anomalies/abnormalities were renal (36/61, 59%), followed by PPROM (13/61, 21.3%) and finally fetal growth restriction (11/61, 18%). Antepartum amnioinfusion is a valuable ancillary technique in prenatal diagnosis as it increases the diagnostic yield from pregnancies presenting with severe oligo- and anhydramnios. Copyright © 2017 Elsevier B.V. All rights reserved.

Single-centre study of the diagnostic performance of plasma metanephrines with seated sampling for the diagnosis of phaeochromocytoma/paraganglioma.

PubMed

Boot, Christopher; Toole, Barry; Johnson, Sarah J; Ball, Stephen; Neely, Dermot

2017-01-01

Background Measurement of plasma metanephrines is regarded as one of the best screening tests for phaeochromocytoma/paraganglioma. Current guidelines recommend that samples are ideally collected in the supine position after 30 min rest and interpreted using supine reference ranges, in order to optimize the diagnostic performance of the test. Current practice in our centre is to collect samples for plasma metanephrines from seated patients. The aim of the study was to determine, if seated sampling for plasma metanephrines provides acceptable diagnostic performance in our centre. Methods Clinical and laboratory data of 113 patients, gathered over a four-year period 2010-2014, were reviewed. All had undergone preoperative plasma metanephrines measurement and had postoperative histopathology confirmation or exclusion of phaeochromocytoma/paraganglioma. Results Of 113 patients included in the study, 40 had a histological diagnosis of phaeochromocytoma/paraganglioma. The remaining 73 patients had an alternative adrenal pathology. The diagnostic sensitivity of normetanephrine or metanephrine above the upper limit of our in-house seated reference range was 93%. However, excluding three cases of paraganglioma determined clinically and biochemically to be non-functional raised the sensitivity to 100%. Diagnostic specificity was 90%. Applying published supine reference ranges made no difference to diagnostic sensitivity in this group of patients but decreased diagnostic specificity to 75%. Conclusions While these data are derived from a relatively small study population, they demonstrate acceptable diagnostic performance for seated plasma metanephrines as a screening test for phaeochromocytoma/paraganglioma. These data highlight a high diagnostic sensitivity for plasma metanephrines with seated sampling in our centre.

Diagnosis of Swimming Induced Pulmonary Edema—A Review

PubMed Central

Grünig, Hannes; Nikolaidis, Pantelis T.; Moon, Richard E.; Knechtle, Beat

2017-01-01

Swimming induced pulmonary edema (SIPE) is a complication that can occur during exercise with the possibility of misdiagnosis and can quickly become life threatening; however, medical literature infrequently describes SIPE. Therefore, the aim of this review was to analyse all individual cases diagnosed with SIPE as reported in scientific sources, with an emphasis on the diagnostic pathways and the key facts resulting in its diagnosis. Due to a multifactorial and complicated pathophysiology, the diagnosis could be difficult. Based on the actual literature, we try to point out important findings regarding history, conditions, clinical findings, and diagnostic testing helping to confirm the diagnosis of SIPE. Thirty-eight cases from seventeen articles reporting the diagnosis of SIPE were selected. We found remarkable differences in the individual described diagnostic pathways. A total of 100% of the cases suffered from an acute onset of breathing problems, occasionally accompanied by hemoptysis. A total of 73% showed initial hypoxemia. In most of the cases (89%), an initial chest X-Ray or chest CT was available, of which one-third (71%) showed radiological signs of pulmonary edema. The majority of the cases (82%) experienced a rapid resolution of symptoms within 48 h, the diagnostic hallmark of SIPE. Due to a foreseeable increase in participation in swimming competitions and endurance competitions with a swimming component, diagnosis of SIPE will be important, especially for medical teams caring for these athletes. PMID:28912730

Development of an On-board Failure Diagnostics and Prognostics System for Solid Rocket Booster

NASA Technical Reports Server (NTRS)

Smelyanskiy, Vadim N.; Luchinsky, Dmitry G.; Osipov, Vyatcheslav V.; Timucin, Dogan A.; Uckun, Serdar

2009-01-01

We develop a case breach model for the on-board fault diagnostics and prognostics system for subscale solid-rocket boosters (SRBs). The model development was motivated by recent ground firing tests, in which a deviation of measured time-traces from the predicted time-series was observed. A modified model takes into account the nozzle ablation, including the effect of roughness of the nozzle surface, the geometry of the fault, and erosion and burning of the walls of the hole in the metal case. The derived low-dimensional performance model (LDPM) of the fault can reproduce the observed time-series data very well. To verify the performance of the LDPM we build a FLUENT model of the case breach fault and demonstrate a good agreement between theoretical predictions based on the analytical solution of the model equations and the results of the FLUENT simulations. We then incorporate the derived LDPM into an inferential Bayesian framework and verify performance of the Bayesian algorithm for the diagnostics and prognostics of the case breach fault. It is shown that the obtained LDPM allows one to track parameters of the SRB during the flight in real time, to diagnose case breach fault, and to predict its values in the future. The application of the method to fault diagnostics and prognostics (FD&P) of other SRB faults modes is discussed.

Image-guided fine-needle aspiration of retroperitoneal masses: The role of the cytopathologist.

PubMed

Mehdi, Ghazala; Maheshwari, Veena; Afzal, Sheerin; Ansari, Hena A; Ahmad, Ibne

2013-01-01

Retroperitoneal tumors constitute a difficult diagnostic category as they are not easily accessible. The advent of image-guided fine-needle aspiration (FNA) has resolved this problem significantly. We present a short study based on guided aspiration of retroperitoneal tumors, in which we have tried to assess the role of image-guided fine-needle aspiration cytology as a tool for pre-operative diagnosis. The study was conducted on patients diagnosed with retroperitoneal masses. FNA was performed under image guidance with the help of ultrasonography and/or computed tomography; smears were prepared and meticulously screened according to a fixed protocol. The results were analyzed to determine sensitivity, specificity, and diagnostic efficacy of cytopathological diagnosis using image-guided FNA techniques. We assessed 38 patients with retroperitoneal masses. In all cases, adequate cellular material was obtained. No major complications were encountered. Statistical analysis was carried out in 35 cases; sensitivity, specificity, and diagnostic accuracy were 100% in these cases. FNA under image guidance should be considered a first-line diagnostic approach for retroperitoneal and other abdominal tumors, although caution should be exercised in case selection. In areas where advanced tests are not available, the cytotechnologist and cytopathologist have a very important role to play in ensuring accurate diagnoses.

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.

Issues in contemporary and potential future molecular diagnostics for dengue.

PubMed

Sekaran, Shamala Devi; Soe, Hui Jen

2017-03-01

Dengue has been the most common arbovirus infection worldwide with 2.5 billion people living in over 100 endemic tropical and subtropical regions. Due to the high number of asymptomatic cases and the signs and symptoms being rather unspecific, dengue cases are often under-reported and might influence dengue surveillance programs. Therefore, a rapid, easy to use, inexpensive, and highly sensitive and specific diagnostic tool is essential for early and accurate diagnosis to ease the clinical management of patients as well as for the development of new interventions. Areas covered: This report discusses the contemporary dengue diagnostic tool, mainly from the aspect of molecular diagnosis where an overview of several nuclei acid amplification tests has been included. Potential molecular diagnostic tools such as biosensor and microarray are also discussed in this report. Expert commentary: Rapidness and accuracy in terms of sensitivity and specificity is imperative in dengue diagnosis for both clinical management and surveillance of dengue to ensure early treatment and corrective control measures can be carried out. In the next five years it is expected that there will be newer tests developed using not only the lateral flow techniques but more specifically biosensors and nanotechnology. These new technologies will have to be validated with the appropriate number and category of samples and to address the issue of cross-reactivity.

History, epidemiology and diagnostics of dengue in the American and Brazilian contexts: a review.

PubMed

Salles, Tiago Souza; da Encarnação Sá-Guimarães, Thayane; de Alvarenga, Evelyn Seam Lima; Guimarães-Ribeiro, Victor; de Meneses, Marcelo Damião Ferreira; de Castro-Salles, Patricia Faria; Dos Santos, Carlucio Rocha; do Amaral Melo, Ana Claudia; Soares, Marcia Regina; Ferreira, Davis Fernandes; Moreira, Monica Ferreira

2018-04-24

Dengue virus (DENV), an arbovirus transmitted by mosquitoes, has become a major threat to American human life, reaching approximately 23 million cases from 1980 to 2017. Brazil is among the countries most affected by this terrible viral disease, with 13.6 million cases. DENV has four different serotypes, DENV1-4, which show a broad clinical spectrum. Dengue creates a staggering epidemiological and economic burden for endemic countries. Without a specific therapy and with a commercial vaccine that presents some problems relative to its full effectiveness, initiatives to improve vector control strategies, early disease diagnostics and the development of vaccines and antiviral drugs are priorities. In this study, we present the probable origins of dengue in America and the trajectories of its spread. Overall, dengue diagnostics are costly, making the monitoring of dengue epidemiology more difficult and affecting physicians' therapeutic decisions regarding dengue patients, especially in developing countries. This review also highlights some recent and important findings regarding dengue in Brazil and the Americas. We also summarize the existing DENV polymerase chain reaction (PCR) diagnostic tests to provide an improved reference since these tests are useful and accurate at discriminating DENV from other flaviviruses that co-circulate in the Americas. Additionally, these DENV PCR assays ensure virus serotyping, enabling epidemiologic monitoring.

Confetti-like Sparing

PubMed Central

Fitzpatrick, Richard E.; Goldman, Mitchel P.

2016-01-01

Diagnostic uncertainty when a patient presents with melasma-like Undings can lead to suboptimal treatment and inaccurate prognostic expectations. In this study, the authors present a unique clinical feature of melasma that they term the “Fitzpatrick macule” and test its Utility in establishing diagnostic certainty. The “Fitzpatrick macule” is a confetti-like macule of regularly pigmented skin located within a larger patch of melasma hyperpigmentation. To test its diagnostic Utility, the authors compared clinical photography of known cases of melasma with common mimickers, such as poikiloderma of Civatte and solar lentiginosis, and determined the positivity rate of the Fitzpatrick macule in each scenario. Their results show that 89.1 percent of clinical photographs of melasma were positive for the presence of Fitzpatrick macules compared to 1.1 percent that were negative. In contrast, 37.5 and 56.3 percent of clinical photographs of poikiloderma of Civatte were positive and negative for Fitzpatrick macules, respectively. Solar lentiginosis showed a 5.6 percent positivity and a 77.8 percent negativity for Fitzpatrick macules. The sensitivity and specificity of Fitzpatrick macules for melasma was 99 and 83 percent, respectively. In summary, the authors report a highly sensitive and specific clinical feature of melasma. In cases of diagnostic uncertainty, the presence of Fitzpatrick macules may aid in establishing a diagnosis of melasma. PMID:27047632

[Contribution of the rapid diagnostic tests for infectious diseases to the patient management in the Great East Japan earthquake].

PubMed

Hatta, Masumitsu; Kaku, Mitsuo

2012-01-01

On 11 March 2011, an earthquake measuring 9.0 on the Richter scale off the northeast coast of Honshu Island, Japan, produced a devastating tsunami that destroyed many towns and villages near the coast in Iwate, Miyagi, and Fukushima prefectures. Miyagi Prefecture was the area most severely devastated by the tsunami, with extensive loss of life and property; hundreds of thousands of people lost their houses and were forced to move to evacuation areas. In the days and weeks following devastating natural disasters, the threat of infectious disease outbreak is high. Rapid diagnostic tests can be performed at or near the site of patient care and the tests were very useful in this disaster, because they enabled us to manage patients appropriately in the settings where medical resources were limited. Here we report actual cases where the rapid diagnostic tests for infectious diseases were useful in the patient management.

Case definition for progressive multifocal leukoencephalopathy following treatment with monoclonal antibodies.

PubMed

Mentzer, Dirk; Prestel, Jürgen; Adams, Ortwin; Gold, Ralf; Hartung, Hans-Peter; Hengel, Hartmut; Kieseier, Bernd C; Ludwig, Wolf-Dieter; Keller-Stanislawski, Brigitte

2012-09-01

Novel immunosuppressive/modulating therapies with monoclonal antibodies (MABs) have been associated with progressive multifocal leukoencephalopathy (PML), a potentially fatal disease of the brain caused by the JC virus. Taking the complex diagnostic testing and heterogeneous clinical presentation of PML into account, an agreed case definition for PML is a prerequisite for a thorough assessment of PML. A working group was established to develop a standardised case definition for PML which permits data comparability across clinical trials, postauthorisation safety studies and passive postmarketing surveillance. The case definition is designed to define levels of diagnostic certainty of reported PML cases following treatment with MABs. It was subsequently used to categorise retrospectively suspected PML cases from Germany reported to the Paul-Ehrlich-Institute as the responsible national competent authority. The algorithm of the case definition is based on clinical symptoms, PCR for JC virus DNA in cerebrospinal fluid, brain MRI, and brain biopsy/autopsy. The case definition was applied to 119 suspected cases of PML following treatment with MABs and is considered to be helpful for case ascertainment of suspected PML cases for various MABs covering a broad spectrum of indications. Even if the available information is not yet complete, the case definition provides a level of diagnostic certainty. The proposed case definition permits data comparability among different medicinal products and among active as well as passive surveillance settings. It may form a basis for meaningful risk analysis and communication for regulators and healthcare professionals.

Diagnostic accuracy of clinical tests for assessment of hamstring injury: a systematic review.

PubMed

Reiman, Michael P; Loudon, Janice K; Goode, Adam P

2013-04-01

Systematic literature review. The diagnosis of a hamstring injury has traditionally relied on various clinical measures (eg, palpation, swelling, manual resistance), as well as the use of diagnostic imaging. But a few studies have suggested the use of specific clinical tests that may be helpful for the diagnostic process. To summarize the current literature on the diagnostic accuracy of orthopaedic special tests for hamstring injuries and to determine their clinical utility. A computer-assisted literature search of the MEDLINE, CINAHL, and Embase databases (along with a manual search of grey literature) was conducted using key words related to diagnostic accuracy of hamstring injuries. To be considered for inclusion in the review, the study required (1) patients with hamstring or posterior thigh pain; (2) a cohort, case-control, or cross-sectional design; (3) inclusion of at least 1 clinical examination test used to evaluate hamstring pathology; (4) comparison against an acceptable reference standard; (5) reporting of diagnostic accuracy of the measures (sensitivity [SN], specificity [SP], or likelihood ratios); and (6) publication in English. SN, SP, and positive and negative likelihood ratios were calculated for each diagnostic test. The search strategy identified 602 potential articles, of which only 3 articles met the inclusion criteria, with only 1 of these 3 articles being of high quality. Two of the studies investigated a single special test, whereas the third article examined a composite clinical assessment employing various special tests. The SN values ranged from 0.55 (95% confidence interval [CI]: 0.46, 0.69) for the active range-of-motion test to 1.00 (95% CI: 0.97, 1.00) for the taking-off-the-shoe test. The SP values ranged from 0.03 (95% CI: 0.00, 0.22) for the composite clinical assessment to 1.00 (95% CI: 0.97, 1.00) for the taking-off-the-shoe test, active range-of-motion test, passive range-of-motion test, and resisted range-of-motion test. The use of a single special test demonstrated stronger SP than SN properties, whereas the composite clinical assessment demonstrated stronger SN than SP properties. Very few studies have investigated the utilization of clinical special tests for the diagnosis of hamstring injuries. Further studies of higher quality design are suggested prior to advocating independent clinical utilization of these special tests. Diagnosis, level 3b.

Diagnostic performance of the atopy patch test with inhalant allergens.

PubMed

Fuiano, N; Diddi, G; Delvecchio, M; Incorvaia, C

2015-01-01

This study evaluated the diagnostic performance of the atopy patch test (APT) compared with skin prick testing (SPT) and in vitro IgE measurement in a large group of patients with atopic dermatitis (AD) with or without respiratory symptoms (RS). The study included 521 patients (292 males, 229 females; age, 0.5-18 years; median age, 6 years) with AD and RS with different clinical presentations: current AD, 47 patients (Group A); current AD and RS, 72 patients (Group B), past AD and RS, 69 patients (Group C); and RS only, 280 patients (Group D). Fifty-three healthy individuals served as controls. All participants underwent the APT, SPT, and CAP/RAST with the most common inhalant allergens. The presence of a control group allowed calculation of specificity and positive and negative predictive values. A significant difference was found for a positive APT versus both SPT and CAP/RAST (P < .0001) but not for SPT versus CAP/RAST. The differences for APT were significant in all group comparisons except group B vs C and group C vs D. In the control group, the APT was positive in 2% of cases (specificity of 96.2%), SPT was positive in 6% of cases (specificity of 88.4%), and CAP/RAST was positive in 4% of cases (specificity of 92.5%). In young patients sensitized to inhalant allergens with AD in addition to RS, the APT has a superior diagnostic performance to SPT and in vitro IgE measurement.

Specific Immunodiffusion Test for Blastomycosis

PubMed Central

Kaufman, Leo; McLaughlin, David W.; Clark, Maxine J.; Blumer, Sharon

1973-01-01

A specific immunodiffusion test for blastomycosis has been developed. The test permitted the detection of approximately 80% of 113 proven cases of blastomycosis. Two diagnostically important precipitins designated A and B were frequently recognized in patients with blastomycosis. Routine use of reference sera containing the A and B precipitins in immunodiffusion tests would permit the specific diagnosis of blastomycosis without the need for parallel tests with coccidioidin and histoplasmin. Images PMID:4201639

Noninvasive Diagnosis of Visceral Leishmaniasis: Development and Evaluation of Two Urine-Based Immunoassays for Detection of Leishmania donovani Infection in India

PubMed Central

Ejazi, Sarfaraz Ahmad; Bhattacharya, Pradyot; Bakhteyar, Md. Asjad Karim; Mumtaz, Aquil Ahmad; Pandey, Krishna; Das, Vidya Nand Ravi; Das, Pradeep; Rahaman, Mehebubar; Goswami, Rama Prosad; Ali, Nahid

2016-01-01

Background Visceral Leishmaniasis (VL), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. Post kala-azar dermal leishmaniasis (PKDL), a skin related outcome, is a potential reservoir for the spread of VL. Diagnostic tests available for VL such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. Serological tests although less invasive than tissue aspiration are incompetent to assess cure. Parasitological examination of slit-skin smear along with the clinical symptoms is routinely used for diagnosis of PKDL. Therefore, a noninvasive test with acceptable sensitivity and competency, additionally, to decide cure would be an asset in disease management and control. Methodology/principal findings We describe here, the development of antibody-capture ELISA and field adaptable dipstick test as noninvasive diagnostic tools for VL and PKDL and as a test of cure in VL treatment. Sensitivity and specificity of urine-ELISA were 97.94% (95/97) and 100% (75/75) respectively, for VL. Importantly, dipstick test demonstrated 100% sensitivity (97/97) and specificity (75/75) in VL diagnosis. Degree of agreement of the two methods with tissue aspiration was 98.83% (κ = 0.97) and 100% (κ = 1), for ELISA and dipstick test, respectively. Both the tests had 100% positivity for PKDL (14/14) cases. ELISA and dipstick test illustrated treatment efficacy in about 90% (16/18) VL cases when eventually turned negative after six months of treatment. Conclusions/significance ELISA and dipstick test found immensely effective for diagnosis of VL and PKDL through urine samples thus, may substitute the existing invasive diagnostics. Utility of these tests as indirect methods of monitoring parasite clearance can define infected versus cured. Urine-based dipstick test is simple, sensitive and above all noninvasive method that may help not only in active VL case detection but also to ascertain treatment response. It can therefore, be deployed widely for interventions in disease management of VL particularly in poor resource outskirts. PMID:27741241

[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.

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.

Implementation of an Integrated On-Board Aircraft Engine Diagnostic Architecture

NASA Technical Reports Server (NTRS)

Armstrong, Jeffrey B.; Simon, Donald L.

2012-01-01

An on-board diagnostic architecture for aircraft turbofan engine performance trending, parameter estimation, and gas-path fault detection and isolation has been developed and evaluated in a simulation environment. The architecture incorporates two independent models: a realtime self-tuning performance model providing parameter estimates and a performance baseline model for diagnostic purposes reflecting long-term engine degradation trends. This architecture was evaluated using flight profiles generated from a nonlinear model with realistic fleet engine health degradation distributions and sensor noise. The architecture was found to produce acceptable estimates of engine health and unmeasured parameters, and the integrated diagnostic algorithms were able to perform correct fault isolation in approximately 70 percent of the tested cases

Screening for ROS1 gene rearrangements in non-small cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target

PubMed Central

Selinger, Christina I; Li, Bob T; Pavlakis, Nick; Links, Matthew; Gill, Anthony J; Lee, Adrian; Clarke, Stephen; Tran, Thang N; Lum, Trina; Yip, Po Yee; Horvath, Lisa; Yu, Bing; Kohonen-Corish, Maija RJ; O’Toole, Sandra A; Cooper, Wendy A

2016-01-01

Aims To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. Methods A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective NSCLC cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in situ hybridisation (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Results Eighty eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining of which 12 (12%) cases were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wildtype and ALK rearrangement negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. Conclusions ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK positive cases and use of IHC to screen for potentially positive cases can be used to enrich for the likelihood of a identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time consuming FISH testing in all cases. PMID:27599111

Screening for ROS1 gene rearrangements in non-small-cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target.

PubMed

Selinger, Christina I; Li, Bob T; Pavlakis, Nick; Links, Matthew; Gill, Anthony J; Lee, Adrian; Clarke, Stephen; Tran, Thang N; Lum, Trina; Yip, Po Y; Horvath, Lisa; Yu, Bing; Kohonen-Corish, Maija R J; O'Toole, Sandra A; Cooper, Wendy A

2017-02-01

To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective non-small-cell lung cancer (NSCLC) cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in-situ hybridization (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Eighty-eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining, 12 (12%) cases of which were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wild-type and anaplastic lymphoma kinase (ALK) rearrangement-negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK-positive cases and use of IHC to screen for potentially positive cases, can be used to enrich for the likelihood of identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time-consuming FISH testing in all cases. © 2016 John Wiley & Sons Ltd.

Detection of fungal DNA in human body fluids and tissues during a multistate outbreak of fungal meningitis and other infections.

PubMed

Gade, Lalitha; Scheel, Christina M; Pham, Cau D; Lindsley, Mark D; Iqbal, Naureen; Cleveland, Angela Ahlquist; Whitney, Anne M; Lockhart, Shawn R; Brandt, Mary E; Litvintseva, Anastasia P

2013-05-01

Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak.

The Effectiveness of Teleglaucoma versus In-Patient Examination for Glaucoma Screening: A Systematic Review and Meta-Analysis

PubMed Central

Thomas, Sera-Melisa; Jeyaraman, Maya; Hodge, William G.; Hutnik, Cindy; Costella, John; Malvankar-Mehta, Monali S.

2014-01-01

Background Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness. Methods A systematic search was conducted to help locate published and unpublished studies. Studies which evaluate teleglaucoma as a screening device for glaucoma were included. A meta-analysis was conducted to provide estimates of diagnostic accuracy, diagnostic odds ratio, and the relative percentage of glaucoma cases detected. The improvements to healthcare service quality and cost data were assessed. Results Of 11237 studies reviewed, 45 were included. Our results indicated that, teleglaucoma is more specific and less sensitive than in-person examination. The pooled estimates of sensitivity was 0.832 [95% CI 0.770, 0.881] and specificity was 0.790 [95% CI 0.668, 0.876]. The relative odds of a positive screen test in glaucoma cases are 18.7 times more likely than a negative screen test in a non-glaucoma cases. Additionally, the mean cost for every case of glaucoma detected was $1098.67 US and of teleglaucoma per patient screened was $922.77 US. Conclusion Teleglaucoma can accurately discriminate between screen test results with greater odds for positive cases. It detects more cases of glaucoma than in-person examination. Both patients and the healthcare systems benefit from early detection, reduction in wait and travel times, increased specialist referral rates, and cost savings. Teleglaucoma is an effective screening tool for glaucoma specifically for remote and under-services communities. PMID:25479593

The effectiveness of teleglaucoma versus in-patient examination for glaucoma screening: a systematic review and meta-analysis.

PubMed

Thomas, Sera-Melisa; Jeyaraman, Maya M; Jeyaraman, Maya; Hodge, William G; Hutnik, Cindy; Costella, John; Malvankar-Mehta, Monali S

2014-01-01

Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness. A systematic search was conducted to help locate published and unpublished studies. Studies which evaluate teleglaucoma as a screening device for glaucoma were included. A meta-analysis was conducted to provide estimates of diagnostic accuracy, diagnostic odds ratio, and the relative percentage of glaucoma cases detected. The improvements to healthcare service quality and cost data were assessed. Of 11237 studies reviewed, 45 were included. Our results indicated that, teleglaucoma is more specific and less sensitive than in-person examination. The pooled estimates of sensitivity was 0.832 [95% CI 0.770, 0.881] and specificity was 0.790 [95% CI 0.668, 0.876]. The relative odds of a positive screen test in glaucoma cases are 18.7 times more likely than a negative screen test in a non-glaucoma cases. Additionally, the mean cost for every case of glaucoma detected was $1098.67 US and of teleglaucoma per patient screened was $922.77 US. Teleglaucoma can accurately discriminate between screen test results with greater odds for positive cases. It detects more cases of glaucoma than in-person examination. Both patients and the healthcare systems benefit from early detection, reduction in wait and travel times, increased specialist referral rates, and cost savings. Teleglaucoma is an effective screening tool for glaucoma specifically for remote and under-services communities.

European specialist porphyria laboratories: diagnostic strategies, analytical quality, clinical interpretation, and reporting as assessed by an external quality assurance program.

PubMed

Aarsand, Aasne K; Villanger, Jørild H; Støle, Egil; Deybach, Jean-Charles; Marsden, Joanne; To-Figueras, Jordi; Badminton, Mike; Elder, George H; Sandberg, Sverre

2011-11-01

The porphyrias are a group of rare metabolic disorders whose diagnosis depends on identification of specific patterns of porphyrin precursor and porphyrin accumulation in urine, blood, and feces. Diagnostic tests for porphyria are performed by specialized laboratories in many countries. Data regarding the analytical and diagnostic performance of these laboratories are scarce. We distributed 5 sets of multispecimen samples from different porphyria patients accompanied by clinical case histories to 18-21 European specialist porphyria laboratories/centers as part of a European Porphyria Network organized external analytical and postanalytical quality assessment (EQA) program. The laboratories stated which analyses they would normally have performed given the case histories and reported results of all porphyria-related analyses available, interpretative comments, and diagnoses. Reported diagnostic strategies initially showed considerable diversity, but the number of laboratories applying adequate diagnostic strategies increased during the study period. We found an average interlaboratory CV of 50% (range 12%-152%) for analytes in absolute concentrations. Result normalization by forming ratios to the upper reference limits did not reduce this variation. Sixty-five percent of reported results were within biological variation-based analytical quality specifications. Clinical interpretation of the obtained analytical results was accurate, and most laboratories established the correct diagnosis in all distributions. Based on a case-based EQA scheme, variations were apparent in analytical and diagnostic performance between European specialist porphyria laboratories. Our findings reinforce the use of EQA schemes as an essential tool to assess both analytical and diagnostic processes and thereby to improve patient care in rare diseases.

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

Retrospective testing and case series study of porcine delta coronavirus in U.S. swine herds.

PubMed

McCluskey, Brian J; Haley, Charles; Rovira, Albert; Main, Rodger; Zhang, Yan; Barder, Sunny

2016-01-01

Porcine deltacoronavirus (PDCoV) was first reported in the United States (US) in February 2014. This was the second novel swine enteric coronavirus detected in the US since May 2013. In this study, we conducted retrospective testing of samples submitted to three veterinary diagnostic laboratories where qualifying biological samples were derived from previously submitted diagnostic case submissions from US commercial swine farms with a clinical history of enteric disease or from cases that had been previously tested for transmissible gastroenteritis virus, PEDV, or rotavirus. Overall, 2286 banked samples were tested from 27 States. Samples were collected in 3 separate years and in 17 different months. Test results revealed 4 positive samples, 3 collected in August 2013 and 1 collected in October 2013. In addition, a case series including 42 operations in 10 States was conducted through administration of a survey. Survey data collected included information on characteristics of swine operations that had experienced PDCoV clinical signs. Special emphasis was placed on obtaining descriptive estimates of biosecurity practices and disease status over time of each operation. Clinical signs of PDCoV were reported to be similar to those of PEDV. The average number of animals on each operation exhibiting clinical signs (morbidity) and the average number of case fatalities was greatest for suckling and weaned pigs. Average operation-level weaned pig morbidity was greatest in the first week of the outbreak while average operation-level suckling pig case fatality was greatest in the second week of the outbreak. The survey included questions regarding biosecurity practices for visitors and operation employees; trucks, equipment and drivers; and feed sources. These questions attempted to identify a likely pathway of introduction of PDCoV onto the operations surveyed. Published by Elsevier B.V.

Prospective survey of veterinary practitioners’ primary assessment of equine colic: clinical features, diagnoses, and treatment of 120 cases of large colon impaction

PubMed Central

2014-01-01

Background Large colon impactions are a common cause of colic in the horse. There are no scientific reports on the clinical presentation, diagnostic tests and treatments used in first opinion practice for large colon impaction cases. The aim of this study was to describe the presentation, diagnostic approach and treatment at the primary assessment of horses with large colon impactions. Methods Data were collected prospectively from veterinary practitioners on the primary assessment of equine colic cases over a 12 month period. Inclusion criteria were a diagnosis of primary large colon impaction and positive findings on rectal examination. Data recorded for each case included history, signalment, clinical and diagnostic findings, treatment on primary assessment and final case outcome. Case outcomes were categorised into three groups: simple medical (resolved with single treatment), complicated medical (resolved with multiple medical treatments) and critical (required surgery, were euthanased or died). Univariable analysis using one-way ANOVA and Tukey’s post-hoc test, Kruskal Wallis with Dunn’s post-hoc test and Chi squared analysis were used to compare between different outcome categories. Results 1032 colic cases were submitted by veterinary practitioners: 120 cases met the inclusion criteria for large colon impaction. Fifty three percent of cases were categorised as simple medical, 36.6% as complicated medical, and 9.2% as critical. Most cases (42.1%) occurred during the winter. Fifty nine percent of horses had had a recent change in management, 43% of horses were not ridden, and 12.5% had a recent / current musculoskeletal injury. Mean heart rate was 43bpm (range 26-88) and most cases showed mild signs of pain (67.5%) and reduced gut sounds (76%). Heart rate was significantly increased and gut sounds significantly decreased in critical compared to simple medical cases (p<0.05). Fifty different treatment combinations were used, with NSAIDs (93%) and oral fluids (71%) being administered most often. Conclusions Large colon impactions typically presented with mild signs of colic; heart rate and gut sounds were the most useful parameters to distinguish between simple and critical cases at the primary assessment. The findings of seasonal incidence and associated management factors are consistent with other studies. Veterinary practitioners currently use a wide range of different treatment combinations for large colon impactions. PMID:25238179

Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?

PubMed Central

Teschke, Rolf; Schulze, Johannes; Eickhoff, Axel; Danan, Gaby

2017-01-01

Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed. High specificity and sensitivity are required for any diagnostic biomarker. Although some risk factors are available to evaluate liver safety of drugs in patients, no valid diagnostic or prognostic biomarker exists currently for idiosyncratic DILI when a liver injury occurred. Identifying a biomarker in idiosyncratic DILI requires detailed knowledge of cellular and biochemical disturbances leading to apoptosis or cell necrosis and causing leakage of specific products in blood. As idiosyncratic DILI is typically a human disease and hardly reproducible in animals, pathogenetic events and resulting possible biomarkers remain largely undisclosed. Potential new diagnostic biomarkers should be evaluated in patients with DILI and RUCAM-based established causality. In conclusion, causality assessment in cases of suspected idiosyncratic DILI is still best achieved using RUCAM since specific biomarkers as diagnostic blood tests that could enhance RUCAM results are not yet available. PMID:28398242

Computer based extraction of phenoptypic features of human congenital anomalies from the digital literature with natural language processing techniques.

PubMed

Karakülah, Gökhan; Dicle, Oğuz; Koşaner, Ozgün; Suner, Aslı; Birant, Çağdaş Can; Berber, Tolga; Canbek, Sezin

2014-01-01

The lack of laboratory tests for the diagnosis of most of the congenital anomalies renders the physical examination of the case crucial for the diagnosis of the anomaly; and the cases in the diagnostic phase are mostly being evaluated in the light of the literature knowledge. In this respect, for accurate diagnosis, ,it is of great importance to provide the decision maker with decision support by presenting the literature knowledge about a particular case. Here, we demonstrated a methodology for automated scanning and determining of the phenotypic features from the case reports related to congenital anomalies in the literature with text and natural language processing methods, and we created a framework of an information source for a potential diagnostic decision support system for congenital anomalies.

CYP1B1 copy number variation is not a major contributor to primary congenital glaucoma.

