Genetic counselors’ (GC) knowledge, awareness, and understanding of clinical next-generation sequencing (NGS) genomic testing

PubMed Central

Boland, PM; Ruth, K; Matro, JM; Rainey, KL; Fang, CY; Wong, YN; Daly, MB; Hall, MJ

2014-01-01

Genomic tests are increasingly complex, less expensive, and more widely available with the advent of next-generation sequencing (NGS). We assessed knowledge and perceptions among genetic counselors pertaining to NGS genomic testing via an online survey. Associations between selected characteristics and perceptions were examined. Recent education on NGS testing was common, but practical experience limited. Perceived understanding of clinical NGS was modest, specifically concerning tumor testing. Greater perceived understanding of clinical NGS testing correlated with more time spent in cancer-related counseling, exposure to NGS testing, and NGS-focused education. Substantial disagreement about the role of counseling for tumor-based testing was seen. Finally, a majority of counselors agreed with the need for more education about clinical NGS testing, supporting this approach to optimizing implementation. PMID:25523111

Increasing Complexity in Rule-Based Clinical Decision Support: The Symptom Assessment and Management Intervention.

PubMed

Lobach, David F; Johns, Ellis B; Halpenny, Barbara; Saunders, Toni-Ann; Brzozowski, Jane; Del Fiol, Guilherme; Berry, Donna L; Braun, Ilana M; Finn, Kathleen; Wolfe, Joanne; Abrahm, Janet L; Cooley, Mary E

2016-11-08

Management of uncontrolled symptoms is an important component of quality cancer care. Clinical guidelines are available for optimal symptom management, but are not often integrated into the front lines of care. The use of clinical decision support (CDS) at the point-of-care is an innovative way to incorporate guideline-based symptom management into routine cancer care. The objective of this study was to develop and evaluate a rule-based CDS system to enable management of multiple symptoms in lung cancer patients at the point-of-care. This study was conducted in three phases involving a formative evaluation, a system evaluation, and a contextual evaluation of clinical use. In Phase 1, we conducted iterative usability testing of user interface prototypes with patients and health care providers (HCPs) in two thoracic oncology clinics. In Phase 2, we programmed complex algorithms derived from clinical practice guidelines into a rules engine that used Web services to communicate with the end-user application. Unit testing of algorithms was conducted using a stack-traversal tree-spanning methodology to identify all possible permutations of pathways through each algorithm, to validate accuracy. In Phase 3, we evaluated clinical use of the system among patients and HCPs in the two clinics via observations, structured interviews, and questionnaires. In Phase 1, 13 patients and 5 HCPs engaged in two rounds of formative testing, and suggested improvements leading to revisions until overall usability scores met a priori benchmarks. In Phase 2, symptom management algorithms contained between 29 and 1425 decision nodes, resulting in 19 to 3194 unique pathways per algorithm. Unit testing required 240 person-hours, and integration testing required 40 person-hours. In Phase 3, both patients and HCPs found the system usable and acceptable, and offered suggestions for improvements. A rule-based CDS system for complex symptom management was systematically developed and tested. The complexity of the algorithms required extensive development and innovative testing. The Web service-based approach allowed remote access to CDS knowledge, and could enable scaling and sharing of this knowledge to accelerate availability, and reduce duplication of effort. Patients and HCPs found the system to be usable and useful. ©David F Lobach, Ellis B Johns, Barbara Halpenny, Toni-Ann Saunders, Jane Brzozowski, Guilherme Del Fiol, Donna L Berry, Ilana M Braun, Kathleen Finn, Joanne Wolfe, Janet L Abrahm, Mary E Cooley. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 08.11.2016.

Five different tests of reaction time evaluated in HIV seropositive men.

PubMed

Dunlop, O; Bjørklund, R A; Abdelnoor, M; Myrvang, B

1992-09-01

In an attempt to develop a short neuropsychological test battery five different tests of reaction time were assessed according to their ability to discriminate between HIV seropositive men and healthy controls. In all tests a patient group with clinical symptoms was slower than the control group. In the complex reaction time test, which has a large cognitive aspect, even a clinically "asymptomatic" group was slower than the control group. The movement test, a new test with a large motor component, identified most slow responders, defining approximately half of the patients with clinical symptoms and one third of the "asymptomatic" patients as such. A test battery consisting of three tests is suggested for serial assessment and screening.

[Automated procedures for microscopic analyses of blood smears: medical testing a MECOS-Ts2 complex].

PubMed

Pliasunova, S A; Balugian, R Sh; Khmel'nitskiĭ, K E; Medovyĭ, V S; Parpara, A A; Piatnitskiĭ, A M; Sokolinskiĭ, B Z; Dem'ianov, V L; Nikolaenko, D S

2006-10-01

The paper presents the results of medical tests of a group of computer-aided procedures for microscopic analysis by means of a MECOS-Ts2 complex (ZAO "MECOS", Russia), which have been conducted at the Republican Children's Clinical Hospital, the Research Institute of Emergency Pediatric Surgery and Traumatology, and Moscow City Clinical Hospital No. 23. Computer-aided procedures for calculating the differential count and for analyzing the morphology of red blood cells were tested on blood smears from a total of 443 patients and donors, computer-aided calculation of the count of reticulocytes was tested on 318 smears. The tests were carried out under the US standard NCCLS-H20A. Manual microscopy (443 smears) and flow blood analysis on a Coulter GEN*S (125 smears) were used as reference methods. The quality of collection of samples and laboriousness were additionally assessed. The certified MECOS-Ts2 subsystems were additionally used as reference tools. The tests indicated the advantage of computer-aided MECOS-Tsl2 complex microscopy over manual microscopy.

Application of the Capilia TB assay for culture confirmation of Mycobacterium tuberculosis complex isolates.

PubMed

Hillemann, D; Rüsch-Gerdes, S; Richter, E

2005-12-01

The usefulness of a low-tech rapid test for culture confirmation of Mycobacterium tuberculosis complex, Capilia TB, was tested on 172 mycobacteria-positive clinical samples. The overall sensitivity and specificity were 92.4% and 100%, respectively. In three of nine false-negative isolates a mutation in the mpb64 gene could be detected.

CAP/ACMG proficiency testing for biochemical genetics laboratories: a summary of performance.

PubMed

Oglesbee, Devin; Cowan, Tina M; Pasquali, Marzia; Wood, Timothy C; Weck, Karen E; Long, Thomas; Palomaki, Glenn E

2018-01-01

PurposeTesting for inborn errors of metabolism is performed by clinical laboratories worldwide, each utilizing laboratory-developed procedures. We sought to summarize performance in the College of American Pathologists' (CAP) proficiency testing (PT) program and identify opportunities for improving laboratory quality. When evaluating PT data, we focused on a subset of laboratories that have participated in at least one survey since 2010.MethodsAn analysis of laboratory performance (2004 to 2014) on the Biochemical Genetics PT Surveys, a program administered by CAP and the American College of Medical Genetics and Genomics. Analytical and interpretive performance was evaluated for four tests: amino acids, organic acids, acylcarnitines, and mucopolysaccharides.ResultsSince 2010, 150 laboratories have participated in at least one of four PT surveys. Analytic sensitivities ranged from 88.2 to 93.4%, while clinical sensitivities ranged from 82.4 to 91.0%. Performance was higher for US participants and for more recent challenges. Performance was lower for challenges with subtle findings or complex analytical patterns.ConclusionUS clinical biochemical genetics laboratory proficiency is satisfactory, with a minority of laboratories accounting for the majority of errors. Our findings underscore the complex nature of clinical biochemical genetics testing and highlight the necessity of continuous quality management.

Delayed LGI1 seropositivity in voltage-gated potassium channel (VGKC)-complex antibody limbic encephalitis

PubMed Central

Sweeney, Michael; Galli, Jonathan; McNally, Scott; Tebo, Anne; Haven, Thomas; Thulin, Perla; Clardy, Stacey L

2017-01-01

We utilise a clinical case to highlight why exclusion of voltage-gated potassium channel (VGKC)-complex autoantibody testing in serological evaluation of patients may delay or miss the diagnosis. A 68-year-old man presented with increasing involuntary movements consistent with faciobrachial dystonic seizures (FBDS). Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) seronegativity. Aggressive immunotherapy with methylprednisolone and plasmapheresis was started early in the course of his presentation. Following treatment with immunotherapy, the patient demonstrated clinical improvement. Repeat serum evaluation 4 months posthospitalisation remained seropositive for VGKC-complex antibodies, with development of LGI1 autoantibody seropositivity. VGKC-complex and LGI1 antibodies remained positive 12 months posthospitalisation. Our findings suggest that clinical symptoms can predate the detection of the antibody. We conclude that when suspicion for autoimmune encephalitis is high in the setting of VGKC autoantibody positivity, regardless of LGI1 or CASPR2 seropositivity, early immunotherapy and repeat testing should be considered. PMID:28432047

Delayed LGI1 seropositivity in voltage-gated potassium channel (VGKC)-complex antibody limbic encephalitis.

PubMed

Sweeney, Michael; Galli, Jonathan; McNally, Scott; Tebo, Anne; Haven, Thomas; Thulin, Perla; Clardy, Stacey L

2017-04-20

We utilise a clinical case to highlight why exclusion of voltage-gated potassium channel (VGKC)-complex autoantibody testing in serological evaluation of patients may delay or miss the diagnosis. A 68-year-old man presented with increasing involuntary movements consistent with faciobrachial dystonic seizures (FBDS). Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) seronegativity. Aggressive immunotherapy with methylprednisolone and plasmapheresis was started early in the course of his presentation. Following treatment with immunotherapy, the patient demonstrated clinical improvement. Repeat serum evaluation 4 months posthospitalisation remained seropositive for VGKC-complex antibodies, with development of LGI1 autoantibody seropositivity. VGKC-complex and LGI1 antibodies remained positive 12 months posthospitalisation. Our findings suggest that clinical symptoms can predate the detection of the antibody. We conclude that when suspicion for autoimmune encephalitis is high in the setting of VGKC autoantibody positivity, regardless of LGI1 or CASPR2 seropositivity, early immunotherapy and repeat testing should be considered. 2017 BMJ Publishing Group Ltd.

Checklist for clinical readiness published

Cancer.gov

Scientists from NCI, together with collaborators from outside academic centers, have developed a checklist of criteria to evaluate the readiness of complex molecular tests that will guide decisions made during clinical trials. The checklist focuses on tes

Ethical and social implications of genetic testing for communication disorders.

PubMed

Arnos, Kathleen S

2008-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests.

Ethical and social implications of genetic testing for communication disorders

PubMed Central

Arnos, Kathleen S.

2013-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. Learning outcomes As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests. PMID:18452941

The laboratory diagnosis of syphilis.

PubMed

Ratnam, Sam

2005-01-01

Syphilis has several clinical manifestations, making laboratory testing a very important aspect of diagnosis. In North America, many unsuspected cases are discovered by laboratory testing. The etiological agent, Treponema pallidum, cannot be cultured, and there is no single optimal alternative test. Serological testing is the most frequently used approach in the laboratory diagnosis of syphilis. The present paper discusses the various serological and alternative tests currently available along with their limitations, and relates their results to the likely corresponding clinical stage of the disease. The need to use multiple tests is discussed, and the importance of quality control is noted. The complexity of syphilis serology means that the services of reference laboratories and clinical experts are often needed.

Molecular identification and amphotericin B susceptibility testing of clinical isolates of Aspergillus from 11 hospitals in Korea.

PubMed

Heo, Min Seok; Shin, Jong Hee; Choi, Min Ji; Park, Yeon Joon; Lee, Hye Soo; Koo, Sun Hoe; Lee, Won Gil; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook

2015-11-01

We investigated the species distribution and amphotericin B (AMB) susceptibility of Korean clinical Aspergillus isolates by using two Etests and the CLSI broth microdilution method. A total of 136 Aspergillus isolates obtained from 11 university hospitals were identified by sequencing the internal transcribed spacer (ITS) and β-tubulin genomic regions. Minimal inhibitory concentrations (MICs) of AMB were determined in Etests using Mueller-Hinton agar (Etest-MH) and RPMI agar (Etest-RPG), and categorical agreement with the CLSI method was assessed by using epidemiological cutoff values. ITS sequencing identified the following six Aspergillus species complexes: Aspergillus fumigatus (42.6% of the isolates), A. niger (23.5%), A. flavus (17.6%), A. terreus (11.0%), A. versicolor (4.4%), and A. ustus (0.7%). Cryptic species identifiable by β-tubulin sequencing accounted for 25.7% (35/136) of the isolates. Of all 136 isolates, 36 (26.5%) had AMB MICs of ≥2 μg/mL by the CLSI method. The categorical agreement of Etest-RPG with the CLSI method was 98% for the A. fumigatus, A. niger, and A. versicolor complexes, 87% for the A. terreus complex, and 37.5% for the A. flavus complex. That of Etest-MH was ≤75% for the A. niger, A. flavus, A. terreus, and A. versicolor complexes but was higher for the A. fumigatus complex (98.3%). Aspergillus species other than A. fumigatus constitute about 60% of clinical Aspergillus isolates, and reduced AMB susceptibility is common among clinical isolates of Aspergillus in Korea. Molecular identification and AMB susceptibility testing by Etest-RPG may be useful for characterizing Aspergillus isolates of clinical relevance.

Genetic counselors' (GC) knowledge, awareness, understanding of clinical next-generation sequencing (NGS) genomic testing.

PubMed

Boland, P M; Ruth, K; Matro, J M; Rainey, K L; Fang, C Y; Wong, Y N; Daly, M B; Hall, M J

2015-12-01

Genomic tests are increasingly complex, less expensive, and more widely available with the advent of next-generation sequencing (NGS). We assessed knowledge and perceptions among genetic counselors pertaining to NGS genomic testing via an online survey. Associations between selected characteristics and perceptions were examined. Recent education on NGS testing was common, but practical experience limited. Perceived understanding of clinical NGS was modest, specifically concerning tumor testing. Greater perceived understanding of clinical NGS testing correlated with more time spent in cancer-related counseling, exposure to NGS testing, and NGS-focused education. Substantial disagreement about the role of counseling for tumor-based testing was seen. Finally, a majority of counselors agreed with the need for more education about clinical NGS testing, supporting this approach to optimizing implementation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessment of complex dissociative disorder patients and simulated dissociation in forensic contexts.

PubMed

Brand, Bethany L; Webermann, Aliya R; Frankel, A Steven

Few assessors receive training in assessing dissociation and complex dissociative disorders (DDs). Potential differential diagnoses include anxiety, mood, psychotic, substance use, and personality disorders, as well as exaggeration and malingering. Individuals with DDs typically elevate on many clinical and validity scales on psychological tests, yet research indicates that they can be distinguished from DD simulators. Becoming informed about the testing profiles of DD individuals and DD simulators can improve the accuracy of differential diagnoses in forensic settings. In this paper, we first review the testing profiles of individuals with complex DDs and contrast them with DD simulators on assessment measures used in forensic contexts, including the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Personality Assessment Inventory (PAI), and the Structured Inventory of Reported Symptoms (SIRS), as well as dissociation-specific measures such as the Dissociative Experiences Scale (DES) and Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D-R). We then provide recommendations for assessing complex trauma and dissociation through the aforementioned assessments. Copyright © 2016 Elsevier Ltd. All rights reserved.

INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

PubMed Central

KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

2014-01-01

Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

Malaria rapid diagnostic tests.

PubMed

Wilson, Michael L

2012-06-01

Global efforts to control malaria are more complex than those for other infectious diseases, in part because of vector transmission, the complex clinical presentation of Plasmodium infections, >1 Plasmodium species causing infection, geographic distribution of vectors and infection, and drug resistance. The World Health Organization approach to global malaria control focuses on 2 components: vector control and diagnosis and treatment of clinical malaria. Although microscopy performed on peripheral blood smears remains the most widely used diagnostic test and the standard against which other tests are measured, rapid expansion of diagnostic testing worldwide will require use of other diagnostic approaches. This review will focus on the malaria rapid diagnostic test (MRDT) for detecting malaria parasitemia, both in terms of performance characteristics of MRDTs and how they are used under field conditions. The emphasis will be on the performance and use of MRDTs in regions of endemicity, particularly sub-Saharan Africa, where most malaria-related deaths occur.

A mixture gatekeeping procedure based on the Hommel test for clinical trial applications.

PubMed

Brechenmacher, Thomas; Xu, Jane; Dmitrienko, Alex; Tamhane, Ajit C

2011-07-01

When conducting clinical trials with hierarchically ordered objectives, it is essential to use multiplicity adjustment methods that control the familywise error rate in the strong sense while taking into account the logical relations among the null hypotheses. This paper proposes a gatekeeping procedure based on the Hommel (1988) test, which offers power advantages compared to other p value-based tests proposed in the literature. A general description of the procedure is given and details are presented on how it can be applied to complex clinical trial designs. Two clinical trial examples are given to illustrate the methodology developed in the paper.

Evaluation of flow cytometric HIT assays in relation to an IgG-Specific immunoassay and clinical outcome.

PubMed

Kerényi, Adrienne; Beke Debreceni, Ildikó; Oláh, Zsolt; Ilonczai, Péter; Bereczky, Zsuzsanna; Nagy, Béla; Muszbek, László; Kappelmayer, János

2017-09-01

Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment caused by platelet activating IgG antibodies generated against the platelet factor 4 (PF4)-heparin complex. Thrombocytopenia and thrombosis are the leading clinical symptoms of HIT. The clinical pretest probability of HIT was evaluated by the 4T score system. Laboratory testing of HIT was performed by immunological detection of antibodies against PF4-heparin complex (EIA) and two functional assays. Heparin-dependent activation of donor platelets by patient plasma was detected by flow cytometry. Increased binding of Annexin-V to platelets and elevated number of platelet-derived microparticles (PMP) were the indicators of platelet activation. EIA for IgG isotype HIT antibodies was performed in 405 suspected HIT patients. Based on negative EIA results, HIT was excluded in 365 (90%) of cases. In 40 patients with positive EIA test result functional tests were performed. Platelet activating antibodies were detected in 17 cases by Annexin V binding. PMP count analysis provided nearly identical results. The probability of a positive flow cytometric assay result was higher in patients with elevated antibody titer. 71% of patients with positive EIA and functional assay had thrombosis. EIA is an important first line laboratory test in the diagnosis of HIT; however, HIT must be confirmed by a functional test. Annexin V binding and PMP assays using flow cytometry are functional HIT tests convenient in a clinical diagnostic laboratory. The positive results of functional assays may predict the onset of thrombosis. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

42 CFR 493.1449 - Standard; Technical supervisor qualifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... service in which the laboratory performs high complexity tests or procedures. The director of a laboratory... may perform anatomic and clinical laboratory procedures and tests in all specialties and... tests in the subspecialty of bacteriology, the individual functioning as the technical supervisor must...

Managing Complexity: Impact of Organization and Processing Style on Nonverbal Memory in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Tsatsanis, Katherine D.; Noens, Ilse L. J.; Illmann, Cornelia L.; Pauls, David L.; Volkmar, Fred R.; Schultz, Robert T.; Klin, Ami

2011-01-01

The contributions of cognitive style and organization to processing and recalling a complex novel stimulus were examined by comparing the Rey Osterrieth Complex Figure (ROCF) test performance of children, adolescents, and adults with ASD to clinical controls (CC) and non-impaired controls (NC) using the "Developmental Scoring System."…

Clinical decision support for personalized medicine: an opportunity for pharmacist-physician collaboration.

PubMed

Barlow, Jane F

2012-06-01

Pharmacogenomics has significant potential to improve the efficacy and safety of medication therapy, but it requires new expertise and adds a new layer of complexity for all healthcare professionals. Pharmacists and pharmacy management systems can play a leading role in providing clinical decision support for the use and interpretation of pharmacogenomic tests. To serve this role effectively, pharmacists will need to expand their expertise in the emerging field of clinical pharmacogenomics. Pharmacy-based clinical programs can expedite the use of pharmacogenomic testing, help physicians interpret the test results and identify future medication risks associated with the patient's phenotype. Over time, some of these functions can be embedded in clinical decision support systems as part of the broader automation of the healthcare system.

Clinical decision making-a functional medicine perspective.

PubMed

Pizzorno, Joseph E

2012-09-01

As 21st century health care moves from a disease-based approach to a more patient-centric system that can address biochemical individuality to improve health and function, clinical decision making becomes more complex. Accentuating the problem is the lack of a clear standard for this more complex functional medicine approach. While there is relatively broad agreement in Western medicine for what constitutes competent assessment of disease and identification of related treatment approaches, the complex functional medicine model posits multiple and individualized diagnostic and therapeutic approaches, most or many of which have reasonable underlying science and principles, but which have not been rigorously tested in a research or clinical setting. This has led to non-rigorous thinking and sometimes to uncritical acceptance of both poorly documented diagnostic procedures and ineffective therapies, resulting in less than optimal clinical care.

Clinical Decision Making—A Functional Medicine Perspective

PubMed Central

2012-01-01

As 21st century health care moves from a disease-based approach to a more patient-centric system that can address biochemical individuality to improve health and function, clinical decision making becomes more complex. Accentuating the problem is the lack of a clear standard for this more complex functional medicine approach. While there is relatively broad agreement in Western medicine for what constitutes competent assessment of disease and identification of related treatment approaches, the complex functional medicine model posits multiple and individualized diagnostic and therapeutic approaches, most or many of which have reasonable underlying science and principles, but which have not been rigorously tested in a research or clinical setting. This has led to non-rigorous thinking and sometimes to uncritical acceptance of both poorly documented diagnostic procedures and ineffective therapies, resulting in less than optimal clinical care. PMID:24278827

Antibacterial, antibiofilm and antioxidant screening of copper(II)-complexes with some S-alkyl derivatives of thiosalicylic acid. Crystal structure of the binuclear copper(II)-complex with S-propyl derivative of thiosalicylic acid

NASA Astrophysics Data System (ADS)

Bukonjić, Andriana M.; Tomović, Dušan Lj.; Nikolić, Miloš V.; Mijajlović, Marina Ž.; Jevtić, Verica V.; Ratković, Zoran R.; Novaković, Slađana B.; Bogdanović, Goran A.; Radojević, Ivana D.; Maksimović, Jovana Z.; Vasić, Sava M.; Čomić, Ljiljana R.; Trifunović, Srećko R.; Radić, Gordana P.

2017-01-01

The spectroscopically predicted structure of the obtained copper(II)-complex with S-propyl derivative of thiosalicylic acid was confirmed by X-ray structural study. The binuclear copper(II)-complex with S-propyl derivative of thiosalicylic acid crystallized in two polymorphic forms with main structural difference in the orientation of phenyl rings relative to corresponding carboxylate groups. The antibacterial activity was tested determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) by using microdilution method. The influence on bacterial biofilm formation was determined by tissue culture plate method. In general, the copper(II)-complexes manifested a selective and moderate activity. The most sensitive bacteria to the effects of Cu(II)-complexes was a clinical isolate of Pseudomonas aeruginosa. For this bacteria MIC and biofilm inhibitory concentration (BIC) values for all tested complexes were in the range or better than the positive control, doxycycline. Also, for the established biofilm of clinical isolate Staphylococcus aureus, BIC values for the copper(II)-complex with S-ethyl derivative of thiosalicylic acid,[Cu2(S-et-thiosal)4(H2O)2] (C3) and copper(II)-complex with S-butyl derivative of thiosalicylic acid, [Cu2(S-bu-thiosal)4(H2O)2] (C5) were in range or better than the positive control. All the complexes acted better against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus aureus ATCC 25923) than Gram-negative bacteria (Proteus mirabilis ATCC 12453, Pseudomonas aeruginosa, and P. aeruginosa ATCC 27855). The complexes showed weak antioxidative properties tested by two methods (1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assay).

Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

PubMed

Peterson, Lisa K; Willis, Rohan; Harris, E Nigel; Branch, Ware D; Tebo, Anne E

2016-01-01

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts. © 2016 Elsevier Inc. All rights reserved.

Historical Increase in the Number of Factors Measured by Commercial Tests of Cognitive Ability: Are We Overfactoring?

ERIC Educational Resources Information Center

Frazier, Thomas W.; Youngstrom, Eric A.

2007-01-01

A historical increase in the number of factors purportedly measured by commercial tests of cognitive ability may result from four distinct pressures including: increasingly complex models of intelligence, test publishers' desires to provide clinically useful assessment instruments with greater interpretive value, test publishers' desires to…

Modeling Complex Workflow in Molecular Diagnostics

PubMed Central

Gomah, Mohamed E.; Turley, James P.; Lu, Huimin; Jones, Dan

2010-01-01

One of the hurdles to achieving personalized medicine has been implementing the laboratory processes for performing and reporting complex molecular tests. The rapidly changing test rosters and complex analysis platforms in molecular diagnostics have meant that many clinical laboratories still use labor-intensive manual processing and testing without the level of automation seen in high-volume chemistry and hematology testing. We provide here a discussion of design requirements and the results of implementation of a suite of lab management tools that incorporate the many elements required for use of molecular diagnostics in personalized medicine, particularly in cancer. These applications provide the functionality required for sample accessioning and tracking, material generation, and testing that are particular to the evolving needs of individualized molecular diagnostics. On implementation, the applications described here resulted in improvements in the turn-around time for reporting of more complex molecular test sets, and significant changes in the workflow. Therefore, careful mapping of workflow can permit design of software applications that simplify even the complex demands of specialized molecular testing. By incorporating design features for order review, software tools can permit a more personalized approach to sample handling and test selection without compromising efficiency. PMID:20007844

Web-Based Activity Within a Sexual Health Economy: Observational Study.

PubMed

Turner, Katy Me; Zienkiewicz, Adam K; Syred, Jonathan; Looker, Katharine J; de Sa, Joia; Brady, Michael; Free, Caroline; Holdsworth, Gillian; Baraitser, Paula

2018-03-07

Regular testing for sexually transmitted infections (STIs) is important to maintain sexual health. Self-sampling kits ordered online and delivered in the post may increase access, convenience, and cost-effectiveness. Sexual health economies may target limited resources more effectively by signposting users toward Web-based or face-to-face services according to clinical need. The aim of this paper was to investigate the impact of two interventions on testing activity across a whole sexual health economy: (1) the introduction of open access Web-based STI testing services and (2) a clinic policy of triage and signpost online where users without symptoms who attended clinics for STI testing were supported to access the Web-based service instead. Data on attendances at all specialist public sexual health providers in an inner-London area were collated into a single database. Each record included information on user demographics, service type accessed, and clinical activity provided, including test results. Clinical activity was categorized as a simple STI test (could be done in a clinic or online), a complex visit (requiring face-to-face consultation), or other. Introduction of Web-based services increased total testing activity across the whole sexual health economy by 18.47% (from 36,373 to 43,091 in the same 6-month period-2014-2015 and 2015-2016), suggesting unmet need for testing in the area. Triage and signposting shifted activity out of the clinic onto the Web-based service, with simple STI testing in the clinic decreasing from 16.90% (920/5443) to 12.25% (511/4172) of total activity, P<.001, and complex activity in the clinic increasing from 69.15% (3764/5443) to 74.86% (3123/4172) of total activity, P<.001. This intervention created a new population of online users with different demographic and clinical profiles from those who use Web-based services spontaneously. Some triage and signposted users (29.62%, 375/1266) did not complete the Web-based testing process, suggesting the potential for missed diagnoses. This evaluation shows that users can effectively be transitioned from face-to-face to Web-based services and that this introduces a new population to Web-based service use and changes the focus of clinic-based activity. Further development is underway to optimize the triage and signposting process to support test completion. ©Katy ME Turner, Adam K Zienkiewicz, Jonathan Syred, Katharine J Looker, Joia de Sa, Michael Brady, Caroline Free, Gillian Holdsworth, Paula Baraitser. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 07.03.2018.

Testing for EMC (electromagnetic compatibility) in the clinical environment.

PubMed

Paperman, D; David, Y; Martinez, M

1996-01-01

Testing for electromagnetic compatibility (EMC) in the clinical environment introduces a host of complex conditions not normally encountered under laboratory conditions. In the clinical environment, various radio-frequency (RF) sources of electromagnetic interference (EMI) may be present throughout the entire spectrum of interest. Isolating and analyzing the impact from the sources of interference to medical devices involves a multidisciplinary approach based on training in, and knowledge of, the following: operation of medical devices and their susceptibility to EMI; RF propagation modalities and interaction theory; spectrum analysis systems and techniques (preferably with signature analysis capabilities) and calibrated antennas; the investigation methodology of suspected EMC problems, and testing protocols and standards. Using combinations of standard test procedures adapted for the clinical environment with personnel that have an understanding of radio-frequency behavior increases the probability of controlling, proactively, EMI in the clinical environment, thus providing for a safe and more effective patient care environment.

Clinical application of high throughput molecular screening techniques for pharmacogenomics

PubMed Central

Wiita, Arun P; Schrijver, Iris

2011-01-01

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing. PMID:23226057

Genetics of hereditary neurological disorders in children.

PubMed

Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

2014-04-01

Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

A cooperative network of trained sites for the conduct of a complex clinical trial: a new concept in multicenter clinical research.

PubMed

Davidson, Robert M; McNeer, J Frederick; Logan, Leanne; Higginbotham, Michael B; Anderson, Jerome; Blackshear, Joseph; Chu, Alan; Hettleman, Bruce; McGrew, Frank; Meesse, Roderick; O'Connor, Christopher; Schneider, Ricky; Wagner, Galen S

2006-02-01

The purpose of this report is to present a model of physicians in full-time clinical practice participating as investigators in multicenter clinical trials, sponsored by a pharmaceutical or medical device company. This gas-exchange substudy was conducted as a pilot study to establish the feasibility of the 10-member EXERcise testing group of the Duke University Cooperative Cardiovascular Society (EXERDUCCS) consortium to perform a complex multicenter trial using cardiopulmonary exercise testing. An active interchange of information was established involving the principal investigator for the substudy, a dedicated full-time project coordinator, a medical director of the overall EXERDUCCS network site, the project coordinator for the sponsor, and all the participating EXERDUCCS investigators and coordinators. The sponsor set as a goal of enrollment of 6 subjects per site, and 8 of the 10 sites met this goal. As a result of the successful enrollment and completion of the study and substudy by the EXERDUCCS sites, the sponsor subsequently increased the payment stipends to the sites to compensate for the extra work and expense incurred. This cooperative experience accomplished several goals: (1) it allowed a complex clinical trial to be successfully completed in a time frame which would not have been possible using only single unconnected sites; (2) it educated the physician-investigators (and their personnel) in exercise cardiopulmonary; and (3) it prepared the sites for future clinical trials involving this methodology.

Presence of voltage-gated potassium channel complex antibody in a case of genetic prion disease

PubMed Central

Jammoul, Adham; Lederman, Richard J; Tavee, Jinny; Li, Yuebing

2014-01-01

Voltage-gated potassium channel (VGKC) complex antibody-mediated encephalitis is a recently recognised entity which has been reported to mimic the clinical presentation of Creutzfeldt-Jakob disease (CJD). Testing for the presence of this neuronal surface autoantibody in patients presenting with subacute encephalopathy is therefore crucial as it may both revoke the bleak diagnosis of prion disease and allow institution of potentially life-saving immunotherapy. Tempering this optimistic view is the rare instance when a positive VGKC complex antibody titre occurs in a definite case of prion disease. We present a pathologically and genetically confirmed case of CJD with elevated serum VGKC complex antibody titres. This case highlights the importance of interpreting the result of a positive VGKC complex antibody with caution and in the context of the overall clinical manifestation. PMID:24903967

Presence of voltage-gated potassium channel complex antibody in a case of genetic prion disease.

PubMed

Jammoul, Adham; Lederman, Richard J; Tavee, Jinny; Li, Yuebing

2014-06-05

Voltage-gated potassium channel (VGKC) complex antibody-mediated encephalitis is a recently recognised entity which has been reported to mimic the clinical presentation of Creutzfeldt-Jakob disease (CJD). Testing for the presence of this neuronal surface autoantibody in patients presenting with subacute encephalopathy is therefore crucial as it may both revoke the bleak diagnosis of prion disease and allow institution of potentially life-saving immunotherapy. Tempering this optimistic view is the rare instance when a positive VGKC complex antibody titre occurs in a definite case of prion disease. We present a pathologically and genetically confirmed case of CJD with elevated serum VGKC complex antibody titres. This case highlights the importance of interpreting the result of a positive VGKC complex antibody with caution and in the context of the overall clinical manifestation. 2014 BMJ Publishing Group Ltd.

When should we test for voltage-gated potassium channel complex antibodies? A retrospective case control study.

PubMed

O'Sullivan, B J; Steele, T; Ellul, M A; Kirby, E; Duale, A; Kier, G; Crooks, D; Jacob, A; Solomon, T; Michael, B D

2016-11-01

Patients with voltage-gated potassium channel (VGKC)-complex antibodies are increasingly recognized as having central, peripheral or combined phenotypes. With increasing awareness, more patients are tested and the clinical spectrum is expanding. Consequently, clinicians may be uncertain as to which patients should or should not be tested. Previous studies have identified common clinical features, but none has looked at the usefulness of these in predicting seropositive disease. We conducted a case-control study of patients tested for VGKC-complex antibodies over 10years at a regional tertiary neurology centre determining which clinical/biochemical features were associated with antibody-positive disease. We found a marked increase in the numbers tested, although the percentage positive remained low. Antibody titre was highest in central disease (p<0.001). Time from presentation to testing was shorter in those with VGKC-disease (p=0.01). Seizures were present in 11 (69%) of those with VGKC-disease versus three (18%) without (odds ratio [OR] 10.3, 95% confidence interval [CI]: 2.0-52.7, p=0.005). There was an inverse correlation between the antibody titre and serum sodium. A multivariate model selected seizures and hyponatraemia as predictive of VGKC disease (sensitivity 75% and specificity 82%); faciobrachial dystonic movements were specific but insensitive. Interestingly serum alkaline phosphatase was higher in those with VGKC-disease (p=0.016) and highest in those with peripheral disease (p=0.015). An ALP>70u/L was strongly associated with antibody positivity (OR 4.11 95% CI: 1.43-11.8, p=0.007) with a sensitivity of 74.2%. The presence of seizures, faciobrachial movements, and hyponatraemia should raise suspicion of VGKC-disease; alkaline phosphatase may represent a novel biomarker, particularly in those with peripheral disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Diagnostic Testing for Aspergillus

PubMed Central

Powers-Fletcher, Margaret V.

2016-01-01

The direct detection of Aspergillus nucleic acid in clinical specimens has the potential to improve the diagnosis of aspergillosis by offering more rapid and sensitive identification of invasive infections than is possible with traditional techniques, such as culture or histopathology. Molecular tests for Aspergillus have been limited historically by lack of standardization and variable sensitivities and specificities. Recent efforts have been directed at addressing these limitations and optimizing assay performance using a variety of specimen types. This review provides a summary of standardization efforts and outlines the complexities of molecular testing for Aspergillus in clinical mycology. PMID:27487954

[Description of clinical thinking by the dual-process theory].

PubMed

Peña G, Luis

2012-06-01

Clinical thinking is a very complex process that can be described by the dual-process theory, it has an intuitive part (that recognizes patterns) and an analytical part (that tests hypotheses). It is vulnerable to cognitive bias that professionals must be aware of, to minimize diagnostic errors.

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

PubMed

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

2017-09-01

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

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

PubMed Central

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

2017-01-01

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

Current insights into the laboratory diagnosis of HIT.

PubMed

Bakchoul, T; Zöllner, H; Greinacher, A

2014-06-01

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune-mediated disorders, the currently available laboratory tests for anti-PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations. © 2014 John Wiley & Sons Ltd.

Evaluation of a new rapid kit, BD MGIT TBc identification test for confirmation of Mycobacterium tuberculosis complex.

PubMed

Kandhakumari, Gandhi; Stephen, Selvaraj

2017-01-01

At present, three rapid kits are available globally for the confirmation of Mycobacterium tuberculosis complex (MTBC) in cultures by MPT64 antigen (MPT64 Ag) detection. These include Capilia TB, SD Bioline, and BD MGIT TBc Identification (TBcID). The third kit is yet to be validated in India. We have tested this kit and compared with SD Bioline using conventional tests as gold standard. Seventy-one MTBC (70 M. tuberculosis and one Mycobacterium bovis) and four nontuberculous mycobacteria (NTM) were isolated from 649 clinical specimens in MGIT 960 and/or Lowenstein-Jensen slants (LJ). MPT64 Ag was detected by both TBcID and SD Bioline kits in all the 71 clinical isolates and the reference strain M. tuberculosis H37Rv. All NTM species tested were negative by the two different kits. Thus, TBcID kit showed 100% concordance in terms of sensitivity and specificity. Rapid kits confirm MTBC cultures within 15 min in contrast to several weeks' time required by conventional techniques.

Clinical relevance of voltage-gated potassium channel–complex antibodies in children.

PubMed

Hacohen, Yael; Singh, Rahul; Rossi, Meghan; Lang, Bethan; Hemingway, Cheryl; Lim, Ming; Vincent, Angela

2015-09-15

To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (.100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients’ condition was independently classified as inflammatory (n 5 159) or noninflammatory (n 5 204). Positive sera (.100 pM) were tested/retested for the VGKC complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (.400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins. VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p 5 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers.400 pM (n512) were found only in inflammatory diseases (p , 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 .400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells. Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined.