PubMed

Souzeau, Emmanuelle; Hayes, Melanie; Ruddle, Jonathan B; Elder, James E; Staffieri, Sandra E; Kearns, Lisa S; Mackey, David A; Zhou, Tiger; Ridge, Bronwyn; Burdon, Kathryn P; Dubowsky, Andrew; Craig, Jamie E

2015-01-01

To evaluate the prevalence and the diagnostic utility of testing for CYP1B1 copy number variation (CNV) in primary congenital glaucoma (PCG) cases unexplained by CYP1B1 point mutations in The Australian and New Zealand Registry of Advanced Glaucoma. In total, 50 PCG cases either heterozygous for disease-causing variants or with no CYP1B1 sequence variants were included in the study. CYP1B1 CNV was analyzed by Multiplex Ligation-dependent Probe Amplification (MLPA). No deletions or duplications were found in any of the cases. This is the first study to report on CYP1B1 CNV in PCG cases. Our findings show that this mechanism is not a major contributor to the phenotype and is of limited diagnostic utility.

Case Series of Fatal Leptospira spp./Dengue Virus Co-Infections—Puerto Rico, 2010–2012

PubMed Central

Pérez Rodríguez, Nicole M.; Galloway, Renee; Blau, Dianna M.; Traxler, Rita; Bhatnagar, Julu; Zaki, Sherif R.; Rivera, Aidsa; Torres, Jose V.; Noyd, David; Santiago-Albizu, Xavier E.; García, Brenda Rivera; Tomashek, Kay M.; Bower, William A.; Sharp, Tyler M.

2014-01-01

Co-infection with pathogens that cause acute febrile illness creates a diagnostic challenge as a result of overlapping clinical manifestations. Here, we describe four fatal cases of Leptospira species/dengue virus co-infection in Puerto Rico. Although all patients sought care early, antibiotic administration was delayed for most. Steroids were administered to all patients, in most cases before antibiotics. These cases show the need for clinicians evaluating patients in or recently returned from the tropics with acute febrile illness to consider both dengue and leptospirosis. Furthermore, they illustrate the need for nucleic acid- or antigen-based rapid diagnostic tests to enable timely patient diagnosis and management. In particular, antibiotic therapy should be initiated early for patients with suspected leptospirosis, and steroids should not be administered to patients with suspected dengue. PMID:25092820

Diagnostic value of screening tests in subgroups of women with recurrent pregnancy loss.

PubMed

Guzel, Ali Irfan; Erkılınç, Selçuk; Özer, Irfan; Celik, Yusuf; Yılmaz, Nafiye; Doğanay, Melike

2015-03-01

To evaluate the diagnostic value of screening laboratory tests in women who had recurrent pregnancy loss (RPL). A total of 252 women with RPL managed in our tertiary referral research and education hospital were included in the study. Risk factors recorded involved age, gravidity, parity, number of prior live births, number of pregnancy losses, and thrombophlia tests. The cases were divided into three different groups and each group was analyzed separately. There was no statistically significant difference between the first and second groups in terms of clinical and laboratory parameters (p > 0.05). In the third group, there was a statistically significant difference among cases in terms of parity, gravidity, number of pregnancy losses, serum AT III levels, APCR, and age of the women. According to the logistic regression model, odds ratios (95% CI) were 6.116 (3.797-9.852), 5.665 (2.657-12.079), 4.763 (3.099-7.321), 4.729 (3.080-7.260), 2.820 (1.836-4.333), and 1.911 (1.232-2.965), respectively. We do not recommend the screening of all women with RPL, but in women with high parity and those who had prior live birth pregnancies, increased AT III, and APCR may be diagnostic markers for subsequent pregnancy loss.

Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea

PubMed Central

Kurosaki, Yohei; Magassouba, N’Faly; Oloniniyi, Olamide K.; Cherif, Mahamoud S.; Sakabe, Saori; Takada, Ayato; Hirayama, Kenji; Yasuda, Jiro

2016-01-01

Given the current absence of specific drugs or vaccines for Ebola virus disease (EVD), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. We have developed a rapid detection assay for Zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) and coupled with a novel portable isothermal amplification and detection platform. The RT-LAMP assay is based on primer sets that target the untranscribed trailer region or nucleoprotein coding region of the viral RNA. The test could specifically detect viral RNAs of Central and West African Ebola virus strains within 15 minutes with no cross-reactivity to other hemorrhagic fever viruses and arboviruses, which cause febrile disease. The assay was evaluated using a total of 100 clinical specimens (serum, n = 44; oral swab, n = 56) collected from suspected EVD cases in Guinea. The specificity of this diagnostic test was 100% for both primer sets, while the sensitivity was 100% and 97.9% for the trailer and nucleoprotein primer sets, respectively, compared with a reference standard RT-PCR test. These observations suggest that our diagnostic assay is useful for identifying EVD cases, especially in the field or in settings with insufficient infrastructure. PMID:26900929

Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea.

PubMed

Kurosaki, Yohei; Magassouba, N'Faly; Oloniniyi, Olamide K; Cherif, Mahamoud S; Sakabe, Saori; Takada, Ayato; Hirayama, Kenji; Yasuda, Jiro

2016-02-01

Given the current absence of specific drugs or vaccines for Ebola virus disease (EVD), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. We have developed a rapid detection assay for Zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) and coupled with a novel portable isothermal amplification and detection platform. The RT-LAMP assay is based on primer sets that target the untranscribed trailer region or nucleoprotein coding region of the viral RNA. The test could specifically detect viral RNAs of Central and West African Ebola virus strains within 15 minutes with no cross-reactivity to other hemorrhagic fever viruses and arboviruses, which cause febrile disease. The assay was evaluated using a total of 100 clinical specimens (serum, n = 44; oral swab, n = 56) collected from suspected EVD cases in Guinea. The specificity of this diagnostic test was 100% for both primer sets, while the sensitivity was 100% and 97.9% for the trailer and nucleoprotein primer sets, respectively, compared with a reference standard RT-PCR test. These observations suggest that our diagnostic assay is useful for identifying EVD cases, especially in the field or in settings with insufficient infrastructure.

[Clinical microbiology laboratory and imported parasitic diseases].

PubMed

Martín-Rabadán, Pablo; Martínez-Ruiz, Rocío; Cuadros, Juan; Cañavate, Carmen

2010-12-01

Imported parasitosis represents an increasingly frequent diagnostic challenge for microbiology laboratories. A surge in immigration and international travel has led to a rise in the number of imported cases of parasitosis, and this trend is expected to continue in the future. The present article addresses this challenge by reviewing recommended diagnostic approaches and tests. Currently, microscopy is always recommended when analysing blood samples for parasites. If malaria is suspected, rapid antigen testing (including at least HRP2 antigen) should also be performed. The work-up for suspected leishmaniasis should include serology, culture, and in selected cases detection of antigen in urine. In suspected Chagas disease, two different serological tests should be performed. PCR for blood protozoa is highly sensitive, although it cannot be used to rule out Chagas disease, since this condition may be present without parasitemia. Accurate diagnosis of intestinal amebiasis usually requires PCR or antigen detection tests. In helminthiasis, traditional microscopy may need to be complemented with other tests, such as agar plate culture for strongyloidiasis, Og4C3 antigen detection for bancroftian filariasis, and antibody detection test for filariasis and schistosomiasis. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Using cytology to increase small animal practice revenue.

PubMed

Hodges, Joanne

2013-11-01

Diagnostic cytology is a useful, noninvasive test with practical foundations in high-quality medicine and applications to practice building. Cytology will generate practice revenue whether assessed in-house or sent to a clinical pathologist. Thorough in-house evaluation is adequate in some cases, but expert opinion is important in many cases. Specimen slides should at least be reviewed in-house for assessment of cellularity and potential artifacts before submission to a reference laboratory. Reference laboratories also provide special stains and advanced molecular diagnostics to help further characterize many neoplastic processes, search for organisms, identify pigments, and address other important aspects of the lesion. Copyright © 2013 Elsevier Inc. All rights reserved.

Phenobarbital-responsive sialadenosis in dogs: case series.

PubMed

Alcoverro, Emili; Tabar, Maria Dolores; Lloret, Albert; Roura, Xavier; Pastor, Josep; Planellas, Marta

2014-12-01

Phenobarbital-responsive sialadenosis (PRS) is a rare idiopathic disease in dogs. Vomiting, retching, and gulping with bilateral enlargement of the submandibular salivary glands are the more frequent clinical signs. A thorough diagnostic examination must be performed to rule out the most important systemic etiologies involved with chronic vomiting, as there is no specific test to diagnose PRS. Diagnosis is confirmed clinically by a rapid and dramatic improvement of clinical signs after instauration of phenobarbital treatment. The aim of this article is to describe the clinical presentation, diagnostic findings, and outcome of a case series of 4 dogs with presumptive PRS. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective comparison of abdominal ultrasonography and radiography in the investigation of feline abdominal disease

PubMed Central

Won, Wylen Wade; Sharma, Ajay; Wu, Wenbo

2015-01-01

Abdominal radiography and ultrasonography are commonly used as part of the initial diagnostic plan for cats with nonspecific signs of abdominal disease. This retrospective study compared the clinical usefulness of abdominal radiography and ultrasonography in 105 feline patients with signs of abdominal disease. The final diagnosis was determined more commonly with ultrasonography (59%) compared to radiography (25.7%). Ultrasonography was also able to provide additional clinically relevant information in 76% of cases, and changed or refined the diagnosis in 47% of cases. Based on these findings, ultrasonography may be sufficient as an initial diagnostic test for the investigation of feline abdominal disease. PMID:26483582

Improving Access to Malaria Rapid Diagnostic Test in Niger State, Nigeria: An Assessment of Implementation up to 2013

PubMed Central

Awoleye, Olatunji Joshua; Thron, Chris

2016-01-01

Nigeria's 2009–2013 malaria strategic plan adopted WHO diagnosis and treatment guidelines, which include the use of rapid diagnostic tests (RDTs) prior to prescribing treatment with artemisinin combination therapies (ACTs). The current study explores accessibility barriers to the use of RDTs in Niger State and makes recommendations for improving the uptake of RDTs. The study employs literature review, review of data from the Niger State Health Management Information System for January–October 2013, and application of Peters' conceptual framework for assessing access to health services. Data showed that 27 percent of public health facilities (HFs) implemented RDTs, with the aid of donor funds. In these facilities, 77 percent of fever cases presented during the study period were tested with RDTs; 53 percent of fever cases were confirmed cases of malaria, while 60 percent of fever cases were treated. Stockouts of RDTs were a major constraint, and severe fever tended to trigger presumptive treatment. We conclude that although implementation of RDTs led to a reduction in the use of ACTs at HFs, more substantial reduction could be achieved if the state government directed more resources towards the acquisition of RDTs as well as raising the level of awareness of potential users. PMID:27042376

Estimating the influenza vaccine effectiveness against medically attended influenza in clinical settings: a hospital-based case-control study with a rapid diagnostic test in Japan.

PubMed

Suzuki, Motoi; Yoshimine, Hiroyuki; Harada, Yoshitaka; Tsuchiya, Naho; Shimada, Ikumi; Ariyoshi, Koya; Inoue, Kenichiro

2013-01-01

Influenza vaccine effectiveness (VE) studies are usually conducted by specialized agencies and require time and resources. The objective of this study was to estimate the influenza VE against medically attended influenza using a test-negative case-control design with rapid influenza diagnostic tests (RIDT) in a clinical setting. A prospective study was conducted at a community hospital in Nagasaki, western Japan during the 2010/11 influenza season. All outpatients aged 15 years and older with influenza-like illnesses (ILI) who had undergone RIDT were enrolled. A test-negative case-control design was applied to estimate the VEs: the cases were ILI patients with positive RIDT results and the controls were ILI patients with negative RIDT results. Information on patient characteristics, including vaccination histories, was collected using questionnaires and medical records. Between December 2010 and April 2011, 526 ILI patients were tested with RIDT, and 476 were eligible for the analysis. The overall VE estimate against medically attended influenza was 47.6%, after adjusting for the patients' age groups, presence of chronic conditions, month of visit, and smoking and alcohol use. The seasonal influenza vaccine reduced the risk of medically attended influenza by 60.9% for patients less than 50 years of age, but a significant reduction was not observed for patients 50 years of age and older. A sensitivity analysis provided similar figures. The test-negative case-control study using RIDT provided moderate influenza VE consistent with other reports. Utilizing the commonly used RIDT to estimate VE provides rapid assessment of VE; however, it may require validation with more specific endpoint.

The Impact of Introducing Malaria Rapid Diagnostic Tests on Fever Case Management: A Synthesis of Ten Studies from the ACT Consortium.

PubMed

Bruxvoort, Katia J; Leurent, Baptiste; Chandler, Clare I R; Ansah, Evelyn K; Baiden, Frank; Björkman, Anders; Burchett, Helen E D; Clarke, Siân E; Cundill, Bonnie; DiLiberto, Debora D; Elfving, Kristina; Goodman, Catherine; Hansen, Kristian S; Kachur, S Patrick; Lal, Sham; Lalloo, David G; Leslie, Toby; Magnussen, Pascal; Mangham-Jefferies, Lindsay; Mårtensson, Andreas; Mayan, Ismail; Mbonye, Anthony K; Msellem, Mwinyi I; Onwujekwe, Obinna E; Owusu-Agyei, Seth; Rowland, Mark W; Shakely, Delér; Staedke, Sarah G; Vestergaard, Lasse S; Webster, Jayne; Whitty, Christopher J M; Wiseman, Virginia L; Yeung, Shunmay; Schellenberg, David; Hopkins, Heidi

2017-10-01

Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.

The Impact of Introducing Malaria Rapid Diagnostic Tests on Fever Case Management: A Synthesis of Ten Studies from the ACT Consortium

PubMed Central

Bruxvoort, Katia J.; Leurent, Baptiste; Chandler, Clare I. R.; Ansah, Evelyn K.; Baiden, Frank; Björkman, Anders; Burchett, Helen E. D.; Clarke, Siân E.; Cundill, Bonnie; DiLiberto, Debora D.; Elfving, Kristina; Goodman, Catherine; Hansen, Kristian S.; Kachur, S. Patrick; Lal, Sham; Lalloo, David G.; Leslie, Toby; Magnussen, Pascal; Mangham-Jefferies, Lindsay; Mårtensson, Andreas; Mayan, Ismail; Mbonye, Anthony K.; Msellem, Mwinyi I.; Onwujekwe, Obinna E.; Owusu-Agyei, Seth; Rowland, Mark W.; Shakely, Delér; Staedke, Sarah G.; Vestergaard, Lasse S.; Webster, Jayne; Whitty, Christopher J. M.; Wiseman, Virginia L.; Yeung, Shunmay; Schellenberg, David; Hopkins, Heidi

2017-01-01

Abstract. Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400–432,513). mRDTs were associated with significantly lower ACT prescription (range 8–69% versus 20–100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs. PMID:28820705

Fan Noise Source Diagnostic Test Computation of Rotor Wake Turbulence Noise

NASA Technical Reports Server (NTRS)

Nallasamy, M.; Envia, E.; Thorp, S. A.; Shabbir, A.

2002-01-01

An important source mechanism of fan broadband noise is the interaction of rotor wake turbulence with the fan outlet guide vanes. A broadband noise model that utilizes computed rotor flow turbulence from a RANS code is used to predict fan broadband noise spectra. The noise model is employed to examine the broadband noise characteristics of the 22-inch Source Diagnostic Test fan rig for which broadband noise data were obtained in wind tunnel tests at the NASA Glenn Research Center. A 9-case matrix of three outlet guide vane configurations at three representative fan tip speeds are considered. For all cases inlet and exhaust acoustic power spectra are computed and compared with the measured spectra where possible. In general, the acoustic power levels and shape of the predicted spectra are in good agreement with the measured data. The predicted spectra show the experimentally observed trends with fan tip speed, vane count, and vane sweep. The results also demonstrate the validity of using CFD-based turbulence information for fan broadband noise calculations.

Factoring quality laboratory diagnosis into the malaria control agenda for sub-Saharan Africa.

PubMed

Aidoo, Michael

2013-09-01

Recent progress in malaria control in sub-Saharan Africa has been achieved primarily through provision of insecticide-treated nets, indoor residual spraying, and antimalarial drugs. Although these interventions are important, proper case identification and accurate measurement of their impact depend on quality diagnostic testing. Current availability of diagnostic testing for malaria in sub-Saharan Africa is inadequate to support disease management, prevention programs, and surveillance needs. Challenges faced include a dearth of skilled workforce, inadequate health systems infrastructure, and lack of political will. A coordinated approach to providing pre-service clinical and laboratory training together with systems that support a scale-up of laboratory services could provide means not only for effective malaria case management but also, management of non-malaria febrile illnesses, disease surveillance, and accurate control program evaluation. A synthesis of the challenges faced in ensuring quality malaria testing and how to include this information in the malaria control and elimination agenda are presented.

Use of molecular testing to identify a cluster of patients with polycythemia vera in eastern Pennsylvania.

PubMed

Seaman, Vincent; Jumaan, Aisha; Yanni, Emad; Lewis, Brian; Neyer, Jonathan; Roda, Paul; Xu, Mingjiang; Hoffman, Ronald

2009-02-01

The role of the environment in the origin of polycythemia vera has not been well documented. Recently, molecular diagnostic tools have been developed to facilitate the diagnosis of polycythemia vera. A cluster of patients with polycythemia vera was suspected in three countries in eastern Pennsylvania where there have long been a concern about environment hazards. Rigorous clinical criteria and JAK2 617V>F testing were used to confirm the diagnosis of polycythemia vera in patients in this area. Participants included cases of polycythemia vera from the 2001 to 2005 state cancer registry as well as self- and physician-referred cases. A diagnosis of polycythemia vera was confirmed in 53% of 62 participants using WHO criteria, which includes JAK2 617V>F testing. A statistically significant cluster of cases (P < 0.001) was identified where the incidence of polycythemia vera was 4.3 times that of the rest of the study area. The area of the cluster contained numerous sources of hazardous material including waste-coal power plants and U.S. Environmental Protection Agency Superfund sites. The diagnosis of polycythemia vera based solely on clinical criteria is frequently erroneous, suggesting that our prior knowledge of the epidemiology of this disease might be inaccurate. The JAK2 617V>F mutational analysis provides diagnostic clarity and permitted the confirmation of a cluster of polycythemia vera cases not identified by traditional clinical and pathologic diagnostic criteria. The close proximity of this cluster to known areas of hazardous material exposure raises concern that such environmental factors might play a role in the origin of polycythemia vera.

Genetics Home Reference: multiple epiphyseal dysplasia

MedlinePlus

... MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How ... manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study. BMC Musculoskelet ...

Diagnostic Accuracy of Chinese Medicine Diagnosis Scale of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease: A Study Protocol.

PubMed

Liu, Xiao-Qi; Peng, Dan-Hong; Wang, Yan-Ping; Xie, Rong; Chen, Xin-Lin; Yu, Chun-Quan; Li, Xian-Tao

2018-05-03

Phlegm and blood stasis syndrome (PBSS) is one of the main syndromes in coronary heart disease (CHD). Syndromes of Chinese medicine (CM) are lack of quantitative and easyimplementation diagnosis standards. To quantify and standardize the diagnosis of PBSS, scales are usually applied. To evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. Six hundred patients with stable angina pectoris of CHD, 300 in case group and 300 in control group, will be recruited from 5 hospitals across China. Diagnosis from 2 experts will be considered as the "gold standard". The study design consists of 2 phases: pilot test is used to evaluate the reliability and validity, and diagnostic test is used to assess the diagnostic accuracy of the scale, including sensitivity, specififi city, likelihood ratio and area under the receiver operator characteristic (ROC) curve. This study will evaluate the diagnostic accuracy of CM diagnosis scale of PBSS in CHD. The consensus of 2 experts may not be ideal as a "gold standard", and itself still requires further study. (No. ChiCTR-OOC-15006599).

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

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.

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.

Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis.

PubMed

van't Hoog, Anna H; Cobelens, Frank; Vassall, Anna; van Kampen, Sanne; Dorman, Susan E; Alland, David; Ellner, Jerrold

2013-01-01

High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

Clinical Utility of Amyloid PET Imaging in the Differential Diagnosis of Atypical Dementias and Its Impact on Caregivers.

PubMed

Bensaïdane, Mohamed Reda; Beauregard, Jean-Mathieu; Poulin, Stéphane; Buteau, François-Alexandre; Guimond, Jean; Bergeron, David; Verret, Louis; Fortin, Marie-Pierre; Houde, Michèle; Bouchard, Rémi W; Soucy, Jean-Paul; Laforce, Robert

2016-04-18

Recent studies have supported a role for amyloid positron emission tomography (PET) imaging in distinguishing Alzheimer's disease (AD) pathology from other pathological protein accumulations leading to dementia. We investigated the clinical utility of amyloid PET in the differential diagnosis of atypical dementia cases and its impact on caregivers. Using the amyloid tracer 18F-NAV4694, we prospectively scanned 28 patients (mean age 59.3 y, s.d. 5.8; mean MMSE 21.4, s.d. 6.0) with an atypical dementia syndrome. Following a comprehensive diagnostic workup (i.e., history taking, neurological examination, blood tests, neuropsychological evaluation, MRI, and FDG-PET), no certain diagnosis could be arrived at. Amyloid PET was then conducted and classified as positive or negative. Attending physicians were asked to evaluate whether this result led to a change in diagnosis or altered management. They also reported their degree of confidence in the diagnosis. Caregivers were met after disclosure of amyloid PET results and completed a questionnaire/interview to assess the impact of the scan. Our cohort was evenly divided between positive (14/28) and negative (14/28) 18F-NAV4694 cases. Amyloid PET resulted in a diagnostic change in 9/28 cases (32.1%: 17.8% changed from AD to non-AD, 14.3% from non-AD to AD). There was a 44% increase in diagnostic confidence. Altered management occurred in 71.4% (20/28) of cases. Knowledge of amyloid status improved caregivers' outcomes in all domains (anxiety, depression, disease perception, future anticipation, and quality of life). This study suggests a useful additive role for amyloid PET in atypical cases with an unclear diagnosis beyond the extensive workup of a tertiary memory clinic. Amyloid PET increased diagnostic confidence and led to clinically significant alterations in management. The information gained from that test was well received by caregivers and encouraged spending quality time with their loved ones.

A 'difficult' insect allergy patient: reliable history of a sting, but all testing negative.

PubMed

Tracy, James M; Olsen, Jonathan A; Carlson, John

2015-08-01

Few conditions are as treatable as allergy to stinging insects, with venom immunotherapy (VIT) providing up to 98% protection to subsequent stings. The challenge with VIT is not in the treatment, but in the diagnosis. To offer VIT, one must determine a history of a systemic reaction to a stinging insect in conjunction with the presence venom-specific IgE. Current diagnostic methods, although sensitive and specific, are imperfect, and some newer testing options are not widely available. A conundrum occasionally faced is the patient with a reliable and compelling history of a systemic allergic reaction yet negative venom-specific testing. This diagnostic dilemma presents an opportunity to consider possible causes for this diagnostic challenge. Our evolving understanding of the role of occult mast cell disease may begin to help us understand this situation and develop appropriate management strategies. Venom-specific skin testing has long been the cornerstone of the evaluation of venom sensitivity and is often combined with in-vitro assays to add clarity, but even these occasionally may fall short. Exploring novel venom diagnostic testing methods may help to fill in some of the diagnostic gaps. Do currently available venom vaccines contain all the key venom species? Are there enough differences between insect species that we may simply be missing the relevant allergens? What is the significance of the antigenicity of carbohydrate moieties in venoms? What is the role of recombinant venom extracts? VIT is the definitive treatment for insect allergic individuals. To utilize VIT, identification of the relevant Hymenoptera is necessary. Unfortunately, this cannot always be accomplished. This deficiency can have several causes: a potential comorbid condition such as occult mast cell disease, limitations of currently available diagnostic resources, or testing vaccines with an insufficient coverage of relevant venom allergens. Exploring these potential causes may help to provide important insight into this important diagnostic conundrum. The use of a case report may help clarify this challenge.

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

IQ Scores Should Be Corrected for the Flynn Effect in High-Stakes Decisions

ERIC Educational Resources Information Center

Fletcher, Jack M.; Stuebing, Karla K.; Hughes, Lisa C.

2010-01-01

IQ test scores should be corrected for high stakes decisions that employ these assessments, including capital offense cases. If scores are not corrected, then diagnostic standards must change with each generation. Arguments against corrections, based on standards of practice, information present and absent in test manuals, and related issues,…

Availability and price of malaria rapid diagnostic tests in the public and private health sectors in 2011: results from 10 nationally representative cross-sectional retail surveys.

PubMed

Poyer, Stephen; Shewchuk, Tanya; Tougher, Sarah; Ye, Yazoume; Mann, Andrea G; Willey, Barbara A; Thomson, Rebecca; Amuasi, John H; Ren, Ruilin; Wamukoya, Marilyn; Taylor, Mark; Nguah, Samuel Blay; Mberu, Blessing; Kalolella, Admirabilis; Juma, Elizabeth; Festo, Charles; Johanes, Boniface; Diap, Graciela; Bruxvoort, Katia; Ansong, Daniel; Hanson, Kara; Arnold, Fred; Goodman, Catherine

2015-06-01

To describe the state of the public and private malaria diagnostics market shortly after WHO updated its guidelines for testing all suspected malaria cases prior to treatment. Ten nationally representative cross-sectional cluster surveys were conducted in 2011 among public and private health facilities, community health workers and retail outlets (pharmacies and drug shops) in nine countries (Tanzania mainland and Zanzibar surveyed separately). Eligible outlets had antimalarials in stock on the day of interview or had stocked antimalarials in the past 3 months. Three thousand four hundred and thirty-nine rapid diagnostic test (RDT) products from 39 manufacturers were audited among 12,197 outlets interviewed. Availability was typically highest in public health facilities, although availability in these facilities varied greatly across countries, from 15% in Nigeria to >90% in Madagascar and Cambodia. Private for-profit sector availability was 46% in Cambodia, 20% in Zambia, but low in other countries. Median retail prices for RDTs in the private for-profit sector ranged from $0.00 in Madagascar to $3.13 in Zambia. The reported number of RDTs used in the 7 days before the survey in public health facilities ranged from 3 (Benin) to 50 (Zambia). Eighteen months after WHO updated its case management guidelines, RDT availability remained poor in the private sector in sub-Saharan Africa. Given the ongoing importance of the private sector as a source of fever treatment, the goal of universal diagnosis will not be achievable under current circumstances. These results constitute national baselines against which progress in scaling-up diagnostic tests can be assessed. © 2015 John Wiley & Sons Ltd.

Malaria rapid diagnostic tests in endemic settings.

PubMed

Maltha, J; Gillet, P; Jacobs, J

2013-05-01

Malaria rapid diagnostic tests (RDTs) are instrument-free tests that provide results within 20 min and can be used by community health workers. RDTs detect antigens produced by the Plasmodium parasite such as Plasmodium falciparum histidine-rich protein-2 (PfHPR2) and Plasmodium lactate dehydrogenase (pLDH). The accuracy of RDTs for the diagnosis of uncomplicated P. falciparum infection is equal or superior to routine microscopy (but inferior to expert microscopy). Sensitivity for Plasmodium vivax is 75-100%; for Plasmodium ovale and Plasmodium malariae, diagnostic performance is poor. Design limitations of RDTs include poor sensitivity at low parasite densities, susceptibility to the prozone effect (PfHRP2-detecting RDTs), false-negative results due to PfHRP2 deficiency in the case of pfhrp2 gene deletions (PfHRP2-detecting RDTs), cross-reactions between Plasmodium antigens and detection antibodies, false-positive results by other infections and susceptibility to heat and humidity. End-user's errors relate to safety, procedure (delayed reading, incorrect sample and buffer volumes) and interpretation (not recognizing invalid test results, disregarding faint test lines). Withholding antimalarial treatment in the case of negative RDT results tends to be infrequent and tendencies towards over-prescription of antibiotics have been noted. Numerous shortcomings in RDT kits' labelling, instructions for use (correctness and readability) and contents have been observed. The World Health Organization and partners actively address quality assurance of RDTs by comparative testing of RDTs, inspections of manufacturing sites, lot testing and training tools but no formal external quality assessment programme of end-user performance exists. Elimination of malaria requires RDTs with lower detection limits, for which nucleic acid amplification tests are under development. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Value of stress ultrasound for the diagnosis of chronic ankle instability compared to manual anterior drawer test, stress radiography, magnetic resonance imaging, and arthroscopy.

PubMed

Cho, Jae Ho; Lee, Doo Hyung; Song, Hyung Keun; Bang, Joon Young; Lee, Kyung Tai; Park, Young Uk

2016-04-01

Clinicians frequently diagnose chronic ankle instability using the manual anterior drawer test and stress radiography. However, both examinations can yield incorrect results and do not reveal the extent of ankle instability. Stress ultrasound has been reported to be a new diagnostic tool for the diagnosis of chronic ankle instability. The purpose of this study was to assess the diagnostic value of stress ultrasound for chronic ankle instability compared to the manual anterior drawer test, stress radiography, magnetic resonance imaging (MRI), and arthroscopy. Twenty-eight consecutive patients who underwent ankle arthroscopy and subsequent modified Broström repair for treatment of chronic ankle instability were included. The arthroscopic findings were used as the reference standard. A standardized physical examination (manual anterior drawer test), stress radiography, MRI, and stress ultrasound were performed to assess the anterior talofibular ligament (ATFL) prior to operation. Ultrasound images were taken in the resting position and the maximal anterior drawer position. Grade 3 lateral instability was verified arthroscopically in all 28 cases with a clinical diagnosis (100%). Twenty-two cases showed grade III instability on the manual anterior drawer test (78.6%). Twenty-four cases displayed anterior translation exceeding 5 mm on stress radiography (86%), and talar tilt angle exceeded 15° in three cases (11 %). Nineteen cases displayed a partial chronic tear (change in thickness or signal intensity), and nine cases displayed complete tear on MRI (100%). Lax and wavy ATFL was evident on stress ultrasound in all cases (100 %). The mean value of the ATFL length was 2.8 ± 0.3 cm for the stressed condition and 2.1 ± 0.2 cm for the resting condition (p < 0.001). Stress ultrasound may be useful for the diagnosis of chronic ankle instability in addition to the manual anterior drawer test and stress radiography. III.

Lessons learned developing a diagnostic tool for HIV-associated dementia feasible to implement in resource-limited settings: pilot testing in Kenya.

PubMed

Kwasa, Judith; Cettomai, Deanna; Lwanya, Edwin; Osiemo, Dennis; Oyaro, Patrick; Birbeck, Gretchen L; Price, Richard W; Bukusi, Elizabeth A; Cohen, Craig R; Meyer, Ana-Claire L

2012-01-01

To conduct a preliminary evaluation of the utility and reliability of a diagnostic tool for HIV-associated dementia (HAD) for use by primary health care workers (HCW) which would be feasible to implement in resource-limited settings. In resource-limited settings, HAD is an indication for anti-retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the treatment for HAD, is now increasingly available in resource-limited settings. Nonetheless, HAD remains under-diagnosed likely because of limited clinical expertise and availability of diagnostic tests. Thus, a simple diagnostic tool which is practical to implement in resource-limited settings is an urgent need. A convenience sample of 30 HIV-infected outpatients was enrolled in Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool for HAD as administered by a primary HCW. This was compared to an expert clinical assessment which included examination by a physician, neuropsychological testing, and in selected cases, brain imaging. Agreement between HCW and an expert examiner on certain tool components was measured using Kappa statistic. The sample was 57% male, mean age was 38.6 years, mean CD4 T-cell count was 323 cells/µL, and 54% had less than a secondary school education. Six (20%) of the subjects were diagnosed with HAD by expert clinical assessment. The diagnostic tool was 63% sensitive and 67% specific for HAD. Agreement between HCW and expert examiners was poor for many individual items of the diagnostic tool (K = .03-.65). This diagnostic tool had moderate sensitivity and specificity for HAD. However, reliability was poor, suggesting that substantial training and formal evaluations of training adequacy will be critical to enable HCW to reliably administer a brief diagnostic tool for HAD.

Specific antigen serologic tests in leprosy: implications for epidemiological surveillance of leprosy cases and household contacts.

PubMed

Carvalho, Ana Paula Mendes; Coelho, Angélica da Conceição Oliveira; Correa-Oliveira, Rodrigo; Lana, Francisco Carlos Félix

2017-09-01

There is a lack of straightforward tests for field application and known biomarkers for predicting leprosy progression in infected individuals. The aim was to analyse the response to infection by Mycobacterium leprae based on the reactivity of specific antigens: natural disaccharide linked to human serum albumin via an octyl (NDOHSA), a semisynthetic phenolic glycolipid-I (PGL-I); Leprosy Infectious Disease Research Institute Diagnostic-1 (LID-1) and natural disaccharide octyl - Leprosy Infectious Disease Research Institute Diagnostic-1 (NDOLID). The study population consisted of 130 leprosy cases diagnosed between 2010 and 2015 and 277 household contacts. An enzyme-linked immunosorbent assay (ELISA) was used to analyse the reactivity of antibodies against NDOHSA, LID-1 and NDOLID. The samples and controls were tested in duplicate, and the antibody titer was expressed as an ELISA index. Data collection was made by home visits with application of questionnaire and dermatological evaluation of all household contacts to identify signs and symptoms of leprosy. Significant differences in the median ELISA results were observed among leprosy cases in treatment, leprosy cases that had completed treatment and household contacts. Higher proportions of seropositivity were observed in leprosy cases in treatment. Seropositivity was also higher in multibacillary in relation to paucibacillary, with the difference reaching statistical significance. Lower titers were observed among cases with a longer treatment time or discharge. For household contacts, the differences according to the clinical characteristics of the leprosy index case were less pronounced than expected. Other factors, such as the endemicity of leprosy, exposure outside the residence and genetic characteristics, appeared to have a greater influence on the seropositivity. Serologic tests could be used as auxiliary tools for determining the operational classification, in addition to identifying infected individuals and as a strategy for surveillance of household contacts.

Field evaluation of a blood based test for active tuberculosis in endemic settings

PubMed Central

Hussainy, Syed Fahadulla; Krishnan, Viwanathan V.; Ambreen, Atiqa; Yusuf, Noshin Wasim; Irum, Shagufta; Rashid, Abdul; Jamil, Muhammad; Zaffar, Fareed; Chaudhry, Muhammad Nawaz; Gupta, Puneet K.; Akhtar, Muhammad Waheed; Khan, Imran H.

2017-01-01

Over 9 million new active tuberculosis (TB) cases emerge each year from an enormous pool of 2 billion individuals latently infected with Mycobacterium tuberculosis (M. tb.) worldwide. About 3 million new TB cases per year are unaccounted for, and 1.5 million die. TB, however, is generally curable if diagnosed correctly and in a timely manner. The current diagnostic methods for TB, including state-of-the-art molecular tests, have failed in delivering the capacity needed in endemic countries to curtail this ongoing pandemic. Efficient, cost effective and scalable diagnostic approaches are critically needed. We report a multiplex TB serology panel using microbead suspension array containing a combination of 11 M.tb. antigens that demonstrated overall sensitivity of 91% in serum/plasma samples from TB patients confirmed by culture. Group wise sensitivities for sputum smear positive and negative patients were 95%, and 88%, respectively. Specificity of the test was 96% in untreated COPD patients and 91% in general healthy population. The sensitivity of this test is superior to that of the frontline sputum smear test with a comparable specificity (30–70%, and 93–99%, respectively). The multiplex serology test can be performed with scalability from 1 to 360 patients per day, and is amenable to automation for higher (1000s per day) throughput, thus enabling a scalable clinical work flow model for TB endemic countries. Taken together, the above results suggest that well defined antibody profiles in blood, analyzed by an appropriate technology platform, offer a valuable approach to TB diagnostics in endemic countries. PMID:28380055

Laparoscopic management and its outcomes in cases with nonpalpable testis.

PubMed

Erdoğan, Cankat; Bahadır, Berktuğ; Taşkınlar, Hakan; Naycı, Ali

2017-06-01

Diagnostic laparoscopy is the gold standard in the algorithm of nonpalpable testis. Testicular tissue is examined and treatment is planned accordingly. In this study we reviewed the place of diagnostic laparoscopy, and evaluated the results and effectiveness of laparoscopy in the diagnosis and management of nonpalpable testis. Children who had diagnostic laparoscopy for nonpalpable testes were included in the study. Physical examination results, ultrasonography (USG) reports, age at surgery, laparoscopic and inguinal exploration findings, surgical procedures, orchiopexy results, early and late-term complications were evaluated. Follow-up visits were performed at 3-month intervals for the first, at 6-month intervals for the 2. year, then at yearly intervals. Testicular size and location was evaluated by during control examination. Overall 58 boys, and 68 testes (26 left: 44.8%; 22 right: 37.9%, and 10 bilateral: 17.2%) were included in the study. Mean age at surgery was 5.5 years (10 months-17 years). Diagnostic value of USG was 15.7%. Diagnostic laparoscopy findings were as follows: Group 1: blind-ended vessels, n=7 (10.2%); Group 2: intraabdominal testes, n=8 (11.7%); Group 3: vas and vessels entering internal ring, n=53 (77.9%). Overall 43 testes underwent orchiopexy, which were normal (n=8) or hypoplastic (n=35). Mean follow-up period was 19 months (1-12 years), and on an average 7 visits were performed (5-14). On follow-up, 5 testes were normal-sized and located in the scrotum, while 4 testes were atrophic and underwent orchiectomy. Two testes were found in the inguinal canal and redo orchiopexy was performed. Control USG revealed reduced testicular blood supply and volume. Laparoscopic surgery is safe and effective in the management of nonpalpable testes. In the majority, routine use of diagnostic laparoscopy in the algorithma does not confer any additional contributions in many patients.

Investigation of Metabolomic Blood Biomarkers for Detection of Adenocarcinoma Lung Cancer

PubMed Central

Fahrmann, Johannes F.; Kim, Kyoungmi; DeFelice, Brian C.; Taylor, Sandra L.; Gandara, David R.; Yoneda, Ken Y.; Cooke, David T.; Fiehn, Oliver; Kelly, Karen; Miyamoto, Suzanne

2015-01-01

Background Untargeted metabolomics was utilized in case control studies of adenocarcinoma (ADC) lung cancer in order to develop and test metabolite classifiers in serum and plasma as potential biomarkers for diagnosing lung cancer. Methods Serum and plasma were collected and used in two independent case-control studies (ADC1 and ADC2). Controls were frequency matched for gender, age and smoking history. There were 52 ADC cases and 31 controls in ADC1 and 43 ADC cases and 43 controls in ADC2. Metabolomics was conducted using gas chromatography time-of-flight mass spectrometry. Differential analysis was performed on ADC1 and the top candidates (FDR < 0.05) for serum and plasma used to develop individual and multiplex-classifiers that were then tested on an independent set of serum and plasma samples (ADC2). Results Aspartate provided the best accuracy (81.4%) for an individual metabolite classifier in serum whereas pyrophosphate had the best accuracy (77.9%) in plasma when independently tested. Multiplex classifiers of either 2 or 4 serum metabolites had an accuracy of 72.7% when independently tested. For plasma, a multi-metabolite classifier consisting of 8 metabolites gave an accuracy of 77.3% when independently tested. Comparison of overall diagnostic performance between the two blood matrices yielded similar performances. However, serum is most ideal given higher sensitivity for low abundant metabolites. Conclusion This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted. Impact These biomarkers could improve early detection and diagnosis of lung cancer. PMID:26282632

Costs and health consequences of chlamydia management strategies among pregnant women in sub-Saharan Africa.

PubMed

Romoren, M; Hussein, F; Steen, T W; Velauthapillai, M; Sundby, J; Hjortdahl, P; Kristiansen, I S

2007-12-01

Chlamydia is the most common bacterial sexually transmitted infection worldwide and a major cause of morbidity-particularly among women and neonates. We compared costs and health consequences of using point-of-care (POC) tests with current syndromic management among antenatal care attendees in sub-Saharan Africa. We also compared erythromycin with azithromycin treatment and universal with age-based chlamydia management. A decision analytical model was developed to compare diagnostic and treatment strategies, using Botswana as a case. Model input was based upon (1) a study of pregnant women in Botswana, (2) literature reviews and (3) expert opinion. We expressed the study outcome in terms of costs (US$), cases cured, magnitude of overtreatment and successful partner treatment. Azithromycin was less costly and more effective than erythromycin. Compared with syndromic management, testing all attendees on their first visit with a 75% sensitive POC test increased the number of cases cured from 1500 to 3500 in a population of 100,000 women, at a cost of US$38 per additional case cured. This cost was lower in high-prevalence populations or if testing was restricted to teenagers. The specific POC tests provided the advantage of substantial reductions in overtreatment with antibiotics and improved partner management. Using POC tests to diagnose chlamydia during antenatal care in sub-Saharan Africa entails greater health benefits than syndromic management does-and at acceptable costs-especially when restricted to younger women. Changes in diagnostic strategy and treatment regimens may improve people's health and even reduce healthcare budgets.

METACOGNITIVE SCAFFOLDS IMPROVE SELF-JUDGMENTS OF ACCURACY IN A MEDICAL INTELLIGENT TUTORING SYSTEM

PubMed Central

Feyzi-Behnagh, Reza; Azevedo, Roger; Legowski, Elizabeth; Reitmeyer, Kayse; Tseytlin, Eugene; Crowley, Rebecca S.

2013-01-01

In this study, we examined the effect of two metacognitive scaffolds on the accuracy of confidence judgments made while diagnosing dermatopathology slides in SlideTutor. Thirty-one (N = 31) first- to fourth-year pathology and dermatology residents were randomly assigned to one of the two scaffolding conditions. The cases used in this study were selected from the domain of Nodular and Diffuse Dermatitides. Both groups worked with a version of SlideTutor that provided immediate feedback on their actions for two hours before proceeding to solve cases in either the Considering Alternatives or Playback condition. No immediate feedback was provided on actions performed by participants in the scaffolding mode. Measurements included learning gains (pre-test and post-test), as well as metacognitive performance, including Goodman-Kruskal Gamma correlation, bias, and discrimination. Results showed that participants in both conditions improved significantly in terms of their diagnostic scores from pre-test to post-test. More importantly, participants in the Considering Alternatives condition outperformed those in the Playback condition in the accuracy of their confidence judgments and the discrimination of the correctness of their assertions while solving cases. The results suggested that presenting participants with their diagnostic decision paths and highlighting correct and incorrect paths helps them to become more metacognitively accurate in their confidence judgments. PMID:24532850

METACOGNITIVE SCAFFOLDS IMPROVE SELF-JUDGMENTS OF ACCURACY IN A MEDICAL INTELLIGENT TUTORING SYSTEM.

PubMed

Feyzi-Behnagh, Reza; Azevedo, Roger; Legowski, Elizabeth; Reitmeyer, Kayse; Tseytlin, Eugene; Crowley, Rebecca S

2014-03-01

In this study, we examined the effect of two metacognitive scaffolds on the accuracy of confidence judgments made while diagnosing dermatopathology slides in SlideTutor. Thirty-one ( N = 31) first- to fourth-year pathology and dermatology residents were randomly assigned to one of the two scaffolding conditions. The cases used in this study were selected from the domain of Nodular and Diffuse Dermatitides. Both groups worked with a version of SlideTutor that provided immediate feedback on their actions for two hours before proceeding to solve cases in either the Considering Alternatives or Playback condition. No immediate feedback was provided on actions performed by participants in the scaffolding mode. Measurements included learning gains (pre-test and post-test), as well as metacognitive performance, including Goodman-Kruskal Gamma correlation, bias, and discrimination. Results showed that participants in both conditions improved significantly in terms of their diagnostic scores from pre-test to post-test. More importantly, participants in the Considering Alternatives condition outperformed those in the Playback condition in the accuracy of their confidence judgments and the discrimination of the correctness of their assertions while solving cases. The results suggested that presenting participants with their diagnostic decision paths and highlighting correct and incorrect paths helps them to become more metacognitively accurate in their confidence judgments.

Predictive power of Koplik's spots for the diagnosis of measles.

PubMed

Zenner, Dominik; Nacul, Luis

2012-03-12

Measles is a major cause of mortality globally. In many countries, management of measles is based on clinical suspicion, but the predictive value of clinical diagnosis depends on knowledge and population prevalence of measles. In the pre-vaccine era with high measles incidence, Koplik's spots (KS) were said to be "pathognomonic". This study prospectively evaluated test properties and diagnostic odds ratios (OR) of KS. Data including KS status were prospectively collected for a six-month period on all suspected measles cases reported to the North-West London Health Protection Unit. Saliva test kits were sent to all cases and KS test properties were analysed against measles confirmation by PCR or IgM testing (gold standard). The positive predictive value (PPV) of clinically suspecting measles was 50%. Using KS as diagnostic tool improved the PPV to 80% and the presence of KS was associated with confirmed measles in the multi-variable analysis (OR 7.2, 95% Confidence Interval 2.1-24.9, p=0.001). We found that Koplik's spots were highly predictive of confirmed measles and could be a good clinical tool to enable prompt measles management and control measures, as action often needs to be taken in the absence of laboratory confirmation. We suggest that current clinical case definitions might benefit from the inclusion of KS.

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.

Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience.

PubMed

Hu, Xuyun; Li, Niu; Xu, Yufei; Li, Guoqiang; Yu, Tingting; Yao, Ru-En; Fu, Lijun; Wang, Jiwen; Yin, Lei; Yin, Yong; Wang, Ying; Jin, Xingming; Wang, Xiumin; Wang, Jian; Shen, Yiping

2017-11-02

PurposeTo evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions.MethodsA total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire.ResultsPOMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case.ConclusionWe adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.GENETICS in MEDICINE advance online publication, 2 November 2017; doi:10.1038/gim.2017.195.

Promises, pitfalls and practicalities of prenatal whole exome sequencing.

PubMed

Best, Sunayna; Wou, Karen; Vora, Neeta; Van der Veyver, Ignatia B; Wapner, Ronald; Chitty, Lyn S

2018-01-01

Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing (WES) approaches have identified genetic diagnoses when conventional tests (karyotype and microarray) were not diagnostic. Here, we review published prenatal WES studies and recent conference abstracts. Thirty-one studies were identified, with diagnostic rates in series of five or more fetuses varying between 6.2% and 80%. Differences in inclusion criteria and trio versus singleton approaches to sequencing largely account for the wide range of diagnostic rates. The data suggest that diagnostic yields will be greater in fetuses with multiple anomalies or in cases preselected following genetic review. Beyond its ability to improve diagnostic rates, we explore the potential of WES to improve understanding of prenatal presentations of genetic disorders and lethal fetal syndromes. We discuss prenatal phenotyping limitations, counselling challenges regarding variants of uncertain significance, incidental and secondary findings, and technical problems in WES. We review the practical, ethical, social and economic issues that must be considered before prenatal WES could become part of routine testing. Finally, we reflect upon the potential future of prenatal genetic diagnosis, including a move towards whole genome sequencing and non-invasive whole exome and whole genome testing. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Aircraft Engine Gas Path Diagnostic Methods: Public Benchmarking Results

NASA Technical Reports Server (NTRS)

Simon, Donald L.; Borguet, Sebastien; Leonard, Olivier; Zhang, Xiaodong (Frank)

2013-01-01

Recent technology reviews have identified the need for objective assessments of aircraft engine health management (EHM) technologies. To help address this issue, a gas path diagnostic benchmark problem has been created and made publicly available. This software tool, referred to as the Propulsion Diagnostic Method Evaluation Strategy (ProDiMES), has been constructed based on feedback provided by the aircraft EHM community. It provides a standard benchmark problem enabling users to develop, evaluate and compare diagnostic methods. This paper will present an overview of ProDiMES along with a description of four gas path diagnostic methods developed and applied to the problem. These methods, which include analytical and empirical diagnostic techniques, will be described and associated blind-test-case metric results will be presented and compared. Lessons learned along with recommendations for improving the public benchmarking processes will also be presented and discussed.

Soft tissue angiofibroma: Clinicopathologic, immunohistochemical and molecular analysis of 14 cases.

PubMed

Bekers, Elise M; Groenen, Patricia J T A; Verdijk, Marian A J; Raaijmakers-van Geloof, Winny L; Roepman, Paul; Vink, Robert; Gilhuijs, Nathalie D B; van Gorp, Joost M; Bovée, Judith V M G; Creytens, David H; Flanagan, Adrienne M; Suurmeijer, Albert J H; Mentzel, Thomas; Arbajian, Elsa; Flucke, Uta

2017-10-01

Soft tissue angiofibroma is rare and has characteristic histomorphological and genetic features. For diagnostic purposes, there are no specific antibodies available. Fourteen lesions (6 females, 8 males; age range 7-67 years) of the lower extremities (12) and trunk (2) were investigated by immunohistochemistry, including for the first time NCOA2. NCOA2 was also tested in a control group of other spindle cell lesions. The known fusion-genes (AHRR-NCOA2 and GTF2I-NCOA2) were examined using RT-PCR in order to evaluate their diagnostic value. Cases in which no fusion gene was detected were additionally analysed by RNA sequencing. All cases tested showed nuclear expression of NCOA2. However, this was not specific since other spindle cell neoplasms also expressed this marker in a high percentage of cases. Other variably positive markers were EMA, SMA, desmin and CD34. STAT6 was negative in the cases tested. By RT-PCR for the most frequently observed fusions, an AHRR-NCOA2 fusion transcript was found in 9/14 cases. GTF2I-NCOA2 was not detected in the remaining cases (n = 3). RNA sequencing revealed three additional positive cases; two harbored a AHRR-NCOA2 fusion and one case a novel GAB1-ABL1 fusion. Two cases failed molecular analysis due to poor RNA quality. In conclusion, the AHRR-NCOA2 fusion is a frequent finding in soft tissue angiofibroma, while GTF2I-NCOA2 seems to be a rare genetic event. For the first time, we report a GAB1-ABL1 fusion in a soft tissue angiofibroma of a child. Nuclear expression of NCOA2 is not discriminating when compared with other spindle cell neoplasms. © 2017 Wiley Periodicals, Inc.

New diagnostic pathways urgently needed. Protocol of PET Guidance I pilot study: positron emission tomography in suspected cardiac implantable electronic device-related infection.

PubMed

Marciniak-Emmons, Marta Barbara; Sterliński, Maciej; Syska, Paweł; Maciąg, Aleksander; Farkowski, Michał Mirosław; Firek, Bohdan; Dziuk, Mirosław; Zając, Dariusz; Pytkowski, Mariusz; Szwed, Hanna

2016-01-01

Cardiovascular implantable electronic device (CIED) infection is a complication of increasing incidence. We present a protocol of an observational case control clinical trial "Positron Emission Tomography Combined With Computed Tomography (PET CT) in Suspected Cardiac Implantable Electronic Device Infection, a Pilot Study - PET Guidance I" (NCT02196753). The aim of this observational clinical trial is to assess and standardise diagnostic algorithms for CIED infections (lead-dependent infective endocarditis, generator pocket infection, fever of unknown origin) with PET CT in Poland. Study group will consist of 20 patients with initial diagnosis of CIED-related infection paired with a control group of 20 patients with implanted CIEDs, who underwent PET CT due to other non-infectious indications and have no data for infectious process in follow-up. All patients included in the study will undergo standard diagnostic pro-cess. Conventional/standard diagnostic and therapeutic process will consist of: medical interview, physical examination, laboratory tests, blood cultures; imaging studies: echocardiography: transthoracic (TTE), and, if there are no contraindications transoesophageal, computed tomography scan for pulmonary embolism if indicated; if there are abnormalities in other systems, decisions concerning further diagnostics will be made at the physician's discretion. As well as standard diagnostic procedures, patients will undergo whole body PET CT scan to localise infection or inflammation. Diagnosis and therapeutic decision will be obtained from the Study Committee. Follow-up will be held within six months with control visits at three and six months. During each follow-up visit, all patients will undergo laboratory tests, two blood cultures collected 1 h apart, and TTE. In case of actual clinical suspicion of infective endocarditis or local generator pocket infection, patients will be referred for further diagnostics. Endpoints for the results assessment - primary endpoints are to standardise PET CT in the diagnostic process: sensitivity, specificity, positive predictive value, and negative predictive value of the diagnosis made by PET CT; secondary endpoints are: assessment of usefulness of PET CT for detection of remote infective complications (metastatic abscesses, infected pulmonary emboli), incidence of particular localisations of infection, influence of PET CT on therapeutic decision: confirmation or change of decision based on PET CT, safety and complications of diagnostic process of CIED-related infections with PET CT. Evaluation of PET CT use for device-related infections in a case control study may be conclusive and improve diagnostic pathway.

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

PubMed

Taylor, Rachel L; Parry, Neil R A; Barton, Stephanie J; Campbell, Christopher; Delaney, Claire M; Ellingford, Jamie M; Hall, Georgina; Hardcastle, Claire; Morarji, Jiten; Nichol, Elisabeth J; Williams, Lindsi C; Douzgou, Sofia; Clayton-Smith, Jill; Ramsden, Simon C; Sharma, Vinod; Biswas, Susmito; Lloyd, I Chris; Ashworth, Jane L; Black, Graeme C; Sergouniotis, Panagiotis I

2017-07-01

To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). Single-center retrospective case series. Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. Diagnostic yield and clinical usefulness of genetic testing. Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology. We propose the introduction of genetic testing early in the diagnostic pathway in children with clinical and/or electrophysiologic findings, suggestive of IRD. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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.

Discordance of exercise thallium testing with coronary arteriography in patients with atypical presentations

NASA Technical Reports Server (NTRS)

Bungo, M. W.; Leland, O. S., Jr.

1983-01-01

Eighty-one patients with diagnostically difficult clinical presentations suggesting coronary artery disease underwent symptom-limited maximal-exercise treadmill testing (ETT) and exercise radionuclide scanning with thallium-201 followed by coronary angiography. Results showed that in nearly half of the patients (47%) these tests were in agreement, while either exercise thallium or ETT was positive in 94% of patients with coronary artery disease. It was found that agreement between exercise thallium and ETT tests predicted disease in 92% of the instances or excluded disease in 82% of the instances. It is concluded that despite frequent discord between these two tests in 53% of the cases, a significant gain in exclusive diagnostic capability is realized when applied to a patient population anticipated to have a disease prevalence equal to the 67% encountered in this study.

Recorded gonorrhoea rates in Denmark, 1900-2010: the impact of clinical testing activity and laboratory diagnostic procedures.

PubMed

Lind, Inga; Hoffmann, Steen

2015-11-30

Assessment of the relations between recorded gonorrhoea rates and clinical testing activity and disposable diagnostic tests. In Denmark, two sources of information on the epidemiology of gonorrhoea are available: (1) a mandatory clinical notification system (since 1867) comprising summary information about geographic distribution, season, age group and gender; in 1994, more detailed anonymous individualised epidemiological information was included; (2) a voluntary countrywide laboratory surveillance system for culture-confirmed cases (since 1957) comprising information about patient's age and gender, infected anatomical sites and medical setting attended. Both surveillance systems showed marked simultaneous changes in gonorrhoea rates, although periodically considerable under-reporting or under-diagnosing was demonstrated. The annual incidence of notified cases peaked in 1919 (474/100,000), in 1944 (583/100,000) and in 1972 (344/100,000). Since 1995, the incidence has been at a low endemic level (1.5-10/100,000) and the total male/female incidence ratios were from 3 to 7 times higher than previously recorded. Among approximately 2 million persons tested during 1974-1988 78,213 men and 63,143 women with culture-confirmed gonorrhoea were identified. During this period, pharyngeal sampling was performed in 36% of men and 25% of women with gonorrhoea; pharyngeal gonorrhoea was found in 10% and 16%, respectively; 40% and 30% of these patients had no concomitant urogenital gonorrhoea. Among men with gonorrhoea, 34% were sampled from the rectum; 9% had rectal gonorrhoea, among whom the rectum was the only infected site in 67%. Crucial factors for case finding are clinical sampling tradition and appropriate laboratory diagnostic facilities. When case finding is insufficient, a reservoir of asymptomatic rectal or pharyngeal gonorrhoea remains unrecognised. 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/

Toward a Framework for Benefit-Risk Assessment in Diagnostic Imaging: Identifying Scenario-specific Criteria.

PubMed

Agapova, Maria; Bresnahan, Brian W; Linnau, Ken F; Garrison, Louis P; Higashi, Mitchell; Kessler, Larry; Devine, Beth

2017-05-01

Diagnostic imaging has many effects and there is no common definition of value in diagnostic radiology. As benefit-risk trade-offs are rarely made explicit, it is not clear which framework is used in clinical guideline development. We describe initial steps toward the creation of a benefit-risk framework for diagnostic radiology. We performed a literature search and an online survey of physicians to identify and collect benefit-risk criteria (BRC) relevant to diagnostic imaging tests. We operationalized a process for selection of BRC with the use of four clinical use case scenarios that vary by diagnostic alternatives and clinical indication. Respondent BRC selections were compared across clinical scenarios and between radiologists and nonradiologists. Thirty-six BRC were identified and organized into three domains: (1) those that account for differences attributable only to the test or device (n = 17); (2) those that account for clinical management and provider experiences (n = 12); and (3) those that capture patient experience (n = 7). Forty-eight survey participants selected 22 criteria from the initial list in the survey (9-11 per case). Engaging ordering physicians increased the number of criteria selected in each of the four clinical scenarios presented. We developed a process for standardizing selection of BRC in guideline development. These results suggest that a process relying on elements of comparative effectiveness and the use of standardized BRC may ensure consistent examination of differences among alternatives by way of making explicit implicit trade-offs that otherwise enter the decision-making space and detract from consistency and transparency. These findings also highlight the need for multidisciplinary teams that include input from ordering physicians. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Tuberculous otitis media: a significant diagnostic challenge.

PubMed

Vaamonde, Pedro; Castro, Crisanto; García-Soto, Nicolas; Labella, Torcuato; Lozano, Ascensión

2004-06-01

This study was undertaken to revise the diagnostic characteristics of tuberculous otitis media (TOM), a disorder that is often diagnosed late, leading to delay in specific treatment. Retrospective study of a longitudinal series of 10 TOM patients over a 7-year period at an institutional referral center. Most patients showed intractable otorrhea, moderately severe hearing loss, and necrotic eardrums with granulation tissue and single perforations. Multiple perforations, facial palsy, and cervical adenopathies were rare (<10% of patients). CT generally showed soft tissue involvement of the middle ear without bone erosion. The most effective laboratory test microbiological culture of exudate (diagnostic efficacy 71%). Specific antibiotic treatment was effective in all cases. The diagnosis of TOM remains a significant challenge for otorhinolaryngologists. If there are strong clinical grounds for suspicion, standard laboratory tests for tuberculosis should be repeated even if initially negative.

The Swedish version of the Ritvo autism and asperger diagnostic scale: revised (RAADS-R). A validation study of a rating scale for adults.

PubMed

Andersen, Lisa M J; Näswall, Katharina; Manouilenko, Irina; Nylander, Lena; Edgar, Johan; Ritvo, Riva Ariella; Ritvo, Edward; Bejerot, Susanne

2011-12-01

There is a paucity of diagnostic instruments for adults with autism spectrum disorder (ASD). This study evaluates the psychometric properties of the Swedish version of the Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), an 80-item self-rating scale designed to assist clinicians diagnosing ASD in adults. It was administered to 75 adults with ASD and 197 comparison cases. Also, a subset completed the Autism Spectrum Quotient (AQ). Three out of four subscales had high internal consistency. Sensitivity was 91% and specificity was 93%. The ASD subjects had significantly higher mean scores on all subscales. ASD females had higher scores than ASD males on the sensory motor subscale, a dimension not included in the AQ. RAADS-R showed promising test re-test reliability.

Diagnostic imaging and spending review: extreme problems call for extreme measures.

PubMed

Ciarrapico, Anna Micaela; Ugenti, Rossana; Di Minco, Lidia; Santori, Elisabetta; Altobelli, Simone; Coco, Irene; D'Onofrio, Silvia; Simonetti, Giovanni

2017-04-01

The number of diagnostic imaging tests has increased dramatically over the past decade and about 5 billion diagnostic examinations are performed worldwide each year. According to Health Ministry, Italy, is in second place for the number of CT and MR tests per thousand inhabitants in 2014 with a score of 83.3 (only Germany has a higher score, 95.2) that is a long way off from the European average of 46.5. It has also the highest ratio of magnetic resonances per person with 24,6 machines per million inhabitants, followed only by Greece and Finland. The development of the New Health Information System (NSIS) in 2010 made uniformly readable the non-homogeneous clinical data from all the different Italian regions and permitted a detailed analysis of all diagnostic imaging within the public outpatient care setting in Italy in 2012. Despite that MRI examinations represented only the 10% of the total number of imaging tests performed, their cost reached 30% of the health-care expenditure for outpatient diagnostic imaging with an overwhelming contribution coming from musculoskeletal MR which accounted for the 73% of the performed MR tests. It is reasonable to assume that these phenomena are likely due to a lack of appropriateness in MR requests that is difficult to analyze due to an absence or invalid query on the prescriptions which together accounted for the 98.7% of cases. Taking into account the above-mentioned situation, this is possibly why the Ministry of Health decided to perform "linear cuts" in expenditure for some diagnostic examinations.

Sensitivity and specificity of HAT Sero-K-SeT, a rapid diagnostic test for serodiagnosis of sleeping sickness caused by Trypanosoma brucei gambiense: a case-control study.

PubMed

Büscher, Philippe; Mertens, Pascal; Leclipteux, Thierry; Gilleman, Quentin; Jacquet, Diane; Mumba-Ngoyi, Dieudonné; Pyana, Patient Pati; Boelaert, Marleen; Lejon, Veerle

2014-06-01

Human African trypanosomiasis (HAT) is a life-threatening infection affecting rural populations in sub-Saharan Africa. Large-scale population screening by antibody detection with the Card Agglutination Test for Trypanosomiasis (CATT)/Trypanosoma brucei (T b) gambiense helped reduce the number of reported cases of gambiense HAT to fewer than 10 000 in 2011. Because low case numbers lead to decreased cost-effectiveness of such active screening, we aimed to assess diagnostic accuracy of a rapid serodiagnostic test (HAT Sero-K-SeT) applicable in primary health-care centres. In our case-control study, we assessed participants older than 11 years who presented for HAT Sero-K-SeT and CATT/T b gambiense at primary care centres or to mobile teams (and existing patients with confirmed disease status at these centres) in Bandundu Province, DR Congo. We defined cases as patients with trypanosomes that had been identified in lymph node aspirate, blood, or cerebrospinal fluid. During screening, we recruited controls without previous history of HAT or detectable trypanosomes in blood or lymph who resided in the same area as the cases. We assessed diagnostic accuracy of three antibody detection tests for gambiense HAT: HAT Sero-K-SeT and CATT/T b gambiense (done with venous blood at the primary care centres) and immune trypanolysis (done with plasma at the Institute of Tropical Medicine, Antwerp, Belgium). Between June 6, 2012, and Feb 25, 2013, we included 134 cases and 356 controls. HAT Sero-K-SeT had a sensitivity of 0·985 (132 true positives, 95% CI 0·947-0·996) and a specificity of 0·986 (351 true negatives, 0·968-0·994), which did not differ significantly from CATT/T b gambiense (sensitivity 95% CI 0·955, 95% CI 0·906-0·979 [128 true positives] and specificity 0·972, 0·949-0·985 [346 true negatives]) or immune trypanolysis (sensitivity 0·985, 0·947-0·996 [132 true positives] and specificity 0·980, 0·960-0·990 [349 true negatives]). The diagnostic accuracy of HAT Sero-K-SeT is adequate for T b gambiense antibody detection in local health centres and could be used for active screening whenever a cold chain and electricity supply are unavailable and CATT/T b gambiense cannot be done. Copyright © 2014 Büscher et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.

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.

Malaria, a difficult diagnosis in a febrile patient with sub-microscopic parasitaemia and polyclonal lymphocyte activation outside the endemic region, in Brazil

PubMed Central

2013-01-01

A case of autochthonous Plasmodium vivax malaria with sub-microscopic parasitaemia and polyclonal B-cell activation (PBA) (as reflected by positive IgM and IgG serology for toxoplasmosis, cytomegalovirus, and antinuclear and rheumatoid factors) was diagnosed by polymerase chain reaction (PCR) after consecutive negative rapid diagnostic test results and blood films. The patient, a 44-year-old man from Rio de Janeiro state, Brazil, had visited the Atlantic Forest, a tourist, non-malaria-endemic area where no autochthonous cases of ’bromeliad malaria‘ has ever been described. The characteristic pattern of fever, associated with PBA, was the clue to malaria diagnosis, despite consecutive negative thick blood smears. The study highlights a need for changes in clinical and laboratory diagnostic approaches, namely the incorporation of PCR as part of the current routine malaria diagnostic methods in non-endemic areas. PMID:24200365

What's in a Label? Is Diagnosis the Start or the End of Clinical Reasoning?

PubMed

Ilgen, Jonathan S; Eva, Kevin W; Regehr, Glenn

2016-04-01

Diagnostic reasoning has received substantial attention in the literature, yet what we mean by "diagnosis" may vary. Diagnosis can align with assignment of a "label," where a constellation of signs, symptoms, and test results is unified into a solution at a single point in time. This "diagnostic labeling" conceptualization is embodied in our case-based learning curricula, published case reports, and research studies, all of which treat diagnostic accuracy as the primary outcome. However, this conceptualization may oversimplify the richly iterative and evolutionary nature of clinical reasoning in many settings. Diagnosis can also represent a process of guiding one's thoughts by "making meaning" from data that are intrinsically dynamic, experienced idiosyncratically, negotiated among team members, and rich with opportunities for exploration. Thus, there are two complementary constructions of diagnosis: 1) the correct solution resulting from a diagnostic reasoning process, and 2) a dynamic aid to an ongoing clinical reasoning process. This article discusses the importance of recognizing these two conceptualizations of "diagnosis," outlines the unintended consequences of emphasizing diagnostic labeling as the primary goal of clinical reasoning, and suggests how framing diagnosis as an ongoing process of meaning-making might change how we think about teaching and assessing clinical reasoning.