Clinical relevance of voltage-gated potassium channel–complex antibodies in children

PubMed Central

Hacohen, Yael; Singh, Rahul; Rossi, Meghan; Lang, Bethan; Hemingway, Cheryl; Lim, Ming

2015-01-01

Objective: To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Methods: Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (>100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients' condition was independently classified as inflammatory (n = 159) or noninflammatory (n = 204). Positive sera (>100 pM) were tested/retested for the VGKC-complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (>400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins. Results: VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p = 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers >400 pM (n = 12) were found only in inflammatory diseases (p < 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 >400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells. Conclusion: Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined. PMID:26296514

Use of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identification of Molds of the Fusarium Genus

PubMed Central

Stubbe, Dirk; De Cremer, Koen; Piérard, Denis; Normand, Anne-Cécile; Piarroux, Renaud; Detandt, Monique; Hendrickx, Marijke

2014-01-01

The rates of infection with Fusarium molds are increasing, and a diverse number of Fusarium spp. belonging to different species complexes can cause infection. Conventional species identification in the clinical laboratory is time-consuming and prone to errors. We therefore evaluated whether matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a useful alternative. The 289 Fusarium strains from the Belgian Coordinated Collections of Microorganisms (BCCM)/Institute of Hygiene and Epidemiology Mycology (IHEM) culture collection with validated sequence-based identities and comprising 40 species were used in this study. An identification strategy was developed, applying a standardized MALDI-TOF MS assay and an in-house reference spectrum database. In vitro antifungal testing was performed to assess important differences in susceptibility between clinically relevant species/species complexes. We observed that no incorrect species complex identifications were made by MALDI-TOF MS, and 82.8% of the identifications were correct to the species level. This success rate was increased to 91% by lowering the cutoff for identification. Although the identification of the correct species complex member was not always guaranteed, antifungal susceptibility testing showed that discriminating between Fusarium species complexes can be important for treatment but is not necessarily required between members of a species complex. With this perspective, some Fusarium species complexes with closely related members can be considered as a whole, increasing the success rate of correct identifications to 97%. The application of our user-friendly MALDI-TOF MS identification approach resulted in a dramatic improvement in both time and accuracy compared to identification with the conventional method. A proof of principle of our MALDI-TOF MS approach in the clinical setting using recently isolated Fusarium strains demonstrated its validity. PMID:25411180

Genetic testing in the epilepsies—Report of the ILAE Genetics Commission

PubMed Central

Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.

2010-01-01

SUMMARY In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk because of a family history (predictive testing). Although genetic testing has many potential benefits, it also has potential harms, and assessment of these potential benefits and harms in particular situations is complex. Moreover, many treating clinicians are unfamiliar with the types of tests available, how to access them, how to decide whether they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients. Because the field is moving rapidly, with new information emerging practically every day, we present a framework for considering the clinical utility of genetic testing that can be applied to many different syndromes and clinical contexts. Given the current state of knowledge, genetic testing has high0020clinical utility in few clinical contexts, but in some of these it carries implications for daily clinical practice. PMID:20100225

Development and validation of panoptic Meso scale discovery assay to quantify total systemic interleukin-6

PubMed Central

Chaturvedi, Shalini; Siegel, Derick; Wagner, Carrie L; Park, Jaehong; van de Velde, Helgi; Vermeulen, Jessica; Fung, Man-Cheong; Reddy, Manjula; Hall, Brett; Sasser, Kate

2015-01-01

Aim Interleukin-6 (IL-6), a multifunctional cytokine, exists in several forms ranging from a low molecular weight (MW 20–30 kDa) non-complexed form to high MW (200–450 kDa), complexes. Accurate baseline IL-6 assessment is pivotal to understand clinical responses to IL-6-targeted treatments. Existing assays measure only the low MW, non-complexed IL-6 form. The present work aimed to develop a validated assay to measure accurately total IL-6 (complexed and non-complexed) in serum or plasma as matrix in a high throughput and easily standardized format for clinical testing. Methods Commercial capture and detection antibodies were screened against humanized IL-6 and evaluated in an enzyme-linked immunosorbent assay format. The best antibody combinations were screened to identify an antibody pair that gave minimum background and maximum recovery of IL-6 in the presence of 100% serum matrix. A plate-based total IL-6 assay was developed and transferred to the Meso Scale Discovery (MSD) platform for large scale clinical testing. Results The top-performing antibody pair from 36 capture and four detection candidates was validated on the MSD platform. The lower limit of quantification in human serum samples (n = 6) was 9.77 pg l–1, recovery ranged from 93.13–113.27%, the overall pooled coefficients of variation were 20.12% (inter-assay) and 8.67% (intra-assay). High MW forms of IL-6, in size fractionated serum samples from myelodysplastic syndrome and rheumatoid arthritis patients, were detected by the assay but not by a commercial kit. Conclusion This novel panoptic (sees all forms) IL-6 MSD assay that measures both high and low MW forms may have clinical utility. PMID:25847183

Implementation Considerations for Multisite Clinical Trials with Cognitive Neuroscience Tasks

PubMed Central

Keefe, Richard S. E.; Harvey, Philip D.

2008-01-01

Multisite clinical trials aimed at cognitive enhancement across various neuropsychiatric conditions have employed standard neuropsychological tests as outcome measures. While these tests have enjoyed wide clinical use and have proven reliable and predictive of functional disability, a number of implementation challenges have arisen when these tests are used in clinical trials. These issues are likely to be magnified in future studies when cognitive neuroscience (CN) procedures are explored in these trials, because in their current forms CN procedures are less standardized and more difficult to teach and monitor. For multisite trials, we anticipate that the most challenging issues will include assuring tester competence, monitoring tester performance, specific challenges with complex assessment methods, and having resources available for adequate monitoring of data quality. Suggestions for overcoming these implementation challenges are offered. PMID:18495645

Novel Signs and Their Clinical Utility in Diagnosing Complex Regional Pain Syndrome (CRPS): A Prospective Observational Cohort Study.

PubMed

Kuttikat, Anoop; Shaikh, Maliha; Oomatia, Amin; Parker, Richard; Shenker, Nicholas

2017-06-01

Delays in diagnosis occur with complex regional pain syndrome (CRPS). We define and prospectively demonstrate that novel bedside tests measuring body perception disruption can identify patients with CRPS postfracture. The objectives of our study were to define and validate 4 bedside tests, to identify the prevalence of positive tests in patients with CRPS and other chronic pain conditions, and to assess the clinical utility (sensitivity, specificity, positive predictive value, negative predictive value) for identifying CRPS within a Fracture cohort. This was a single UK teaching hospital prospective cohort study with 313 recruits from pain-free volunteers and patients with chronic pain conditions.Four novel tests were Finger Perception (FP), Hand Laterality identification (HL), Astereognosis (AS), and Body Scheme (BS) report. Five questionnaires (Brief Pain Inventory, Upper Extremity Functional Index, Lower Extremity Functional Index, Neglect-like Symptom Questionnaire, Hospital Anxiety and Depression Score) assessed the multidimensional pain experience. FP and BS were the best performing tests. Prospective monitoring of fracture patients showed that out of 7 fracture patients (total n=47) who had both finger misperception and abnormal BS report at initial testing, 3 developed persistent pain with 1 having a formal diagnosis of CRPS. Novel signs are reliable, easy to perform, and present in chronic pain patients. FP and BS have significant clinical utility in predicting persistent pain in a fracture group thereby allowing targeted early intervention.

Pathology consultation on urine compliance testing and drug abuse screening.

PubMed

Ward, Michael B; Hackenmueller, Sarah A; Strathmann, Frederick G

2014-11-01

Compliance testing in pain management requires a distinct approach compared with classic clinical toxicology testing. Differences in the patient populations and clinical expectations require modifications to established reporting cutoffs, assay performance expectations, and critical review of how best to apply the available testing methods. Although other approaches to testing are emerging, immunoassay screening followed by mass spectrometry confirmation remains the most common testing workflow for pain management compliance and drug abuse testing. A case-based approach was used to illustrate the complexities inherent to and uniqueness of pain management compliance testing for both clinicians and laboratories. A basic understanding of the inherent strengths and weaknesses of immunoassays and mass spectrometry provides the clinician a better understanding of how best to approach pain management compliance testing. Pain management compliance testing is a textbook example of an emerging field requiring open communication between physician and performing laboratory to fully optimize patient care. Copyright© by the American Society for Clinical Pathology.

Embedded performance validity testing in neuropsychological assessment: Potential clinical tools.

PubMed

Rickards, Tyler A; Cranston, Christopher C; Touradji, Pegah; Bechtold, Kathleen T

2018-01-01

The article aims to suggest clinically-useful tools in neuropsychological assessment for efficient use of embedded measures of performance validity. To accomplish this, we integrated available validity-related and statistical research from the literature, consensus statements, and survey-based data from practicing neuropsychologists. We provide recommendations for use of 1) Cutoffs for embedded performance validity tests including Reliable Digit Span, California Verbal Learning Test (Second Edition) Forced Choice Recognition, Rey-Osterrieth Complex Figure Test Combination Score, Wisconsin Card Sorting Test Failure to Maintain Set, and the Finger Tapping Test; 2) Selecting number of performance validity measures to administer in an assessment; and 3) Hypothetical clinical decision-making models for use of performance validity testing in a neuropsychological assessment collectively considering behavior, patient reporting, and data indicating invalid or noncredible performance. Performance validity testing helps inform the clinician about an individual's general approach to tasks: response to failure, task engagement and persistence, compliance with task demands. Data-driven clinical suggestions provide a resource to clinicians and to instigate conversation within the field to make more uniform, testable decisions to further the discussion, and guide future research in this area.

Assuring the Quality of Next-Generation Sequencing in Clinical Microbiology and Public Health Laboratories.

PubMed

Gargis, Amy S; Kalman, Lisa; Lubin, Ira M

2016-12-01

Clinical microbiology and public health laboratories are beginning to utilize next-generation sequencing (NGS) for a range of applications. This technology has the potential to transform the field by providing approaches that will complement, or even replace, many conventional laboratory tests. While the benefits of NGS are significant, the complexities of these assays require an evolving set of standards to ensure testing quality. Regulatory and accreditation requirements, professional guidelines, and best practices that help ensure the quality of NGS-based tests are emerging. This review highlights currently available standards and guidelines for the implementation of NGS in the clinical and public health laboratory setting, and it includes considerations for NGS test validation, quality control procedures, proficiency testing, and reference materials. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Estimating Preferences for Complex Health Technologies: Lessons Learned and Implications for Personalized Medicine.

PubMed

Marshall, Deborah A; Gonzalez, Juan Marcos; MacDonald, Karen V; Johnson, F Reed

2017-01-01

We examine key study design challenges of using stated-preference methods to estimate the value of whole-genome sequencing (WGS) as a specific example of genomic testing. Assessing the value of WGS is complex because WGS provides multiple findings, some of which can be incidental in nature and unrelated to the specific health concerns that motivated the test. In addition, WGS results can include actionable findings (variants considered to be clinically useful and can be acted on), findings for which evidence for best clinical action is not available (variants considered clinically valid but do not meet as high of a standard for clinical usefulness), and findings of unknown significance. We consider three key challenges encountered in designing our national study on the value of WGS-layers of uncertainty, potential downstream consequences with endogenous aspects, and both positive and negative utility associated with testing information-and potential solutions as strategies to address these challenges. We conceptualized the decision to acquire WGS information as a series of sequential choices that are resolved separately. To determine the value of WGS information at the initial decision to undergo WGS, we used contingent valuation questions, and to elicit respondent preferences for reducing risks of health problems and the consequences of taking the steps to reduce these risks, we used a discrete-choice experiment. We conclude by considering the implications for evaluating the value of other complex health technologies that involve multiple forms of uncertainty. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity

PubMed Central

Zhang, Michael Y.; Keel, Siobán B.; Walsh, Tom; Lee, Ming K.; Gulsuner, Suleyman; Watts, Amanda C.; Pritchard, Colin C.; Salipante, Stephen J.; Jeng, Michael R.; Hofmann, Inga; Williams, David A.; Fleming, Mark D.; Abkowitz, Janis L.; King, Mary-Claire; Shimamura, Akiko

2015-01-01

Accurate and timely diagnosis of inherited bone marrow failure and inherited myelodysplastic syndromes is essential to guide clinical management. Distinguishing inherited from acquired bone marrow failure/myelodysplastic syndrome poses a significant clinical challenge. At present, diagnostic genetic testing for inherited bone marrow failure/myelodysplastic syndrome is performed gene-by-gene, guided by clinical and laboratory evaluation. We hypothesized that standard clinically-directed genetic testing misses patients with cryptic or atypical presentations of inherited bone marrow failure/myelodysplastic syndrome. In order to screen simultaneously for mutations of all classes in bone marrow failure/myelodysplastic syndrome genes, we developed and validated a panel of 85 genes for targeted capture and multiplexed massively parallel sequencing. In patients with clinical diagnoses of Fanconi anemia, genomic analysis resolved subtype assignment, including those of patients with inconclusive complementation test results. Eight out of 71 patients with idiopathic bone marrow failure or myelodysplastic syndrome were found to harbor damaging germline mutations in GATA2, RUNX1, DKC1, or LIG4. All 8 of these patients lacked classical clinical stigmata or laboratory findings of these syndromes and only 4 had a family history suggestive of inherited disease. These results reflect the extensive genetic heterogeneity and phenotypic complexity of bone marrow failure/myelodysplastic syndrome phenotypes. This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes. PMID:25239263

Recent progress in the design and clinical development of electronic-nose technologies

Treesearch

Dan Wilson

2016-01-01

Electronic-nose (e-nose) devices are instruments designed to detect and discriminate between precise complex gaseous mixtures of volatile organic compounds derived from specific organic sources, such as clinical test samples from patients, based on electronic aroma signature patterns (distinct digital sensor responses) resulting from the combined outputs of a...

In search of memory tests equivalent for experiments on animals and humans.

PubMed

Brodziak, Andrzej; Kołat, Estera; Różyk-Myrta, Alicja

2014-12-19

Older people often exhibit memory impairments. Contemporary demographic trends cause aging of the society. In this situation, it is important to conduct clinical trials of drugs and use training methods to improve memory capacity. Development of new memory tests requires experiments on animals and then clinical trials in humans. Therefore, we decided to review the assessment methods and search for tests that evaluate analogous cognitive processes in animals and humans. This review has enabled us to propose 2 pairs of tests of the efficiency of working memory capacity in animals and humans. We propose a basic set of methods for complex clinical trials of drugs and training methods to improve memory, consisting of 2 pairs of tests: 1) the Novel Object Recognition Test - Sternberg Item Recognition Test and 2) the Object-Location Test - Visuospatial Memory Test. We postulate that further investigations of methods that are equivalent in animals experiments and observations performed on humans are necessary.

Factors influencing organizational adoption and implementation of clinical genetic services.

PubMed

Hamilton, Alison B; Oishi, Sabine; Yano, Elizabeth M; Gammage, Cynthia E; Marshall, Nell J; Scheuner, Maren T

2014-03-01

We sought to identify characteristics of genetic services that facilitate or hinder adoption. We conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology, pathology/laboratory medicine) within 13 Veterans Administration facilities. Genetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as advantageous for their facilities or their patients; compatible with organizational norms of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had knowledgeable clinicians interested in developing services and organizational-level facilitators such as accessible genetic test-ordering processes. Adoption and implementation of genetic services will require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of genetic information for the outcomes that matter to health-care organizations.

Effect of surgical periodontal treatment associated to antimicrobial photodynamic therapy on chronic periodontitis: A randomized controlled clinical trial.

PubMed

Martins, Sérgio H L; Novaes, Arthur B; Taba, Mario; Palioto, Daniela B; Messora, Michel R; Reino, Danilo M; Souza, Sérgio L S

2017-07-01

This randomized controlled clinical trial evaluated the effects of an adjunctive single application of antimicrobial photodynamic therapy (aPDT) in Surgical Periodontal Treatment (ST) in patients with severe chronic periodontitis (SCP). In a split-mouth design, 20 patients with SCP were treated with aPDT+ST (Test Group, TG) or ST only (Control Group, CG). aPDT was applied in a single episode, using a diode laser and a phenothiazine photosensitizer. All patients were monitored until 90 days after surgical therapy. Levels of 40 subgingival species were measured by checkerboard DNA-DNA hybridization at baseline, 60 and 150 days. Clinical and microbiological parameters were evaluated. In deep periodontal pockets depth (PPD ≥5 mm), Test Group presented a significantly higher decrease in PPD than Control Group at 90 days after surgical therapy (p < .05). Test Group also demonstrated significantly less periodontal pathogens of red complex (Treponema denticola) (p < .05). A single episode of aPDT used in adjunct to open flap debridement of the root surface in the surgical treatment of SCP: i) significantly improved clinical periodontal parameters; ii) eliminates periodontal pathogens of the red complex more effectively (NCT02734784). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Satisfying regulatory and accreditation requirements for quality control.

PubMed

Ehrmeyer, Sharon S

2013-03-01

The Clinical Laboratory Improvement Amendments of 1988 (CLIA) requires all US clinical laboratories that test "materials derived from the human body for the purpose of providing information for the diagnosis, prevention, or treatment of any disease..." to be regulated. The CLIA mandates are site neutral; based on test complexity; and focus on the three phases of the testing process (preanalytical, analytical, and postanalytical). Many testing sites choose to meet the CLIA requirements by following the testing standards of a professional accreditation organization deemed by the Centers for Medicare and Medicaid Services. The three principal organizations are The Joint Commission, the College of American Pathologists, and COLA. Copyright © 2013 Elsevier Inc. All rights reserved.

Bayesian Classification Models for Premature Ventricular Contraction Detection on ECG Traces.

PubMed

Casas, Manuel M; Avitia, Roberto L; Gonzalez-Navarro, Felix F; Cardenas-Haro, Jose A; Reyna, Marco A

2018-01-01

According to the American Heart Association, in its latest commission about Ventricular Arrhythmias and Sudden Death 2006, the epidemiology of the ventricular arrhythmias ranges from a series of risk descriptors and clinical markers that go from ventricular premature complexes and nonsustained ventricular tachycardia to sudden cardiac death due to ventricular tachycardia in patients with or without clinical history. The premature ventricular complexes (PVCs) are known to be associated with malignant ventricular arrhythmias and sudden cardiac death (SCD) cases. Detecting this kind of arrhythmia has been crucial in clinical applications. The electrocardiogram (ECG) is a clinical test used to measure the heart electrical activity for inferences and diagnosis. Analyzing large ECG traces from several thousands of beats has brought the necessity to develop mathematical models that can automatically make assumptions about the heart condition. In this work, 80 different features from 108,653 ECG classified beats of the gold-standard MIT-BIH database were extracted in order to classify the Normal, PVC, and other kind of ECG beats. Three well-known Bayesian classification algorithms were trained and tested using these extracted features. Experimental results show that the F1 scores for each class were above 0.95, giving almost the perfect value for the PVC class. This gave us a promising path in the development of automated mechanisms for the detection of PVC complexes.

Psychometric testing of the clinical nurse leader staff satisfaction instrument.

PubMed

Spiva, LeeAnna; Hart, Patricia L; Wesley, Mary Lou; Gallagher, Erin; McVay, Frank; Waggoner, Jessica; Jarrell, Nicole; Threatt, Jamie L

2014-01-01

Patient care is changing rapidly with increased complexity of care, patient volumes, and financial constraints with rising health care costs and limited reimbursements. In response, the clinical nurse leader (CNL) role was developed. No appropriate instrument exists to measure staff satisfaction with the CNL role. This study describes the development and testing of an instrument designed to measure staff satisfaction with implementation of the CNL role. The psychometric properties and factor structure of the Clinical Nurse Leader Staff Satisfaction (CNLSS) instrument was examined. A 2-factor solution was discovered for the CNLSS. Cronbach's alpha coefficients were acceptable for the subscales and instrument. The CNLSS is a valid and reliable instrument. Future research should focus on establishing test-retest reliability and construct validity.

Against Genetic Tests for Athletic Talent: The Primacy of the Phenotype.

PubMed

Loland, Sigmund

2015-09-01

New insights into the genetics of sport performance lead to new areas of application. One area is the use of genetic tests to identify athletic talent. Athletic performances involve a high number of complex phenotypical traits. Based on the ACCE model (review of Analytic and Clinical validity, Clinical utility, and Ethical, legal and social implications), a critique is offered of the lack of validity and predictive power of genetic tests for talent. Based on the ideal of children's right to an open future, a moral argument is given against such tests on children and young athletes. A possible role of genetic tests in sport is proposed in terms of identifying predisposition for injury. In meeting ACCE requirements, such tests could improve individualised injury prevention and increase athlete health. More generally, limitations of science are discussed in the identification of talent and in the understanding of complex human performance phenotypes. An alternative approach to talent identification is proposed in terms of ethically sensitive, systematic and evidence-based holistic observation over time of relevant phenotypical traits by experienced observers. Talent identification in sport should be based on the primacy of the phenotype.

Limitations of direct-to-consumer advertising for clinical genetic testing.

PubMed

Gollust, Sarah E; Hull, Sara Chandros; Wilfond, Benjamin S

2002-10-09

Although direct-to-consumer (DTC) advertisements for pharmaceuticals have been appearing in the mass media for 20 years, DTC advertisements for genetic testing have only recently appeared. Advertisements for genetic testing can provide both consumers and physicians with information about test availability in an expanding market. However, 3 factors limit the value and appropriateness of advertisements: complex information, a complicated social context surrounding genetics, and a lack of consensus about the clinical utility of some tests. Consideration of several advertisements suggests that they overstate the value of genetic testing for consumers' clinical care. Furthermore, advertisements may provide misinformation about genetics, exaggerate consumers' risks, endorse a deterministic relationship between genes and disease, and reinforce associations between diseases and ethnic groups. Advertising motivated by factors other than evidence of the clinical value of genetic tests can manipulate consumers' behavior by exploiting their fears and worries. At this time, DTC advertisements are inappropriate, given the public's limited sophistication regarding genetics and the lack of comprehensive premarket review of tests or oversight of advertisement content. Existing Federal Trade Commission and Food and Drug Administration regulations for other types of health-related advertising should be applied to advertisements for genetic tests.

Challenges for allergy diagnosis in regions with complex pollen exposures.

PubMed

Barber, Domingo; Díaz-Perales, Araceli; Villalba, Mayte; Chivato, Tomas

2015-02-01

Over the past few decades, significant scientific progress has influenced clinical allergy practice. The biological standardization of extracts was followed by the massive identification and characterization of new allergens and their progressive use as diagnostic tools including allergen micro arrays that facilitate the simultaneous testing of more than 100 allergen components. Specific diagnosis is the basis of allergy practice and is always aiming to select the best therapeutic or avoidance intervention. As a consequence, redundant or irrelevant information might be adding unnecessary cost and complexity to daily clinical practice. A rational use of the different diagnostic alternatives would allow a significant improvement in the diagnosis and treatment of allergic patients, especially for those residing in complex pollen exposure areas.

Emotion Regulation Enhancement of Cognitive Behavior Therapy for College Student Problem Drinkers: A Pilot Randomized Controlled Trial

ERIC Educational Resources Information Center

Ford, Julian D.; Grasso, Damion J.; Levine, Joan; Tennen, Howard

2018-01-01

This pilot randomized clinical trial tested an emotion regulation enhancement to cognitive behavior therapy (CBT) with 29 college student problem drinkers with histories of complex trauma and current clinically significant traumatic stress symptoms. Participants received eight face-to-face sessions of manualized Internet-supported CBT for problem…

Neutral heel lateral push test: The first clinical examination of spring ligament integrity.

PubMed

Pasapula, Chandra; Devany, Adam; Magan, Ahmed; Memarzadeh, A; Pasters, V; Shariff, S

2015-06-01

The spring (calcaneonavicular) ligament is an intricate multiligament complex whose primary role is to stabilise the medial longitudinal arch and head of talus. Clinical suspicion of a spring ligament injury in isolation is roused when persistent medial midfoot pain is present with associated pes planus following trauma. We undertook a cadaveric study on 21 specimens to assess the use of a neutral heel lateral push test to examine the spring ligament in a standardised procedure, measuring lateral translation with graduated antegrade and retrograde defunctioning of surrounding structures and the spring ligament. In all specimens, a significant displacement occurred on incision of the spring ligament regardless of order of dissection. The degree of displacement increased by an insignificant amount as surrounding structures were incised at each incremental force applied. The neutral heel push test is the first clinical examination to be described to determine integrity of the spring ligament complex. Our study objectively demonstrates that lateral displacement in relation to the mid and hind-foot is influenced most significantly by the integrity of the spring ligament and to a lesser extent by tibialis posterior and flexor digitorum longus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Voltage-Gated Potassium Channel Antibodies in Slow-Progression Motor Neuron Disease.

PubMed

Godani, Massimiliano; Zoccarato, Marco; Beronio, Alessandro; Zuliani, Luigi; Benedetti, Luana; Giometto, Bruno; Del Sette, Massimo; Raggio, Elisa; Baldi, Roberta; Vincent, Angela

2017-01-01

The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression. © 2016 S. Karger AG, Basel.

Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape.

PubMed

Benda, Norbert; Brandt, Andreas

2018-01-01

Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

76 FR 80905 - TRICARE Evaluation of Centers for Medicare & Medicaid Services Approved Laboratory Developed...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

... potential high utilization and potential high clinical impact on TRICARE beneficiaries. If no submission is... reviewed in numerical order beginning with the test listed as having the highest priority. Those selected... laboratories that use LDTs as well as FDA approved tests. Laboratories performing moderate or high complexity...

Assessment of Competence in Clinical Reasoning and Decision-Making under Uncertainty: The Script Concordance Test Method

ERIC Educational Resources Information Center

Ramaekers, Stephan; Kremer, Wim; Pilot, Albert; van Beukelen, Peter; van Keulen, Hanno

2010-01-01

Real-life, complex problems often require that decisions are made despite limited information or insufficient time to explore all relevant aspects. Incorporating authentic uncertainties into an assessment, however, poses problems in establishing results and analysing their methodological qualities. This study aims at developing a test on clinical…

College of American Pathologists' laboratory standards for next-generation sequencing clinical tests.

PubMed

Aziz, Nazneen; Zhao, Qin; Bry, Lynn; Driscoll, Denise K; Funke, Birgit; Gibson, Jane S; Grody, Wayne W; Hegde, Madhuri R; Hoeltge, Gerald A; Leonard, Debra G B; Merker, Jason D; Nagarajan, Rakesh; Palicki, Linda A; Robetorye, Ryan S; Schrijver, Iris; Weck, Karen E; Voelkerding, Karl V

2015-04-01

The higher throughput and lower per-base cost of next-generation sequencing (NGS) as compared to Sanger sequencing has led to its rapid adoption in clinical testing. The number of laboratories offering NGS-based tests has also grown considerably in the past few years, despite the fact that specific Clinical Laboratory Improvement Amendments of 1988/College of American Pathologists (CAP) laboratory standards had not yet been developed to regulate this technology. To develop a checklist for clinical testing using NGS technology that sets standards for the analytic wet bench process and for bioinformatics or "dry bench" analyses. As NGS-based clinical tests are new to diagnostic testing and are of much greater complexity than traditional Sanger sequencing-based tests, there is an urgent need to develop new regulatory standards for laboratories offering these tests. To develop the necessary regulatory framework for NGS and to facilitate appropriate adoption of this technology for clinical testing, CAP formed a committee in 2011, the NGS Work Group, to deliberate upon the contents to be included in the checklist. Results . -A total of 18 laboratory accreditation checklist requirements for the analytic wet bench process and bioinformatics analysis processes have been included within CAP's molecular pathology checklist (MOL). This report describes the important issues considered by the CAP committee during the development of the new checklist requirements, which address documentation, validation, quality assurance, confirmatory testing, exception logs, monitoring of upgrades, variant interpretation and reporting, incidental findings, data storage, version traceability, and data transfer confidentiality.

Automated analysis of free speech predicts psychosis onset in high-risk youths

PubMed Central

Bedi, Gillinder; Carrillo, Facundo; Cecchi, Guillermo A; Slezak, Diego Fernández; Sigman, Mariano; Mota, Natália B; Ribeiro, Sidarta; Javitt, Daniel C; Copelli, Mauro; Corcoran, Cheryl M

2015-01-01

Background/Objectives: Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals. AIMS: In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis. Methods: Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed. Results: Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms. Conclusions: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry. PMID:27336038

[Application of nootropic agents in complex treatment of patients with concussion of the brain].

PubMed

Tkachev, A V

2007-01-01

65 patients with a mild craniocereberal trauma have been observed. Medical examination included among general clinical methods the following methods: KT (MRT) of the brain, oculist examination including the observation of eye fundus. For objectification of a patient' complaints the authors used orientation and Galvestona's amnesia tests, feeling scale (psychological test), the table to determine the level of memory. Tests have been carried out on the first, tenth and thirty day of the treatment. Patients of the first group received in a complex treatment -pramistar, patients of the second group - piracetam. Patients of both groups noted considerable improvement during a complex treatment (disappearance of headache, dizziness and nausea) and at the same time patients receiving pramistar had better restoration of orientation and feeling. Pramistar was also more effective in patients with amnesia.

Correlations Between Clinical Judgement and Learning Style Preferences of Nursing Students in the Simulation Room.

PubMed

Hallin, Karin; Haggstrom, Marie; Backstrom, Britt; Kristiansen, Lisbeth Porskrog

2015-09-28

Health care educators account for variables affecting patient safety and are responsible for developing the highly complex process of education planning. Clinical judgement is a multidimensional process, which may be affected by learning styles. The aim was to explore three specific hypotheses to test correlations between nursing students' team achievements in clinical judgement and emotional, sociological and physiological learning style preferences. A descriptive cross-sectional study was conducted with Swedish university nursing students in 2012-2013. Convenience sampling was used with 60 teams with 173 nursing students in the final semester of a three-year Bachelor of Science in nursing programme. Data collection included questionnaires of personal characteristics, learning style preferences, determined by the Dunn and Dunn Productivity Environmental Preference Survey, and videotaped complex nursing simulation scenarios. Comparison with Lasater Clinical Judgement Rubric and Non-parametric analyses were performed. Three significant correlations were found between the team achievements and the students' learning style preferences: significant negative correlation with 'Structure' and 'Kinesthetic' at the individual level, and positive correlation with the 'Tactile' variable. No significant correlations with students' 'Motivation', 'Persistence', 'Wish to learn alone' and 'Wish for an authoritative person present' were seen. There were multiple complex interactions between the tested learning style preferences and the team achievements of clinical judgement in the simulation room, which provides important information for the becoming nurses. Several factors may have influenced the results that should be acknowledged when designing further research. We suggest conducting mixed methods to determine further relationships between team achievements, learning style preferences, cognitive learning outcomes and group processes.

A cost-effective interdisciplinary approach to microbiologic send-out test use.

PubMed

Aesif, Scott W; Parenti, David M; Lesky, Linda; Keiser, John F

2015-02-01

Use of reference laboratories for selected laboratory testing (send-out tests) represents a significant source of laboratory costs. As the use of more complex molecular analyses becomes common in the United States, strategies to reduce costs in the clinical laboratory must evolve in order to provide high-value, cost-effective medicine. To report a strategy that employs clinical pathology house staff and key hospital clinicians in the effective use of microbiologic send-out testing. The George Washington University Hospital is a 370-bed academic hospital in Washington, DC. In 2012 all requisitions for microbiologic send-out tests were screened by the clinical pathology house staff prior to final dispensation. Tests with questionable utility were brought to the attention of ordering clinicians through the use of interdisciplinary rounds and direct face-to-face consultation. Screening resulted in a cancellation rate of 38% of send-out tests, with proportional cost savings. Nucleic acid tests represented most of the tests screened and the largest percentage of cost saved through screening. Following consultation, requested send-out tests were most often canceled because of a lack of clinical indication. Direct face-to-face consultation with ordering physicians is an effective, interdisciplinary approach to managing the use of send-out testing in the microbiology laboratory.

Refining the structure and content of clinical genomic reports.

PubMed

Dorschner, Michael O; Amendola, Laura M; Shirts, Brian H; Kiedrowski, Lesli; Salama, Joseph; Gordon, Adam S; Fullerton, Stephanie M; Tarczy-Hornoch, Peter; Byers, Peter H; Jarvik, Gail P

2014-03-01

To effectively articulate the results of exome and genome sequencing we refined the structure and content of molecular test reports. To communicate results of a randomized control trial aimed at the evaluation of exome sequencing for clinical medicine, we developed a structured narrative report. With feedback from genetics and non-genetics professionals, we developed separate indication-specific and incidental findings reports. Standard test report elements were supplemented with research study-specific language, which highlighted the limitations of exome sequencing and provided detailed, structured results, and interpretations. The report format we developed to communicate research results can easily be transformed for clinical use by removal of research-specific statements and disclaimers. The development of clinical reports for exome sequencing has shown that accurate and open communication between the clinician and laboratory is ideally an ongoing process to address the increasing complexity of molecular genetic testing. © 2014 Wiley Periodicals, Inc.

Refining the Structure and Content of Clinical Genomic Reports

PubMed Central

DORSCHNER, MICHAEL O.; AMENDOLA, LAURA M.; SHIRTS, BRIAN H.; KIEDROWSKI, LESLI; SALAMA, JOSEPH; GORDON, ADAM S.; FULLERTON, STEPHANIE M.; TARCZY-HORNOCH, PETER; BYERS, PETER H.; JARVIK, GAIL P.

2014-01-01

To effectively articulate the results of exome and genome sequencing we refined the structure and content of molecular test reports. To communicate results of a randomized control trial aimed at the evaluation of exome sequencing for clinical medicine, we developed a structured narrative report. With feedback from genetics and non-genetics professionals, we developed separate indication-specific and incidental findings reports. Standard test report elements were supplemented with research study-specific language, which highlighted the limitations of exome sequencing and provided detailed, structured results, and interpretations. The report format we developed to communicate research results can easily be transformed for clinical use by removal of research-specific statements and disclaimers. The development of clinical reports for exome sequencing has shown that accurate and open communication between the clinician and laboratory is ideally an ongoing process to address the increasing complexity of molecular genetic testing. PMID:24616401

Spanish normative studies in young adults (NEURONORMA young adults project): norms for the Rey-Osterrieth Complex Figure (copy and memory) and Free and Cued Selective Reminding Test.

PubMed

Palomo, R; Casals-Coll, M; Sánchez-Benavides, G; Quintana, M; Manero, R M; Rognoni, T; Calvo, L; Aranciva, F; Tamayo, F; Peña-Casanova, J

2013-05-01

The Rey-Osterrieth Complex Figure (ROCF) and the Free and Cued Selective Reminding Test (FCSRT) are widely used in clinical practice. The ROCF assesses visual perception, constructional praxis, and visuo-spatial memory. The FCSRT assesses verbal learning and memory. In this study, as part of the Spanish normative studies project in young adults (NEURONORMA young adults), we present age- and education-adjusted normative data for both tests obtained by using linear regression techniques. The sample consisted of 179 healthy participants ranging in age from 18 to 49 years. We provide tables for converting raw scores to scaled scores in addition to tables with scores adjusted by socio-demographic factors. The results showed that education affects scores for some of the memory tests and the figure-copying task. Age was only found to have an effect on the performance of visuo-spatial memory tests, and the effect of sex was negligible. The normative data obtained will be extremely useful in the clinical neuropsychological evaluation of young Spanish adults. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Age-Associated Differences in Cognitive Performance in Older Community Dwelling Schizophrenia Patients: Differential Sensitivity of Clinical Neuropsychological and Experimental Information Processing Tests

PubMed Central

Bowie, Christopher R.; Reichenberg, Abraham; McClure, Margaret M.; Leung, Winnie L.; Harvey, Philip D.

2008-01-01

Cognitive dysfunction is a common feature of schizophrenia and deficits are present before the onset of psychosis, and are moderate to severe by the time of the first episode. Controversy exists over the course of cognitive dysfunction after the first episode. This study examined age-associated differences in performance on clinical neuropsychological (NP) and information processing tasks in a sample of geriatric community living schizophrenia patients (n=172). Compared to healthy control subjects (n=70), people with schizophrenia did not differ on NP tests across age groups but showed evidence for age-associated cognitive worsening on the more complex components of an information-processing test. Age-related changes in cognitive function in schizophrenia may be a function of both the course of illness and the processing demands of the cognitive measure of interest. Tests with fixed difficulty, such as clinical NP tests, may differ in their sensitivity from tests for which parametric difficulty manipulations can be performed. PMID:18053687

Management of heart failure in the new era: the role of scores.