HPV Virus Transcriptional Status Assessment in a Case of Sinonasal Carcinoma.

PubMed

Ilardi, Gennaro; Russo, Daniela; Varricchio, Silvia; Salzano, Giovanni; Dell'Aversana Orabona, Giovanni; Napolitano, Virginia; Di Crescenzo, Rosa Maria; Borzillo, Alessandra; Martino, Francesco; Merolla, Francesco; Mascolo, Massimo; Staibano, Stefania

2018-03-16

Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, there are no definitive, reliable and cost-effective, diagnostic tests approved by the FDA for the unequivocal determination of HPV status in head and neck cancers. We followed an exhaustive algorithm to correctly test HPV infection, including a sequential approach with p16INK4a IHC, viral DNA genotyping and in situ hybridization for E6/E7 mRNA. Here, we report a case of sinonasal carcinoma with discordant results using HPV test assays. The tumor we describe showed an irregular immunoreactivity for p16INK4a, and it tested positive for HPV DNA; nevertheless, it was negative for HR-HPV mRNA. We discuss the possible meaning of this discrepancy. It would be advisable to test HPV transcriptional status of sinonasal carcinoma on a diagnostic routine basis, not only by p16INK4a IHC assay, but also by HPV DNA genotyping and HR-HPV mRNA assessment.

Diagnostic Yield of 2 Strategies for Adult Celiac Disease Identification in Primary Care.

PubMed

Scoglio, Riccardo; Trifirò, Gianluca; Sandullo, Antonino; Marangio, Giovanni; D'Agate, Cinzia; Costa, Stefano; Pellegrino, Salvatore; Alibrandi, Angela; Aiello, Andrea; Currò, Giovanni; Cuzzupè, Chiara; Comisi, Fabrizio; Amato, Salvatore; Conti Nibali, Roberto; Oteri, Sergio; Magazzu, Giuseppe; Carroccio, Antonio

2017-12-18

To compare the diagnostic yield and cost-consequences of 2 strategies, screening regardless of symptoms versus case finding (CF), using a point-of-care test (POCT), for the detection of celiac disease (CD) in primary care, to bridge the diagnostic gap of CD in adults. All subjects under 75 years of age who consecutively went to their general practitioners' offices were offered POCT for anti-transglutaminase immunoglobulin A antibodies. The POCT was performed on all subjects who agreed, and then a systematic search for symptoms or conditions associated with higher risk for CD was performed, immediately after the test but before knowing the test results. The 2 resulting groups were: (a) POCT positive and (b) symptomatic subject at CF. Subjects were defined as symptomatic at CF in the presence of 1 or more symptoms. All POCT-positive or symptomatic subjects at CF were referred to the CD Centers for confirmation of CD. Data on resource consumption were gathered from patients' charts. Cost of examinations, and diagnostic and laboratory tests were estimated with regional outpatient tariffs (Sicily), and a price of &OV0556;2.5 was used for each POCT. Of a total of 2197 subjects who agreed to participate in the study, 36 (1.6%) and 671 (30.5%) were POCT positive and symptomatic at CF, respectively. The yield from the screening and CF was 5 new celiac patients. The total cost and mean cost for each new CD case were &OV0556;7497.35 and &OV0556;1499.47 for the POCT screening strategy, and &OV0556;9855.14 and &OV0556;1971.03 for the CF strategy, respectively. Assuming consecutive use of both strategies, performing POCT only in symptomatic subjects at CF, the calculated yield would be 4 new diagnoses with a total cost of &OV0556;2345.84 and a mean cost of &OV0556;586.46 for each newly diagnosed patient. Only 1 patient was celiac despite a negative POCT. Testing symptomatic subjects at CF only by POCT seems the most cost-effective strategy to bridge the diagnostic gap of adult CD in primary care.

Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review

PubMed Central

Prasad, Namrata; Murdoch, David R.; Reyburn, Hugh; Crump, John A.

2015-01-01

Background With apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries. Methods and Findings We conducted a systematic review of studies conducted in low-and-middle income countries 1980–2013 that prospectively assessed consecutive febrile patients admitted to hospital using rigorous laboratory-based case definitions. We found 45 eligible studies describing 54,578 patients; 9,771 (17.9%) had a positive result for ≥1 pathogen meeting diagnostic criteria. There were no eligible studies identified from Southern and Middle Africa, Eastern Asia, Oceania, Latin American and Caribbean regions, and the European region. The median (range) number of diagnostic tests meeting our confirmed laboratory case definitions was 2 (1 to 11) per study. Of diagnostic tests, 5,052 (10.3%) of 49,143 had confirmed bacterial or fungal bloodstream infection; 709 (3.8%) of 18,142 had bacterial zoonosis; 3,488 (28.5%) of 12,245 had malaria; and 1,804 (17.4%) of 10,389 had a viral infection. Conclusions We demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens. High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed. PMID:26126200

Development of principles of two-cascaded laser speckle-microscopy with implication to high-precision express diagnostics of chlamydial infection

NASA Astrophysics Data System (ADS)

Ulianova, Onega; Moiseeva, Yulia; Filonova, Nadezhda; Subbotina, Irina; Zaitsev, Sergey; Saltykov, Yury; Polyanina, Tatiana; Lyapina, Anna; Ulyanov, Sergey; Larionova, Olga; Utz, Sergey; Feodorova, Valentina

2018-04-01

Principles of two-cascaded laser speckle-microscopy prospect for application to express diagnostics of chlamydial infection are developed. Prototype of two-cascaded speckle-microscope is designed and tested. Specific case of illumination of bacterial cells by dynamic speckles is considered. Express method of detection of epithelial cells, containing defects, which are caused by Chlamydia trachomatis bacteria, is suggested. Results of improved recognition of C. trachomatis bacteria are discussed.

A Case Report of Salmonella muenchen Enteritis Causing Rhabdomyolysis and Myocarditis in a Previously Healthy 26-Year-Old Man.

PubMed

Chapple, Will; Martell, Jon; Wilson, Joy S; Matsuura, Don T

2017-04-01

This case report examines an unusual presentation of a non-typhoidal Salmonella serovar with limited prevalence in the literature. This is the first case report to associate specifically the Salmonella muenchen serovar with rhabdomyolysis and myocarditis. This case report reviews the diagnostic criteria for myocarditis and explores the diagnostic dilemma of troponin elevation in the setting of rhabdomyolysis. It demonstrates that Salmonella muenchen has the ability to present in a broad range of individuals with complications extending beyond classical gastrointestinal symptoms. This report also concludes that diagnosis of the many possible complications from non-typhoidal Salmonella infections can be difficult due to patient comorbidities, variability in the severity of the illnesses, laboratory test limitations, and imaging limitations. When a patient presents with elevated troponins in the setting of rhabdomyolysis a careful workup should be done to evaluate for ischemic causes, myocarditis, or false elevation secondary to rhabdomyolysis.

[Thalassaemia diagnostics].

PubMed

Kusters, Elske; Kerkhoffs, Jean-Louis H; van Rossum, André P

2014-01-01

The thalassaemias are characterised by quantitative aberrations in the production of the globin chains that make up haemoglobin, and are a subgroup of the haemoglobinopathies. In this LabQuiz we show how thalassaemia carrier status can be indicated in the results of regular laboratory tests, and discuss the laboratory diagnostics that can confirm or rule out thalassaemia. In these two cases we will present a man of Moroccan descent, and two brothers of Filipino descent, all with anaemia and microcytosis. We show it is possible to differentiate between iron-deficiency anaemia and thalassaemia carrier status on the basis of a complete blood count and measurement of ferritin levels, and which laboratory diagnostics can be subsequently performed in order to confirm a suspicion of thalassaemia. The background section discusses the properties and pitfalls of routine laboratory diagnostics for the thalassaemias, and thalassaemia diagnostics in the Dutch newborn screening programme.

Decision support in psychiatry – a comparison between the diagnostic outcomes using a computerized decision support system versus manual diagnosis

PubMed Central

Bergman, Lars G; Fors, Uno GH

2008-01-01

Background Correct diagnosis in psychiatry may be improved by novel diagnostic procedures. Computerized Decision Support Systems (CDSS) are suggested to be able to improve diagnostic procedures, but some studies indicate possible problems. Therefore, it could be important to investigate CDSS systems with regard to their feasibility to improve diagnostic procedures as well as to save time. Methods This study was undertaken to compare the traditional 'paper and pencil' diagnostic method SCID1 with the computer-aided diagnostic system CB-SCID1 to ascertain processing time and accuracy of diagnoses suggested. 63 clinicians volunteered to participate in the study and to solve two paper-based cases using either a CDSS or manually. Results No major difference between paper and pencil and computer-supported diagnosis was found. Where a difference was found it was in favour of paper and pencil. For example, a significantly shorter time was found for paper and pencil for the difficult case, as compared to computer support. A significantly higher number of correct diagnoses were found in the diffilt case for the diagnosis 'Depression' using the paper and pencil method. Although a majority of the clinicians found the computer method supportive and easy to use, it took a longer time and yielded fewer correct diagnoses than with paper and pencil. Conclusion This study could not detect any major difference in diagnostic outcome between traditional paper and pencil methods and computer support for psychiatric diagnosis. Where there were significant differences, traditional paper and pencil methods were better than the tested CDSS and thus we conclude that CDSS for diagnostic procedures may interfere with diagnosis accuracy. A limitation was that most clinicians had not previously used the CDSS system under study. The results of this study, however, confirm that CDSS development for diagnostic purposes in psychiatry has much to deal with before it can be used for routine clinical purposes. PMID:18261222

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.

Point-of-care diagnostics: extending the laboratory network to reach the last mile.

PubMed

Drain, Paul K; Rousseau, Christine

2017-03-01

More point-of-care (POC) diagnostic tests are becoming available for HIV diagnosis and treatment in resource-limited settings. These novel technologies have the potential to foster decentralized HIV care and treatment for the benefit of clinical laboratories, HIV clinics, and HIV-infected patients. There continue to be many business, technological, and operational challenges that limit product development and regulatory approval, which limits products available for the required operational and cost-effectiveness studies and delays policy adoption and implementation. Although the rapid HIV diagnostic test has been widely successful, the pathways for POC CD4 cell count and HIV viral load assay analyzers have been more challenging. We describe significant hurdles for product development, approval, and implementation, which include the business case, technical development, clinical impact, and integrating laboratory and clinical networks. The objective of this review is to highlight the obstacles for developing and implementing appropriate strategies for POC HIV testing assays to improve the clinical services for HIV-infected patients in resource-limited settings.

A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence.

PubMed

Nikoloulopoulos, Aristidis K

2017-10-01

A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that it is superior to the standard generalized linear mixed model in this context. Here, we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate generalized linear mixed model as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analyzing the data of two published meta-analyses. Our study suggests that there can be an improvement on trivariate generalized linear mixed model in fit to data and makes the argument for moving to vine copula random effects models especially because of their richness, including reflection asymmetric tail dependence, and computational feasibility despite their three dimensionality.

Compression evaluation of surgery video recordings retaining diagnostic credibility (compression evaluation of surgery video)

NASA Astrophysics Data System (ADS)

Duplaga, M.; Leszczuk, M. I.; Papir, Z.; Przelaskowski, A.

2008-12-01

Wider dissemination of medical digital video libraries is affected by two correlated factors, resource effective content compression that directly influences its diagnostic credibility. It has been proved that it is possible to meet these contradictory requirements halfway for long-lasting and low motion surgery recordings at compression ratios close to 100 (bronchoscopic procedures were a case study investigated). As the main supporting assumption, it has been accepted that the content can be compressed as far as clinicians are not able to sense a loss of video diagnostic fidelity (a visually lossless compression). Different market codecs were inspected by means of the combined subjective and objective tests toward their usability in medical video libraries. Subjective tests involved a panel of clinicians who had to classify compressed bronchoscopic video content according to its quality under the bubble sort algorithm. For objective tests, two metrics (hybrid vector measure and hosaka Plots) were calculated frame by frame and averaged over a whole sequence.

Generalized reactions during skin testing with clindamycin in drug hypersensitivity: a report of 3 cases and review of the literature.

PubMed

Papakonstantinou, Eleni; Müller, Sabine; Röhrbein, Jan H; Wieczorek, Dorothea; Kapp, Alexander; Jakob, Thilo; Wedi, Bettina

2018-04-01

The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described. To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature. Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients. Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnostic, therapeutic and economic consequences of a positive urinary antigen test for Legionella spp. in patients admitted with community-acquired pneumonia: a 7-year retrospective evaluation.

PubMed

Engel, M F; van Manen, L; Hoepelman, A I M; Thijsen, S; Oosterheert, J J

2013-09-01

A positive urinary antigen test for Legionella spp. (Legionella urinary antigen test; LUAT) allows an early switch from empiric to targeted treatment (TT) in hospitalised, community-acquired pneumonia (CAP) patients. We aimed to evaluate the diagnostic, therapeutic and economic consequences of this frequently used test 7 years after its implementation. We retrospectively evaluated LUATs performed between 2005 and 2011 in two teaching hospitals. All tests performed in hospitalised CAP patients were used in the economic evaluation and positive tests were included in the treatment evaluation. Data on patient characteristics, admission and outcome were retrieved from the patients' files. The number of days gained by making a rapid aetiological diagnosis, the number of days TT could be provided and their costs were calculated. Of 4485 LUATs, 2504 (56%) were performed for CAP including 55 (1%) positive tests (€1041/positive test). In 26 (60%) of the 43 included positive tests, LUAT was the only test showing Legionella spp. Subsequently, earlier TT was possible in the remaining cases during 209 cumulative admission days (€274/TT day). LUAT led to detection of Legionella spp. 13 days earlier per case (€203/day) as compared with culture/serology alone. Timely LUAT use in accordance with current guidelines allows early detection and treatment of CAP caused by Legionella spp. at considerable expense.

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India.

PubMed

Sachdeva, Kuldeep Singh; Raizada, Neeraj; Sreenivas, Achuthan; Van't Hoog, Anna H; van den Hof, Susan; Dewan, Puneet K; Thakur, Rahul; Gupta, R S; Kulsange, Shubhangi; Vadera, Bhavin; Babre, Ameet; Gray, Christen; Parmar, Malik; Ghedia, Mayank; Ramachandran, Ranjani; Alavadi, Umesh; Arinaminpathy, Nimalan; Denkinger, Claudia; Boehme, Catharina; Paramasivan, C N

2015-01-01

Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold.

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

PubMed Central

Sachdeva, Kuldeep Singh; Raizada, Neeraj; Sreenivas, Achuthan; van't Hoog, Anna H.; van den Hof, Susan; Dewan, Puneet K.; Thakur, Rahul; Gupta, R. S.; Kulsange, Shubhangi; Vadera, Bhavin; Babre, Ameet; Gray, Christen; Parmar, Malik; Ghedia, Mayank; Ramachandran, Ranjani; Alavadi, Umesh; Arinaminpathy, Nimalan; Denkinger, Claudia; Boehme, Catharina; Paramasivan, C. N.

2015-01-01

Background Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. Methods This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. Results In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Conclusion Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold. PMID:25996389

Elevated human chorionic gonadotropin levels in patients with chronic kidney disease: Case series and review of literature.

PubMed

Soni, S; Menon, M C; Bhaskaran, M; Jhaveri, K D; Molmenti, E; Muoio, V

2013-11-01

Women are often subjected to serum human chorionic gonadotropin (HCG) testing prior to diagnostic and therapeutic interventions. A positive result leads to further testing to rule out pregnancy and avoid possible fetal teratogenicity. The impact of chronic kidney disease (CKD) on HCG testing has not been studied. We report a series of 5 women out of 62 with CKD, who had a positive HCG test on routine pre-transplant screening at a single transplant center. We analyzed their case records retrospectively. Despite aggressive investigation, their elevated HCG levels remained unexplained. The positive test contributed to delays in transplantation and increased overall cost of treatment.

Follicular adenoma in ectopic thyroid. A case-report.

PubMed

Consalvo, Vincenzo; Barbieri, Gerarda; Rossetti, Amalia Rosaria Rita; Romano, Mafalda; Contieri, Rosaria; Tramontano, Salvatore; Rescigno, Carmela; Infranzi, Massimo; Lombardi, Domenico

2017-01-01

The term ectopic thyroid refers to the presence of thyroid tissue located far from its usual anatomic placement and with no vascular connection to the main gland. The presence of swelling in atypical locations is diagnostically differentiated from other pathologies like pleomorphic adenoma or carcinoma, inflammatory lesions like sialadenitis, neurogenic tumors, paraganglioma, fibrolipoma and lymphadenopaties of diverse etiologies. Here we present the case of a submandibular ectopic thyroid in a 67year old woman. She came to our attention for a left submandibular swelling. The anamnesis did not show related pathologies, as well as blood tests. Diagnostic image studies and a FNAC were performed. The mass was surgically removed and histopatology showed a follicular adenoma in the contest of the capsulated lesion. It is important to not underestimate these types of lesions and procede with hematochemical, instrumental tests and above all surgery that can eliminate any diagnostic uncertainty and on the whole be therapeutic. It should not be forgotten that ectopic thyroid tissue can be a site for adenoma or papillary carcinoma and thus any watch and wait strategy should be avoided. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Potential impact of amyloid imaging on diagnosis and intended management in patients with progressive cognitive decline.

PubMed

Grundman, Michael; Pontecorvo, Michael J; Salloway, Stephen P; Doraiswamy, P Murali; Fleisher, Adam S; Sadowsky, Carl H; Nair, Anil K; Siderowf, Andrew; Lu, Ming; Arora, Anupa K; Agbulos, Abigail; Flitter, Matthew L; Krautkramer, Michael J; Sarsour, Khaled; Skovronsky, Daniel M; Mintun, Mark A

2013-01-01

Florbetapir F18 has been approved by the Food and Drug Administration for in vivo assessment of amyloid pathology in patients undergoing evaluation for Alzheimer disease (AD). The aim of this study was to determine the impact of amyloid imaging on the diagnoses and management of patients undergoing evaluation for cognitive decline. Patients were recruited to participate at 19 clinical sites. The site physician provided a provisional diagnosis, an estimate of their diagnostic confidence, and their plan for diagnostic evaluation and management both before and after receiving the results from amyloid imaging with florbetapir F18. Analyses compared the frequency of AD and non-AD diagnoses, plans for ancillary testing, and intended patient management before and after florbetapir imaging. A total of 229 patients participated in the trial (113 amyloid positive, 116 amyloid negative). After receiving the results of the florbetapir scan, diagnosis changed in 125/229, or 54.6% [95% confidence intervals (CI), 48.1%-60.9%], of cases, and diagnostic confidence increased by an average of 21.6% (95% CI, 18.3%-24.8%). A total of 199/229 or 86.9% (95% CI, 81.9%-90.7%) of cases had at least 1 change in their management plan. Intended cholinesterase inhibitor or memantine treatment increased by 17.7% (95% CI, 11.8%-25.8%) of all cases with positive scans and decreased by 23.3% (95% CI, 16.5%-31.8%) of all those with negative scans. Among subjects who had not yet undergone a completed work up, planned brain structural imaging (computed tomographic/magnetic resonance imaging) decreased by 24.4% (95% CI, 17.5%-32.8%) and planned neuropsychological testing decreased by 32.8% (95% CI, 25.0%-41.6%). In summary, amyloid imaging results altered physician's diagnostic thinking, intended testing, and management of patients undergoing evaluation for cognitive decline.

[SPECT in diagnostic services and medical certification: a case report of depression in head injury].

PubMed

Banaś, Anna

2003-01-01

A case of severe organic affective disorder after head trauma with loss of consciousness is presented. While CT in this case was normal, SPECT brain perfusion imaging showed hipoperfusion in the right frontal lobe and the left temporal-parietal region. The psychologic tests: Benton, Bender, MMPI confirmed changes in CNS as well. These findings help to explain the severity and chronicity of disorders and medical certification.

Early diagnosis in glaucoma.

PubMed

Garway-Heath, David F

2008-01-01

This chapter reviews the evidence for the clinical application of vision function tests and imaging devices to identify early glaucoma, and sets out a scheme for the appropriate use and interpretation of test results in screening/case-finding and clinic settings. In early glaucoma, signs may be equivocal and the diagnosis is often uncertain. Either structural damage or vision function loss may be the first sign of glaucoma; neither one is consistently apparent before the other. Quantitative tests of visual function and measurements of optic-nerve head and retinal nerve fiber layer anatomy are useful to either raise or lower the probability that glaucoma is present. The posttest probability for glaucoma may be calculated from the pretest probability and the likelihood ratio of the diagnostic criterion, and the output of several diagnostic devices may be combined to achieve a final probability. However, clinicians need to understand how these diagnostic devices make their measurements, so that the validity of each test result can be adequately assessed. Only then should the result be used, together with the patient history and clinical examination, to derive a diagnosis.

Still's Disease in a Pediatric Patient after Liver Transplantation.

PubMed

Meza, Juan-Carlos; Muñoz-Buitrón, Evelyn; Bonilla-Abadía, Fabio; Cañas, Carlos Alberto; Tobón, Gabriel J

2013-01-01

Still's disease (SD) is a multisystemic inflammatory disease characterized by persistent arthritis and in many cases with fever of unknown origin. Diagnosis of SD is challenging because of nonspecific characteristics and especially in the case of a patient with solid organ transplantation and immunosuppressive therapy where multiple causes of fever are possible. There is no diagnostic test for SD, even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, and useful imaging studies for the diagnosis or followup of SD have not been developed. We report the case of a 9-year-old child who presented with high grade fever associated with joint pain after a history of liver transplantation and immunosuppressive therapy. Laboratory tests showed increased acute phase reactants, elevated ferritin, and leukocytosis. An 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed identifying abnormal hypermetabolic areas localized in spleen, transplanted liver, and bone marrow secondary to inflammatory process. All infectious, autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed and a steroid-based regimen was initiated with adequate response and no evidence of recurrence. To our knowledge this is the first case of SD following a solid organ transplant.

Normal pressure hydrocephalus: Diagnostic and predictive evaluationon

PubMed Central

Damasceno, Benito Pereira

2009-01-01

In typical cases, normal pressure hydrocephalus (NPH) manifests itself with the triad of gait disturbance, which begins first, followed by mental deterioration and urinary incontinence associated with ventriculomegaly (on CT or MRI) and normal cerebrospinal fluid (CSF) pressure. These cases present minor diagnostic difficulties and are the most likely to improve after shunting. Problems arise when NPH shows atypical or incomplete clinical manifestations (25–50% of cases) or is mimicked by other diseases. In this scenario, other complementary tests have to be used, preferentially those that can best predict surgical outcome. Radionuclide cisternography, intracranial pressure monitoring (ICP) and lumbar infusion tests can show CSF dynamics malfunction, but none are able to confirm whether the patient will benefit from surgery. The CSF tap test (CSF-TT) is the only procedure that can temporarily simulate the effect of definitive shunt. Since the one tap CSF-TT has low sensitivity, it cannot be used to exclude patients from surgery. In such cases, we have to resort to a repeated CSF-TT (RTT) or continuous lumbar external drainage (LED). The most reliable prediction would be achieved if RTT or LED proved positive, in addition to the occurrence of B-waves during more than 50% of ICP recording time. This review was based on a PubMed literature search from 1966 to date. It focuses on clinical presentation, neuroimaging, complementary prognostic tests, and differential diagnosis of NPH, particularly on the problem of selecting appropriate candidates for shunt. PMID:29213603

Human rabies in India: an audit from a rabies diagnostic laboratory.

PubMed

Mani, Reeta Subramaniam; Anand, Ashwini Manoor; Madhusudana, Shampur Narayan

2016-04-01

Rabies, an acute progressive encephalomyelitis, continues to be a serious public health problem in India and many other countries in Asia and Africa. The low level of commitment to rabies control is partly attributable to challenges in laboratory diagnosis and lack of adequate surveillance to indicate the disease burden. A laboratory audit of human rabies cases was undertaken to disseminate information on the clinical, demographic, prophylactic and most importantly the laboratory diagnostic aspects of rabies. A retrospective analysis of all clinically suspected human rabies cases, whose samples were received at a rabies diagnostic laboratory in South India in the last 3 years, was performed. Clinical and demographic details of patients were obtained. The clinical samples included cerebrospinal fluid (CSF), serum, saliva and nuchal skin biopsy collected antemortem, and brain tissue obtained post-mortem. Various laboratory tests were performed for diagnosis. Clinical samples from 128 patients with suspected rabies, from 11 states in India, were received for diagnostic confirmation. About 94% of the victims reported dog-bites, more than a third of them were children and most of the victims did not receive adequate post-exposure prophylaxis. Antemortem confirmation of rabies by a combination of laboratory diagnostic assays (detection of viral RNA in CSF, skin and saliva, and neutralising antibodies in CSF) could be achieved in 40.6% cases. Increasing awareness about adequate post-exposure prophylaxis, additional rabies diagnostic facilities, and enhanced human and animal rabies surveillance to indicate the true disease burden are essential to control this fatal disease. © 2016 John Wiley & Sons Ltd.

Verification and classification bias interactions in diagnostic test accuracy studies for fine-needle aspiration biopsy.

PubMed

Schmidt, Robert L; Walker, Brandon S; Cohen, Michael B

2015-03-01

Reliable estimates of accuracy are important for any diagnostic test. Diagnostic accuracy studies are subject to unique sources of bias. Verification bias and classification bias are 2 sources of bias that commonly occur in diagnostic accuracy studies. Statistical methods are available to estimate the impact of these sources of bias when they occur alone. The impact of interactions when these types of bias occur together has not been investigated. We developed mathematical relationships to show the combined effect of verification bias and classification bias. A wide range of case scenarios were generated to assess the impact of bias components and interactions on total bias. Interactions between verification bias and classification bias caused overestimation of sensitivity and underestimation of specificity. Interactions had more effect on sensitivity than specificity. Sensitivity was overestimated by at least 7% in approximately 6% of the tested scenarios. Specificity was underestimated by at least 7% in less than 0.1% of the scenarios. Interactions between verification bias and classification bias create distortions in accuracy estimates that are greater than would be predicted from each source of bias acting independently. © 2014 American Cancer Society.

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.

Impact of clinical awareness and diagnostic tests on the underdiagnosis of Clostridium difficile infection.

PubMed

Alcalá, L; Reigadas, E; Marín, M; Martín, A; Catalán, P; Bouza, E

2015-08-01

A multicenter study of Clostridium difficile infection (CDI) performed during 2008 in Spain revealed that two of every three episodes went undiagnosed or were misdiagnosed owing to nonsensitive diagnostic tests or lack of clinical suspicion and request. Since then, efforts have been made to improve the diagnostic tests used by laboratories and to increase the awareness of this disease among both clinicians and microbiologists. Our objective was to evaluate the impact of these efforts by assessing the current magnitude of underdiagnosis of CDI in Spain using two point-prevalence studies performed on one day each in January and July of 2013. A total of 111 Spanish laboratories selected all unformed stool specimens received for microbiological diagnosis on these days, and toxigenic culture was performed at a central reference laboratory. Toxigenic isolates were characterized both pheno- and genotypically. The reference laboratory detected 103 episodes of CDI in patients aged 2 years or more. Half (50.5 %) of the episodes were not diagnosed in the participating laboratories, owing to insensitive diagnostic tests (15.5 %) or the lack of clinical suspicion and request (35.0 %). The main ribotypes were 014, 078/126, 001/072, and 106. Ribotype 027 caused 2.9 % of all cases. Despite all the interventions undertaken, CDI remains a highly neglected disease because of the lack of sensitive diagnostic tests in some institutions and, especially, the absence of clinical suspicion, mainly in patients with community-associated CDI. Toxigenic C. difficile should be routinely sought in unformed stools sent for microbiological diagnosis, regardless of their origin.

[Oral allergy syndrome in patients with pollen allergy].

PubMed

Chimielewska, Anna; Mazur, Marcel; Sacha, Malgorzata; Myszkowska, Dorota; Dyga, Wojciech; Obtułowicz, Krystyna; Czarnobilska, Ewa

2013-01-01

The symptoms of pollen allergy in the European population occur in a period of increased pollen precipitation, and take the form of allergic rhinitis and conjunctivitis, bronchial asthma, contact urticaria, and food allergy. Diagnosis in addition to medical history, takes into account the positive results of skin tests and elevated allergen-specific IgE antibodies (specific IgE) in serum. These studies are considered to be objective diagnostic tests confirming the diagnosis of pollen allergy. Not in every case there is a correspondence of symptoms and results of diagnostic tests, which puts into question the accuracy of the diagnosis of pollen allergy. The aim of this study was to test the characteristics of patients with oral allergy syndrome on the background of all patients with pollen allergy and evaluation of the diagnostic value of history, skin tests and specific IgE levels in the diagnosis of patients with pollen allergy and oral allergy syndrome. A retrospective analysis of the cases of 85 patients with a diagnosis of pollen allergy and the 30 patients with OAS was performed. In our study the most common sensitizing allergen in patients with OAS was birch pollen, while patients showing no symptoms of OAS were equally sensitive to timothy and birch pollen. The main food responsible for the presence of the OAS in the mechanism of cross-allergy to pollen was an apple. Among patients with OAS we did not show significantly higher incidence of polyvalent allergies. It was shown, however, that there is a tendency that the maximum concentration of allergen-specific IgE causing clinically significant symptoms, ie in line with the pollen season, is higher in the OAS patients than in the absence of OAS. Further research is needed using new diagnostic methods, which would predict future symptoms after eating certain foods in particularly endangered patients with pollen allergy.

Measurement Issues: Screening and diagnostic instruments for autism spectrum disorders – lessons from research and practice

PubMed Central

Charman, Tony; Gotham, Katherine

2012-01-01

Background and Scope Significant progress has been made over the past two decades in the development of screening and diagnostic instruments for autism spectrum disorders (ASD). This article reviews this progress, including recent innovations, focussing on those instruments for which the strongest research data on validity exists, and then turns to addressing issues arising from their use in clinical settings. Findings Research studies have evaluated the ability of screens to prospectively identify cases of ASD in population-based and clinically-referred samples, as well as the accuracy of diagnostic instruments to map onto ‘gold standard’ clinical best estimate diagnosis. However, extension of the findings to clinical services must be done with caution, with a full understanding that instrument properties are sample-specific. Furthermore, we are limited by the lack of a true test for ASD, which remains a behaviourally-defined disorder. In addition screening and diagnostic instruments help clinicians least in the cases where they are most in want of direction, since their accuracy will always be lower for marginal cases. Conclusion Instruments help clinicians to collect detailed, structured information and increase accuracy and reliability of referral for in-depth assessment and recommendations for support, but further research is needed to refine their effective use in clinical settings. PMID:23539140

Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

PubMed

Floridia, Marco; Ciccacci, Fausto; Andreotti, Mauro; Hassane, Archa; Sidumo, Zita; Magid, Nurja A; Sotomane, Horacio; David, Muhlavasse; Mutemba, Elsa; Cebola, Junia; Mugunhe, Remigio Josè; Riccardi, Fabio; Marazzi, Maria Cristina; Giuliano, Marina; Palombi, Leonardo; Mancinelli, Sandro

2017-11-13

Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/μL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation in very advanced HIV/tuberculosis disease. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Hypertensive emergency masquerading as phaeochromocytoma: a report of two cases.

PubMed

Hulkower, Raphael; Gubbi, Sriram; Meholli, Mimoza; Schubart, Ulrich

2017-08-07

We report two cases of patients who were hospitalised for hypertensive emergency. In both cases, laboratory testing during admission revealed elevated normetanephrines in the range of 4-5 times the upper limit of normal using liquid chromatography with mass spectrometry. Imaging studies did not localise any phaeochromocytoma or paraganglioma (PPGL). Repeat biochemical testing after discharge was within normal limits in both cases. These observations suggest that hypertensive emergency should be recognised as a potential cause of 'false-positive' laboratory findings in the diagnostic assessment for PPGL. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Molecular Diagnostics in Pathology: Time for a Next-Generation Pathologist?

PubMed

Fassan, Matteo

2018-03-01

- Comprehensive molecular investigations of mainstream carcinogenic processes have led to the use of effective molecular targeted agents in most cases of solid tumors in clinical settings. - To update readers regarding the evolving role of the pathologist in the therapeutic decision-making process and the introduction of next-generation technologies into pathology practice. - Current literature on the topic, primarily sourced from the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database, were reviewed. - Adequate evaluation of cytologic-based and tissue-based predictive diagnostic biomarkers largely depends on both proper pathologic characterization and customized processing of biospecimens. Moreover, increased requests for molecular testing have paralleled the recent, sharp decrease in tumor material to be analyzed-material that currently comprises cytology specimens or, at minimum, small biopsies in most cases of metastatic/advanced disease. Traditional diagnostic pathology has been completely revolutionized by the introduction of next-generation technologies, which provide multigene, targeted mutational profiling, even in the most complex of clinical cases. Combining traditional and molecular knowledge, pathologists integrate the morphological, clinical, and molecular dimensions of a disease, leading to a proper diagnosis and, therefore, the most-appropriate tailored therapy.