PubMed

Mantegazza, Valentina; Badagliacca, Roberto; Nodari, Savina; Parati, Gianfranco; Lombardi, Carolina; Di Somma, Salvatore; Carluccio, Erberto; Dini, Frank Lloyd; Correale, Michele; Magrì, Damiano; Agostoni, Piergiuseppe

2016-08-01

Heart failure is a widespread syndrome involving several organs, still characterized by high mortality and morbidity, and whose clinical course is heterogeneous and hardly predictable.In this scenario, the assessment of heart failure prognosis represents a fundamental step in clinical practice. A single parameter is always unable to provide a very precise prognosis. Therefore, risk scores based on multiple parameters have been introduced, but their clinical utility is still modest. In this review, we evaluated several prognostic models for acute, right, chronic, and end-stage heart failure based on multiple parameters. In particular, for chronic heart failure we considered risk scores essentially based on clinical evaluation, comorbidities analysis, baroreflex sensitivity, heart rate variability, sleep disorders, laboratory tests, echocardiographic imaging, and cardiopulmonary exercise test parameters. What is at present established is that a single parameter is not sufficient for an accurate prediction of prognosis in heart failure because of the complex nature of the disease. However, none of the scoring systems available is widely used, being in some cases complex, not user-friendly, or based on expensive or not easily available parameters. We believe that multiparametric scores for risk assessment in heart failure are promising but their widespread use needs to be experienced.

How much does language proficiency by non-native listeners influence speech audiometric tests in noise?

PubMed

Warzybok, Anna; Brand, Thomas; Wagener, Kirsten C; Kollmeier, Birger

2015-01-01

The current study investigates the extent to which the linguistic complexity of three commonly employed speech recognition tests and second language proficiency influence speech recognition thresholds (SRTs) in noise in non-native listeners. SRTs were measured for non-natives and natives using three German speech recognition tests: the digit triplet test (DTT), the Oldenburg sentence test (OLSA), and the Göttingen sentence test (GÖSA). Sixty-four non-native and eight native listeners participated. Non-natives can show native-like SRTs in noise only for the linguistically easy speech material (DTT). Furthermore, the limitation of phonemic-acoustical cues in digit triplets affects speech recognition to the same extent in non-natives and natives. For more complex and less familiar speech materials, non-natives, ranging from basic to advanced proficiency in German, require on average 3-dB better signal-to-noise ratio for the OLSA and 6-dB for the GÖSA to obtain 50% speech recognition compared to native listeners. In clinical audiology, SRT measurements with a closed-set speech test (i.e. DTT for screening or OLSA test for clinical purposes) should be used with non-native listeners rather than open-set speech tests (such as the GÖSA or HINT), especially if a closed-set version in the patient's own native language is available.

Developing a Decision Support System for Tobacco Use Counseling Using Primary Care Physicians

PubMed Central

Marcy, Theodore W.; Kaplan, Bonnie; Connolly, Scott W.; Michel, George; Shiffman, Richard N.; Flynn, Brian S.

2009-01-01

Background Clinical decision support systems (CDSS) have the potential to improve adherence to guidelines, but only if they are designed to work in the complex environment of ambulatory clinics as otherwise physicians may not use them. Objective To gain input from primary care physicians in designing a CDSS for smoking cessation to ensure that the design is appropriate to a clinical environment before attempts to test this CDSS in a clinical trial. This approach is of general interest to those designing similar systems. Design and Approach We employed an iterative ethnographic process that used multiple evaluation methods to understand physician preferences and workflow integration. Using results from our prior survey of physicians and clinic managers, we developed a prototype CDSS, validated content and design with an expert panel, and then subjected it to usability testing by physicians, followed by iterative design changes based on their feedback. We then performed clinical testing with individual patients, and conducted field tests of the CDSS in two primary care clinics during which four physicians used it for routine patient visits. Results The CDSS prototype was substantially modified through these cycles of usability and clinical testing, including removing a potentially fatal design flaw. During field tests in primary care clinics, physicians incorporated the final CDSS prototype into their workflow, and used it to assist in smoking cessation interventions up to eight times daily. Conclusions A multi-method evaluation process utilizing primary care physicians proved useful for developing a CDSS that was acceptable to physicians and patients, and feasible to use in their clinical environment. PMID:18713526

Reliability and validity of the C-BiLLT: a new instrument to assess comprehension of spoken language in young children with cerebral palsy and complex communication needs.

PubMed

Geytenbeek, Joke J; Mokkink, Lidwine B; Knol, Dirk L; Vermeulen, R Jeroen; Oostrom, Kim J

2014-09-01

In clinical practice, a variety of diagnostic tests are available to assess a child's comprehension of spoken language. However, none of these tests have been designed specifically for use with children who have severe motor impairments and who experience severe difficulty when using speech to communicate. This article describes the process of investigating the reliability and validity of the Computer-Based Instrument for Low Motor Language Testing (C-BiLLT), which was specifically developed to assess spoken Dutch language comprehension in children with cerebral palsy and complex communication needs. The study included 806 children with typical development, and 87 nonspeaking children with cerebral palsy and complex communication needs, and was designed to provide information on the psychometric qualities of the C-BiLLT. The potential utility of the C-BiLLT as a measure of spoken Dutch language comprehension abilities for children with cerebral palsy and complex communication needs is discussed.

Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of molds of the Fusarium genus.

PubMed

Triest, David; Stubbe, Dirk; De Cremer, Koen; Piérard, Denis; Normand, Anne-Cécile; Piarroux, Renaud; Detandt, Monique; Hendrickx, Marijke

2015-02-01

The rates of infection with Fusarium molds are increasing, and a diverse number of Fusarium spp. belonging to different species complexes can cause infection. Conventional species identification in the clinical laboratory is time-consuming and prone to errors. We therefore evaluated whether matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a useful alternative. The 289 Fusarium strains from the Belgian Coordinated Collections of Microorganisms (BCCM)/Institute of Hygiene and Epidemiology Mycology (IHEM) culture collection with validated sequence-based identities and comprising 40 species were used in this study. An identification strategy was developed, applying a standardized MALDI-TOF MS assay and an in-house reference spectrum database. In vitro antifungal testing was performed to assess important differences in susceptibility between clinically relevant species/species complexes. We observed that no incorrect species complex identifications were made by MALDI-TOF MS, and 82.8% of the identifications were correct to the species level. This success rate was increased to 91% by lowering the cutoff for identification. Although the identification of the correct species complex member was not always guaranteed, antifungal susceptibility testing showed that discriminating between Fusarium species complexes can be important for treatment but is not necessarily required between members of a species complex. With this perspective, some Fusarium species complexes with closely related members can be considered as a whole, increasing the success rate of correct identifications to 97%. The application of our user-friendly MALDI-TOF MS identification approach resulted in a dramatic improvement in both time and accuracy compared to identification with the conventional method. A proof of principle of our MALDI-TOF MS approach in the clinical setting using recently isolated Fusarium strains demonstrated its validity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[The clinico-laboratory characteristics of cases of diseases connected with viruses of the California encephalitis complex in the inhabitants of Moscow].

PubMed

Kolobukhina, L V; L'vov, D K; Butenko, A M; Kuznetsov, A A; Galkina, I V

1989-10-01

To study the role of viruses of the California encephalitis virus complex (the family Bunyaviridae) in infectious pathology, 187 fever patients admitted to the Clinical Infectious Hospital in May-September 1986 were examined. In 10 of these patients the neutralization test revealed the presence of diagnostically significant changes in neutralizing antibodies (neutralization indices), which was indicative of the role played by Tahyna virus or other related viruses belonging to the California encephalitis virus complex in the etiology of the diseases. The analysis of the clinical picture showed that in all patients the disease took an acute course in its initial stage, starting with shivering and characterized by high fever, headache, pronounced toxicosis, the possibility of the formation of intracerebral hypertension and pneumonia.

Adapting the Bilingual Aphasia Test to Rarotongan (Cook Islands Maori): Linguistic and Clinical Considerations

ERIC Educational Resources Information Center

Amberber, Amanda Miller

2011-01-01

This article describes the adaptation of the Bilingual Aphasia Test (BAT) to the Rarotongan dialect of Cook Islands Maori, a Polynesian language spoken in the Cook Islands and expatriate communities. A brief linguistic sketch of Rarotongan is presented. As Rarotongan is characterised by a complex pronominal system, "a" versus "o" possession and…

A novel approach to the use of subgingival controlled-release chlorhexidine delivery in chronic periodontitis: a randomized clinical trial.

PubMed

Gonzales, Jose R; Harnack, Lutz; Schmitt-Corsitto, Gabriella; Boedeker, Rolf H; Chakraborty, Trinad; Domann, Eugen; Meyle, Joerg

2011-08-01

We aimed to analyze clinical, microbiologic, and serologic effects of chlorhexidine (CHX) chips used as a subgingival controlled-release delivery device before and immediately after scaling and root planing (SRP). Twenty-four patients presenting with ≥12 teeth with probing depth (PD) ≥5 mm and bleeding on probing were assigned in test or control groups. After prophylaxis, CHX chips (test) or placebo chips (control) were placed in pockets with PD ≥5 mm. Ten days later, SRP was performed in all teeth with PD ≥4 mm in a single appointment. Immediately after SRP, new chips were inserted in all pockets with PD ≥5 mm. Parameters were assessed at baseline; beginning of SRP; and 1, 3, and 6 months after treatment. Subgingival samples were obtained at baseline; beginning of SRP; and at 1 month after treatment. Periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola were analyzed. Serum levels of high sensitive C-reactive and lipopolysaccharide-binding proteins were measured. The changes of the parameters between and within the groups were tested by Mann-Whitney U test (P <0.05). All clinical and serologic parameters improved in both groups over time. There was a significant difference in clinical attachment level (CAL) gain from baseline to 6 months between groups (1.17 mm in the test group versus 0.79 mm in the placebo group) (P <0.05). The treatment with CHX chips showed a greater reduction of the microorganisms of the "red complex" after 1 month (P = 0.02). The use of CHX chips before and immediately after SRP improved CAL and reduced the subgingival microorganisms of the red complex in the treatment of chronic periodontitis.

Influence of Herbal Complexes Containing Licorice on Potassium Levels: A Retrospective Study

PubMed Central

Jung, WooSang; Kwon, SeungWon; Im, JinWook; Park, SeongUk; Moon, SangKwan; Park, JungMi; Ko, ChangNam; Cho, KiHo

2014-01-01

To observe the influence of these complexes on potassium levels in a clinical setting, we investigated the influence of herbal complexes containing licorice on potassium levels. We retrospectively examined the medical records of patients treated with herbal complexes containing licorice from January 1, 2010, to December 31, 2010. We recorded the changes in the levels of potassium, creatinine, and blood urea nitrogen and examined the differences between before and after herbal complexes intake using a paired t-test. In addition, we investigated the prevalence of hypokalemia among these patients and reviewed such patients. We identified 360 patients who did not show significant changes in the levels of potassium and creatinine (P = 0.815, 0.289). We observed hypokalemia in 6 patients. However, in 5 patients, the hypokalemia did not appear to be related to the licorice. Thus, we could suggest that herbal complexes containing licorice do not significantly influence the potassium levels in routine clinical herbal therapies. However, we propose that follow-up examination for potassium levels is required to prevent any unpredictable side effects of administration of licorice in routine herbal medicine care. PMID:25045393

Understanding the complexity of redesigning care around the clinical microsystem.

PubMed

Barach, P; Johnson, J K

2006-12-01

The microsystem is an organizing design construct in which social systems cut across traditional discipline boundaries. Because of its interdisciplinary focus, the clinical microsystem provides a conceptual and practical framework for simplifying complex organizations that deliver care. It also provides an important opportunity for organizational learning. Process mapping and microworld simulation may be especially useful for redesigning care around the microsystem concept. Process mapping, in which the core processes of the microsystem are delineated and assessed from the perspective of how the individual interacts with the system, is an important element of the continuous learning cycle of the microsystem and the healthcare organization. Microworld simulations are interactive computer based models that can be used as an experimental platform to test basic questions about decision making misperceptions, cause-effect inferences, and learning within the clinical microsystem. Together these tools offer the user and organization the ability to understand the complexity of healthcare systems and to facilitate the redesign of optimal outcomes.

Clinical efficacy of anti-glycopeptidolipid-core IgA test for diagnosing Mycobacterium avium complex infection in lung.

PubMed

Numata, Takanori; Araya, Jun; Yoshii, Yutaka; Shimizu, Kenichiro; Hara, Hiromichi; Nakayama, Katsutoshi; Kuwano, Kazuyoshi

2015-11-01

It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test. We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital. A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029). The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases. © 2015 Asian Pacific Society of Respirology.

A quick behavioral dichotic word test is prognostic for clinical response to cognitive therapy for depression: A replication study.

PubMed

Bruder, Gerard E; Haggerty, Agnes; Siegle, Greg J

2017-02-01

There are no commonly used clinical indicators of whether an individual will benefit from cognitive therapy (CT) for depression. A prior study found right ear (left hemisphere) advantage for perceiving dichotic words predicted CT response. This study replicates this finding at a different research center in clinical trials that included clinically representative samples and community therapists. Right-handed individuals with unipolar major depressive disorder who subsequently received 12-14 weeks of CT at the University of Pittsburgh were tested on dichotic fused words and complex tones tests. Responders to CT showed twice the mean right ear advantage in dichotic fused words performance than non-responders. Patients with a right ear advantage greater than the mean for healthy controls had an 81% response rate to CT, whereas those with performance lower than the mean for controls had a 46% response rate. Individuals with a right ear advantage, indicative of strong left hemisphere language dominance, may be better at utilizing cognitive processes and left frontotemporal cortical regions critical for success of CT for depression. Findings at two clinical research centers suggest that verbal dichotic listening may be a clinically disseminative brief, inexpensive and easily automated test prognostic for response to CT across diverse clinical settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies.

PubMed

Lang, Bethan; Makuch, Mateusz; Moloney, Teresa; Dettmann, Inga; Mindorf, Swantje; Probst, Christian; Stoecker, Winfried; Buckley, Camilla; Newton, Charles R; Leite, M Isabel; Maddison, Paul; Komorowski, Lars; Adcock, Jane; Vincent, Angela; Waters, Patrick; Irani, Sarosh R

2017-04-01

Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined. Sera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin ( 125 I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of 125 I-αDTX and 125 I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2. VGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated 125 I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical-serological correlations and a limited immunotherapy response. Double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies. 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/.

Agile Acceptance Test-Driven Development of Clinical Decision Support Advisories: Feasibility of Using Open Source Software.

PubMed

Basit, Mujeeb A; Baldwin, Krystal L; Kannan, Vaishnavi; Flahaven, Emily L; Parks, Cassandra J; Ott, Jason M; Willett, Duwayne L

2018-04-13

Moving to electronic health records (EHRs) confers substantial benefits but risks unintended consequences. Modern EHRs consist of complex software code with extensive local configurability options, which can introduce defects. Defects in clinical decision support (CDS) tools are surprisingly common. Feasible approaches to prevent and detect defects in EHR configuration, including CDS tools, are needed. In complex software systems, use of test-driven development and automated regression testing promotes reliability. Test-driven development encourages modular, testable design and expanding regression test coverage. Automated regression test suites improve software quality, providing a "safety net" for future software modifications. Each automated acceptance test serves multiple purposes, as requirements (prior to build), acceptance testing (on completion of build), regression testing (once live), and "living" design documentation. Rapid-cycle development or "agile" methods are being successfully applied to CDS development. The agile practice of automated test-driven development is not widely adopted, perhaps because most EHR software code is vendor-developed. However, key CDS advisory configuration design decisions and rules stored in the EHR may prove amenable to automated testing as "executable requirements." We aimed to establish feasibility of acceptance test-driven development of clinical decision support advisories in a commonly used EHR, using an open source automated acceptance testing framework (FitNesse). Acceptance tests were initially constructed as spreadsheet tables to facilitate clinical review. Each table specified one aspect of the CDS advisory's expected behavior. Table contents were then imported into a test suite in FitNesse, which queried the EHR database to automate testing. Tests and corresponding CDS configuration were migrated together from the development environment to production, with tests becoming part of the production regression test suite. We used test-driven development to construct a new CDS tool advising Emergency Department nurses to perform a swallowing assessment prior to administering oral medication to a patient with suspected stroke. Test tables specified desired behavior for (1) applicable clinical settings, (2) triggering action, (3) rule logic, (4) user interface, and (5) system actions in response to user input. Automated test suite results for the "executable requirements" are shown prior to building the CDS alert, during build, and after successful build. Automated acceptance test-driven development and continuous regression testing of CDS configuration in a commercial EHR proves feasible with open source software. Automated test-driven development offers one potential contribution to achieving high-reliability EHR configuration. Vetting acceptance tests with clinicians elicits their input on crucial configuration details early during initial CDS design and iteratively during rapid-cycle optimization. ©Mujeeb A Basit, Krystal L Baldwin, Vaishnavi Kannan, Emily L Flahaven, Cassandra J Parks, Jason M Ott, Duwayne L Willett. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 13.04.2018.

Evaluating measurement models in clinical research: covariance structure analysis of latent variable models of self-conception.

PubMed

Hoyle, R H

1991-02-01

Indirect measures of psychological constructs are vital to clinical research. On occasion, however, the meaning of indirect measures of psychological constructs is obfuscated by statistical procedures that do not account for the complex relations between items and latent variables and among latent variables. Covariance structure analysis (CSA) is a statistical procedure for testing hypotheses about the relations among items that indirectly measure a psychological construct and relations among psychological constructs. This article introduces clinical researchers to the strengths and limitations of CSA as a statistical procedure for conceiving and testing structural hypotheses that are not tested adequately with other statistical procedures. The article is organized around two empirical examples that illustrate the use of CSA for evaluating measurement models with correlated error terms, higher-order factors, and measured and latent variables.

Construct validity of the pediatric evaluation of disability inventory computer adaptive test (PEDI-CAT) in children with medical complexity.

PubMed

Dumas, Helene M; Fragala-Pinkham, Maria A; Rosen, Elaine L; O'Brien, Jane E

2017-11-01

To assess construct (convergent and divergent) validity of the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) in a sample of children with complex medical conditions. Demographics, clinical information, PEDI-CAT normative score, and the Post-Acute Acuity Rating for Children (PAARC) level were collected for all post-acute hospital admissions (n = 110) from 1 April 2015 to 1 March 2016. Correlations between the PEDI-CAT Daily Activities, Mobility, and Social/Cognitive domain scores for the total sample and across three age groups (infant, preschool, and school-age) were calculated. Differences in mean PEDI-CAT scores for each domain across two groups, children with "Less Complexity," or "More Complexity" based on PAARC level were examined. All correlations for the total sample and age subgroups were statistically significant and trends across age groups were evident with the stronger associations between domains for the infant group. Significant differences were found between mean PEDI-CAT Daily Activities, Mobility, and Social/Cognitive normative scores across the two complexity groups with children in the "Less Complex" group having higher PEDI-CAT scores for all domains. This study provides evidence indicating the PEDI-CAT can be used with confidence in capturing and differentiating children's level of function in a post-acute care setting. Implications for Rehabilitation The PEDI-CAT is measure of function for children with a variety of conditions and can be used in any clinical setting. Convergent validity of the PEDI-CAT's Daily Activities, Mobility, and Social/Cognitive domains was significant and particularly strong for infants and young children with medical complexity. The PEDI-CAT was able to discriminate groups of children with differing levels of medical complexity admitted to a pediatric post-acute care hospital.

Correlations between Clinical Judgement and Learning Style Preferences of Nursing Students in the Simulation Room

PubMed Central

Hallin, Karin; Häggström, Marie; Bäckström, Britt; Kristiansen, Lisbeth Porskrog

2016-01-01

Background: Health care educators account for variables affecting patient safety and are responsible for developing the highly complex process of education planning. Clinical judgement is a multidimensional process, which may be affected by learning styles. The aim was to explore three specific hypotheses to test correlations between nursing students’ team achievements in clinical judgement and emotional, sociological and physiological learning style preferences. Methods: A descriptive cross-sectional study was conducted with Swedish university nursing students in 2012-2013. Convenience sampling was used with 60 teams with 173 nursing students in the final semester of a three-year Bachelor of Science in nursing programme. Data collection included questionnaires of personal characteristics, learning style preferences, determined by the Dunn and Dunn Productivity Environmental Preference Survey, and videotaped complex nursing simulation scenarios. Comparison with Lasater Clinical Judgement Rubric and Non-parametric analyses were performed. Results: Three significant correlations were found between the team achievements and the students’ learning style preferences: significant negative correlation with ‘Structure’ and ‘Kinesthetic’ at the individual level, and positive correlation with the ‘Tactile’ variable. No significant correlations with students’ ‘Motivation’, ‘Persistence’, ‘Wish to learn alone’ and ‘Wish for an authoritative person present’ were seen. Discussion and Conclusion: There were multiple complex interactions between the tested learning style preferences and the team achievements of clinical judgement in the simulation room, which provides important information for the becoming nurses. Several factors may have influenced the results that should be acknowledged when designing further research. We suggest conducting mixed methods to determine further relationships between team achievements, learning style preferences, cognitive learning outcomes and group processes. PMID:26755461

DECIDE: a software for computer-assisted evaluation of diagnostic test performance.

PubMed

Chiecchio, A; Bo, A; Manzone, P; Giglioli, F

1993-05-01

The evaluation of the performance of clinical tests is a complex problem involving different steps and many statistical tools, not always structured in an organic and rational system. This paper presents a software which provides an organic system of statistical tools helping evaluation of clinical test performance. The program allows (a) the building and the organization of a working database, (b) the selection of the minimal set of tests with the maximum information content, (c) the search of the model best fitting the distribution of the test values, (d) the selection of optimal diagnostic cut-off value of the test for every positive/negative situation, (e) the evaluation of performance of the combinations of correlated and uncorrelated tests. The uncertainty associated with all the variables involved is evaluated. The program works in a MS-DOS environment with EGA or higher performing graphic card.

Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre

PubMed Central

Paterson, Ross W; Zandi, Michael S; Armstrong, Richard; Vincent, Angela; Schott, Jonathan M

2014-01-01

Background Voltage-gated potassium channel (VGKC)-complex antibodies can be associated with a range of immunotherapy-responsive clinical presentations including limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. However, there are patients with positive levels in whom the significance is uncertain. Objective To evaluate the clinical significance associated with positive (>100 pM) VGKC-complex antibodies. Methods Over a 4-year period, 1053 samples were sent for testing of which 55 were positive. The clinical presentations, final diagnoses and responses to immunotherapies, when given, were assessed retrospectively and the likelihood of autoimmunity was categorised as definite, possible, unlikely or undetermined (modified from Zuliani et al 2012). Results Only 4 of the 32 patients with low-positive (100–400 pM) levels were considered definitely autoimmune, 3 with peripheral nerve hyperexcitability and 1 with a thymoma; 3 were given immunotherapies. Of the remaining 28 with low-positive levels, 13 (3 of whom had tumours) were considered possibly autoimmune, and 15 were unlikely or undetermined; 1 was given immunotherapy unsuccessfully. Of the 23 patients with high-positive (>400 pM) levels, 12 were given immunotherapies, 11 of whom showed a good response. 11 were considered definitely autoimmune, 10 with limbic encephalitis (antibody specificity: 5 LGI1, 1 contactin2, 2 negative, 2 untested) and 1 with a tumour. In the remaining 12, autoimmunity was considered possible (n=9; most had not received immunotherapies), or unlikely (n=3). Conclusions As antibody testing becomes more widely available, and many samples are referred from patients with less clear-cut diagnoses, it is important to assess the utility of the results. VGKC-complex antibodies in the range of 100–400 pM (0.1–0.4 nM) were considered clinically relevant in rare conditions with peripheral nerve hyperexcitability and appeared to associate with tumours (12.5%). By contrast high-positive (>400 pM; >0.4 nM) levels were considered definitely (38%) or possibly (49%) clinically relevant, but not all patients had a ‘classical’ limbic encephalitis and some did not receive immunotherapies. PMID:23757422

Clinical relevance of positive voltage-gated potassium channel (VGKC)-complex antibodies: experience from a tertiary referral centre.

PubMed

Paterson, Ross W; Zandi, Michael S; Armstrong, Richard; Vincent, Angela; Schott, Jonathan M

2014-06-01

Voltage-gated potassium channel (VGKC)-complex antibodies can be associated with a range of immunotherapy-responsive clinical presentations including limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. However, there are patients with positive levels in whom the significance is uncertain. To evaluate the clinical significance associated with positive (>100 pM) VGKC-complex antibodies. Over a 4-year period, 1053 samples were sent for testing of which 55 were positive. The clinical presentations, final diagnoses and responses to immunotherapies, when given, were assessed retrospectively and the likelihood of autoimmunity was categorised as definite, possible, unlikely or undetermined (modified from Zuliani et al 2012). Only 4 of the 32 patients with low-positive (100-400 pM) levels were considered definitely autoimmune, 3 with peripheral nerve hyperexcitability and 1 with a thymoma; 3 were given immunotherapies. Of the remaining 28 with low-positive levels, 13 (3 of whom had tumours) were considered possibly autoimmune, and 15 were unlikely or undetermined; 1 was given immunotherapy unsuccessfully. Of the 23 patients with high-positive (>400 pM) levels, 12 were given immunotherapies, 11 of whom showed a good response. 11 were considered definitely autoimmune, 10 with limbic encephalitis (antibody specificity: 5 LGI1, 1 contactin2, 2 negative, 2 untested) and 1 with a tumour. In the remaining 12, autoimmunity was considered possible (n=9; most had not received immunotherapies), or unlikely (n=3). As antibody testing becomes more widely available, and many samples are referred from patients with less clear-cut diagnoses, it is important to assess the utility of the results. VGKC-complex antibodies in the range of 100-400 pM (0.1-0.4 nM) were considered clinically relevant in rare conditions with peripheral nerve hyperexcitability and appeared to associate with tumours (12.5%). By contrast high-positive (>400 pM; >0.4 nM) levels were considered definitely (38%) or possibly (49%) clinically relevant, but not all patients had a 'classical' limbic encephalitis and some did not receive immunotherapies.

Immunotherapy with the storage mite lepidoglyphus destructor.

PubMed

Armentia-Medina, A; Tapias, J A; Martín, J F; Ventas, P; Fernández, A

1995-01-01

We carried out a double-blind clinical trial of immunotherapy on 35 patients sensitized to the storage mite Lepidoglyphus destructor (Ld). Before and after 12 months of specific hyposensitization (Abelló Lab., Spain) we performed in vivo (skin tests with Ld, methacholine and challenge tests), and in vitro tests (specific IgE, IgG, IgG1 and IgG4 to Ld and specific IgE, IgG, IgG1 and IgG4 to their major allergen Lep dI). We also monitored the efficacy and safety of the immunotherapy with clinical and analytical controls (symptoms and medication score, detection of immune complexes). After therapy we found a significant decrease in specific skin reactivity, dose of positive challenge tests, and hyperresponsiveness to methacholine. Sputum eosinophilia decreased. Specific IgE to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to Ld and Lep DI. The placebo group showed no changes in these variables. There were no severe secondary reactions after treatment with the extract. Patients-self-evaluation was favourable and their labour absence decreased. No development of circulating immune complexes was associated with this immunotherapy.

The 26S Proteasome Complex: An Attractive Target for Cancer Therapy

PubMed Central

Frankland-Searby, Sarah; Bhaumik, Sukesh R.

2011-01-01

The 26S proteasome complex engages in an ATP-dependent proteolytic degradation of a variety of oncoproteins, transcription factors, cell cycle specific cyclins, cyclin-dependent kinase inhibitors, ornithine decarboxylase, and other key regulatory cellular proteins. Thus, the proteasome regulates either directly or indirectly many important cellular processes. Altered regulation of these cellular events is linked to the development of cancer. Therefore, the proteasome has become an attractive target for the treatment of numerous cancers. Several proteasome inhibitors that target the proteolytic active sites of the 26S proteasome complex have been developed and tested for anti-tumor activities. These proteasome inhibitors have displayed impressive anti-tumor functions by inducing apoptosis in different tumor types. Further, the proteasome inhibitors have been shown to induce cell cycle arrest, and inhibit angiogenesis, cell-cell adhesion, cell migration, immune and inflammatory responses, and DNA repair response. A number of proteasome inhibitors are now in clinical trials to treat multiple myeloma and solid tumors. Many other proteasome inhibitors with different efficiencies are being developed and tested for anti-tumor activities. Several proteasome inhibitors currently in clinical trials have shown significantly improved anti-tumor activities when combined with other drugs such as histone deacetylase (HDAC) inhibitors, Akt (protein kinase B) inhibitors, DNA damaging agents, Hsp90 (heat shock protein 90) inhibitors, and lenalidomide. The proteasome inhibitor bortezomib is now in the clinic to treat multiple myeloma and mantle cell lymphoma. Here, we discuss the 26S proteasome complex in carcinogenesis and different proteasome inhibitors with their potential therapeutic applications in treatment of numerous cancers. PMID:22037302

Closing the gap between knowledge and clinical application: challenges for genomic translation.

PubMed

Burke, Wylie; Korngiebel, Diane M

2015-01-01

Despite early predictions and rapid progress in research, the introduction of personal genomics into clinical practice has been slow. Several factors contribute to this translational gap between knowledge and clinical application. The evidence available to support genetic test use is often limited, and implementation of new testing programs can be challenging. In addition, the heterogeneity of genomic risk information points to the need for strategies to select and deliver the information most appropriate for particular clinical needs. Accomplishing these tasks also requires recognition that some expectations for personal genomics are unrealistic, notably expectations concerning the clinical utility of genomic risk assessment for common complex diseases. Efforts are needed to improve the body of evidence addressing clinical outcomes for genomics, apply implementation science to personal genomics, and develop realistic goals for genomic risk assessment. In addition, translational research should emphasize the broader benefits of genomic knowledge, including applications of genomic research that provide clinical benefit outside the context of personal genomic risk.

Evaluation of the Vitek MS v3.0 Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry System for Identification of Mycobacterium and Nocardia Species.

PubMed

Body, Barbara A; Beard, Melodie A; Slechta, E Susan; Hanson, Kimberly E; Barker, Adam P; Babady, N Esther; McMillen, Tracy; Tang, Yi-Wei; Brown-Elliott, Barbara A; Iakhiaeva, Elena; Vasireddy, Ravikiran; Vasireddy, Sruthi; Smith, Terry; Wallace, Richard J; Turner, S; Curtis, L; Butler-Wu, Susan; Rychert, Jenna

2018-06-01

This multicenter study was designed to assess the accuracy and reproducibility of the Vitek MS v3.0 matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry system for identification of Mycobacterium and Nocardia species compared to DNA sequencing. A total of 963 clinical isolates representing 51 taxa were evaluated. In all, 663 isolates were correctly identified to the species level (69%), with another 231 (24%) correctly identified to the complex or group level. Fifty-five isolates (6%) could not be identified despite repeat testing. All of the tuberculous mycobacteria (45/45; 100%) and most of the nontuberculous mycobacteria (569/606; 94%) were correctly identified at least to the group or complex level. However, not all species or subspecies within the M. tuberculosis , M. abscessus , and M. avium complexes and within the M. fortuitum and M. mucogenicum groups could be differentiated. Among the 312 Nocardia isolates tested, 236 (76%) were correctly identified to the species level, with an additional 44 (14%) correctly identified to the complex level. Species within the N. nova and N. transvalensis complexes could not always be differentiated. Eleven percent of the isolates (103/963) underwent repeat testing in order to get a final result. Identification of a representative set of Mycobacterium and Nocardia species was highly reproducible, with 297 of 300 (99%) replicates correctly identified using multiple kit lots, instruments, analysts, and sites. These findings demonstrate that the system is robust and has utility for the routine identification of mycobacteria and Nocardia in clinical practice. Copyright © 2018 American Society for Microbiology.

Clinical examination and physical assessment of hip joint-related pain in athletes.

PubMed

Reiman, Michael P; Thorborg, Kristian

2014-11-01

Evidence-based clinical examination and assessment of the athlete with hip joint related pain is complex. It requires a systematic approach to properly differentially diagnose competing potential causes of athletic pain generation. An approach with an initial broad focus (and hence use of highly sensitive tests/measures) that then is followed by utilizing more specific tests/measures to pare down this imprecise differential diagnosis list is suggested. Physical assessment measures are then suggested to discern impairments, activity and participation restrictions for athletes with hip-join related pain, hence guiding the proper treatment approach. 5.

Examination of acetabular labral tear: a continued diagnostic challenge.

PubMed

Reiman, Michael P; Mather, Richard C; Hash, Thomas W; Cook, Chad E

2014-02-01

Acetabular labrum tears (ALT) are present in 22-55% of individuals with hip or groin pain. Tears can occur as a result of trauma or degeneration and are markedly associated with femoral acetabular morphological variations. An ALT can lead to biomechanical deficiencies and a loss of stability to the coxafemoral joint due to the labrum serving as a stabilising structure of this joint. The diagnosis of ALT is complex and multidimensional. Although tremendous improvements in diagnostic utility for ALT have occurred in the past 25 years, there are few patient history, clinical examination and special test findings that are unique to the condition. Imaging methods such as MRI, CT and ultrasonography have demonstrated reasonable accuracy, but not at a level that allows use as a stand-alone measure. Outcomes measures that focus on functional limitation or that are used to measure recovery should envelop the complexities of the condition and be captured using both self-report and physical performance measures. Only when patient history, objective testing, clinical examination special testing and imaging are combined can a clinician fully elucidate the multidimensional diagnosis of ALT.

Clinical Laboratories – Production Factories or Specialized Diagnostic Centers

PubMed Central

Tóth, Judit

2016-01-01

Since a large proportion of medical decisions are based on laboratory results, clinical laboratories should meet the increasing demand of clinicians and their patients. Huge central laboratories may process over 10 million tests annually; they act as production factories, measuring emergency and routine tests with sufficient speed and accuracy. At the same time, they also serve as specialized diagnostic centers where well-trained experts analyze and interpret special test results. It is essential to improve and constantly monitor this complex laboratory service, by several methods. Sample transport by pneumatic tube system, use of an advanced laboratory information system and point-of-care testing may result in decreased total turnaround time. The optimization of test ordering may result in a faster and more cost-effective laboratory service. Autovalidation can save time for laboratory specialists, when the analysis of more complex results requires their attention. Small teams of experts responsible for special diagnostic work, and their interpretative reporting according to predetermined principles, may help to minimize subjectivity of these special reports. Although laboratory investigations have become so diversely developed in the past decades, it is essential that the laboratory can provide accurate results relatively quickly, and that laboratory specialists can support the diagnosis and monitoring of patients by adequate interpretation of esoteric laboratory methods. PMID:27683528

Correlates and importance of neglect-like symptoms in complex regional pain syndrome.

PubMed

Wittayer, Matthias; Dimova, Violeta; Birklein, Frank; Schlereth, Tanja

2018-05-01

Neglect-like symptoms (NLS) are frequently observed in complex regional pain syndrome (CRPS). The clinical meaning of NLS, however, is largely unknown. Therefore, this study sets out to assess the importance of NLS for patient outcome and to explore their clinical correlates. We assessed NLS in a group of 53 patients with CRPS and compared the results to 28 healthy volunteers. To define the origin of the NLS reports, we tested the subjective visual midline, performed a limb-laterality recognition test, and quantitative sensory testing. In addition, psychological and pain assessment scales were completed. Tests were analyzed with univariate and multivariate approaches. After 6 months, patients were reassessed and the influence of NLS on pain outcome was determined. Most patients reported NLS in the questionnaire, whereas subjective visual midline and limb-laterality recognition test in contrast to previous studies did not reveal perceptual disturbances. Neglect-like symptom scores were associated with pain and pain catastrophizing in acute CRPS and anxiety and thermal sensory loss in chronic CRPS. Furthermore, high NLS scores had a negative impact on pain outcome after 6 months. Our results indicate that NLS have a different meaning in acute and chronic CRPS and might be of prognostic value. Possibly, treatment should focus on reducing NLS.

Interferences from blood collection tube components on clinical chemistry assays

PubMed Central

Bowen, Raffick A.R.; Remaley, Alan T.

2014-01-01

Improper design or use of blood collection devices can adversely affect the accuracy of laboratory test results. Vascular access devices, such as catheters and needles, exert shear forces during blood flow, which creates a predisposition to cell lysis. Components from blood collection tubes, such as stoppers, lubricants, surfactants, and separator gels, can leach into specimens and/or adsorb analytes from a specimen; special tube additives may also alter analyte stability. Because of these interactions with blood specimens, blood collection devices are a potential source of pre-analytical error in laboratory testing. Accurate laboratory testing requires an understanding of the complex interactions between collection devices and blood specimens. Manufacturers, vendors, and clinical laboratorians must consider the pre-analytical challenges in laboratory testing. Although other authors have described the effects of endogenous substances on clinical assay results, the effects/impact of blood collection tube additives and components have not been well systematically described or explained. This review aims to identify and describe blood collection tube additives and their components and the strategies used to minimize their effects on clinical chemistry assays. PMID:24627713

Diagnostic performances of clinical laboratory tests using Triton X-100 to reduce the biohazard associated with routine testing of Ebola virus-infected patients.

PubMed

Tempestilli, Massimo; Pucci, Luigia; Notari, Stefania; Di Caro, Antonino; Castilletti, Concetta; Rivelli, Maria Rosaria; Agrati, Chiara; Pucillo, Leopoldo Paolo

2015-11-01

Ebola virus, an enveloped virus, is the cause of the largest and most complex Ebola virus disease (EVD) outbreak in West Africa. Blood or body fluids of an infected person may represent a biohazard to laboratory workers. Laboratory tests of virus containing specimens should be conducted in referral centres at biosafety level 4, but based on the severity of clinical symptoms, basic laboratories might be required to execute urgent tests for patients suspected of EVD. The aim of this work was to compare the analytical performances of laboratory tests when Triton X-100, a chemical agent able to inactivate other enveloped viruses, was added to specimens. Results of clinical chemistry, coagulation and haematology parameters on samples before and after the addition of 0.1% (final concentration) of Triton X-100 and 1 h of incubation at room temperature were compared. Overall, results showed very good agreement by all statistical analyses. Triton X-100 at 0.1% did not significantly affect the results for the majority of the analytes tested. Triton X-100 at 0.1% can be used to reduce the biohazard in performing laboratory tests on samples from patients with EVD without affecting clinical decisions.