[Evaluation of the toxoplasmosis seroprevalence in pregnant women and creating a diagnostic algorithm].

PubMed

Mumcuoglu, Ipek; Toyran, Alparslan; Cetin, Feyza; Coskun, Feride Alaca; Baran, Irmak; Aksu, Neriman; Aksoy, Altan

2014-04-01

Toxoplasma gondii, an obligatory intracellular protozoon is widely distributed around the world and can infect all mammals and birds. While acquired toxoplasmosis is usually asymptomatic in healthy subjects, acute infection during pregnancy may lead to abortion, stillbirth, fetal neurological and ocular damages. For the prevention of congenital toxoplasmosis it is recommended that a screening programme and a diagnostic algorithm in pregnant women should be implemented while considering the cost effectiveness. Thus, it is necessary to determine the seroprevalence of toxoplasmosis in pregnant women and the actual risk of T.gondii transmission during pregnancy in a certain area. The aims of this study were to detect the T.gondii seropositivity in the pregnant women admitted to our hospital and to create a diagnostic algorithm in order to solve the problems arising from interpretation of the serological test results. A total of 6140 women aged 15-49 years who were admitted to our hospital between April 1st, 2010 to July 31st, 2013, were evaluated retrospectively. In the serum samples, T.gondii IgM, IgG and IgG avidity tests were performed by VIDAS automated analyzer using TOXO IgM, TOXO IgG II and TOXO IgG avidity kits (bioMerieux, France). It was noted that, both T.gondii IgM and IgG tests were requested from 4758 (77.5%) of the pregnant women, while only IgM test from 1382 (22.5%) cases. Sole IgM positivity was found as 0.2% (11/6140), IgG as 26.4% (1278/4758) and both IgM + IgG as 0.9% (44/4758). T.gondii IgG avidity tests were requested from 12 of 44 women who were found both IgM and IgG positive and eight of them revealed high avidity and four low avidity. Avidity test was ordered for the 91 (7.1%) of 1278 sole IgG positive cases and four of them were found to have low avidity. IgG avidity test was ordered for 554 (16.2%) of IgM and/or IgG negative subjects, however, the test was not performed according to rejection criteria of the laboratory. It was noticed that no re-testing was requested for none of the seronegative cases (3428/4758; 72%) during their follow-up. In our study, total Toxoplasma seropositivity rate among pregnant women was detected as 28% (1330/4758), showing statistically significant increase (p< 0.05) with age. There was no significant difference (p> 0.05) in the seropositivity rate between the years (2010-2013). Following the evaluation of the test orders, the problems related to test orders and interpretation of the test results were determined and a diagnostic algorithm to be used in our hospital, was established to minimize such problems in toxoplasma serology. It was concluded that a diagnostic algorithm related to toxoplasmosis serology should be implemented for the appropriate evaluation of the risk of acute toxoplasmosis during pregnancy. Such an approach is necessary to support the clinical diagnosis and to minimize the anxiety in pregnant women about congenital toxoplasmosis.

ALK immunohistochemistry for ALK gene rearrangement screening in non-small cell lung cancer: a systematic review and meta-analysis.

PubMed

Pyo, Jung-Soo; Kang, Guhyun; Sohn, Jin Hee

2016-12-23

The aim of this study was to investigate the diagnostic accuracy of anaplastic lymphoma kinase (ALK) immunohistochemistry (IHC) for ALK gene rearrangement in non-small cell lung cancer (NSCLC) through systematic review, meta-analysis and diagnostic test accuracy review. The current study included 11,806 NSCLC cases in 42 eligible studies. We performed concordance analyses between ALK IHC and fluorescence in situ hybridization (FISH). The diagnostic accuracy of ALK IHC was analyzed based on ALK IHC criteria and antibodies. The overall ALK IHC results were positive in 13.2%. The overall concordance rate between ALK IHC and FISH was 0.950 (95% confidence interval [CI], 0.927-0.966). In the ALK IHC-positive and negative groups, the concordance rates were 0.805 (95% CI 0.733-0.861) and 0.985 (95% CI 0.978-0.990), respectively. The ALK FISH-positive rates were 0.009 (95% CI 0.004-0.023), 0.378 (95% CI 0.217-0.572), 0.628 (95% CI 0.420-0.796) and 0.900 (95% CI 0.840-0.939) in the ALK IHC 0, 1+, 2+ and 3+ groups, respectively. In diagnostic test accuracy review for ALK IHC, the pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.91 (95% CI 0.90-0.91), respectively. The diagnostic odds ratio and the area under the curve on the summary receiver operating characteristic curve were 266.56 (95% CI 110.83-641.14) and 0.983, respectively. Our results suggested that ALK IHC equivocal (score 1+ and 2+) cases should not be considered as IHC-negative in screening for ALK gene rearrangement. Additional detailed criteria for ALK IHC equivocal cases are necessary to determine how to best apply this approach in daily practice.

Illness script development in pre-clinical education through case-based clinical reasoning training

PubMed Central

Keemink, Yvette; van Dijk, Savannah; ten Cate, Olle

2018-01-01

Objectives To assess illness script richness and maturity in preclinical students after they attended a specifically structured instructional format, i.e., a case based clinical reasoning (CBCR) course. Methods In a within-subject experimental design, medical students who had finished the CBCR course participated in an illness script experiment. In the first session, richness and maturity of students’ illness scripts for diseases discussed during the CBCR course were compared to illness script richness and maturity for similar diseases not included in the course. In the second session, diagnostic performance was tested, to test for differences between CBCR cases and non-CBCR cases. Scores on the CBCR course exam were related to both experimental outcomes. Results Thirty-two medical students participated. Illness script richness for CBCR diseases was almost 20% higher than for non-CBCR diseases, on average 14.47 (SD=3.25) versus 12.14 (SD=2.80), respectively (p<0.001). In addition, students provided more information on Enabling Conditions and less on Fault-related aspects of the disease. Diagnostic performance was better for the diseases discussed in the CBCR course, mean score 1.63 (SD=0.32) versus 1.15 (SD=0.29) for non-CBCR diseases (p<0.001). A significant correlation of exam results with recognition of CBCR cases was found (r=0.571, p<0.001), but not with illness script richness (r=–0.006, p=NS). Conclusions The CBCR-course fosters early development of clinical reasoning skills by increasing the illness script richness and diagnostic performance of pre-clinical students. However, these results are disease-specific and therefore we cannot conclude that students develop a more general clinical reasoning ability. PMID:29428911

Illness script development in pre-clinical education through case-based clinical reasoning training.

PubMed

Keemink, Yvette; Custers, Eugene J F M; van Dijk, Savannah; Ten Cate, Olle

2018-02-09

To assess illness script richness and maturity in preclinical students after they attended a specifically structured instructional format, i.e., a case based clinical reasoning (CBCR) course. In a within-subject experimental design, medical students who had finished the CBCR course participated in an illness script experiment. In the first session, richness and maturity of students' illness scripts for diseases discussed during the CBCR course were compared to illness script richness and maturity for similar diseases not included in the course. In the second session, diagnostic performance was tested, to test for differences between CBCR cases and non-CBCR cases. Scores on the CBCR course exam were related to both experimental outcomes. Thirty-two medical students participated. Illness script richness for CBCR diseases was almost 20% higher than for non-CBCR diseases, on average 14.47 (SD=3.25) versus 12.14 (SD=2.80), respectively (p<0.001). In addition, students provided more information on Enabling Conditions and less on Fault-related aspects of the disease. Diagnostic performance was better for the diseases discussed in the CBCR course, mean score 1.63 (SD=0.32) versus 1.15 (SD=0.29) for non-CBCR diseases (p<0.001). A significant correlation of exam results with recognition of CBCR cases was found (r=0.571, p<0.001), but not with illness script richness (r=-0.006, p=NS). The CBCR-course fosters early development of clinical reasoning skills by increasing the illness script richness and diagnostic performance of pre-clinical students. However, these results are disease-specific and therefore we cannot conclude that students develop a more general clinical reasoning ability.

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.

Improving prescribing practices with rapid diagnostic tests (RDTs): synthesis of 10 studies to explore reasons for variation in malaria RDT uptake and adherence

PubMed Central

Leurent, Baptiste; Baiden, Frank; Baltzell, Kimberly; Björkman, Anders; Bruxvoort, Katia; Clarke, Siân; DiLiberto, Deborah; Elfving, Kristina; Goodman, Catherine; Hopkins, Heidi; Lal, Sham; Liverani, Marco; Magnussen, Pascal; Mårtensson, Andreas; Mbacham, Wilfred; Mbonye, Anthony; Onwujekwe, Obinna; Roth Allen, Denise; Shakely, Delér; Staedke, Sarah; Vestergaard, Lasse S; Whitty, Christopher J M; Wiseman, Virginia; Chandler, Clare I R

2017-01-01

Objectives The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts. Design A comparative case study approach, analysing variation in outcomes across different settings. Setting Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case. Participants 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria. Interventions The interventions included different mRDT training packages, supervision, supplies and community sensitisation. Outcome measures Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial). Results Outcomes varied widely across cases: 12–100% mRDT uptake; 44–98% adherence to positive mRDTs; 27–100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs. Conclusions Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce. PMID:28274962

Predictive value of the "clue cells" investigation and the amine volatilization test in vaginal infections caused by Gardnerella vaginalis.

PubMed Central

Marquez-Davila, G; Martinez-Barreda, C E

1985-01-01

Although still controversial, an etiologic role of Gardnerella vaginalis is imputed in vaginitis. Besides isolation of the organism by culture, two alternative diagnostic procedures have been claimed to be useful: the investigation of "clue cells" in clinical specimens and the amine volatilization test or fishy odor perception in genital secretions. Herein we report on the findings of the simultaneous use of G. vaginalis isolation, the clue cell test and amine volatilization perception in specimens from 1,263 consecutive female patients referred to our clinic. Our results show that the simultaneous use of both alternative tests is very useful as a screening procedure. A negative result of both tests predicts a negative culture result in 99% of the cases. However, a positive result of either or both should be considered as an indication to proceed to culture and not as diagnostic of infection. PMID:3878365

Analysis of the diagnostic pathway and delay in patients with amyotrophic lateral sclerosis in the Valencian Community.

PubMed

Vázquez-Costa, J F; Martínez-Molina, M; Fernández-Polo, M; Fornés-Ferrer, V; Frasquet-Carrera, M; Sevilla-Mantecón, T

2018-06-11

Amyotrophic lateral sclerosis (ALS) is an insidious, clinically heterogeneous neurodegenerative disease associated with a diagnostic delay of approximately 12 months. No study conducted to date has analysed the diagnostic pathway in Spain. We gathered data on variables related to the diagnostic pathway and delay for patients diagnosed with ALS between October 2013 and July 2017. The study included 143 patients with ALS (57% men; 68% spinal onset). Patients were diagnosed in public centres in 86% of cases and in private centres in 14%.The mean diagnostic delay was 13.1 months (median 11.7). Patients were examined by neurologists a mean time of 7.9 months after symptom onset, with diagnosis being made 5.2 months later. Half of all patients underwent unnecessary diagnostic tests and multiple electrophysiological studies before diagnosis was established. Diagnostic delay was longer in cases of spinal onset (P = .008) due to onset of the disease in the lower limbs. No differences were found between the public and private healthcare systems (P = .897). The diagnostic delay in ALS in Spain is similar to that of neighboring countries and seems to depend on disease-related factors, not on the healthcare system. Patients with lower-limb onset ALS constitute the greatest diagnostic challenge. Misdiagnosis is frequent, and partly attributable to an incorrect approach or erroneous interpretation of electrophysiological studies. Specific training programmes for neurologists and general neurophysiologists and early referral to reference centers may help to reduce diagnostic delay. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Six consecutive false positive cases from cell-free fetal DNA testing in a single referring centre

PubMed Central

Dugo, Nella; Padula, Francesco; Mobili, Luisa; Brizzi, Cristiana; D’Emidio, Laura; Cignini, Pietro; Mesoraca, Alvaro; Bizzoco, Domenico; Cima, Antonella; Giorlandino, Claudio

2014-01-01

Introduction recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive Prenatal Testing) in routine clinical practice emphasizing its high sensibility and specificity. In any case, false positive and false negative findings may result from placental mosaicism, because cell-free fetal DNA originates mainly from placenta. Case we report six cases of women who underwent chorionic villus sampling (CVS) or amniocentesis to confirm the results from NIPT: two Turner syndromes, two Triple X, one Patau syndrome, one Edward syndrome. Results using classic cytogenetic analysis and, also, Array - Comparative Genomic Hybridization (Array CGH) the karyotype of all 5 fetuses was found to be normal. Conclusion results from NIPT must always be confirmed by invasive prenatal diagnosis. It is mandatory to inform the patient that the CVS and amniocentesis still represent the only form of prenatal diagnostic test available. PMID:25332757

Epidemic outbreaks, diagnostics, and control measures of the H5N1 highly pathogenic avian influenza in the Kingdom of Saudi Arabia, 2007-08.

PubMed

Lu, Huaguang; Ismail, Mahmoud Moussa; Khan, Owais Ahmed; Al Hammad, Yousef; Abdel Rhman, Salah Shaban; Al-Blowi, Mohamed Hamad

2010-03-01

The first outbreak of H5N1 highly pathogenic avian influenza (HPAI) in the Kingdom of Saudi Arabia (KSA) occurred in two "backyard" flocks of Houbara bustards and falcons in February 2007. Subsequent outbreaks were seen through the end of 2007 in "backyard" birds including native chickens, ostriches, turkeys, ducks, and peacocks. From November 2007 through January 2008, H5N1 HPAI outbreaks occurred in 19 commercial poultry premises, including two broiler breeder farms, one layer breeder farm, one ostrich farm, and 15 commercial layer farms, with approximately 4.75 million birds affected. Laboratory diagnosis of all H5N1-positive cases was conducted at the Central Veterinary Diagnostic Laboratory (CVDL) in Riyadh, Saudi Arabia. A combination of diagnostic tests was used to confirm the laboratory diagnosis. A rapid antigen-capture test and real-time reverse transcriptase-PCR (rtRT-PCR) assay on clinical and field specimens were conducted initially. Meanwhile, virus isolation in specific-pathogen-free embryonating chicken eggs was performed and was followed by hemagglutinin (HA) and hemagglutination inhibition tests, then rapid antigen-capture and rtRT-PCR tests on HA-positive allantoic fluid samples. In most HPAI cases, a complete laboratory diagnosis was made within 24-48 hr at the CVDL. Saudi Arabian government officials made immediate decisions to depopulate all H5N1-affected and nonaffected flocks within a 5-km radius area and applied quarantine zones to prevent the virus from spreading to other areas. Other control measures, such as closure of live bird markets and intensive surveillance tests on all poultry species within quarantine zones, were in place during the outbreaks. As a result, the HPAI outbreaks were quickly controlled, and no positive cases were detected after January 29, 2008. The KSA was declared free of HPAI on April 30, 2008, by the World Animal Health Organization.

The value and safety of specific nasal provocation in the diagnosis of allergic rhinitis in mild persistent asthma under inhaled steroid therapy.

PubMed

Tuskan, Tansu Cengiz; Gemicioglu, Bilun; Ikitimur, Hande; Yilmaz, Nail; Tuskan, Kemal; Oz, Ferhan; Can, Gunay

2010-01-01

Although specific nasal provocation is an objective diagnostic test for allergic rhinitis, it can also increase the lower airway responsiveness in asthmatic patients. Our goal was to determine the value and safety of specific nasal provocation test for the diagnosis of allergic rhinitis in mild persistent asthmatic patients under low-dose inhaled steroid therapy. The study was performed on 32 mild persistent, stable, mite-sensitive allergic asthmatics (group 1), 9 mild persistent nonallergic asthmatics (group 2) and 9 healthy non-smokers (group 3). Nasal symptoms were noted, paranasal sinus computerized tomography (PNCT) and rhinoscopic evaluations were performed. Cases with pathologic-anatomic changes in PNCT and rhinoscopy were excluded. Symptom scoring, flow-volume, peak expiratory flow (PEF), serum and nasal lavage eosinophil cationic protein (ECP) and nasal lavage eosinophil counts were performed before mite specific nasal provocation test and at the 0th, 4th and 24th hours following the test. No adverse effects were observed in all diagnostic procedures. Total diagnostic value of nasal symptoms were found to be at 92%, while being 70% for rhinoscopy and 88% for specific nasal provocation test respectively in the diagnosis of allergic rhinitis in group 1. Statistically significant differences were found between basal nasal lavage eosinophil values (p < 0.001) and ECP levels (p < 0.05) when group 1 was compared with both group 2 and group 3. In the remaining measured values between three groups, no statistically significant differences were found. Specific nasal provocation test is a safe method for mild house dust mite allergic asthma cases under low-dose inhaled steroid therapy, but history of rhinitis might be sufficient for the diagnosis of allergic rhinitis.

A Novel Predictive Equation for Potential Diagnosis of Cholangiocarcinoma

PubMed Central

Kraiklang, Ratthaphol; Pairojkul, Chawalit; Khuntikeo, Narong; Imtawil, Kanokwan; Wongkham, Sopit; Wongkham, Chaisiri

2014-01-01

Cholangiocarcinoma (CCA) is the second most common-primary liver cancer. The difficulties in diagnosis limit successful treatment of CCA. At present, histological investigation is the standard diagnosis for CCA. However, there are some poor-defined tumor tissues which cannot be definitively diagnosed by general histopathology. As molecular signatures can define molecular phenotypes related to diagnosis, prognosis, or treatment outcome, and CCA is the second most common cancer found after hepatocellularcarcinoma (HCC), the aim of this study was to develop a predictive model which differentiates CCA from HCC and normal liver tissues. An in-house PCR array containing 176 putative CCA marker genes was tested with the training set tissues of 20 CCA and 10 HCC cases. The molecular signature of CCA revealed the prominent expression of genes involved in cell adhesion and cell movement, whereas HCC showed elevated expression of genes related to cell proliferation/differentiation and metabolisms. A total of 69 genes differentially expressed in CCA and HCC were optimized statistically to formulate a diagnostic equation which distinguished CCA cases from HCC cases. Finally, a four-gene diagnostic equation (CLDN4, HOXB7, TMSB4 and TTR) was formulated and then successfully validated using real-time PCR in an independent testing set of 68 CCA samples and 77 non-CCA controls. Discrimination analysis showed that a combination of these genes could be used as a diagnostic marker for CCA with better diagnostic parameters with high sensitivity and specificity than using a single gene marker or the usual serum markers (CA19-9 and CEA). This new combination marker may help physicians to identify CCA in liver tissues when the histopathology is uncertain. PMID:24586698

Plasmodium vivax molecular diagnostics in community surveys: pitfalls and solutions.

PubMed

Gruenberg, Maria; Moniz, Clara Antunes; Hofmann, Natalie Ellen; Wampfler, Rahel; Koepfli, Cristian; Mueller, Ivo; Monteiro, Wuelton Marcelo; Lacerda, Marcus; de Melo, Gisely Cardoso; Kuehn, Andrea; Siqueira, Andre M; Felger, Ingrid

2018-01-30

A distinctive feature of Plasmodium vivax infections is the overall low parasite density in peripheral blood. Thus, identifying asymptomatic infected individuals in endemic communities requires diagnostic tests with high sensitivity. The detection limits of molecular diagnostic tests are primarily defined by the volume of blood analysed and by the copy number of the amplified molecular marker serving as the template for amplification. By using mitochondrial DNA as the multi-copy template, the detection limit can be improved more than tenfold, compared to standard 18S rRNA targets, thereby allowing detection of lower parasite densities. In a very low transmission area in Brazil, application of a mitochondrial DNA-based assay increased prevalence from 4.9 to 6.5%. The usefulness of molecular tests in malaria epidemiological studies is widely recognized, especially when precise prevalence rates are desired. Of concern, however, is the challenge of demonstrating test accuracy and quality control for samples with very low parasite densities. In this case, chance effects in template distribution around the detection limit constrain reproducibility. Rigorous assessment of false positive and false negative test results is, therefore, required to prevent over- or under-estimation of parasite prevalence in epidemiological studies or when monitoring interventions.

Use of Fine Needle Aspirate from Peripheral Nerves of Pure-neural Leprosy for Cytology and Polymerase Chain Reaction to Confirm the Diagnosis: A Follow-up Study of 4 Years.

PubMed

De, Abhishek; Hasanoor Reja, Abu Hena; Aggarwal, Ishad; Sen, Sumit; Sil, Amrita; Bhattacharya, Basudev; Sharma, Nidhi; Ansari, Asad; Sarda, Aarti; Chatterjee, Gobinda; Das, Sudip

2017-01-01

Pure neural leprosy (PNL) still remains a diagnostic challenge because of the absence of sine qua non skin lesions of leprosy and a confirmatory diagnostic method. The authors had earlier described a simple yet objective technique of combining fine needle aspiration cytology (FNAC) coupled with a multiplex polymerase chain reaction (PCR) in a pilot study, wherein the technique showed promise of a reliable diagnostic tool. In the pursuit of further evidence, the authors carried out a 4-year study with PNL cases to find the efficacy and reliability of the said method in a larger sample size. This study was conducted to find the efficacy, reliability, and reproducibility of FNAC coupled with multiplex PCR and Ziehl-Neelsen (ZN) staining in identifying the cases of PNL. All cases that were suspected to be suffering from PNL, following evaluation by two independent observers were included in the study and were subjected to FNAC from the affected nerve, and the aspirates were evaluated for cytology, ZN staining, and multiplex PCR for Mycobacterium leprae genome. In addition, serum anti-PGL1 levels were also performed in all the study subjects. Fifteen non-PNL cases were also included in the control arm. A total of 47 cases were included in the test arm and subjected to FNAC. Conventional ZN staining could demonstrate acid-fast bacilli (AFB) in only 15 out of 47 cases (31.91%) while M. leprae DNA could be elicited in 37 (78.72%) cases by the multiplex PCR. Only 13 (27.65%) out of 47 cases showed anti-PGLI-1 antibody positivity. On cytological examination of the nerve aspirates, only 11 (23.40%) cases showed epithelioid cells whereas nonspecific inflammation was seen in 26 (75.60%) cases. The results of this study conducted over a larger sample size corroborate with the findings of our pilot study. In a resource poor set up, FNAC in combination with ZN staining and multiplex PCR is a rapid, simple, and easily performed test, which can give a reproducible and objective diagnosis in cases of PNL.

Improved Signal Processing Technique Leads to More Robust Self Diagnostic Accelerometer System

NASA Technical Reports Server (NTRS)

Tokars, Roger; Lekki, John; Jaros, Dave; Riggs, Terrence; Evans, Kenneth P.

2010-01-01

The self diagnostic accelerometer (SDA) is a sensor system designed to actively monitor the health of an accelerometer. In this case an accelerometer is considered healthy if it can be determined that it is operating correctly and its measurements may be relied upon. The SDA system accomplishes this by actively monitoring the accelerometer for a variety of failure conditions including accelerometer structural damage, an electrical open circuit, and most importantly accelerometer detachment. In recent testing of the SDA system in emulated engine operating conditions it has been found that a more robust signal processing technique was necessary. An improved accelerometer diagnostic technique and test results of the SDA system utilizing this technique are presented here. Furthermore, the real time, autonomous capability of the SDA system to concurrently compensate for effects from real operating conditions such as temperature changes and mechanical noise, while monitoring the condition of the accelerometer health and attachment, will be demonstrated.

Debris characterization diagnostic for the NIF

NASA Astrophysics Data System (ADS)

Miller, M. C.; Celeste, J. R.; Stoyer, M. A.; Suter, L. J.; Tobin, M. T.; Grun, J.; Davis, J. F.; Barnes, C. W.; Wilson, D. C.

2001-01-01

Generation of debris from targets and by x-ray ablation of surrounding materials will be a matter of concern for experimenters and National Ignition Facility (NIF) operations. Target chamber and final optics protection, for example debris shield damage, drive the interest for NIF operations. Experimenters are primarily concerned with diagnostic survivability, separation of mechanical versus radiation induced test object response in the case of effects tests, and radiation transport through the debris field when the net radiation output is used to benchmark computer codes. In addition, radiochemical analysis of activated capsule debris during ignition shots can provide a measure of the ablator <ρr>. Conceptual design of the Debris Monitor and Rad-Chem Station, one of the NIF core diagnostics, is presented. Methods of debris collection, particle size and mass analysis, impulse measurement, and radiochemical analysis are given. A description of recent experiments involving debris collection and impulse measurement on the OMEGA and Pharos lasers is also provided.

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.

Characteristics associated with requests by pathologists for second opinions on breast biopsies

PubMed Central

Geller, Berta M; Nelson, Heidi D; Weaver, Donald L; Frederick, Paul D; Allison, Kimberly H; Onega, Tracy; Carney, Patricia A; Tosteson, Anna N A; Elmore, Joann G

2018-01-01

Aims Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests. Methods Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations. Results 115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses. Conclusions Pathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions. PMID:28465449

Effects of pressure ulcer classification system education programme on knowledge and visual differential diagnostic ability of pressure ulcer classification and incontinence-associated dermatitis for clinical nurses in Korea.

PubMed

Lee, Yun Jin; Kim, Jung Yoon

2016-03-01

The objective of this study was to evaluate the effect of pressure ulcer classification system education on clinical nurses' knowledge and visual differential diagnostic ability of pressure ulcer (PU) classification and incontinence-associated dermatitis (IAD). One group pre and post-test was used. A convenience sample of 407 nurses, participating in PU classification education programme of continuing education, were enrolled. The education programme was composed of a 50-minute lecture on PU classification and case-studies. The PU Classification system and IAD knowledge test (PUCS-KT) and visual differential diagnostic ability tool (VDDAT), consisting of 21 photographs including clinical information were used. Paired t-test was performed using SPSS/WIN 20.0. The overall mean difference of PUCS-KT (t = -11·437, P<0·001) and VDDAT (t = -21·113, P<0·001) was significantly increased after PU classification education. Overall understanding of six PU classification and IAD after education programme was increased, but lacked visual differential diagnostic ability regarding Stage III PU, suspected deep tissue injury (SDTI), and Unstageable. Continuous differentiated education based on clinical practice is needed to improve knowledge and visual differential diagnostic ability for PU classification, and comparison experiment study is required to examine effects of education programmes. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

A preface on advances in diagnostics for infectious and parasitic diseases: detecting parasites of medical and veterinary importance.

PubMed

Stothard, J Russell; Adams, Emily

2014-12-01

There are many reasons why detection of parasites of medical and veterinary importance is vital and where novel diagnostic and surveillance tools are required. From a medical perspective alone, these originate from a desire for better clinical management and rational use of medications. Diagnosis can be at the individual-level, at close to patient settings in testing a clinical suspicion or at the community-level, perhaps in front of a computer screen, in classification of endemic areas and devising appropriate control interventions. Thus diagnostics for parasitic diseases has a broad remit as parasites are not only tied with their definitive hosts but also in some cases with their vectors/intermediate hosts. Application of current diagnostic tools and decision algorithms in sustaining control programmes, or in elimination settings, can be problematic and even ill-fitting. For example in resource-limited settings, are current diagnostic tools sufficiently robust for operational use at scale or are they confounded by on-the-ground realities; are the diagnostic algorithms underlying public health interventions always understood and well-received within communities which are targeted for control? Within this Special Issue (SI) covering a variety of diseases and diagnostic settings some answers are forthcoming. An important theme, however, throughout the SI is to acknowledge that cross-talk and continuous feedback between development and application of diagnostic tests is crucial if they are to be used effectively and appropriately.

Current challenges in diagnostic imaging of venous thromboembolism.

PubMed

Huisman, Menno V; Klok, Frederikus A

2015-01-01

Because the clinical diagnosis of deep-vein thrombosis and pulmonary embolism is nonspecific, integrated diagnostic approaches for patients with suspected venous thromboembolism have been developed over the years, involving both non-invasive bedside tools (clinical decision rules and D-dimer blood tests) for patients with low pretest probability and diagnostic techniques (compression ultrasound for deep-vein thrombosis and computed tomography pulmonary angiography for pulmonary embolism) for those with a high pretest probability. This combination has led to standardized diagnostic algorithms with proven safety for excluding venous thrombotic disease. At the same time, it has become apparent that, as a result of the natural history of venous thrombosis, there are special patient populations in which the current standard diagnostic algorithms are not sufficient. In this review, we present 3 evidence-based patient cases to underline recent developments in the imaging diagnosis of venous thromboembolism. © 2015 by The American Society of Hematology. All rights reserved.

Molecular diagnosis of Legionella infections--Clinical utility of front-line screening as part of a pneumonia diagnostic algorithm.

PubMed

Gadsby, Naomi J; Helgason, Kristjan O; Dickson, Elizabeth M; Mills, Jonathan M; Lindsay, Diane S J; Edwards, Giles F; Hanson, Mary F; Templeton, Kate E

2016-02-01

Urinary antigen testing for Legionella pneumophila serogroup 1 is the leading rapid diagnostic test for Legionnaires' Disease (LD); however other Legionella species and serogroups can also cause LD. The aim was to determine the utility of front-line L. pneumophila and Legionella species PCR in a severe respiratory infection algorithm. L. pneumophila and Legionella species duplex real-time PCR was carried out on 1944 specimens from hospitalised patients over a 4 year period in Edinburgh, UK. L. pneumophila was detected by PCR in 49 (2.7%) specimens from 36 patients. During a LD outbreak, combined L. pneumophila respiratory PCR and urinary antigen testing had optimal sensitivity and specificity (92.6% and 98.3% respectively) for the detection of confirmed cases. Legionella species was detected by PCR in 16 (0.9%) specimens from 10 patients. The 5 confirmed and 1 probable cases of Legionella longbeachae LD were both PCR and antibody positive. Front-line L. pneumophila and Legionella species PCR is a valuable addition to urinary antigen testing as part of a well-defined algorithm. Cases of LD due to L. longbeachae might be considered laboratory-confirmed when there is a positive Legionella species PCR result and detection of L. longbeachae specific antibody response. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Automated chest-radiography as a triage for Xpert testing in resource-constrained settings: a prospective study of diagnostic accuracy and costs

NASA Astrophysics Data System (ADS)

Philipsen, R. H. H. M.; Sánchez, C. I.; Maduskar, P.; Melendez, J.; Peters-Bax, L.; Peter, J. G.; Dawson, R.; Theron, G.; Dheda, K.; van Ginneken, B.

2015-07-01

Molecular tests hold great potential for tuberculosis (TB) diagnosis, but are costly, time consuming, and HIV-infected patients are often sputum scarce. Therefore, alternative approaches are needed. We evaluated automated digital chest radiography (ACR) as a rapid and cheap pre-screen test prior to Xpert MTB/RIF (Xpert). 388 suspected TB subjects underwent chest radiography, Xpert and sputum culture testing. Radiographs were analysed by computer software (CAD4TB) and specialist readers, and abnormality scores were allocated. A triage algorithm was simulated in which subjects with a score above a threshold underwent Xpert. We computed sensitivity, specificity, cost per screened subject (CSS), cost per notified TB case (CNTBC) and throughput for different diagnostic thresholds. 18.3% of subjects had culture positive TB. For Xpert alone, sensitivity was 78.9%, specificity 98.1%, CSS $13.09 and CNTBC $90.70. In a pre-screening setting where 40% of subjects would undergo Xpert, CSS decreased to $6.72 and CNTBC to $54.34, with eight TB cases missed and throughput increased from 45 to 113 patients/day. Specialists, on average, read 57% of radiographs as abnormal, reducing CSS ($8.95) and CNTBC ($64.84). ACR pre-screening could substantially reduce costs, and increase daily throughput with few TB cases missed. These data inform public health policy in resource-constrained settings.

Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Hearing Loss

PubMed Central

Chandrasekharan, Subhashini; Fiffer, Melissa

2011-01-01

Genetic testing for heritable hearing loss involves a mix of patented and unpatented genes, mutations and testing methods. More than half of all hearing loss is linked to inherited mutations, and five genes are most commonly tested in the United States. There are no patents on three of these genes, but Athena Diagnostics holds exclusive licenses to test for a common mutation in the GJB2 gene associated with about 50% of all cases, as well as mutations in the MTRNR1 gene. This fragmented intellectual property landscape made hearing loss a useful case study for assessing whether patent rights in genetic testing can proliferate or overlap, and whether it is possible to gather the rights necessary to perform testing. Testing for hearing loss is widely available, primarily from academic medical centers. Based on literature reviews and interviews with researchers, research on the genetics of hearing loss has generally not been impeded by patents. There is no consistent evidence of a premium in testing prices attributable to patent status. Athena Diagnostics has, however, used its intellectual property to discourage other providers from offering some tests. There is no definitive answer about the suitability of current patenting and licensing of commonly tested genes because of continuing legal uncertainty about the extent of enforcement of patent rights. Clinicians have also expressed concerns that multiplex tests will be difficult to develop because of overlapping intellectual property and conflict with Athena’s sole provider business model. PMID:20393307

Unusual association of amyotrophic lateral sclerosis and myasthenia gravis: A dysregulation of the adaptive immune system?