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer

PubMed Central

Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi

2018-01-01

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle. PMID:29856804

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

PubMed

Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi; Esumi, Hiroyasu

2018-01-01

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

Illustrating idiographic methods for translation research: moderation effects, natural clinical experiments, and complex treatment-by-subgroup interactions.

PubMed

Ridenour, Ty A; Wittenborn, Andrea K; Raiff, Bethany R; Benedict, Neal; Kane-Gill, Sandra

2016-03-01

A critical juncture in translation research involves the preliminary studies of intervention tools, provider training programs, policies, and other mechanisms used to leverage knowledge garnered at one translation stage into another stage. Potentially useful for such studies are rigorous techniques for conducting within-subject clinical trials, which have advanced incrementally over the last decade. However, these methods have largely not been utilized within prevention or translation contexts. The purpose of this manuscript is to demonstrate the flexibility, wide applicability, and rigor of idiographic clinical trials for preliminary testing of intervention mechanisms. Specifically demonstrated are novel uses of state-space modeling for testing intervention mechanisms of short-term outcomes, identifying heterogeneity in and moderation of within-person treatment mechanisms, a horizontal line plot to refine sampling design during the course of a clinic-based experimental study, and the need to test a treatment's efficacy as treatment is administered along with (e.g., traditional 12-month outcomes).

Clinical, Electrophysiological, and Serological Evaluation of Patients with Cramp-Fasciculation Syndrome

PubMed Central

POYRAZ, Mürüvvet; MATUR, Zeliha; AYSAL, Fikret; TÜZÜN, Erdem; HANOĞLU, Lütfü; ÖGE, A. Emre

2017-01-01

Introduction Cramp-fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability syndrome. There are only a few reports on clinical and serological profile of a CFS cohort that was followed up by a single outpatient clinic. Methods Clinical, electrophysiological, and serological features of 6 CFS patients (5 men, 1 woman; 27–65 years old) were investigated. Results All patients presented with cramps, fasciculations, muscle pain, and autonomic symptoms, and 2 also reported numbness and burning sensation in limbs, suggestive of neuropathic pain. Antibodies to uncharacterized voltage-gated potassium channel (VGKC)-complex proteins were found in 2 patients and to contactin-associated protein-like 2 (CASPR2) in 1 patient. None of the patients had a tumor. Most of the patients revealed prolonged after-discharges following tibial nerve stimulation. Nerve conduction studies and R-R interval variability tests were normal, whereas sympathetic skin responses were increased in amplitude in 3 seronegative patients. Five patients showed favorable response to carbamazepine or pregabalin treatment, whereas 1 VGKC-antibody-positive patient was resistant to carbamazepine and immunosuppressant treatment. Conclusion Neuropathic pain and VGKC-complex antibodies may be encountered in CFS patients. Although autonomic symptoms are commonly found in CFS, routine autonomic system tests which are done in electrophysiology laboratories might yield normal results. PMID:28680318

Clinical, Electrophysiological, and Serological Evaluation of Patients with Cramp-Fasciculation Syndrome.

PubMed

Poyraz, Mürüvvet; Matur, Zeliha; Aysal, Fikret; Tüzün, Erdem; Hanoğlu, Lütfü; Öge, A Emre

2017-06-01

Cramp-fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability syndrome. There are only a few reports on clinical and serological profile of a CFS cohort that was followed up by a single outpatient clinic. Clinical, electrophysiological, and serological features of 6 CFS patients (5 men, 1 woman; 27-65 years old) were investigated. All patients presented with cramps, fasciculations, muscle pain, and autonomic symptoms, and 2 also reported numbness and burning sensation in limbs, suggestive of neuropathic pain. Antibodies to uncharacterized voltage-gated potassium channel (VGKC)-complex proteins were found in 2 patients and to contactin-associated protein-like 2 (CASPR2) in 1 patient. None of the patients had a tumor. Most of the patients revealed prolonged after-discharges following tibial nerve stimulation. Nerve conduction studies and R-R interval variability tests were normal, whereas sympathetic skin responses were increased in amplitude in 3 seronegative patients. Five patients showed favorable response to carbamazepine or pregabalin treatment, whereas 1 VGKC-antibody-positive patient was resistant to carbamazepine and immunosuppressant treatment. Neuropathic pain and VGKC-complex antibodies may be encountered in CFS patients. Although autonomic symptoms are commonly found in CFS, routine autonomic system tests which are done in electrophysiology laboratories might yield normal results.

Genetic testing for inherited ocular disease: delivering on the promise at last?

PubMed

Gillespie, Rachel L; Hall, Georgina; Black, Graeme C

2014-01-01

Genetic testing is of increasing clinical utility for diagnosing inherited eye disease. Clarifying a clinical diagnosis is important for accurate estimation of prognosis, facilitating genetic counselling and management of families, and in the future will direct gene-specific therapeutic strategies. Often, precise diagnosis of genetic ophthalmic conditions is complicated by genetic heterogeneity, a difficulty that the so-called 'next-generation sequencing' technologies promise to overcome. Despite considerable counselling and ethical complexities, next-generation sequencing offers to revolutionize clinical practice. This will necessitate considerable adjustment to standard practice but has the power to deliver a personalized approach to genomic medicine for many more patients and enhance the potential for preventing vision loss. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

Pre-Clinical Testing of New Hydroxybutyrate Analogues

DTIC Science & Technology

2011-07-01

complex I and II sites. Several years ago, we evaluated the use of ketone bodies as secondary sources of energy for mitochondria compromised due to...hydroxybutyrate (DβHB), a ketone body normally produced by hepatocytes and astrocytes and infused via Alzet pump, protected the substantia nigra...crisis in the neurons . In an earlier study, bypassing this complex I deficiency using D-- hydroxybutyrate (DHB) in the MPTP (1-methyl-4-phenyl-1,2,3,6

Complex I deficiency related to T10158C mutation ND3 gene: A further definition of the clinical spectrum.

PubMed

Grosso, Salvatore; Carluccio, Maria Alessandra; Cardaioli, Elena; Cerase, Alfonso; Malandrini, Alessandro; Romano, Chiara; Federico, Antonio; Dotti, Maria Teresa

2017-03-01

Complex I deficiency is the most common energy generation disorder which may clinically present at any age with a wide spectrum of symptoms and signs. The T10158C mutation ND3 gene is rare and occurs in patients showing an early rapid neurological deterioration invariably leading to death after a few months. We report a 9year-old boy with a mtDNA T10158C mutation showing a mild MELAS-like phenotype and brain MRI features congruent with both MELAS and Leigh syndrome. Epilepsia partialis continua also occurred in the clinical course and related to a mild cortical atrophy of the left perisylvian area. The present case confirms that the clinical spectrum of Complex I deficiency related to T10158C mutation ND3 gene is wider than previously described. Our observation further suggests that testing mutation in the MT-ND3 gene should be included in the diagnostic work-up of patients presenting with epilepsia partialis continua accompanied by suspicion of mitochondrial disorder. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Instability of monoclonal myeloma protein may be identified as susceptibility to penetration and binding by newly synthesized Congo red derivatives.

PubMed

Spólnik, Paweł; Konieczny, Leszek; Piekarska, Barbara; Rybarska, Janina; Stopa, Barbara; Zemanek, Grzegorz; Król, Marcin; Roterman, Irena

2004-06-01

Monoclonal myeloma proteins often have an abnormal, unstable structure, and tend to aggregate with fatal clinical consequences. A method for early clinical identification of this aggregation tendency is impatiently awaited. This work proposes the use of supramolecular dyes as specific ligands to reveal protein instability. Disclosure of excessive polypeptide chain flexibility in unstable monoclonal proteins, leading to increased susceptibility to penetration by foreign compounds, appeared possible when new supramolecular Congo red-derived dyes with different protein-binding capabilities were used for complexation. Two basic protein instability levels, local and global, were differentiated by comparing the extent of protein loading with dye and the subsequent electrophoretic migration rate of the complexes. A simple electrophoretic test is proposed for assessment of the instability of monoclonal proteins in clinical conditions.

Analyses of the Complexity of Patients Undergoing Attended Polysomnography in the Era of Home Sleep Apnea Tests

PubMed Central

Colaco, Brendon; Herold, Daniel; Johnson, Matthew; Roellinger, Daniel; Naessens, James M.; Morgenthaler, Timothy I.

2018-01-01

Study Objectives: Health care complexity includes dimensions of patient comorbidity and the level of services needed to meet patient demands. Home sleep apnea tests (HSAT) are increasingly used to test medically uncomplicated patients suspected of having moderate to severe obstructive sleep apnea (OSA). Patients with significant comorbidities or other sleep disorders are not candidates for HSAT and require attended in-center polysomnography. We hypothesized that this trend would result in increasingly complex patients being studied in sleep centers. Methods: Our study had two parts. To ascertain trends in sleep patient comorbidity, we used administrative diagnostic codes from patients undergoing polysomnography at the Mayo Clinic Center for Sleep Medicine from 2005 to June 2015 to calculate the Charlson and the Elixhauser comorbidity indices. We measured the level of services provided in two ways: (1) in a subset of patients from the past 2 months of 2015, we evaluated correlation of these morbidity indices with an internally developed Polysomnogram Clinical Index (PSGCI) rating anticipated patient care needs from 0 to 3 and (2) we measured the sleep study complexity based on polysomnography protocol design. Results: In 43,780 patients studied from 2005 to June 2015, the Charlson index increased from a mean of 1.38 to 1.88 (3.1% per year, P < .001) and the mean Elixhauser index increased from 2.61 to 3.35 (2.5% per year, P < .001). Both comorbidity indices were significantly higher at the highest (Level 3) level of the PSGCI (P < .001), and sleep study complexity increased over time. Conclusions: The complexity of patients undergoing attended polysomnography has increased by 28% to 36% over the past decade as measured by validated comorbidity indices, and these indices correlate with the complexity of rendered care during polysomnography. These findings have implications for increasing requirements for staffing, monitoring capabilities, and facility design of future sleep centers. Commentary: A commentary on this article appears in this issue on page 499. Citation: Colaco B, Herold D, Johnson M, Roellinger D, Naessens JM, Morgenthaler TI. Analyses of the complexity of patients undergoing attended polysomnography in the era of home sleep apnea tests. J Clin Sleep Med. 2018;14(4):631–639. PMID:29609716

The cost of genetic testing for ocular disease: who pays?

PubMed

Capasso, Jenina E

2014-09-01

To facilitate ophthalmologists' understanding on the cost of genetic testing in ocular disease, the complexities of insurance coverage and its impact on the availability of testing. Many insurance carriers address coverage for genetic testing in written clinical policies. They provide criteria for medically necessary testing. These policies mostly cover testing for individuals who are symptomatic and in whom testing will have a direct impact on medical treatment. In cases in which no treatments are currently available, other than research trials, patients may have difficulty in getting insurance coverage for genetic testing. Genetic testing for inherited eye diseases can be costly but has many benefits to patient care, including confirmation of a diagnosis, insight into prognostic information, and identification of associated health risks, inheritance patterns, and possible current and future treatments. As gene therapy advances progress, the availability for treatment in ocular diseases, coverage for genetic testing by third-party payers could increase on the basis of current clinical policies.

Site-Specific Expression of Polycomb-Group Genes Encoding the HPC-HPH/PRC1 Complex in Clinically Defined Primary Nodal and Cutaneous Large B-Cell Lymphomas

PubMed Central

Raaphorst, Frank M.; Vermeer, Maarten; Fieret, Elly; Blokzijl, Tjasso; Dukers, Danny; Sewalt, Richard G.A.B.; Otte, Arie P.; Willemze, Rein; Meijer, Chris J.L.M.

2004-01-01

Polycomb-group (PcG) genes preserve cell identity by gene silencing, and contribute to regulation of lymphopoiesis and malignant transformation. We show that primary nodal large B-cell lymphomas (LBCLs), and secondary cutaneous deposits from such lymphomas, abnormally express the BMI-1, RING1, and HPH1 PcG genes in cycling neoplastic cells. By contrast, tumor cells in primary cutaneous LBCLs lacked BMI-1 expression, whereas RING1 was variably detected. Lack of BMI-1 expression was characteristic for primary cutaneous LBCLs, because other primary extranodal LBCLs originating from brain, testes, and stomach were BMI-1-positive. Expression of HPH1 was rarely detected in primary cutaneous LBCLs of the head or trunk and abundant in primary cutaneous LBCLs of the legs, which fits well with its earlier recognition as a distinct clinical pathological entity with different clinical behavior. We conclude that clinically defined subclasses of primary LBCLs display site-specific abnormal expression patterns of PcG genes of the HPC-HPH/PRC1 PcG complex. Some of these patterns (such as the expression profile of BMI-1) may be diagnostically relevant. We propose that distinct expression profiles of PcG genes results in abnormal formation of HPC-HPH/PRC1 PcG complexes, and that this contributes to lymphomagenesis and different clinical behavior of clinically defined LBCLs. PMID:14742259

Clinical uses of liver stem cells.

PubMed

Dan, Yock Young

2012-01-01

Liver transplantation offers a definitive cure for many liver and metabolic diseases. However, the complex invasive procedure and paucity of donor liver graft organs limit its clinical applicability. Liver stem cells provide a potentially limitless source of cells that would be useful for a variety of clinical applications. These stem cells or hepatocytes generated from them can be used in cellular transplantation, bioartificial liver devices and drug testing in the development of new drugs. In this chapter, we review the technical aspects of clinical applications of liver stem cells and the progress made to date in the clinical setting. The difficulties and challenges of realizing the potential of these cells are discussed.

Design of a Tablet Computer App for Facilitation of a Molecular Blood Culture Test in Clinical Microbiology and Preliminary Usability Evaluation.

PubMed

Samson, Lasse L; Pape-Haugaard, Louise; Meltzer, Michelle C; Fuchs, Martin; Schønheyder, Henrik C; Hejlesen, Ole

2016-03-18

User mobility is an important aspect of the development of clinical information systems for health care professionals. Mobile phones and tablet computers have obtained widespread use by health care professionals, offering an opportunity for supporting the access to patient information through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular-based diagnostic test used for rapid identification of pathogens in positive blood cultures. To facilitate the workflow of the MuxBCT, a specialized tablet computer app was developed as an accessory to the diagnostic test. The app aims to reduce the complexity of the test by step-by-step guidance of microscopy and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). The objective of the study was to describe the design considerations of the MuxBCT app and the results of a preliminary usability evaluation. The MuxBCT tablet app was developed and set up for use in a clinical microbiology laboratory. A near-live simulation study was conducted in the clinical microbiology laboratory to evaluate the usability of the MuxBCT app. The study was designed to achieve a high degree of realism as participants carried out a scenario representing the context of use for the MuxBCT app. As the MuxBCT was under development, the scenario involved the use of molecular blood culture tests similar to the MuxBCT for identification of microorganisms from positive blood culture samples. The study participants were observed, and their interactions with the app were recorded. After the study, the participants were debriefed to clarify observations. Four medical laboratory technicians, for example, representative of end users of the app, participated in the clinical simulation study. Using the MuxBCT app, the study participants successfully identified and reported all microorganisms from the positive blood cultures examined. Three of the four participants reported that they found the app useful, while one study participant reported that she would prefer to make notes on paper and later enter them into the LIS. The preliminary usability evaluation results indicate that use of the MuxBCT tablet app can facilitate the workflow of the MuxBCT diagnostic test.

Knowledge in schizophrenia: The Portuguese version of KAST (Knowledge About Schizophrenia Test) and analysis of social-demographic and clinical factors' influence.

PubMed

Daltio, C S; Attux, C; Ferraz, M B

2015-10-01

Schizophrenia is a complex disorder, and the knowledge about it can have a positive impact. The purpose of this study was to make the translation and cultural adaptation of the Knowledge About Schizophrenia Test (KAST) into Portuguese and determine the influence of clinical and socio-demographic factors on knowledge. The test was applied to 189 caregivers of patients enrolled in Schizophrenia Program of the Federal University of São Paulo, 30 caregivers of clinical patients of the General Outpatient Clinic of the same University, and 30 health professionals. The face and content validity of the test was established. The mean value (SD) obtained with the application of the final version to caregivers of schizophrenic patients was 12.96 (2.45) - maximum 17. Level of knowledge increased considering the following order: caregivers of clinical patients, caregivers of patients with schizophrenia and mental health professionals. The intraclass correlation coefficient (0.592) obtained in the test-retest was statistically significant. An influence of social class, race, gender and education of the caregiver on the test was observed, and the last two factors were more relevant. The KAST translated and adapted into Portuguese is a valid instrument and can be used as an evaluation tool on psychoeducational interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

Ethical and clinical practice considerations for genetic counselors related to direct-to-consumer marketing of genetic tests.

PubMed

Wade, Christopher H; Wilfond, Benjamin S

2006-11-15

Several companies utilize direct-to-consumer (DTC) advertising for genetic tests and some, but not all, bypass clinician involvement by offering DTC purchase of the tests. This article examines how DTC marketing strategies may affect genetic counselors, using available cardiovascular disease susceptibility tests as an illustration. The interpretation of these tests is complex and includes consideration of clinical validity and utility, and the further complications of gene-environment interactions and pleiotropy. Although it is unclear to what extent genetic counselors will encounter clients who have been exposed to DTC marketing strategies, these strategies may influence genetic counseling interactions if they produce directed interest in specific tests and unrealistic expectations for the tests' capacity to predict disease. Often, a client's concern about risk for cardiovascular diseases is best addressed by established clinical tests and a family history assessment. Ethical dilemmas may arise for genetic counselors who consider whether to accept clients who request test interpretation or to order DTC-advertised tests that require a clinician's authorization. Genetic counselors' obligations to care for clients extend to interpreting DTC tests, although this obligation may be fulfilled by referral or consultation with specialists. Genetic counselors do not have an obligation to order DTC-advertised tests that have minimal clinical validity and utility at a client's request. This can be a justified restriction on autonomy based on consideration of risks to the client, the costs, and the implications for society. Published 2006 Wiley-Liss, Inc.

Setting performance standards for medical practice: a theoretical framework.