PubMed

Del Mar Amador, Maria; Vandenberghe, Nadia; Berhoune, Nawel; Camdessanché, Jean-Philippe; Gronier, Sophie; Delmont, Emilien; Desnuelle, Claude; Cintas, Pascal; Pittion, Sophie; Louis, Sarah; Demeret, Sophie; Lenglet, Timothée; Meininger, Vincent; Salachas, François; Pradat, Pierre-François; Bruneteau, Gaëlle

2016-06-01

Myasthenia gravis is an autoimmune disorder affecting neuromuscular junctions that has been associated with a small increased risk of amyotrophic lateral sclerosis (ALS). Here, we describe a retrospective series of seven cases with a concomitant diagnosis of ALS and myasthenia gravis, collected among the 18 French reference centers for ALS in a twelve year period. After careful review, only six patients strictly met the diagnostic criteria for both ALS and myasthenia gravis. In these patients, limb onset of ALS was reported in five (83%) cases. Localization of myasthenia gravis initial symptoms was ocular in three (50%) cases, generalized in two (33%) and bulbar in one (17%). Median delay between onset of the two conditions was 19 months (6-319 months). Anti-acetylcholine receptor antibodies testing was positive in all cases. All patients were treated with riluzole and one had an associated immune-mediated disease. In the one last ALS case, the final diagnosis was false-positivity for anti-acetylcholine receptor antibodies. The co-occurrence of ALS and myasthenia gravis is rare and requires strict diagnostic criteria. Its demonstration needs thoughtful interpretation of electrophysiological results and exclusion of false positivity for myasthenia gravis antibody testing in some ALS cases. This association may be triggered by a dysfunction of adaptive immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

[Early form of toxoplasmosis with accompanying enlargement of lymph nodes].

PubMed

Małafiej, Eugeniusz; Spiewak, Ewa; Frankowska, Joanna; Maciejewska, Ewa

2004-05-01

The paper describes a case of a 42-year-old female presented rapidly increasing enlargement of lymph nodes. Initially it was believed to be an effect of proliferous systemic changes. The diagnostic procedures did not confirm the initial diagnosis but they evoked a lot of stress of the patient as well as her psychic discomfort resulting from a number of biopsies. Serological tests carried out in the further course of the diagnostic procedure showed that the increased nodular reaction should be attributed to Toxoplasma gondii invasion, which was indicated by the presence of IgM and IgA antibodies and low avidity of IgG. The early administration of specific treatment with spiramycin led to the regression of the clinical symptoms and gradual normalization of the serological test. The case is worth attention for several reasons: 1. it indicates that it is necessary to consider T. gondii infection in basic clinical practice, which is frequently ignored, 2. it illustrates the effectiveness of early specific treatment, 3. it demonstrates the importance of well selected and properly interpreted microbiological tests.

Biomedical visual data analysis to build an intelligent diagnostic decision support system in medical genetics.

PubMed

Kuru, Kaya; Niranjan, Mahesan; Tunca, Yusuf; Osvank, Erhan; Azim, Tayyaba

2014-10-01

In general, medical geneticists aim to pre-diagnose underlying syndromes based on facial features before performing cytological or molecular analyses where a genotype-phenotype interrelation is possible. However, determining correct genotype-phenotype interrelationships among many syndromes is tedious and labor-intensive, especially for extremely rare syndromes. Thus, a computer-aided system for pre-diagnosis can facilitate effective and efficient decision support, particularly when few similar cases are available, or in remote rural districts where diagnostic knowledge of syndromes is not readily available. The proposed methodology, visual diagnostic decision support system (visual diagnostic DSS), employs machine learning (ML) algorithms and digital image processing techniques in a hybrid approach for automated diagnosis in medical genetics. This approach uses facial features in reference images of disorders to identify visual genotype-phenotype interrelationships. Our statistical method describes facial image data as principal component features and diagnoses syndromes using these features. The proposed system was trained using a real dataset of previously published face images of subjects with syndromes, which provided accurate diagnostic information. The method was tested using a leave-one-out cross-validation scheme with 15 different syndromes, each of comprised 5-9 cases, i.e., 92 cases in total. An accuracy rate of 83% was achieved using this automated diagnosis technique, which was statistically significant (p<0.01). Furthermore, the sensitivity and specificity values were 0.857 and 0.870, respectively. Our results show that the accurate classification of syndromes is feasible using ML techniques. Thus, a large number of syndromes with characteristic facial anomaly patterns could be diagnosed with similar diagnostic DSSs to that described in the present study, i.e., visual diagnostic DSS, thereby demonstrating the benefits of using hybrid image processing and ML-based computer-aided diagnostics for identifying facial phenotypes. Copyright © 2014. Published by Elsevier B.V.

DDS: The Dental Diagnostic Simulation System.

ERIC Educational Resources Information Center

Tira, Daniel E.

The Dental Diagnostic Simulation (DDS) System provides an alternative to simulation systems which represent diagnostic case studies of relatively limited scope. It may be used to generate simulated case studies in all of the dental specialty areas with case materials progressing through the gamut of the diagnostic process. The generation of a…

A Diagnostic Study of Pre-Service Teachers' Competency in Multiple-Choice Item Development

ERIC Educational Resources Information Center

Asim, Alice E.; Ekuri, Emmanuel E.; Eni, Eni I.

2013-01-01

Large class size is an issue in testing at all levels of Education. As a panacea to this, multiple choice test formats has become very popular. This case study was designed to diagnose pre-service teachers' competency in constructing questions (IQT); direct questions (DQT); and best answer (BAT) varieties of multiple choice items. Subjects were 88…

The accuracy of the first response histidine-rich protein2 rapid diagnostic test compared with malaria microscopy for guiding field treatment in an outbreak of falciparum malaria.

PubMed

Ghouth, Abdulla Salim Bin; Nasseb, Faraj Mubarak; Al-Kaldy, Khaled Hussin

2012-01-01

Recent WHO guidelines recommended a universal "test and treat" strategy for malaria mainly by use of the rapid diagnostic test (RDT) in all areas. There are concerns about RDT that use the antigen histidine-rich protein2 (HRP2) to detect Plasmodium falciparum, because infection can persist after effective treatment. The aim of this paper is to describe the accuracy of the first response (HRP2)-RDT compared with malaria microscopy used for guiding the field treatment of patients in an outbreak situation in the Al-Rahabah area in Al-Rydah district in Hadramout/Yemen. An ad hoc cross sectional survey of all febrile patients in the affected area was conducted in May 2011. The field team was developed including the case management group and the entomology group. The group of case management prepared their plan based on "test and treat" strategy by using First Response Malaria Antigen HRP2 rapid diagnostic test for falciparum malaria, artemsinin-based combination therapy (ACT) according to the national policy of anti-malaria drugs in Yemen were supplied to treat those who were found to be RDT positive in the field; also blood smear films were taken from every patient with fever in order to validate the use of the RDT in the field. Blood film slides prepared and read by skilled lab technicians, the fourth reading was done by one lab expert in the malaria referral lab. The accuracy parameters of HRP2 compared with microscopy are: Sensitivity (74%), specificity (94%). The positive predictive value is 68% and the negative predictive value is 96%. Total agreement is 148/162 (93%) and the overall prevalence is 14%. All the positive malaria cases were of P. falciparum either coming from RDT or microscopy. HRP2-rapid test is an acceptable test as a guide for field treatment in an outbreak situation where prompt response is indicated. Good prepared blood film slides should be used as it is feasible to evaluate the accuracy of RDTs as a quality control tool.

Comparison of Antigen Detection and Nested PCR in CSF Samples of HIV Positive and Negative Patients with Suspected Cryptococcal Meningitis in a Tertiary Care Hospital.

PubMed

Kumari, Sunita; Verma, Rajesh Kumar; Singh, Dharmendra Prasad; Yadav, Ramakant

2016-04-01

The cases of cryptococcal meningitis and other forms of cryptococcosis have increased in recent time and the present scenario of the condition with significant morbidity and mortality is actually posing a serious threat to the community, so an early and prompt diagnosis is necessary to prevent serious complications and thus improving the overall disease outcome. Comparison of diagnostic efficacy of nested Polymerase Chain Reaction (PCR) with Latex Agglutination Test (LAT) in the Cerebro Spinal Fluid (CSF) samples of the cases of meningitis in HIV positive and negative cases. We have compared the diagnostic efficacy of Latex Agglutination Test (LAT) with nested Polymerase Chain Reaction (PCR) in 200 Cerebrospinal Fluid (CSF) samples, including 14 HIV positive also, in the cases of suspected cryptococcal meningitis. Nested PCR was done in all cases reporting positive by LAT and results were then compared with that of India ink and culture on Sabouraud Dextrose Agar (SDA), and the isolates were further identified by urease, nitrate and sugar assimilation tests. Of the 200 cases, including 14 HIV positive, LAT was positive in 46 cases while 154 were negative. Out of these 46 LAT positive cases, nested PCR was positive in 40 cases only, while culture and India ink was positive in 38 and 33 cases respectively. Majority of the cases, 30 (65.2%) were between age group 21-50 years, while 2 (4.3%) in 0-20, and 14 (30.4%) in 51-80 years age group. Although negative staining like India ink and nigrosin are most widely used techniques, but these suffer with subjective error. Rapid method like LAT is available but it always has the scope of false positive and negative results. In such cases nested PCR can help in establishing final diagnosis.

Examining the Application of the DC-IA-A Diagnostic Criteria for Internet Addiction Disorder in At-Risk College Students.

PubMed

Hsu, Wen-Yu; Chang, Shan-Mei; Chiu, Nan-Ying; Lin, Sunny S J; Tseng, Yin-Hsing

2015-01-01

Internet addiction disorder is a relatively new condition, and the criteria for its diagnosis have been developed only over the last several years. The criteria for Internet addiction remain controversial. We strive to further elucidate the clinical validity of the diagnostic criteria for Internet addiction. To test items of the diagnostic criteria for Internet addiction among adolescents, we conducted a clinical interview study of college students based on longitudinal data on their risky use of the Internet. Forty-one high-risk cases were selected from a 3-year 5-time point longitudinal survey of 716 college freshmen. We examined disputes relevant to symptoms and impairment in the DC-IA-A (Diagnostic Criteria for Internet Addiction among Taiwanese Adolescents). Of the 41 cases, 21 were diagnosed with Internet addiction via a psychiatric interview. In the Internet addiction disorder group, 23.8% of cases had a diagnosis of depression, whereas only 15.0% of the cases in the non-Internet addiction group had a diagnosis of depression. Two major criteria (A8 and A3) had low incidences in these high-risk college students and thus did not help provide a differential diagnosis between the groups. We suggest that A8, 'excessive effort spent on activities necessary to obtain access to the Internet', should be omitted, and that A3, 'tolerance: a marked increase in the duration of Internet use needed to achieve satisfaction', should be modified. A1 and A9 should be discussed regarding their role in the diagnosis of Internet addiction disorder. Additional well-designed studies examining the diagnostic criteria and the relationship between factors are needed. © 2015 S. Karger AG, Basel.

Improving Papanicolaou test quality and reducing medical errors by using Toyota production system methods.

PubMed

Raab, Stephen S; Andrew-Jaja, Carey; Condel, Jennifer L; Dabbs, David J

2006-01-01

The objective of the study was to determine whether the Toyota production system process improves Papanicolaou test quality and patient safety. An 8-month nonconcurrent cohort study that included 464 case and 639 control women who had a Papanicolaou test was performed. Office workflow was redesigned using Toyota production system methods by introducing a 1-by-1 continuous flow process. We measured the frequency of Papanicolaou tests without a transformation zone component, follow-up and Bethesda System diagnostic frequency of atypical squamous cells of undetermined significance, and diagnostic error frequency. After the intervention, the percentage of Papanicolaou tests lacking a transformation zone component decreased from 9.9% to 4.7% (P = .001). The percentage of Papanicolaou tests with a diagnosis of atypical squamous cells of undetermined significance decreased from 7.8% to 3.9% (P = .007). The frequency of error per correlating cytologic-histologic specimen pair decreased from 9.52% to 7.84%. The introduction of the Toyota production system process resulted in improved Papanicolaou test quality.

Computer-Aided Diagnostic (CAD) Scheme by Use of Contralateral Subtraction Technique

NASA Astrophysics Data System (ADS)

Nagashima, Hiroyuki; Harakawa, Tetsumi

We developed a computer-aided diagnostic (CAD) scheme for detection of subtle image findings of acute cerebral infarction in brain computed tomography (CT) by using a contralateral subtraction technique. In our computerized scheme, the lateral inclination of image was first corrected automatically by rotating and shifting. The contralateral subtraction image was then derived by subtraction of reversed image from original image. Initial candidates for acute cerebral infarctions were identified using the multiple-thresholding and image filtering techniques. As the 1st step for removing false positive candidates, fourteen image features were extracted in each of the initial candidates. Halfway candidates were detected by applying the rule-based test with these image features. At the 2nd step, five image features were extracted using the overlapping scale with halfway candidates in interest slice and upper/lower slice image. Finally, acute cerebral infarction candidates were detected by applying the rule-based test with five image features. The sensitivity in the detection for 74 training cases was 97.4% with 3.7 false positives per image. The performance of CAD scheme for 44 testing cases had an approximate result to training cases. Our CAD scheme using the contralateral subtraction technique can reveal suspected image findings of acute cerebral infarctions in CT images.

Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort.

PubMed

Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; Boulle, Andrew; Vogt, Monica; Gupta-Wright, Ankur; Nicol, Mark P; Meintjes, Graeme

2017-03-21

We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9-99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50-11.75). Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.

Battling Malaria in Rural Zambia with Modern Technology: A Qualitative Study on the Value of Cell Phones, Geographical Information Systems, Asymptomatic Carriers and Rapid Diagnostic Tests to Identify, Treat and Control Malaria.

PubMed

Nygren, David; Isaksson, Arvid Lissel

2014-02-04

During the last decade much progress has been made in reducing malaria transmission in Macha, Southern Province, Zambia. Introduction of artemisinin combination therapies as well as mass screenings of asymptomatic carriers is believed to have contributed the most. When an endemic malaria situation is moving towards a non-endemic situation the resident population loses acquired immunity and therefore active case detection and efficient surveillance is crucial to prevent epidemic outbreaks. Our purpose was to evaluate the impact of cell phone surveillance and geographical information systems on malaria control in Macha. Furthermore, it evaluates what screening and treatment of asymptomatic carriers and implementation of rapid diagnostic tests in rural health care has led to. Ten in-depth semi-structured interviews, field observations and data collection were performed at the Macha Research Trust and at surrounding rural health centers. This qualitative method was inspired by rapid assessment procedure. The cell phone surveillance has been easily integrated in health care, and its integration with Geographical Information Systems has provided the ability to follow malaria transmission on a weekly basis. In addition, active case detection of asymptomatic carriers has been fruitful, which is reflected in it soon being applied nationwide. Furthermore, rapid diagnostic tests have provided rural health centers with reliable malaria diagnostics, thereby decreasing excessive malaria treatments and selection for drug resistance. This report reflects the importance of asymptomatic carriers in targeting malaria elimination, as well as development of effective surveillance systems when transmission decreases. Such an approach would be cost-efficient in the long run through positive effects in reduced child mortality and relief in health care.

The Impact of Measurement Noise in GPA Diagnostic Analysis of a Gas Turbine Engine

NASA Astrophysics Data System (ADS)

Ntantis, Efstratios L.; Li, Y. G.

2013-12-01

The performance diagnostic analysis of a gas turbine is accomplished by estimating a set of internal engine health parameters from available sensor measurements. No physical measuring instruments however can ever completely eliminate the presence of measurement uncertainties. Sensor measurements are often distorted by noise and bias leading to inaccurate estimation results. This paper explores the impact of measurement noise on Gas Turbine GPA analysis. The analysis is demonstrated with a test case where gas turbine performance simulation and diagnostics code TURBOMATCH is used to build a performance model of a model engine similar to Rolls-Royce Trent 500 turbofan engine, and carry out the diagnostic analysis with the presence of different levels of measurement noise. Conclusively, to improve the reliability of the diagnostic results, a statistical analysis of the data scattering caused by sensor uncertainties is made. The diagnostic tool used to deal with the statistical analysis of measurement noise impact is a model-based method utilizing a non-linear GPA.

Chlorhexidine allergy in four specialist allergy centres in the United Kingdom, 2009–13: clinical features and diagnostic tests

PubMed Central

Helbert, M.; Sargur, R.; Swallow, K.; Harper, N.; Garcez, T.; Savic, S.; Savic, L.; Eren, E.

2017-01-01

Summary We describe an observational survey of diagnostic pathways in 104 patients attending four specialist allergy clinics in the United Kingdom following perioperative hypersensitivity reactions to chlorhexidine reactions. The majority were life‐threatening. Men undergoing urological or cardiothoracic surgery predominated. Skin prick testing and specific immunoglobulin (sIg)E testing were the most common tests used for diagnosis. Fifty‐three per cent of diagnoses were made on the basis of a single positive test. Where multiple tests were performed the sensitivity of intradermal, basophil activation and skin prick testing was 68% (50–86%), 50% (10–90%) and 35% (17–55%), respectively. Seven per cent were negative on screening tests initially, and 12 cases were only positive for a single test despite multiple testing. Intradermal tests appeared most sensitive in this context. Additional sensitization to other substances used perioperatively, particularly neuromuscular blocking agents (NMBA), was found in 28 patients, emphasizing the need to test for possible allergy to all drugs to which the patient was exposed even where chlorhexidine is positive. PMID:28194756

The Daniel K. Inouye College of Pharmacy Scripts: Updates on Clostridium difficile Infection: Advances in Laboratory Testing to Aid Diagnosis and Treatment.

PubMed

Lteif, Louis

2017-02-01

Clostridium difficile remains a major source of nosocomial infections and associated diarrhea. More recently, community-acquired cases are on the rise creating a concern for a serious public health threat. Appropriate infection control precautions as well as prevention and optimal management may help to avoid detrimental outbreaks. A key step is utilizing laboratory testing for quick and accurate diagnosis of potential cases. This overview article describes Clostridium difficile infection control and prevention methods and updates the most recent management strategies including a focus on the utilization and interpretation of laboratory diagnostic testing and appropriate treatment.

Superior Diagnostic Performance of Malaria Rapid Diagnostic Tests as compared to Blood Smears in U.S. Clinical Practice

PubMed Central

Stauffer, William M.; Cartwright, Charles P.; Olson, Douglas; Juni, Billie Anne; Taylor, Charlotte M; Bowers, Susan H.; Hanson, Kevan L.; Rosenblatt, Jon E.; Boulware, David R.

2010-01-01

Background Approximately 4 million U.S. travelers to developing countries are ill enough to seek healthcare with 1,500 malaria cases reported in the U.S. annually. The diagnosis of malaria is frequently delayed due to the time to prepare malaria blood films and lack of technical expertise. An easy, reliable rapid diagnostic test (RDT) with high sensitivity and negative predictive value (NPV), particularly for Plasmodium falciparum, would be clinically useful. The study objective was to determine the diagnostic performance of the FDA-approved NOW® Malaria Test in comparison to traditional thick and thin blood smears for malaria diagnosis. Methods This prospective study tested 852 consecutive blood samples sent for thick and thin smears with blinded, malaria rapid tests at three hospital laboratories during 2003–2006. Polymerase chain reaction (PCR) verified positive tests and discordant results. Results Malaria occurred in 11% (95/852). The rapid test had superior performance than the standard Giemsa thick blood smear (P=.003). The rapid test’s sensitivity for all malaria was 97% (92/95) vs. 85% (81/95) by blood smear, and the RDT had superior NPV of 99.6% vs. 98.2% (P=.001). The P. falciparum performance was excellent with 100% rapid test sensitivity versus only 88% (65/74) by blood smear (P=.003). Conclusions This operational study demonstrates the FDA-approved rapid malaria test is superior to a single set of blood smears performed under routine U.S. clinical laboratory conditions. The most valuable clinical role of the RDT is in the rapid diagnosis or the exclusion of P. falciparum malaria, which is particularly useful in outpatient settings when evaluating febrile travelers. PMID:19686072

Current companion diagnostics in advanced colorectal cancer; getting a bigger and better piece of the pie

PubMed Central

Loree, Jonathan M.; Raghav, Kanwal P. S.

2017-01-01

While the treatment of colorectal cancer continues to rely heavily on conventional cytotoxic therapy, an increasing number of targeted agents are under development. Many of these treatments require companion diagnostic tests in order to define an appropriate population that will derive benefit. In addition, a growing number of biomarkers provide prognostic information about a patient’s malignancy. As we learn more about these biomarkers and their assays, selecting the appropriate companion diagnostic becomes increasingly important. In the case of many biomarkers, there are numerous assays which could provide the same information to a treating physician, however each assay has strengths and weaknesses. Institutions must balance cost, assay sensitivity, turn-around time, and labor resources when selecting which assay to offer. In this review we will discuss the current state of companion diagnostics available in metastatic colorectal cancer and explore emerging biomarkers and their assays. We will focus on KRAS, BRAF, HER2, and PIK3CA testing, as well as microsatellite stability assessment and multigene panels. PMID:28280626

High diagnostic accuracy of subcutaneous Triptorelin test compared with GnRH test for diagnosing central precocious puberty in girls.

PubMed

Freire, Analía Verónica; Escobar, María Eugenia; Gryngarten, Mirta Graciela; Arcari, Andrea Josefina; Ballerini, María Gabriela; Bergadá, Ignacio; Ropelato, María Gabriela

2013-03-01

The GnRH test is the gold standard to confirm the diagnosis of central precocious puberty (CPP); however, this compound is not always readily available. Diagnostic accuracy of subcutaneous GnRH analogues tests compared to classical GnRH test has not been reported. To evaluate the diagnostic accuracy of Triptorelin test (index test) compared to the GnRH test (reference test) in girls with suspicion of CPP. A prospective, case-control, randomized clinical trial was performed. CPP or precocious thelarche (PT) was diagnosed according to maximal LH response to GnRH test and clinical characteristics during follow-up. Forty-six girls with premature breast development randomly underwent two tests: (i) intravenous GnRH 100 μg, (ii) subcutaneous Triptorelin acetate (0.1 mg/m(2), to a maximum of 0.1 mg) with blood sampling at 0, 3 and 24 h for LH, FSH and estradiol ascertainment. Gonadotrophins and estradiol responses to Triptorelin test were measured by ultrasensitive assays. Clinical features were similar between CPP (n = 33) and PT (n = 13) groups. Using receiver operating characteristic curves, maximal LH response (LH-3 h) under Triptorelin test ≥ 7 IU/l by immunofluorometric assay (IFMA) or ≥ 8 IU/l by electrochemiluminescence immunoassay (ECLIA) confirmed the diagnosis of CPP with specificity of 1.00 (95% CI: 0.75-1.00) and sensitivity 0.76 (95% CI: 0.58-0.89). Considering either LH-3 h or maximal estradiol response at 24 h (cut-off value, 295 pm), maintaining the specificity at 1.00, the test sensitivity increased to 0.94 (95% CI: 0.80-0.99) and the diagnostic efficiency to 96%. The Triptorelin test had high accuracy for the differential diagnosis of CPP vs PT in girls providing a valid alternative to the classical GnRH test. This test also allowed a comprehensive evaluation of the pituitary-ovarian axis. © 2012 Blackwell Publishing Ltd.

[Protocols for the diagnostic verification of lymph node toxoplasmosis].

PubMed

Carosi, G; Ghezzi, L G; Filice, G; Maccabruni, A; Parisi, A; Carnevale, G

1983-05-31

The protocol we have fixed for the diagnosis of lymphonodal toxoplasmosis includes a precise succession of tests: 1) specific repeated serological tests (I.H.A.T., I.F.A.T., IgM--I.F.A.T. on total serum and on pure IgM fraction); 2) lymphonodal biopsy for histological examination and biological test (isolation procedure in mouse). We have evaluated the effectiveness of our protocol in 20 cases that we observed during 1980.

Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls Experienced in the THROMKID Quality Project.

PubMed

Maurer, M; Mesters, R; Schneppenheim, R; Knoefler, R; Streif, W

2015-05-01

Primary haemostasis defects comprise von Willebrand disease (VWD) and platelet disorders (PD). Although presenting with mild to moderate bleeding tendency in most cases, severe bleeding and blood loss may occur unexpectedly in trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the wide spectrum of clinical and laboratory manifestations. Platelet-type von Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD. Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs. A literature review revealed difficulties in diagnostic work-up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic use of platelet concentrates. A telephone survey of diagnostic practice with regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type 2B and PT-VWD remained unclear, but PT-VWD may be underestimated. An international study estimated that PT-VWD constitutes up to 15% of the total number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties with diagnosis and showed that some centres did not exclude PT-VWD in type 2B patients. Some authors emphasize that genetic testing is the gold standard for diagnosis, but functional testing allows immediate diagnosis. Due to the important therapeutic implications we suggest that type 2B VWD be confirmed by genetic testing and that in case of a negative result PT-VWD should be excluded. PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD should be treated with platelet concentrates. © Georg Thieme Verlag KG Stuttgart · New York.

Cost effectiveness of OptiMal® rapid diagnostic test for malaria in remote areas of the Amazon Region, Brazil

PubMed Central

2010-01-01

Background In areas with limited structure in place for microscopy diagnosis, rapid diagnostic tests (RDT) have been demonstrated to be effective. Method The cost-effectiveness of the Optimal® and thick smear microscopy was estimated and compared. Data were collected on remote areas of 12 municipalities in the Brazilian Amazon. Data sources included the National Malaria Control Programme of the Ministry of Health, the National Healthcare System reimbursement table, hospitalization records, primary data collected from the municipalities, and scientific literature. The perspective was that of the Brazilian public health system, the analytical horizon was from the start of fever until the diagnostic results provided to patient and the temporal reference was that of year 2006. The results were expressed in costs per adequately diagnosed cases in 2006 U.S. dollars. Sensitivity analysis was performed considering key model parameters. Results In the case base scenario, considering 92% and 95% sensitivity for thick smear microscopy to Plasmodium falciparum and Plasmodium vivax, respectively, and 100% specificity for both species, thick smear microscopy is more costly and more effective, with an incremental cost estimated at US$549.9 per adequately diagnosed case. In sensitivity analysis, when sensitivity and specificity of microscopy for P. vivax were 0.90 and 0.98, respectively, and when its sensitivity for P. falciparum was 0.83, the RDT was more cost-effective than microscopy. Conclusion Microscopy is more cost-effective than OptiMal® in these remote areas if high accuracy of microscopy is maintained in the field. Decision regarding use of rapid tests for diagnosis of malaria in these areas depends on current microscopy accuracy in the field. PMID:20937094

Increased Sensitivity of Diagnostic Mutation Detection by Re-analysis Incorporating Local Reassembly of Sequence Reads.

PubMed

Watson, Christopher M; Camm, Nick; Crinnion, Laura A; Clokie, Samuel; Robinson, Rachel L; Adlard, Julian; Charlton, Ruth; Markham, Alexander F; Carr, Ian M; Bonthron, David T

2017-12-01

Diagnostic genetic testing programmes based on next-generation DNA sequencing have resulted in the accrual of large datasets of targeted raw sequence data. Most diagnostic laboratories process these data through an automated variant-calling pipeline. Validation of the chosen analytical methods typically depends on confirming the detection of known sequence variants. Despite improvements in short-read alignment methods, current pipelines are known to be comparatively poor at detecting large insertion/deletion mutations. We performed clinical validation of a local reassembly tool, ABRA (assembly-based realigner), through retrospective reanalysis of a cohort of more than 2000 hereditary cancer cases. ABRA enabled detection of a 96-bp deletion, 4-bp insertion mutation in PMS2 that had been initially identified using a comparative read-depth approach. We applied an updated pipeline incorporating ABRA to the entire cohort of 2000 cases and identified one previously undetected pathogenic variant, a 23-bp duplication in PTEN. We demonstrate the effect of read length on the ability to detect insertion/deletion variants by comparing HiSeq2500 (2 × 101-bp) and NextSeq500 (2 × 151-bp) sequence data for a range of variants and thereby show that the limitations of shorter read lengths can be mitigated using appropriate informatics tools. This work highlights the need for ongoing development of diagnostic pipelines to maximize test sensitivity. We also draw attention to the large differences in computational infrastructure required to perform day-to-day versus large-scale reprocessing tasks.

Pleural tuberculosis: medical thoracoscopy greatly increases the diagnostic accuracy

PubMed Central

Mori, Pier Anselmo; Majori, Maria; Anghinolfi, Miriam; Silini, Enrico Maria; Gnetti, Letizia; Motta, Federica; Larini, Sandra; Montecchini, Sara; Pisi, Roberta; Calderaro, Adriana

2018-01-01

Our objective was to evaluate the efficacy of a standardised work-up in the diagnosis of pleural tuberculosis (TB) that included fibreoptic bronchoscopy and medical thoracoscopy. A consecutive series of 52 pleural TB patients observed during the period 2001–2015 was evaluated retrospectively. 20 females, mean (range) age 39.7 (18–74) years, and 32 males, mean (range) age 45.75 (21–83) years, were included (28 non-EU citizens (53.8%)). The diagnosis of TB infections was established by identification (using stains, culture or molecular tests) of Mycobacterium tuberculosis in the pleura, sputum and/or bronchial specimens, or by evidence of caseous granulomas on pleural biopsies. Patients with and without lung lesions were considered separately. The diagnostic yield of the microbiological tests on pleural fluid was 17.3% (nine out of 52 patients). Among the 18 patients with lung lesions, bronchial samples (washing, lavage or biopsy) were positive in 50% of cases (nine patients). Cultures of pleural biopsies were positive in 63% of cases (29 out of 46 patients); pleural histology was relevant in all patients. Without pleural biopsy, a diagnosis would have been reached in 15 out of 52 patients (28.6%) and in four of them only following culture at 30–40 days. An integrated diagnostic work-up that includes all the diagnostic methods of interventional pulmonology is required for a diagnosis of pleural TB. In the majority of patients, a diagnosis can be reached only with pleural biopsy. PMID:29318136

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.

Chemical burns of the oral mucosa: report of a case.

PubMed

Isenberg, S R; Hier, L A; Chauvin, P J

1996-03-01

Clinical diagnosis of a chemical burn of the oral mucous membranes may be a diagnostic challenge. This article's intent is to illustrate the typical appearance of a chemical mucosal burn and to increase awareness of the various compounds which, when in contact with the mucous membranes, can result in a burn. The authors present a case involving a self-inflicted chemical injury of the oral mucous membranes and illustrate how the submission of an easily-obtained tissue specimen for pathologic examination may aid in the diagnosis. Because these superficial tissues can be obtained and submitted without the need for local anesthetic, pathologic examination is a quick, easy, and valuable diagnostic test when a patient's history is difficult to obtain or intentionally misleading.

Two unusual anatomic variations create a diagnostic dilemma in distal ulnar nerve compression.

PubMed

Kiehn, Mark W; Derrick, Allison J; Iskandar, Bermans J

2008-09-01

Diagnosis of peripheral neuropathies is based upon patterns of functional deficits and electrodiagnostic testing. However, anatomic variations can lead to confounding patterns of physical and electrodiagnostic findings. Authors present a case of ulnar nerve compression due to a rare combination of anatomic variations, aberrant branching pattern, and FCU insertion at the wrist, which posed a diagnostic and therapeutic dilemma. The literature related to isolated distal ulnar motor neuropathy and anatomic variations of the ulnar nerve and adjacent structures is also reviewed. This case demonstrates how anatomic variations can complicate the interpretation of clinical and electrodiagnostic findings and underscores the importance of thorough exploration of the nerve in consideration for possible variations. (c) 2008 Wiley-Liss, Inc.

Occupational and Environmental Bronchiolar Disorders

PubMed Central

Cummings, Kristin J.; Kreiss, Kathleen

2015-01-01

Occupational and environmental causes of bronchiolar disorders are recognized on the basis of case reports, case series, and, less commonly, epidemiologic investigations. Pathology may be limited to the bronchioles or also involve other components of the respiratory tract, including the alveoli. A range of clinical, functional, and radiographic findings, including symptomatic disease lacking abnormalities on noninvasive testing, poses a diagnostic challenge and highlights the value of surgical biopsy. Disease clusters in workplaces and communities have identified new etiologies, drawn attention to indolent disease that may otherwise have been categorized as idiopathic, and expanded the spectrum of histopathologic responses to an exposure. More sensitive noninvasive diagnostic tools, evidence-based therapies, and ongoing epidemiologic investigation of at-risk populations are needed to identify, treat, and prevent exposure-related bronchiolar disorders. PMID:26024345

The Utility of Malaria Rapid Diagnostic Tests as a Tool in Enhanced Surveillance for Malaria Elimination in Vanuatu

PubMed Central

Guintran, Jean-Olivier; Iata, Harry; Anderson, Karen; Nausien, Johnny; Gresty, Karryn J; Waters, Norman C.; Vestergaard, Lasse S.; Taleo, George; Cheng, Qin

2016-01-01

Background As part of efforts to eliminate malaria, Vanuatu has piloted the implementation of enhanced malaria surveillance and response strategies since 2011. This involves passive case detection (PCD) in health facilities, proactive case detection (Pro-ACD) and reactive case detection (Re-ACD) in communities using malaria rapid diagnostic tests (RDTs). While RDTs improve case management, their utility for detection of malaria infections in ACDs in this setting is unclear. Methods The utility of malaria RDTs as diagnostic tools was evaluated in PCD, in five rounds of Pro-ACDs and five rounds of Re-ACDs conducted in Tafea and Torba Provinces between 2011 and 2014. The number of malaria infections detected by RDTs was compared to that detected by PCR from collected used-RDTs. Results PCD in Tafea Province (2013) showed a RDT-positive rate of 0.21% (2/939) and a PCR-positive rate of 0.44% (2/453), indicating less than 1% of suspected malaria cases in Tafea Province were due to malaria. In Pro-ACDs conducted in Tafea and Torba Provinces, RDT-positive rates in 2013 and 2014 were 0.14% (3/2145) and 0% (0/2823), respectively, while the corresponding PCR-positive rates were 0.72% (9/1242) and 0.79% (9/1141). PCR identified villages in both provinces appearing to be transmission foci with a small number of low-density infections, mainly P. falciparum infections. In five rounds of Re-ACD, RDTs did not identify any additional infections while PCR detected only one among 173 subjects screened. Conclusions PCD and Pro-ACDs demonstrate that both Tafea and Torba Provinces in Vanuatu has achieved very low malaria prevalence. In these low-transmission areas, conducting Pro-ACD and Re-ACDs using RDTs appears not cost-effective and may have limited impact on interrupting malaria transmission due to the small number of infections identified by RDTs and considerable operational resources invested. More sensitive, field deployable and affordable diagnostic tools will improve malaria surveillance in malaria elimination settings. PMID:27902755

[Quality of genetic services--analysis of medical genetic expert opinions solicited by private health insurance companies].

PubMed

Nippert, Reinhardt Peter; Schmidtke, Jörg

2012-01-01

Service quality for patients with genetic conditions can be assessed through the analysis of clinical genetic data sets, as was the case in this study. It represents a secondary analysis of a compilation of a single genetic expert's medical opinions covering the years 2000 to 2009, solicited by private health insurance companies with the intention of probing into medical necessity and adequacy of genetic testing ordered by physicians. Genetic testing has become an increasingly important part of clinical diagnostic services. Controlling these services does not only reduce costs but also saves patients from unwarranted over-utilisation. Therefore, the reasons given by doctors when ordering genetic tests are part of the quality of service delivery. The study revealed that more than 30% of the molecular genetic tests ordered lack sound medical reasoning and 30% of the cases studied show violation or neglect of guidelines and recommendations for diagnostic procedures with respect to genetic testing. In essence, the findings indicate a need for human genetic information among physicians. Their professional organisations are called upon to design and offer CME/CPD programmes in medical genetics to maintain and continually improve the quality of medical genetic care for patients with genetic conditions. Copyright © 2012. Published by Elsevier GmbH.

Interpretation of Negative Molecular Test Results in Patients With Suspected or Confirmed Ebola Virus Disease: Report of Two Cases.

PubMed

Edwards, Jeffrey K; Kleine, Christian; Munster, Vincent; Giuliani, Ruggero; Massaquoi, Moses; Sprecher, Armand; Chertow, Daniel S

2015-12-01

Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) is the most sensitive quantitative diagnostic assay for detection of Ebola virus in multiple body fluids. Despite the strengths of this assay, we present 2 cases of Ebola virus disease (EVD) and highlight the potential for false-negative results during the early and late stages of EVD. The first case emphasizes the low negative-predictive value of qRT-PCR during incubation and the early febrile stage of EVD, and the second case emphasizes the potential for false-negative results during recovery and late neurologic complications of EVD. Careful interpretation of test results are needed to guide difficult admission and discharge decisions in suspected or confirmed EVD.

Comparison of the serum and salivary antibodies to detect gastric Helicobacter pylori infection in Kashan (Iran).

PubMed

Piroozmand, Ahmad; Soltani, Babak; Razavizadeh, Mohsen; Matini, Amir Hasan; Gilasi, Hamid Reza; Zavareh, Abbas Nassaji; Soltani, Siamak

2017-12-01

Helicobacter pylori ( H. pylori ) is an important and common contagious human pathogen which may cause peptic ulcer and also gastric cancer. The definite diagnosis of it is made through invasive tests. Recently, non-invasive tests including serologic tests of serum and saliva have been conducted for diagnosis of H. pylori infection. In this research, the diagnostic values of serum and salivary serology were compared together to use salivary anti- H. pylori test as an alternative method in the future. During this prospective case-control study on patients who were candidates for endoscopy and gastric biopsy from March 2015 to April 2016 in Shahid Beheshti hospital, Kashan, Iran, serum and salivary samples were obtained for measurement of Immunoglobulin G (IgG) antibody levels against H. pylori by enzyme-linked immunosorbent assay (ELISA). Histopathology was the gold standard test. Statistical analysis was performed by SPSS software version 16. Statistical tests included Kolmogorov-Smirnov, independent-samples t-test, Chi-square, Mann-Whitney U, Kruskal-Wallis, McNemar and correlation. Of 123 patients, sixty-one patients (49.6%) were H. pylori -positive according to histology. The median levels of anti- H. pylori antibodies in serum (p<0.001) and saliva (p<0.001) of H. pylori -positive cases were significantly higher than H. pylori -negative cases. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and accuracy of serologic tests in serum were 75%, 79%, 3.5, 0.3, 77% and for saliva were 85%, 82%, 4.7, 0.18, 84% respectively. Diagnostic values of salivary ELISA are comparable to serum ELISA and can be used as an alternative modality for diagnosis of H. pylori infection.

Effectiveness of screening for gestational diabetes during the late gestational period among pregnant Turkish women.

PubMed

Kurtbas, Handan; Keskin, H Levent; Avsar, A Filiz

2011-06-01

To assess the incidence of gestational diabetes mellitus (GDM) beyond 30 gestational weeks (GW) in pregnant Turkish women and to determine the criteria for repeating the test during the late period of gestation when the results were normal after the initial screen. Two hundred pregnant women were enrolled. Maternal age, gravidity, parity and presence of other risk factors (family history of diabetes mellitus, habitual abortions, prior fetal macrosomia, obesity, gestational hypertension history) were collected. First, GDM was evaluated between the 24th and 28th GW by screening (50-g glucose challenge test) and diagnostic tests. This protocol was repeated again at least 1 month from the first screen at the 30th-34th GW in all patients, except those diagnosed with GDM due to an abnormal 3-h test. The results were compared with the clinical risk factors. In total, 19.5% of the cases had positive results in the first screening test. Six patients were diagnosed with GDM. Among the remaining 194 pregnancies, another 10 cases were diagnosed as having GDM with repeated tests, and the incidence of newly diagnosed GDM was 5.2%. Only the mean age (34.2 years) (P = 0.010) and a history of delivering a macrosomic infant (P < 0.010) were significantly high in the late-gestation GDM-positive cases. Even when early screening tests are negative, pregnancies with advanced maternal ages and those with a history of delivering a macrosomic infant should be re-evaluated for GDM during the late gestational period with screening and diagnostic tests. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Diagnostic Value of Leukocyte Esterase Test Strip Reagents for Rapid Clinical Diagnosis of Spontaneous Bacterial Peritonitis in Patients Admitted to Hospital Emergency Departments in Iran.

PubMed

Hashemian, Amir Masoud; Ahmadi, Koorosh; Zamani Moghaddam, Hamid; Zakeri, Hosein; Davoodi Navakh, Seyed Akbar; Sharifi, Mohammad Davood; Bahrami, Abdollah

2015-10-01

Spontaneous bacterial peritonitis (SBP) is a common and important clinical problem and is life-threatening in decompensated liver disease. Ascites fluid test by leukocyte esterase test strip has been recently proposed as an effective and rapid method to diagnose SBP in patients with cirrhosis. This study aimed to evaluate sensitivity and specificity of leukocyte esterase test strip in the diagnosis of SBP. The population of this research was all patients with cirrhosis and ascites admitted to the emergency room at Imam Reza (AS) hospital, Mashhad. A written consent was taken for inclusion in the study. 50 mL ascites sample was taken from all patients for use in a urine test strip (LER) (Urine Test Strips Convergys®Urine Matrix 11). The patient's ascites samples were evaluated for cell counting. Positive dipstick test for LER in this study considered as grade 3 +. The values of WBC > 500 cell/mm(3) or PMN > 250 cell/mm(3) considered as positive result of the gold standard method for the diagnosis of SBP. In this study, 100 patients with ascites due to cirrhosis, with an average age of 38.9 ± 6.54 years were evaluated. Twenty cases had positive results, of whom 17 cases were also detected based on the standard diagnostic criteria and other three cases were healthy individuals. Thus, sensitivity, specificity, positive and negative predictive values, and accuracy of the method were 95%, 96.3%, 85%, 97.5% and 95%, respectively. The use of leukocyte esterase urine dipstick test can be a quick and easy method in early diagnosis of SBP to start the treatment until preparation of SBP-cell count results.

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

Initial derivation of diagnostic clusters combining history elements and physical examination tests for symptomatic knee osteoarthritis.

PubMed

Décary, Simon; Feldman, Debbie; Frémont, Pierre; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Fallaha, Michel; Pelletier, Bruno; Belzile, Sylvain; Sylvestre, Marie-Pierre; Vendittoli, Pascal-André; Desmeules, François

2018-05-21

The aim of the present study was to assess the validity of clusters combining history elements and physical examination tests to diagnose symptomatic knee osteoarthritis (SOA) compared with other knee disorders. This was a prospective diagnostic accuracy study, in which 279 consecutive patients consulting for a knee complaint were assessed. History elements and standardized physical examination tests were obtained independently by a physiotherapist and compared with an expert physician's composite diagnosis, including clinical examination and imaging. Recursive partitioning was used to develop diagnostic clusters for SOA. Diagnostic accuracy measures were calculated, including sensitivity, specificity, and positive and negative likelihood ratios (LR+/-), with associated 95% confidence intervals (CIs). A total of 129 patients had a diagnosis of SOA (46.2%). Most cases (76%) had combined tibiofemoral and patellofemoral knee OA and 63% had radiological Kellgren-Lawrence grades of 2 or 3. Different combinations of history elements and physical examination tests were used in clusters accurately to discriminate SOA from other knee disorders. These included age of patients, body mass index, presence of valgus/varus knee misalignment, palpable knee crepitus and limited passive knee extension. Two clusters to rule in SOA reached an LR+ of 13.6 (95% CI 6.5 to 28.4) and three clusters to rule out SOA reached an LR- of 0.11 (95% CI 0.06 to 0.20). Diagnostic clusters combining history elements and physical examination tests were able to support the differential diagnosis of SOA compared with various knee disorders without relying systematically on imaging. This could support primary care clinicians' role in the efficient management of these patients. Copyright © 2018 John Wiley & Sons, Ltd.

Diagnostic sensitivity and specificity of a participatory disease surveillance method for highly pathogenic avian influenza in household chicken flocks in Indonesia.

PubMed

Robyn, M; Priyono, W B; Kim, L M; Brum, E

2012-06-01

A study was conducted to assess the diagnostic sensitivity and specificity of a disease surveillance method for diagnosis of highly pathogenic avian influenza (HPAI) outbreaks in household chicken flocks used by participatory disease surveillance (PDS) teams in Yogyakarta Province, Indonesia. The Government of Indonesia, in partnership with the Food and Agriculture Organization of the United Nations, has implemented a PDS method for the detection of HPAI outbreaks in poultry since 2006. The PDS method in Indonesia utilizes both a clinical case definition (CD) and the result of a commercial rapid antigen test kit Yogyakarta 55611, to diagnose HPAI outbreaks, primarily in backyard chicken flocks. The following diagnostic sensitivities and specificities were obtained relative to real-time reverse transcription-PCR as the gold standard diagnostic test: 1) 89% sensitivity (CI95: 75%-97%) and 96% specificity (CI95: 89%-99%) for the PDS CD alone; 2) 86% sensitivity (CI95: 71%-95%) and 99% specificity (CI95: 94%-100%) for the rapid antigen test alone; and 3) 84% sensitivity (CI95: 68%-94%) and 100% specificity (CI95: 96%-100%) for the PDS CD result combined with the rapid antigen test result. Based on these results, HPAI outbreaks in extensively raised household chickens can be diagnosed with sufficient sensitivity and specificity using the PDS method as implemented in Indonesia. Subject to further field evaluation, data from this study suggest that the diagnostic sensitivity of the PDS method may be improved by expanding the PDS CD to include more possible clinical presentations of HPAI and by increasing the number of rapid antigen tests to three different birds with HPAI-compatible signs of same flock.

Diagnostic accuracy of two multiplex real-time polymerase chain reaction assays for the diagnosis of meningitis in children in a resource-limited setting.

PubMed

Khumalo, Jermaine; Nicol, Mark; Hardie, Diana; Muloiwa, Rudzani; Mteshana, Phindile; Bamford, Colleen

2017-01-01

Accurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children. We developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H. influenzae, enteroviruses, mumps virus and herpes simplex virus. We tested residual CSF samples from children presenting to a local paediatric hospital over a one-year period, whose CSF showed an abnormal cell count. Results were compared with routine diagnostic tests and the final discharge diagnosis. We calculated accuracy of the bacterial RT-PCR assay compared to CSF culture and using World Health Organisation definitions of laboratory-confirmed bacterial meningitis. From 292 samples, bacterial DNA was detected in 12 (4.1%) and viral nucleic acids in 94 (32%). Compared to CSF culture, the sensitivity and specificity of the bacterial RT-PCR was 100% and 97.2% with complete agreement in organism identification. None of the cases positive by viral RT-PCR had a bacterial cause confirmed on CSF culture. Only 9/90 (10%) of patients diagnosed clinically as bacterial meningitis or partially treated bacterial meningitis tested positive with the bacterial RT-PCR. In this population the use of 2 multiplex RT-PCRs targeting 6 common pathogens gave promising results. If introduced into routine diagnostic testing, these multiplex RT-PCR assays would supplement other diagnostic tests, and have the potential to limit unnecessary antibiotic therapy and hospitalisation.

Diagnostic accuracy of two multiplex real-time polymerase chain reaction assays for the diagnosis of meningitis in children in a resource-limited setting

PubMed Central

Khumalo, Jermaine; Nicol, Mark; Hardie, Diana; Muloiwa, Rudzani; Mteshana, Phindile

2017-01-01

Introduction Accurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children. Methods We developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H. influenzae, enteroviruses, mumps virus and herpes simplex virus. We tested residual CSF samples from children presenting to a local paediatric hospital over a one-year period, whose CSF showed an abnormal cell count. Results were compared with routine diagnostic tests and the final discharge diagnosis. We calculated accuracy of the bacterial RT-PCR assay compared to CSF culture and using World Health Organisation definitions of laboratory-confirmed bacterial meningitis. Results From 292 samples, bacterial DNA was detected in 12 (4.1%) and viral nucleic acids in 94 (32%). Compared to CSF culture, the sensitivity and specificity of the bacterial RT-PCR was 100% and 97.2% with complete agreement in organism identification. None of the cases positive by viral RT-PCR had a bacterial cause confirmed on CSF culture. Only 9/90 (10%) of patients diagnosed clinically as bacterial meningitis or partially treated bacterial meningitis tested positive with the bacterial RT-PCR. Discussion In this population the use of 2 multiplex RT-PCRs targeting 6 common pathogens gave promising results. If introduced into routine diagnostic testing, these multiplex RT-PCR assays would supplement other diagnostic tests, and have the potential to limit unnecessary antibiotic therapy and hospitalisation. PMID:28346504

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...

[Peripheral lymphadenopathy in childhood--recommendations for diagnostic evaluation].

PubMed

Benesch, M; Kerbl, R; Wirnsberger, A; Stünzner, D; Mangge, H; Schenkeli, R; Deutsch, J

2000-01-01

Enlargement of peripheral lymph nodes most commonly caused by a local inflammatory process is frequently seen in childhood. The aim of the present study was to analyze the most common causes of peripheral lymphadenopathy and to develop a simple algorithm for the primary diagnostic evaluation of peripheral lymph node enlargement in this age group. Between April and September 1999 87 unselected children (median age: 5 1/2 years) with peripheral lymphadenopathy were referred to the Department of Pediatrics, University of Graz, for further investigation. EBV infection was diagnosed in 20 (23.0%) children. 19 (21.8%) patients had acute bacterial lymphadenitis. In 21 (24.1%) patients lymph node enlargement was classified as "post/parainfectious (viral)". Four patients each had toxoplasmosis and cat scratch disease. In 11 (12.6%) patients neither physical nor laboratory examinations revealed pathologic results. Among the remaining 8 children sarcoidosis and Hodgkin disease was diagnosed in one patient each. Small, soft, mobile, nontender, cervical, axillary or inguinal lymph nodes do not require further investigations. In case of enlarged, tender lymph nodes with overlying skin erythema and fever diagnostic evaluation should include complete blood count, erythrocyte sedimentation rate and/or c-reactive protein level, supplemented by appropriate antibody testing (EBV, CMV, Toxoplasma gondii, Bartonella henselae). Firm, enlarged, painless lymph nodes which are matted together and fixed to the skin or underlying tissues necessitate a more detailed diagnostic evaluation in order to exclude malignant or granulomatous diseases. Our study demonstrated that primary diagnostic evaluation of childhood peripheral lymphadenopathy is mainly based on clinical grounds. In most cases a small number of additionally performed laboratory tests allow to correctly identify the cause of the peripheral lymph node enlargement.

Occurrence of severe gastroenteritis in pups after canine parvovirus vaccine administration: a clinical and laboratory diagnostic dilemma.

PubMed

Decaro, Nicola; Desario, Costantina; Elia, Gabriella; Campolo, Marco; Lorusso, Alessio; Mari, Viviana; Martella, Vito; Buonavoglia, Canio

2007-01-26

A total of 29 faecal samples collected from dogs with diarrhoea following canine parvovirus (CPV) vaccination were tested by minor groove binder (MGB) probe assays for discrimination between CPV vaccine and field strains and by diagnostic tests for detection of other canine pathogens. Fifteen samples tested positive only for CPV field strains; however, both vaccine and field strains were detected in three samples. Eleven samples were found to contain only the vaccine strain, although eight of them tested positive for other pathogens of dogs. Only three samples were found to contain the vaccine strain without evidence of canine pathogens. The present study confirms that most cases of parvovirus-like disease occurring shortly after vaccination are related to infection with field strains of canine parvovirus type 2 (CPV-2) rather than to reversion to virulence of the modified live virus contained in the vaccine.

Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer.

PubMed

Allen, Victoria B; Gurusamy, Kurinchi Selvan; Takwoingi, Yemisi; Kalia, Amun; Davidson, Brian R

2016-07-06

Surgical resection is the only potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Laparoscopy can detect metastases not visualised on CT scanning, enabling better assessment of the spread of cancer (staging of cancer). This is an update to a previous Cochrane Review published in 2013 evaluating the role of diagnostic laparoscopy in assessing the resectability with curative intent in people with pancreatic and periampullary cancer. To determine the diagnostic accuracy of diagnostic laparoscopy performed as an add-on test to CT scanning in the assessment of curative resectability in pancreatic and periampullary cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OvidSP (from inception to 15 May 2016), and Science Citation Index Expanded (from 1980 to 15 May 2016). We included diagnostic accuracy studies of diagnostic laparoscopy in people with potentially resectable pancreatic and periampullary cancer on CT scan, where confirmation of liver or peritoneal involvement was by histopathological examination of suspicious (liver or peritoneal) lesions obtained at diagnostic laparoscopy or laparotomy. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. Two review authors independently performed data extraction and quality assessment using the QUADAS-2 tool. The specificity of diagnostic laparoscopy in all studies was 1 because there were no false positives since laparoscopy and the reference standard are one and the same if histological examination after diagnostic laparoscopy is positive. The sensitivities were therefore meta-analysed using a univariate random-effects logistic regression model. The probability of unresectability in people who had a negative laparoscopy (post-test probability for people with a negative test result) was calculated using the median probability of unresectability (pre-test probability) from the included studies, and the negative likelihood ratio derived from the model (specificity of 1 assumed). The difference between the pre-test and post-test probabilities gave the overall added value of diagnostic laparoscopy compared to the standard practice of CT scan staging alone. We included 16 studies with a total of 1146 participants in the meta-analysis. Only one study including 52 participants had a low risk of bias and low applicability concern in the patient selection domain. The median pre-test probability of unresectable disease after CT scanning across studies was 41.4% (that is 41 out of 100 participants who had resectable cancer after CT scan were found to have unresectable disease on laparotomy). The summary sensitivity of diagnostic laparoscopy was 64.4% (95% confidence interval (CI) 50.1% to 76.6%). Assuming a pre-test probability of 41.4%, the post-test probability of unresectable disease for participants with a negative test result was 0.20 (95% CI 0.15 to 0.27). This indicates that if a person is said to have resectable disease after diagnostic laparoscopy and CT scan, there is a 20% probability that their cancer will be unresectable compared to a 41% probability for those receiving CT alone.A subgroup analysis of people with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The post-test probability of unresectable disease after being considered resectable on both CT and diagnostic laparoscopy was 18% compared to 40.0% for those receiving CT alone. Diagnostic laparoscopy may decrease the rate of unnecessary laparotomy in people with pancreatic and periampullary cancer found to have resectable disease on CT scan. On average, using diagnostic laparoscopy with biopsy and histopathological confirmation of suspicious lesions prior to laparotomy would avoid 21 unnecessary laparotomies in 100 people in whom resection of cancer with curative intent is planned.

The Relationship between Types of Attention and Auditory Processing Skills: Reconsidering Auditory Processing Disorder Diagnosis

PubMed Central

Stavrinos, Georgios; Iliadou, Vassiliki-Maria; Edwards, Lindsey; Sirimanna, Tony; Bamiou, Doris-Eva

2018-01-01

Measures of attention have been found to correlate with specific auditory processing tests in samples of children suspected of Auditory Processing Disorder (APD), but these relationships have not been adequately investigated. Despite evidence linking auditory attention and deficits/symptoms of APD, measures of attention are not routinely used in APD diagnostic protocols. The aim of the study was to examine the relationship between auditory and visual attention tests and auditory processing tests in children with APD and to assess whether a proposed diagnostic protocol for APD, including measures of attention, could provide useful information for APD management. A pilot study including 27 children, aged 7–11 years, referred for APD assessment was conducted. The validated test of everyday attention for children, with visual and auditory attention tasks, the listening in spatialized noise sentences test, the children's communication checklist questionnaire and tests from a standard APD diagnostic test battery were administered. Pearson's partial correlation analysis examining the relationship between these tests and Cochrane's Q test analysis comparing proportions of diagnosis under each proposed battery were conducted. Divided auditory and divided auditory-visual attention strongly correlated with the dichotic digits test, r = 0.68, p < 0.05, and r = 0.76, p = 0.01, respectively, in a sample of 20 children with APD diagnosis. The standard APD battery identified a larger proportion of participants as having APD, than an attention battery identified as having Attention Deficits (ADs). The proposed APD battery excluding AD cases did not have a significantly different diagnosis proportion than the standard APD battery. Finally, the newly proposed diagnostic battery, identifying an inattentive subtype of APD, identified five children who would have otherwise been considered not having ADs. The findings show that a subgroup of children with APD demonstrates underlying sustained and divided attention deficits. Attention deficits in children with APD appear to be centred around the auditory modality but further examination of types of attention in both modalities is required. Revising diagnostic criteria to incorporate attention tests and the inattentive type of APD in the test battery, provides additional useful data to clinicians to ensure careful interpretation of APD assessments. PMID:29441033

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

Analysis of binary responses with outcome-specific misclassification probability in genome-wide association studies.

PubMed

Rekaya, Romdhane; Smith, Shannon; Hay, El Hamidi; Farhat, Nourhene; Aggrey, Samuel E

2016-01-01

Errors in the binary status of some response traits are frequent in human, animal, and plant applications. These error rates tend to differ between cases and controls because diagnostic and screening tests have different sensitivity and specificity. This increases the inaccuracies of classifying individuals into correct groups, giving rise to both false-positive and false-negative cases. The analysis of these noisy binary responses due to misclassification will undoubtedly reduce the statistical power of genome-wide association studies (GWAS). A threshold model that accommodates varying diagnostic errors between cases and controls was investigated. A simulation study was carried out where several binary data sets (case-control) were generated with varying effects for the most influential single nucleotide polymorphisms (SNPs) and different diagnostic error rate for cases and controls. Each simulated data set consisted of 2000 individuals. Ignoring misclassification resulted in biased estimates of true influential SNP effects and inflated estimates for true noninfluential markers. A substantial reduction in bias and increase in accuracy ranging from 12% to 32% was observed when the misclassification procedure was invoked. In fact, the majority of influential SNPs that were not identified using the noisy data were captured using the proposed method. Additionally, truly misclassified binary records were identified with high probability using the proposed method. The superiority of the proposed method was maintained across different simulation parameters (misclassification rates and odds ratios) attesting to its robustness.

Diagnostic challenges and case management of the first imported case of Plasmodium knowlesi in Sri Lanka.

PubMed

Dewanee Ranaweera, A; Danansuriya, Manjula N; Pahalagedera, Kusumawathie; de A W Gunasekera, W M Kumudunayana T; Dharmawardena, Priyani; Mak, Keng Wai; Wong, Pei-Sze Jeslyn; Li, Mei-Zhi Irene; Tan, Cheong Huat; Hapuarachchi, Hapuarachchige C; Herath, Hema D B; Fernando, Deepika

2017-03-21

Sri Lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. Imported malaria remains a challenge to resurgence of the disease. The diagnostic challenges encountered and the rapid response initiated to manage a Plasmodium infection, which was later confirmed as Plasmodium knowlesi, the first reported case from Sri Lanka, is discussed. An army officer who returned from Malaysia in October 2016 was found to be positive for Plasmodium both by microscopy and rapid diagnostic test (RDT) by the Anti Malaria Campaign Sri Lanka (AMC) during his third visit to a health care provider. Microscopy findings were suspicious of P. knowlesi infection as the smears showed parasite stages similar to both Plasmodium malariae and Plasmodium falciparum. Nested PCR at AMC confirmed Plasmodium genus, but not the species. In the absence of species confirmation, the patient was treated as a case of P. falciparum. The presence of P. knowlesi was later confirmed by a semi-nested PCR assay performed at the Environmental Health Institute, National Environmental Agency in Singapore. The parasite strain was also characterized by sequencing the circumsporozoite gene. Extensive case investigation including parasitological and entomological surveillance was carried out. Plasmodium knowlesi should be suspected in patients returning from countries in the South Asian region where the parasite is prevalent and when blood smear results are inconclusive.

Current Perception Threshold for Assessment of the Neurological Components of Hand-Arm Vibration Syndrome: A Review

PubMed Central

Kurozawa, Youichi; Hosoda, Takenobu; Nasu, Yoshiro

2010-01-01

Current perception threshold (CPT) has been proposed as a quantitative method for assessment of peripheral sensory nerve function. The aim of this review of selected reports is to provide an overview of CPT measurement for the assessment of the neurological component of hand-arm vibration syndrome (HAVS). The CPT values at 2000 Hz significantly increased for patients with HAVS. This result supports the previous histological findings that demyelination is found predominantly in the peripheral nerves in the hands of men exposed to hand-arm vibration. Diagnostic sensitivity and specificity were high for severe cases of Stockholm sensorineural (SSN) stage 3 compared with non-exposed controls, but not high for mild cases of SSN stage 1 or 2 and for carpal tunnel syndrome associated with HAVS. However, there are only a few studies on the diagnostic validity of the CPT test for the neurological components of HAVS. Further research is needed and should include diagnostic validity and standardizing of measurement conditions such as skin temperature. PMID:24031119

Accuracy of clinical diagnosis versus the World Health Organization case definition in the Amoy Garden SARS cohort.

PubMed

Wong, W N; Sek, Antonio C H; Lau, Rick F L; Li, K M; Leung, Joe K S; Tse, M L; Ng, Andy H W; Stenstrom, Robert

2003-11-01

To compare the diagnostic accuracy of emergency department (ED) physicians with the World Health Organization (WHO) case definition in a large community-based SARS (severe acute respiratory syndrome) cohort. This was a cohort study of all patients from Hong Kong's Amoy Garden complex who presented to an ED SARS screening clinic during a 2-month outbreak. Clinical findings and WHO case definition criteria were recorded, along with ED diagnoses. Final diagnoses were established independently based on relevant diagnostic tests performed after the ED visit. Emergency physician diagnostic accuracy was compared with that of the WHO SARS case definition. Sensitivity, specificity, predictive values and likelihood ratios were calculated using standard formulae. During the study period, 818 patients presented with SARS-like symptoms, including 205 confirmed SARS, 35 undetermined SARS and 578 non-SARS. Sensitivity, specificity and accuracy were 91%, 96% and 94% for ED clinical diagnosis, versus 42%, 86% and 75% for the WHO case definition. Positive likelihood ratios (LR+) were 21.1 for physician judgement and 3.1 for the WHO criteria. Negative likelihood ratios (LR-) were 0.10 for physician judgement and 0.67 for the WHO criteria, indicating that clinician judgement was a much more powerful predictor than the WHO criteria. Physician clinical judgement was more accurate than the WHO case definition. Reliance on the WHO case definition as a SARS screening tool may lead to an unacceptable rate of misdiagnosis. The SARS case definition must be revised if it is to be used as a screening tool in emergency departments and primary care settings.

Dyspnoea, thoracic pain and fever in a young caucasian female: A case report.

PubMed

Fois, Alessandro Giuseppe; Trisolini, Rocco; Ginesu, Giorgio Carlo; Zinellu, Elisabetta; Negri, Silvia; Cancellieri, Alessandra; Garau, Alessandra; Pirina, Pietro

2018-05-31

The diagnostic approach to patients with mediastinal pathology is not always simple and an improper diagnostic work-up can lead to significant diagnosis delay. We report on the case of a young woman who was admitted to the Emergency Department complaining of thoracic pain, dyspnoea, fever and productive cough. The physical examination showed a painful swelling over the sternum's upper left margin, which had become evident 4 months earlier. A Computer Tomography showed the presence of a retrosternal oval lesion (5.5 x 4 cm) infiltrating the thoracic wall and showed the presence of discretely enlarged mediastinal lymph nodes in several mediastinal stations. The Multidisciplinary Team decided to perform an ultrasound-guided biopsy of the retrosternal mass that showed an inflammatory pattern, whereas microbiology tests proved negative. The lack of improvement with medical therapy (non steroideal anti-inflammatories and antibiotics) and the clinical suspicion of malignancy led us to perform a surgical biopsy of the mass that finally proved to be diagnostic for Hodgkin's lymphoma. Mediastinal masses with an aggressive behavior, should always be considered to be potentially malignant. Surgical biopsy, sometimes, can be the only way to correctly diagnose the pathological process, especially in the case of Hodgkin's lymphoma in which few diagnostic cells (Reed-Sternberg cells) are generally embedded in an abundant inflammatory background tissue. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

FNA, core biopsy, or both for the diagnosis of lung carcinoma: Obtaining sufficient tissue for a specific diagnosis and molecular testing.

PubMed

Coley, Shana M; Crapanzano, John P; Saqi, Anjali

2015-05-01

Increasingly, minimally invasive procedures are performed to assess lung lesions and stage lung carcinomas. In cases of advanced-stage lung cancer, the biopsy may provide the only diagnostic tissue. The aim of this study was to determine which method-fine-needle aspiration (FNA), core biopsy (CBx), or both (B)--is optimal for providing sufficient tissue for rendering a specific diagnosis and pursuing molecular studies for guiding tumor-specific treatment. A search was performed for computed tomography-guided lung FNA, CBx, or B cases with rapid onsite evaluation. Carcinomas were assessed for the adequacy to render a specific diagnosis; this was defined as enough refinement to subtype a primary carcinoma or to assess a metastatic origin morphologically and/or immunohistochemically. In cases of primary lung adenocarcinoma, the capability of each modality to yield sufficient tissue for molecular studies (epidermal growth factor receptor, KRAS, or anaplastic lymphoma kinase) was also assessed. There were 210 cases, and 134 represented neoplasms, including 115 carcinomas. For carcinomas, a specific diagnosis was reached in 89% of FNA cases (33 of 37), 98% of CBx cases (43 of 44), and 100% of B cases (34 of 34). For primary lung adenocarcinomas, adequate tissue remained to perform molecular studies in 94% of FNA cases (16 of 17), 100% of CBx cases (19 of 19), and 86% of B cases (19 of 22). No statistical difference was found among the modalities for either reaching a specific diagnosis (p = .07, Fisher exact test) or providing sufficient tissue for molecular studies (p = .30, Fisher exact test). The results suggest that FNA, CBx, and B are comparable for arriving at a specific diagnosis and having sufficient tissue for molecular studies: they specifically attained the diagnostic and prognostic goals of minimally invasive procedures for lung carcinoma. © 2015 American Cancer Society.

Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association

PubMed Central

Ladogana, Saverio; Maruzzi, Matteo; Samperi, Piera; Perrotta, Silverio; Del Vecchio, Giovanni C.; Notarangelo, Lucia D.; Farruggia, Piero; Verzegnassi, Federico; Masera, Nicoletta; Saracco, Paola; Fasoli, Silvia; Miano, Maurizio; Girelli, Gabriella; Barcellini, Wilma; Zanella, Alberto; Russo, Giovanna

2017-01-01

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia. The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants. PMID:28151390

Development of a highly sensitive immunochromatographic detection kit for H5 influenza virus hemagglutinin using silver amplification.

PubMed

Wada, Atsuhiko; Sakoda, Yoshihiro; Oyamada, Takayoshi; Kida, Hiroshi

2011-12-01

H5N1, a highly pathogenic avian influenza virus (HPAIV), has become a serious epizootic threat to the poultry population in Asia. In addition, significant numbers of human cases of HPAIV infection have been reported to date. To prevent the spread of HPAIV among humans and to allow for timely medical intervention, a rapid and high sensitive method is needed to detect and subtype the causative HPAIVs. In the present study, a silver amplification technique used in photographic development was combined with immunochromatography technologies and a highly sensitive and rapid diagnostic test to detect the hemagglutinin of H5 influenza viruses was developed. The sensitivity of the test kit was increased 500 times by silver amplification. The sensitivity of the method was more than 10 times higher than those of conventional rapid influenza diagnostic tests, which detect viral nucleoproteins. The diagnostic system developed in the present study can therefore provide rapid and highly sensitive results and will be useful for diagnosis of H5 HPAIV infection in humans and animals. Copyright © 2011 Elsevier B.V. All rights reserved.

Validation of a new algorithm for a quick and easy RT-PCR-based ALK test in a large series of lung adenocarcinomas: Comparison with FISH, immunohistochemistry and next generation sequencing assays.

PubMed

Marchetti, Antonio; Pace, Maria Vittoria; Di Lorito, Alessia; Canarecci, Sara; Felicioni, Lara; D'Antuono, Tommaso; Liberatore, Marcella; Filice, Giampaolo; Guetti, Luigi; Mucilli, Felice; Buttitta, Fiamma

2016-09-01

Anaplastic Lymphoma Kinase (ALK) gene rearrangements have been described in 3-5% of lung adenocarcinomas (ADC) and their identification is essential to select patients for treatment with ALK tyrosine kinase inhibitors. For several years, fluorescent in situ hybridization (FISH) has been considered as the only validated diagnostic assay. Currently, alternative methods are commercially available as diagnostic tests. A series of 217 ADC comprising 196 consecutive resected tumors and 21 ALK FISH-positive cases from an independent series of 702 ADC were investigated. All specimens were screened by IHC (ALK-D5F3-CDx-Ventana), FISH (Vysis ALK Break-Apart-Abbott) and RT-PCR (ALK RGQ RT-PCR-Qiagen). Results were compared and discordant cases subjected to Next Generation Sequencing. Thirty-nine of 217 samples were positive by the ALK RGQ RT-PCR assay, using a threshold cycle (Ct) cut-off ≤35.9, as recommended. Of these positive samples, 14 were negative by IHC and 12 by FISH. ALK RGQ RT-PCR/FISH discordant cases were analyzed by the NGS assay with results concordant with FISH data. In order to obtain the maximum level of agreement between FISH and ALK RGQ RT-PCR data, we introduced a new scoring algorithm based on the ΔCt value. A ΔCt cut-off level ≤3.5 was used in a pilot series. Then the algorithm was tested on a completely independent validation series. By using the new scoring algorithm and FISH as reference standard, the sensitivity and the specificity of the ALK RGQ RT-PCR(ΔCt) assay were 100% and 100%, respectively. Our results suggest that the ALK RGQ RT-PCR test could be useful in clinical practice as a complementary assay in multi-test diagnostic algorithms or even, if our data will be confirmed in independent studies, as a standalone or screening test for the selection of patients to be treated with ALK inhibitors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identification of Shifts and Trends in Hydrometric Data in Canada Based on Several Detection Tests

NASA Astrophysics Data System (ADS)

Lauzon, N.; Lence, B. J.

2004-05-01

This work proposes new detection tests based on the Kohonen neural network and on fuzzy c-means for the identification of shifts and trends in data sequences. Annual mean and maximum flow sequences are considered as application case, for they have often been considered for the study of shifts and trends in hydrologic data. In recent years, several studies for the identification of trends have been accomplished with North American hydrometric data, often making use of only one detection test. The assumption here is that one cannot rely on only one test, and consequently several are employed in this work. A total of eight tests are considered, four for shifts and four for trends. Four of these tests, two for shifts and two for trends, are conventional statistical tests that are regularly employed, while the other four are developed based on the Kohonen neural network and on fuzzy c-means. Data from a group of 40 hydrometric stations across Canada are assessed for the detection of shifts and trends in time periods of 30, 40 and 50 years. While the results obtained confirm the conclusions of previous studies performed on similar groups of data, they also indicate that each test may behave differently from one another. For example, one test may detect a trend in a given sequence while the other tests do not, or vice-versa. Thus, the strategy of using several tests ensures not only that they may confirm each others diagnostics but also may complement each other in the case of divergent diagnostics, with the possibility of improving the final conclusion on the detection of shifts and trends. Using artificial intelligence techniques for the construction of detection tests constitutes also a departure from the use of statistics, and a discussion in this work on complementary studies (i.e. detection on multivariate cases) highlights the possibility of enhanced performance by the artificial intelligence-based tests compared with conventional detection tests.

Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG against Hemolysin E and Lipopolysaccharide

PubMed Central

Huw Davies, D.; Jain, Aarti; Nakajima, Rie; Liang, Li; Jasinskis, Algis; Supnet, Medalyn; Felgner, Philip L.; Teng, Andy; Pablo, Jozelyn; Molina, Douglas M.; Obaro, Stephen K.

2016-01-01

Inexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (∼500 seropositive antigens) and mainly low level, with a small number of stronger “hits,” whereas the profile in U.S. adults was < 1/5 as broad, consistent with endemic exposure in Nigeria. Nigerian profiles were largely unaffected by clinical diagnosis, although the response against t1477 (hemolysin E) consistently emerged as stronger in typhoid cases. The response to LPS was also a strong discriminator of healthy controls and typhoid, although LPS did not discriminate between typhoid and nontyphoidal Salmonella (NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease. PMID:27215295

Histopathologic and mutational analysis of a case of blue nevus-like melanoma.

PubMed

Dai, Julia; Tetzlaff, Michael T; Schuchter, Lynn M; Elder, David E; Elenitsas, Rosalie

2016-09-01

Blue nevi are a heterogeneous group of dermal melanocytic proliferations that share a common clinical appearance but remain controversial in their histopathologic and biologic distinction. While common blue nevi and cellular blue nevi are well-defined entities that are classified without significant controversy, the distinction between atypical cellular blue nevi and blue nevus-like melanoma remains diagnostically challenging. We report a case of a 46-year-old female with recurrent blue nevus-like melanoma of the scalp with liver metastases; mutational analysis showed GNA11 Q209L and BAP1 Q393 mutations. To our knowledge, this is the first case of blue nevus-like melanoma with GNA11 and BAP1 mutations. These particular mutations and the predilection for liver metastases in our patient's case underscore a fundamental biological relationship between blue nevi and uveal melanoma and suggest the two entities may prove amenable to similar diagnostic and prognostic testing and targeted therapies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of diagnostic ionizing radiation on pregnancy via TEM

NASA Astrophysics Data System (ADS)

Mohammed, W. H.; Artoli, A. M.

2008-08-01

In Sudan, X-rays are routinely used at least once for measurements of pelvis during the gestation period, though this is highly prohibited worldwide, except for a few life threatening cases. To demonstrate the effect of diagnostic ionizing radiation on uterus, fetus and neighboring tissues to the ovaries, two independent experiments on pregnant rabbits were conducted. The first experiment was a proof of concept that diagnostic ionizing radiation is hazardous throughout the gestation period. The second experiment was done through Transmission Electron Microscopy (TEM) to elucidate the morphological changes in the ultra structure of samples taken from irradiated pregnant rabbits. This study uses TEM to test the effect of diagnostic radiation of less than 0.6 Gray on the cellular level. Morphological changes have been captured and the images were analyzed to quantify these effects.

A connectionist model for diagnostic problem solving

NASA Technical Reports Server (NTRS)

Peng, Yun; Reggia, James A.

1989-01-01

A competition-based connectionist model for solving diagnostic problems is described. The problems considered are computationally difficult in that (1) multiple disorders may occur simultaneously and (2) a global optimum in the space exponential to the total number of possible disorders is sought as a solution. The diagnostic problem is treated as a nonlinear optimization problem, and global optimization criteria are decomposed into local criteria governing node activation updating in the connectionist model. Nodes representing disorders compete with each other to account for each individual manifestation, yet complement each other to account for all manifestations through parallel node interactions. When equilibrium is reached, the network settles into a locally optimal state. Three randomly generated examples of diagnostic problems, each of which has 1024 cases, were tested, and the decomposition plus competition plus resettling approach yielded very high accuracy.

Advancing prevention of sexually transmitted infections through point-of-care testing: target product profiles and landscape analysis.

PubMed

Toskin, Igor; Murtagh, Maurine; Peeling, Rosanna W; Blondeel, Karel; Cordero, Joanna; Kiarie, James

2017-12-01

Advancing the field of point-of-care testing (POCT) for STIs can rapidly and substantially improve STI control and prevention by providing targeted, essential STI services (case detection and screening). POCT enables definitive diagnosis and appropriate treatment in a single visit and home and community-based testing. Since 2014, the WHO Department of Reproductive Health and Research, in collaboration with technical partners, has completed four landscape analyses of promising diagnostics for use at or near the point of patient care to detect syphilis, Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis and the human papillomavirus. The analyses comprised a literature review and interviews. Two International Technical Consultations on STI POCTs (2014 and 2015) resulted in the development of target product profiles (TPP). Experts in STI microbiology, laboratory diagnostics, clinical management, public health and epidemiology participated in the consultations with representation from all WHO regions. The landscape analysis identified diagnostic tests that are either available on the market, to be released in the near future or in the pipeline. The TPPs specify 28 analytical and operational characteristics of POCTs for use in different populations for surveillance, screening and case management. None of the tests that were identified in the landscape analysis met all of the targets of the TPPs. More efforts of the global health community are needed to accelerate access to affordable quality-assured STI POCTs, particularly in low- and middle-income countries, by supporting the development of new diagnostic platforms as well as strengthening the validation and implementation of existing diagnostics according to internationally endorsed standards and the best available evidence. © World Health Organization 2017. Licensee BMJ Publishing Group Limited. This is an open access article distributed under the terms of the Creative Commons Attribution IGO License (https://creativecommons.org/licenses/by/3.0/igo), which permits use, distribution,and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. In any reproduction of this article there should not be any suggestion that WHO or this article endorse any specific organization or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL.

Diagnostic value of non stress test in latent phase of labor and maternal and fetal outcomes.

PubMed

Raouf, Shiva; Sheikhan, Fatemeh; Hassanpour, Shirin; Bani, Soheila; Torabi, Rogayye; Shamsalizadeh, Neda

2014-10-28

The Non Stress Test (NST) is the one of the significant diagnostic fetal well being testes. The purpose of this study is to access diagnostic value of NST during latent phase of labor by considering maternal and neonatal outcomes. This case study control study was performed on 450 healthy pregnant women with gestational age between 38-42 weeks in AL-Zahra teaching hospital in Tabriz, Iran. All participants underwent NST after being admitted to labor during their latent phase of delivery. Participants were divided into groups including the study group which included 150 participants with non-reactive NST results whereas 300 subjects with reactive NST results assigned in the control group. Subjects in both groups were hospitalized for pregnancy termination because of the delivery time. In order to find out the importance of routine performance of NST during delivery, the relationship between NST results and maternal and fetal outcomes was evaluated. Several criteria including type of delivery, meconium defecation, descent arrest, bradicardia, Apgar score, and still birth were compared between two types. Finding of this study showed that descent arrest occurred in 2.7% of the subjects in the study group, whereas it occurred in 4.7% of the participants in the control group (p=0.44). Bradicardia found in 28% of the participants in study group and 3.3% of the control group (p<0.001). The low Apgar Score was found in 2.7% of case group however; no the low apgar score detected in the control group. Meconium defecation observed in 11.3% of the subjects in the study group and 9.7% of the participants in control group (p=0.62). The amount of stillbirth were found in control group. There was a significant difference between the results of both groups in terms of bradicardia, descent arrest, and the low Apgar score and cesarean section. Results of this study revealed that participants in study group with nonreactive NST results had more fetal complications than those with reactive NST results. NST was found to be a value diagnostic test for diagnosis of fetal distress during delivery in the latent phase. This findings of this study suggest that NST should be performed routinely as a valuable diagnostic test during the latent phase of delivery.

Contribution of the private sector healthcare service providers to malaria diagnosis in a prevention of re-introduction setting.

PubMed

Fernando, Sumadhya Deepika; Dharmawardana, Priyani; Epasinghe, Geethanee; Senanayake, Niroshana; Rodrigo, Chaturaka; Premaratne, Risintha; Wickremasinghe, Rajitha

2016-10-18

Sri Lanka is currently in the prevention of re-introduction phase of malaria. The engagement of the private sector health care institutions in malaria surveillance is important. The purpose of the study was to determine the number of diagnostic tests carried out, the number of positive cases identified and the referral system for diagnosis in the private sector and to estimate the costs involved. This prospective study of private sector laboratories within the Colombo District of Sri Lanka was carried out over a 6-month period in 2015. The management of registered private sector laboratories was contacted individually and the purpose of the study was explained. A reporting format was developed and introduced for monthly reporting. Forty-one laboratories were eligible to be included in the study and 28 participated by reporting data on a monthly basis. Excluding blood bank samples and routine testing for foreign employment, malaria diagnostic tests were carried out on 973 individuals during the 6-month period and nine malaria cases were identified. In 2015, a total of 36 malaria cases were reported from Sri Lanka. Of these, 24 (67 %) were diagnosed in the Colombo District and 50 % of them were diagnosed in private hospitals. An equal number of cases were diagnosed from the private sector and government sector in the Colombo District in 2015. The private sector being a major contributor in the detection of imported malaria cases in the country should be actively engaged in the national malaria surveillance system.

Diagnosis and management of clinical and subclinical cobalamin deficiencies: why controversies persist in the age of sensitive metabolic testing.

PubMed

Carmel, Ralph

2013-05-01

In the past two decades, sensitive biochemical tests have uncovered cobalamin deficiency much more frequently than ever before. Almost all cases involve mild, biochemical changes without clinical manifestations (subclinical cobalamin deficiency; SCCD), whose health impact is unclear. Because the causes of SCCD are most often unknown, nonmalabsorptive, and seldom documented, controversy and confusion surround the diagnostic criteria and, inevitably, consequences and management of SCCD. To complicate matters, our grasp of the rarer clinical deficiency, usually a serious, progressive medical disease rooted in severe malabsorption, has receded as absorption testing has disappeared. Reexamining the accumulation of assumptions and misperceptions about cobalamin deficiency and distinguishing SCCD from clinical deficiency is long overdue. The biology of cobalamin provides an important starting point: cobalamin stores exceed daily losses so greatly and binding proteins regulate absorption so effectively that deficiency typically achieves clinical expression only after years of severe, relentless malabsorption. Dietary insufficiency, mild, partial malabsorption, and other incomplete, intermittent causes can usually produce only SCCD. Thus, the most fundamental difference between the two deficiencies is the relentlessness of the underlying cause, which determines prognosis and health impact. Inattention to absorptive status has exacerbated the limitations of biochemical testing. All the biochemical tests are highly sensitive but specificity is poor, no diagnostic gold standard exists, and diagnostic cutpoints fluctuate excessively. To limit the adverse diagnostic consequences, the diagnosis of SCCD, whose need for treatment is unclear, should be deferred unless at least two tests are abnormal. Indeed, cobalamin biology indicates that the absorption system, while enhancing cobalamin delivery, also sets a strict upper limit on it, which suggests that cobalamin excess is undesirable. Solving cobalamin deficiency requires balanced assessment of the different imperatives of clinical and public health concerns, better rationalization of diagnostic testing, consistent definitions of normality in relation to SCCD, and rational cutpoint selection. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Characteristics associated with requests by pathologists for second opinions on breast biopsies.

PubMed

Geller, Berta M; Nelson, Heidi D; Weaver, Donald L; Frederick, Paul D; Allison, Kimberly H; Onega, Tracy; Carney, Patricia A; Tosteson, Anna N A; Elmore, Joann G

2017-11-01

Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests. Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations. 115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses. Pathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions. 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/.

The diagnostic management of upper extremity deep vein thrombosis: A review of the literature.

PubMed

Kraaijpoel, Noémie; van Es, Nick; Porreca, Ettore; Büller, Harry R; Di Nisio, Marcello

2017-08-01

Upper extremity deep vein thrombosis (UEDVT) accounts for 4% to 10% of all cases of deep vein thrombosis. UEDVT may present with localized pain, erythema, and swelling of the arm, but may also be detected incidentally by diagnostic imaging tests performed for other reasons. Prompt and accurate diagnosis is crucial to prevent pulmonary embolism and long-term complications as the post-thrombotic syndrome of the arm. Unlike the diagnostic management of deep vein thrombosis (DVT) of the lower extremities, which is well established, the work-up of patients with clinically suspected UEDVT remains uncertain with limited evidence from studies of small size and poor methodological quality. Currently, only one prospective study evaluated the use of an algorithm, similar to the one used for DVT of the lower extremities, for the diagnostic workup of clinically suspected UEDVT. The algorithm combined clinical probability assessment, D-dimer testing and ultrasonography and appeared to safely and effectively exclude UEDVT. However, before recommending its use in routine clinical practice, external validation of this strategy and improvements of the efficiency are needed, especially in high-risk subgroups in whom the performance of the algorithm appeared to be suboptimal, such as hospitalized or cancer patients. In this review, we critically assess the accuracy and efficacy of current diagnostic tools and provide clinical guidance for the diagnostic management of clinically suspected UEDVT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnostic value of two commercial chromatographic "patient-side" tests in the diagnosis of acute canine leptospirosis.

PubMed

Gloor, C I; Schweighauser, A; Francey, T; Rodriguez-Campos, S; Vidondo, B; Bigler, B; Schuller, S

2017-03-01

To determine the diagnostic performance of two patient-side tests (RDT-1: Test-it™ and RDT-2 Witness®Lepto) in the early diagnosis of canine leptospirosis. Retrospective study of 108 dogs with leptospirosis and 53 controls. Leptospirosis was diagnosed based on compatible clinical and clinicopathologic signs and either a single microscopic agglutination test titre_ >800 (n=49), seroconversion (n=53), positive urine real time PCR (RT-PCR) (n=1), evidence of spirochaetes in silver-stained tissues (n=1) or a combination of these (n=4). Leptospirosis was excluded in dogs with a convincing alternative diagnosis and single microscopic agglutination testing titres _<200 (n=46) or lack of seroconversion (n=7). Indices of diagnostic accuracy of the rapid diagnostic tests were calculated by comparing admission rapid diagnostic test results to the final disease status. Rapid diagnostic test-1 was performed in 118 dogs, rapid diagnostic test-2 in 69 dogs and both tests in 26 dogs. Weak positive results occurred frequently representing 22·6% (rapid diagnostic test-1) and 32·3% (rapid diagnostic test-2) of all positive tests in dogs with leptospirosis. If weak positive rapid diagnostic tests were considered positive, rapid diagnostic test-1 and rapid diagnostic test-2 had sensitivities of 82 and 76%, specificities of 91 and 100%, positive predictive values of 94% and 100% and negative predictive values of 73% and 74%, respectively. There were some technical problems with rapid diagnostic test-1. The diagnostic performance of the rapid diagnostic tests is similar to that reported for the microscopic agglutination test. Both can support a diagnosis of leptospirosis with high specificity but leptospirosis cannot be excluded based on a negative admission test result. Both RDTs are useful in conjunction with other confirmatory tests. © 2017 British Small Animal Veterinary Association.

Chronic idiopathic anal pain. Results of a diagnostic-therapeutic protocol in a colorectal referral unit.

PubMed

Armañanzas, Laura; Arroyo, Antonio; Ruiz-Tovar, Jaime; López, Alberto; Santos, Jair; Moya, Pedro; Gómez, María Amparo; Candela, Fernando; Calpena, Rafael

2015-01-01

Chronic idiopathic anal pain (CIAP) remains a diagnosis of exclusion. Its study and management still lack a standardized protocol. The aim of this study is to evaluate the results obtained with the diagnostic-therapeutic protocol established in our service. We performed a retrospective study of patients diagnosed with CIAP at the Colorectal Unit of the General University Hospital of Elche, between 2005 and 2011. We evaluated 57 patients with a diagnosis of chronic anal pain for functional anorectal disease (FAD). After the application of our diagnostic protocol, final diagnosis of chronic anal pain (CAP) was achieved in 43 cases (75%), including 22 cases of descending perineum syndrome, 12 of proctalgia fugax, 2 of pudendal neuritis and 7 of coccydynia. In 14 patients exclusion diagnosis of CIAP was established. Among the therapies used on patients with CIAP, biofeedback combined with conservative measures improved symptoms in 43% of the cases. Sacral nerve stimulation was assessed in patients who did not respond to other treatments. Through proper anamnesis, physical examination and complementary tests, a specific diagnosis of the cause of CAP by FAD can be achieved, reducing exclusion diagnosis of CIAP to 25% of cases. Conservative measures combined with biofeedback achieved an improvement in pain in more than 40% of the cases of CIAP in our study. Sacral nerve stimulation can be considered as a treatment option in refractory cases. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

[Detecting the markers of HIV infection with the new enzyme immunoassay diagnostic kit "DS-EIA-HIV-AB-AG-SPECTRUM" at the laboratories of AIDS prevention and control centers in the Volga Federal District].

PubMed

Ivanova, N I; Peksheva, O Iu

2009-03-01

A possibility of simultaneously detecting specific antibodies to HIV-1 and HIV-2 by enzyme immunoassay (EIA) at lower concentrations than those by immunoblotting (IB), and well as an additional possibility of earlier diagnosis of HIV infection, by identifying the HIV-1 antigen p24 lay the foundation of the "DS-EIA-HIV-AB-AG-SPECTRUM" test system made by OOO "Research-and-Production Association "Diagnosticheskiye Sistemy" (Diagnostic Systems). These peculiarities were compared with those of IB at a number of laboratories of AIDS prevention and control centers in the Volga Federal District, by using native serum/plasma samples and a specially designed control panel. The analysis of the conducted studies to identify HIV-1 and HIV-2 antibodies and HIV-1 antigen p24 in 65 plasma/serum samples in the "DS-EIA-HIV-AB-AG-SPECTRUM" and "LIA-HIV-1/2" (OOO "Niarmedik plus") test systems while confirming the positive result indicated agreement in 57 (87.7%) cases. The diagnostic possibilities of the "DS-EIA-HIV-AB-AG-SPECTRUM" test system versus the "New Lav-Blot I" one to make a laboratory diagnosis of HIV infection were studied. Irrefragable answers as to the availability of HIV-1 markers in the study serum samples on the enciphered panel were provided by IB in 73.3% of cases and EIA in 92%.

Performance of nested RT-PCR on CSF for tuberculous meningitis diagnosis in HIV-infected patients.

PubMed

Gualberto, F A S; Gonçalves, M G; Fukasawa, L O; Santos, A M Ramos Dos; Sacchi, C T; Harrison, L H; Boulware, D R; Vidal, J E

2017-10-01

Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.

Is diagnostic accuracy for detecting pulmonary nodules in chest CT reduced after a long day of reading?

NASA Astrophysics Data System (ADS)

Krupinski, Elizabeth A.; Berbaum, Kevin S.; Caldwell, Robert; Schartz, Kevin M.

2012-02-01

Radiologists are reading more cases with more images, especially in CT and MRI and thus working longer hours than ever before. There have been concerns raised regarding fatigue and whether it impacts diagnostic accuracy. This study measured the impact of reader visual fatigue by assessing symptoms, visual strain via dark focus of accommodation, and diagnostic accuracy. Twenty radiologists and 20 radiology residents were given two diagnostic performance tests searching CT chest sequences for a solitary pulmonary nodule before (rested) and after (tired) a day of clinical reading. 10 cases used free search and navigation, and the other 100 cases used preset scrolling speed and duration. Subjects filled out the Swedish Occupational Fatigue Inventory (SOFI) and the oculomotor strain subscale of the Simulator Sickness Questionnaire (SSQ) before each session. Accuracy was measured using ROC techniques. Using Swensson's technique yields an ROC area = 0.86 rested vs. 0.83 tired, p (one-tailed) = 0.09. Using Swensson's LROC technique yields an area = 0.73 rested vs. 0.66 tired, p (one-tailed) = 0.09. Using Swensson's Loc Accuracy technique yields an area = 0.77 rested vs. 0.72 tired, p (one-tailed) = 0.13). Subjective measures of fatigue increased significantly from early to late reading. To date, the results support our findings with static images and detection of bone fractures. Radiologists at the end of a long work day experience greater levels of measurable visual fatigue or strain, contributing to a decrease in diagnostic accuracy. The decrease in accuracy was not as great however as with static images.

[Genetic diagnostics of pathogenic splicing abnormalities in the clinical laboratory--pitfalls and screening approaches].

PubMed

Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao

2010-12-01

In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.

Atypical Ewing sarcoma breakpoint region 1 fluorescence in-situ hybridization signal patterns in bone and soft tissue tumours: diagnostic experience with 135 cases.

PubMed

Vargas, A Cristina; Selinger, Christina I; Satgunaseelan, Laveniya; Cooper, Wendy A; Gupta, Ruta; Stalley, Paul; Brown, Wendy; Soper, Judy; Schatz, Julie; Boyle, Richard; Thomas, David M; Tattersall, Martin H N; Bhadri, Vivek A; Maclean, Fiona; Bonar, S Fiona; Scolyer, Richard A; Karim, Rooshdiya Z; McCarthy, Stanley W; Mahar, Annabelle; O'Toole, Sandra A

2016-12-01

Recurrent Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements characterize a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in-situ hybridization (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not associated classically with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5' centromeric region or 3' telomeric region signals) that do not fulfil the published diagnostic criteria for rearrangements. Using an EWSR1 break-apart probe, we performed FISH assays on formalin-fixed paraffin-embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic work-up. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% of the non-rearranged cases. In addition, we observed tumours unrelated to those described classically as EWSR1-associated that were technically EWSR1-rearranged in 6% of cases. Borderline levels of rearrangement (affecting 10-30% of lesional cells) were present in an additional 17% of these cases. While our study confirmed that FISH is a sensitive and specific tool in the diagnosis of EWSR1-associated tumours, atypical FISH signals and classical rearrangement in entities other than EWSR1-associated tumours can occur. Therefore, it is essential that the FISH result not be used as an isolated test, but must be evaluated in the context of clinical features, imaging, pathological and immunohistochemical findings. © 2016 John Wiley & Sons Ltd.

Early experiences on the feasibility, acceptability, and use of malaria rapid diagnostic tests at peripheral health centres in Uganda-insights into some barriers and facilitators.

PubMed

Asiimwe, Caroline; Kyabayinze, Daniel J; Kyalisiima, Zephaniah; Nabakooza, Jane; Bajabaite, Moses; Counihan, Helen; Tibenderana, James K

2012-01-23

While feasibility of new health technologies in well-resourced healthcare settings is extensively documented, it is largely unknown in low-resourced settings. Uganda's decision to deploy and scale up malaria rapid diagnostic tests (mRDTs) in public health facilities and at the community level provides a useful entry point for documenting field experience, acceptance, and predictive variables for technology acceptance and use. These findings are important in informing implementation of new health technologies, plans, and budgets in low-resourced national disease control programmes. A cross-sectional qualitative descriptive study at 21 health centres in Uganda was undertaken in 2007 to elucidate the barriers and facilitators in the introduction of mRDTs as a new diagnostic technology at lower-level health facilities. Pre-tested interview questionnaires were administered through pre-structured patient exit interviews and semi-structured health worker interviews to gain an understanding of the response to this implementation. A conceptual framework on technology acceptance and use was adapted for this study and used to prepare the questionnaires. Thematic analysis was used to generate themes from the data. A total of 52 of 57 health workers (92%) reported a belief that a positive mRDT result was true, although only 41 of 57 (64%) believed that treatment with anti-malarials was justified for every positive mRDT case. Of the same health workers, only 49% believed that a negative mRDT result was truly negative. Factors linked to these findings were related to mRDT acceptance and use, including the design and characteristics of the device, availability and quality of mRDT ancillary supplies, health worker capacity to investigate febrile cases testing negative with the device and provide appropriate treatment, availability of effective malaria treatments, reliability of the health commodity supply chain, existing national policy recommendations, individual health worker dynamism, and vitality of supervision. mRDTs were found to be acceptable to and used by the target users, provided clear policy guidelines exist, ancillary tools are easy to use and health supplies beyond the diagnostic tools are met. Based on our results, health workers' needs for comprehensive case management should be met, and specific guidance for managing febrile patients with negative test outcomes should be provided alongside the new health technology. The extent, to which the implementation process of mRDT-led, parasite-based diagnosis accommodates end user beliefs, attitudes, perceptions, and satisfaction, as well as technology learnability and suitability, influences the level of acceptance and use of mRDTs. The effectiveness of the health system in providing the enabling environment and the integration of the diagnostic tool into routine service delivery is critical.

Diagnostic criteria for Patulous Eustachian Tube: A proposal by the Japan Otological Society.

PubMed

Kobayashi, Toshimitsu; Morita, Masahiro; Yoshioka, Satoshi; Mizuta, Kunihiro; Ohta, Shigeto; Kikuchi, Toshiaki; Hayashi, Tatsuya; Kaneko, Akihiro; Yamaguchi, Nobumasa; Hashimoto, Sho; Kojima, Hiromi; Murakami, Shingo; Takahashi, Haruo

2018-02-01

Patulous Eustachian Tube (PET) is of increasing importance in otology. However, despite the abundance of diseases requiring a differential diagnosis from PET, such as superior semicircular canal dehiscence syndrome, perilymphatic fistula, acute low-tone sensorineural hearing loss, etc., there are currently no established diagnostic criteria for PET. In view of these circumstances, the Japan Otological Society (JOS) Eustachian Tube Committee proposed the diagnostic criteria for Patulous Eustachian Tube in 2012, in order to promote clinical research on PET. A revision was made in 2016, maintaining the original concept that the criteria should be very simple, avoid any contamination of "Definite PET" with uncertain cases. Moreover, it was also intended to minimize the number of cases that could be accidentally excluded even in the presence of some suspected findings ("Possible PET"). The criteria can be used by all otolaryngologists even without using the Eustachian tube function test apparatus. However, the use of such an apparatus may increase the chances of detecting "Definite PET". The algorithm for the diagnosis of PET using the criteria has also been described. The JOS diagnostic criteria for Patulous Eustachian Tube will further promote international scientific communication on PET. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetics and the investigation of developmental delay/intellectual disability.

PubMed

Srour, Myriam; Shevell, Michael

2014-04-01

Global developmental delay and intellectual disabilities are common reasons for diagnostic assessment by paediatricians. There are a multiplicity of possible causes many of which have genetic, management and treatment implications for the child and family. Genetic causes are estimated to be responsible for approximately a quarter to one-half of identified cases. The multiplicity of individually rare genetic causes challenges the practitioner with respect to the selection of diagnostic tests and accurate diagnosis. To assist the practitioner practice guidelines have been formulated and these are reviewed and summarised in this particular article.

[Autoantibody-associated autoimmune encephalitis and cerebellitis : Clinical presentation, diagnostic work-up and treatment].

PubMed

Lewerenz, J; Jarius, S; Wildemann, B; Wandinger, K-P; Leypoldt, F

2016-12-01

There is no other field of neurology where clinically relevant serological biomarkers have witnessed a surge in importance over the past decade resembling that in autoimmune encephalitis and cerebellitis. A multitude of newly discovered neuronal autoantibodies facilitate early diagnosis, estimation of prognosis, and therapeutic decision-making. However, this has led to growing uncertainty with regard to meaningful patient selection, the appropriate extent of testing, and management of seronegative cases. This review summarizes the essential aspects of the clinical presentation, diagnostic work-up, pathophysiology, and treatment of autoimmune encephalitis and cerebellitis.