PubMed

Southgate, L; Hays, R B; Norcini, J; Mulholland, H; Ayers, B; Woolliscroft, J; Cusimano, M; McAvoy, P; Ainsworth, M; Haist, S; Campbell, M

2001-05-01

The assessment of performance in the real world of medical practice is now widely accepted as the goal of assessment at the postgraduate level. This is largely a validity issue, as it is recognised that tests of knowledge and in clinical simulations cannot on their own really measure how medical practitioners function in the broader health care system. However, the development of standards for performance-based assessment is not as well understood as in competency assessment, where simulations can more readily reflect narrower issues of knowledge and skills. This paper proposes a theoretical framework for the development of standards that reflect the more complex world in which experienced medical practitioners work. The paper reflects the combined experiences of a group of education researchers and the results of literature searches that included identifying current health system data sources that might contribute information to the measurement of standards. Standards that reflect the complexity of medical practice may best be developed through an "expert systems" analysis of clinical conditions for which desired health care outcomes reflect the contribution of several health professionals within a complex, three-dimensional, contextual model. Examples of the model are provided, but further work is needed to test validity and measurability.

The Biological and Clinical Significance of Androgen Receptor Variants

DTIC Science & Technology

2014-04-01

immunohistochemistry. We tested two antibodies purportedly specific for AR-V7: 1) a mouse monoclonal antibody available from A&G Precision Antibody...a gift from Dr. Luo and tested on AR-V7- high and -low cases from the mixed-grade cohort in our lab. We used a monoclonal antibody against AR as a...fold, as compared with conventional avidin- biotinylated enzyme complex (ABC) procedures. We tested this protocol on four cases of the mixed-grade

Agile Acceptance Test–Driven Development of Clinical Decision Support Advisories: Feasibility of Using Open Source Software

PubMed Central

Baldwin, Krystal L; Kannan, Vaishnavi; Flahaven, Emily L; Parks, Cassandra J; Ott, Jason M; Willett, Duwayne L

2018-01-01

Background Moving to electronic health records (EHRs) confers substantial benefits but risks unintended consequences. Modern EHRs consist of complex software code with extensive local configurability options, which can introduce defects. Defects in clinical decision support (CDS) tools are surprisingly common. Feasible approaches to prevent and detect defects in EHR configuration, including CDS tools, are needed. In complex software systems, use of test–driven development and automated regression testing promotes reliability. Test–driven development encourages modular, testable design and expanding regression test coverage. Automated regression test suites improve software quality, providing a “safety net” for future software modifications. Each automated acceptance test serves multiple purposes, as requirements (prior to build), acceptance testing (on completion of build), regression testing (once live), and “living” design documentation. Rapid-cycle development or “agile” methods are being successfully applied to CDS development. The agile practice of automated test–driven development is not widely adopted, perhaps because most EHR software code is vendor-developed. However, key CDS advisory configuration design decisions and rules stored in the EHR may prove amenable to automated testing as “executable requirements.” Objective We aimed to establish feasibility of acceptance test–driven development of clinical decision support advisories in a commonly used EHR, using an open source automated acceptance testing framework (FitNesse). Methods Acceptance tests were initially constructed as spreadsheet tables to facilitate clinical review. Each table specified one aspect of the CDS advisory’s expected behavior. Table contents were then imported into a test suite in FitNesse, which queried the EHR database to automate testing. Tests and corresponding CDS configuration were migrated together from the development environment to production, with tests becoming part of the production regression test suite. Results We used test–driven development to construct a new CDS tool advising Emergency Department nurses to perform a swallowing assessment prior to administering oral medication to a patient with suspected stroke. Test tables specified desired behavior for (1) applicable clinical settings, (2) triggering action, (3) rule logic, (4) user interface, and (5) system actions in response to user input. Automated test suite results for the “executable requirements” are shown prior to building the CDS alert, during build, and after successful build. Conclusions Automated acceptance test–driven development and continuous regression testing of CDS configuration in a commercial EHR proves feasible with open source software. Automated test–driven development offers one potential contribution to achieving high-reliability EHR configuration. Vetting acceptance tests with clinicians elicits their input on crucial configuration details early during initial CDS design and iteratively during rapid-cycle optimization. PMID:29653922

Impact of clinical inertia on cardiovascular risk factors in patients with diabetes.

PubMed

Whitford, David L; Al-Anjawi, Hussam A; Al-Baharna, Marwa M

2014-07-01

To determine whether clinical inertia is associated with simpler interventions occurring more often than complex changes and the association between clinical inertia and outcomes. Prevalence of clinical inertia over a 30 month period for hyperglycaemia, hypertension and dyslipidaemia was calculated in a random sample (n=334) of patients attending a diabetes clinic. Comparisons between prevalence of clinical inertia and outcomes for each condition were examined using parametric tests of association. There was less clinical inertia in hyperglycaemia (29% of consultations) compared with LDL (80% of consultations) and systolic BP (68% of consultations). Consultations where therapy was intensified had a greater reduction in risk factor levels than when no change was made. No association was found between treatment intensity scores and changes in HbA1c, LDL or blood pressure over 30 months. Physicians are no more likely to intervene in conditions where simple therapeutic changes are necessary as opposed to complex changes. Greater clinical inertia leads to poorer outcomes. There continues to be substantial clinical inertia in routine clinical practice. Physicians should adopt a holistic approach to cardiovascular risk reduction in patients with diabetes, adhere more closely to established management guidelines and emphasize personal individualized target setting. Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Predicting clinical concussion measures at baseline based on motivation and academic profile.

PubMed

Trinidad, Katrina J; Schmidt, Julianne D; Register-Mihalik, Johna K; Groff, Diane; Goto, Shiho; Guskiewicz, Kevin M

2013-11-01

The purpose of this study was to predict baseline neurocognitive and postural control performance using a measure of motivation, high school grade point average (hsGPA), and Scholastic Aptitude Test (SAT) score. Cross-sectional. Clinical research center. Eighty-eight National Collegiate Athletic Association Division I incoming student-athletes (freshman and transfers). Participants completed baseline clinical concussion measures, including a neurocognitive test battery (CNS Vital Signs), a balance assessment [Sensory Organization Test (SOT)], and motivation testing (Rey Dot Counting). Participants granted permission to access hsGPA and SAT total score. Standard scores for each CNS Vital Signs domain and SOT composite score. Baseline motivation, hsGPA, and SAT explained a small percentage of the variance of complex attention (11%), processing speed (12%), and composite SOT score (20%). Motivation, hsGPA, and total SAT score do not explain a significant amount of the variance in neurocognitive and postural control measures but may still be valuable to consider when interpreting neurocognitive and postural control measures.

Predictive genetic testing for complex diseases: a public health perspective

PubMed Central

Marzuillo, C.; De Vito, C.; D’Andrea, E.; Rosso, A.

2014-01-01

From a public health perspective, systematic, evidence-based technology assessments and economic evaluations are needed to guide the incorporation of genomics into clinical and public health practice. However, scientific evidence on the effectiveness of predictive genetic tests is difficult to obtain. This review first highlights the similarities and differences between traditional screening tests and predictive genetic testing for complex diseases and goes on to describe frameworks for the evaluation of genetic testing that have been developed in recent years providing some evidence that currently genetic tests are not used in an appropriate way. Nevertheless, evidence-based recommendations are already available for some genomic applications that can reduce morbidity and mortality and many more are expected to emerge over the next decade. The time is now ripe for the introduction of a range of genetic tests into healthcare practice, but this will require the development of specific health policies, proper public health evaluations, organizational changes within the healthcare systems, capacity building among the healthcare workforce and the education of the public. PMID:24049051

Effect of home testing of international normalized ratio on clinical events.

PubMed

Matchar, David B; Jacobson, Alan; Dolor, Rowena; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Vertrees, Julia E; Shih, Mei-Chiung; Holodniy, Mark; Lavori, Philip

2010-10-21

Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes. We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death). The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001). As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.).

Differentiation of Mycobacterium tuberculosis complex from non-tubercular mycobacteria by nested multiplex PCR targeting IS6110, MTP40 and 32kD alpha antigen encoding gene fragments.

PubMed

Sinha, Pallavi; Gupta, Anamika; Prakash, Pradyot; Anupurba, Shampa; Tripathi, Rajneesh; Srivastava, G N

2016-03-12

Control of the global burden of tuberculosis is obstructed due to lack of simple, rapid and cost effective diagnostic techniques that can be used in resource poor-settings. To facilitate the early diagnosis of TB directly from clinical specimens, we have standardized and validated the use of nested multiplex PCR, targeting gene fragments IS6110, MTP40 and 32kD α-antigen encoding genes specific for Mycobacterium tuberculosis complex and non-tubercular mycobacteria (NTM), in comparison to smear microscopy, solid culture and single step multiplex PCR. The results were evaluated in comparison to a composite reference standard (CRS) comprising of microbiological results (smear and culture), clinical, radiological and cytopathological findings, clinical treatment and response to anti-tubercular therapy. The nested multiplex PCR (nMPCR) assay was evaluated to test its utility in 600 (535 pulmonary and 65 extra-pulmonary specimens) clinically suspected TB cases. All specimens were processed for smear, culture, single step multiplex PCR and nested multiplex PCR testing. Out of 535 screened pulmonary and 65 extra-pulmonary specimens, 329 (61.5%) and 19 (29.2%) cases were culture positive for M. tuberculosis. Based on CRS, 450 patients had "clinical TB" (definitive-TB, probable-TB and possible-TB). Remaining 150 were confirmed "non-TB" cases. For culture, the sensitivity was low, 79.3% for pulmonary and 54.3% for extra-pulmonary cases. The sensitivity and specificity results for nMPCR test were evaluated taken composite reference standard as a gold standard. The sensitivity of the nMPCR assay was 97.1% for pulmonary and 91.4% for extra-pulmonary TB cases with specificity of 100% and 93.3% respectively. Nested multiplex PCR using three gene primers is a rapid, reliable and highly sensitive and specific diagnostic technique for the detection and differentiation of M. tuberculosis complex from NTM genome and will be useful in diagnosing paucibacillary samples. Nested multiplex PCR assay was found to be better than single step multiplex PCR for assessing the diagnosis of TB.

Dosimetry for audit and clinical trials: challenges and requirements

NASA Astrophysics Data System (ADS)

Kron, T.; Haworth, A.; Williams, I.

2013-06-01

Many important dosimetry audit networks for radiotherapy have their roots in clinical trial quality assurance (QA). In both scenarios it is essential to test two issues: does the treatment plan conform with the clinical requirements and is the plan a reasonable representation of what is actually delivered to a patient throughout their course of treatment. Part of a sound quality program would be an external audit of these issues with verification of the equivalence of plan and treatment typically referred to as a dosimetry audit. The increasing complexity of radiotherapy planning and delivery makes audits challenging. While verification of absolute dose delivered at a reference point was the standard of external dosimetry audits two decades ago this is often deemed inadequate for verification of treatment approaches such as Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT). As such, most dosimetry audit networks have successfully introduced more complex tests of dose delivery using anthropomorphic phantoms that can be imaged, planned and treated as a patient would. The new challenge is to adapt this approach to ever more diversified radiotherapy procedures with image guided/adaptive radiotherapy, motion management and brachytherapy being the focus of current research.

Rv1458c: a new diagnostic marker for identification of Mycobacterium tuberculosis complex in a novel duplex PCR assay.

PubMed

Shrivastava, Kamal; Garima, Kushal; Narang, Anshika; Bhattacharyya, Kausik; Vishnoi, Ekta; Singh, Roshan Kumar; Chaudhry, Anil; Prasad, Rajendra; Bose, Mridula; Varma-Basil, Mandira

2017-03-01

We explored the efficiency of Rv1458c, the gene encoding a putative ABC drug transporter specific for the Mycobacterium tuberculosis complex (MTBC), as a diagnostic marker. A 190 bp region of Rv1458c and a 300 bp region of hsp65 were targeted in a novel duplex PCR assay and the results were compared with those for PCR restriction analysis(PRA) using the restriction enzymes NruI and BamHI. Species identification of a subset of the isolates (n=50) was confirmed by sequencing. Clinical isolates of M. tuberculosis (n=426) obtained from clinically suspected patients of pulmonary tuberculosis and mycobacterial (n=13) and non-mycobacterial (n=8) reference strains were included in the study. The duplex PCR assay correctly identified 320/426 isolates as MTBC and 106/426 isolates as non-tuberculous mycobacteria(NTM). The test was 100 % specific and sensitive when compared with NruI/BamHI PCR restriction analysis and highlighted the use of Rv1458c as a diagnostic marker for MTBC. The duplex PCR assay could be developed for use as a screening test to identify MTBC in clinical specimens in peripheral laboratories with limited resources.

Identifying balance and fall risk in community-dwelling older women: the effect of executive function on postural control.

PubMed

Muir-Hunter, Susan W; Clark, Jennifer; McLean, Stephanie; Pedlow, Sam; Van Hemmen, Alysia; Montero Odasso, Manuel; Overend, Tom

2014-01-01

The mechanisms linking cognition, balance function, and fall risk among older adults are not fully understood. An evaluation of the effect of cognition on balance tests commonly used in clinical practice to assess community-dwelling older adults could enhance the identification of at-risk individuals. The study aimed to determine (1) the association between cognition and clinical tests of balance and (2) the relationship between executive function (EF) and balance under single- and dual-task testing. Participants (24 women, mean age of 76.18 [SD 16.45] years) completed six clinical balance tests, four cognitive tests, and two measures of physical function. Poor balance function was associated with poor performance on cognitive testing of EF. In addition, the association with EF was strongest under the dual-task timed up-and-go (TUG) test and the Fullerton Advanced Balance Scale. Measures of global cognition were associated only with the dual-task performance of the TUG. Postural sway measured with the Standing Balance Test, under single- or dual-task test conditions, was not associated with cognition. Decreased EF was associated with worse performance on functional measures of balance. The relationship between EF and balance was more pronounced with dual-task testing using a complex cognitive task combined with the TUG.

Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach

PubMed Central

Fernandez, Bridget A.; Scherer, Stephen W.

2017-01-01

Autism spectrum disorder (ASD) encompasses a group of neurodevelopmental conditions diagnosed solely on the basis of behavioral assessments that reveal social deficits. Progress has been made in understanding its genetic underpinnings, but most ASD-associated genetic variants, which include copy number variants (CNVs) and mutations in ASD-risk genes, account for no more than 1 % of ASD cases. This high level of genetic heterogeneity leads to challenges obtaining and interpreting genetic testing in clinical settings. The traditional definition of syndromic ASD is a disorder with a clinically defined pattern of somatic abnormalities and a neurobehavioral phenotype that may include ASD. Most have a known genetic cause. Examples include fragile X syndrome and tuberous sclerosis complex. We propose dividing syndromic autism into the following two groups: (i) ASD that occurs in the context of a clinically defined syndrome-recognizing these disorders depends on the familiarity of the clinician with the features of the syndrome, and the diagnosis is typically confirmed by targeted genetic testing (eg, mutation screening of FMR1); (ii) ASD that occurs as a feature of a molecularly defined syndrome-for this group of patients, ASD-associated variants are identified by genome-wide testing that is not hypothesis driven (eg, microarray, whole exome sequencing). These ASD groups cannot be easily clinically defined because patients with a given variant have variable somatic abnormalities (dysmorphism and birth defects). In this article, we review common diagnoses from the above categories and suggest a testing strategy for patients, guided by determining whether the individual has essential or complex ASD; patients in the latter group have multiple morphologic anomalies on physical examination. Finally, we recommend that the syndromic versus nonsyndromic designation ultimately be replaced by classification of ASD according to its genetic etiology, which will inform about the associated spectrum and penetrance of neurobehavioral and somatic manifestations. PMID:29398931

Automation bias in electronic prescribing.

PubMed

Lyell, David; Magrabi, Farah; Raban, Magdalena Z; Pont, L G; Baysari, Melissa T; Day, Richard O; Coiera, Enrico

2017-03-16

Clinical decision support (CDS) in e-prescribing can improve safety by alerting potential errors, but introduces new sources of risk. Automation bias (AB) occurs when users over-rely on CDS, reducing vigilance in information seeking and processing. Evidence of AB has been found in other clinical tasks, but has not yet been tested with e-prescribing. This study tests for the presence of AB in e-prescribing and the impact of task complexity and interruptions on AB. One hundred and twenty students in the final two years of a medical degree prescribed medicines for nine clinical scenarios using a simulated e-prescribing system. Quality of CDS (correct, incorrect and no CDS) and task complexity (low, low + interruption and high) were varied between conditions. Omission errors (failure to detect prescribing errors) and commission errors (acceptance of false positive alerts) were measured. Compared to scenarios with no CDS, correct CDS reduced omission errors by 38.3% (p < .0001, n = 120), 46.6% (p < .0001, n = 70), and 39.2% (p < .0001, n = 120) for low, low + interrupt and high complexity scenarios respectively. Incorrect CDS increased omission errors by 33.3% (p < .0001, n = 120), 24.5% (p < .009, n = 82), and 26.7% (p < .0001, n = 120). Participants made commission errors, 65.8% (p < .0001, n = 120), 53.5% (p < .0001, n = 82), and 51.7% (p < .0001, n = 120). Task complexity and interruptions had no impact on AB. This study found evidence of AB omission and commission errors in e-prescribing. Verification of CDS alerts is key to avoiding AB errors. However, interventions focused on this have had limited success to date. Clinicians should remain vigilant to the risks of CDS failures and verify CDS.

The Complexity of Clinical Huntington's Disease: Developments in Molecular Genetics, Neuropathology and Neuroimaging Biomarkers.

PubMed

Tippett, Lynette J; Waldvogel, Henry J; Snell, Russell G; Vonsattel, Jean-Paul; Young, Anne B; Faull, Richard L M

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by extensive neuronal loss in the striatum and cerebral cortex, and a triad of clinical symptoms affecting motor, cognitive/behavioural and mood functioning. The mutation causing HD is an expansion of a CAG tract in exon 1 of the HTT gene. This chapter provides a multifaceted overview of the clinical complexity of HD. We explore recent directions in molecular genetics including the identification of loci that are genetic modifiers of HD that could potentially reveal therapeutic targets beyond the HTT gene transcript and protein. The variability of clinical symptomatology in HD is considered alongside recent findings of variability in cellular and neurochemical changes in the striatum and cerebral cortex in human brain. We review evidence from structural neuroimaging methods of progressive changes of striatum, cerebral cortex and white matter in pre-symptomatic and symptomatic HD, with a particular focus on the potential identification of neuroimaging biomarkers that could be used to test promising disease-specific and modifying treatments. Finally we provide an overview of completed clinical trials in HD and future therapeutic developments.

The fuzzy cube and causal efficacy: representation of concomitant mechanisms in stroke.

PubMed

Jobe, Thomas H.; Helgason, Cathy M.

1998-04-01

Twentieth century medical science has embraced nineteenth century Boolean probability theory based upon two-valued Aristotelian logic. With the later addition of bit-based, von Neumann structured computational architectures, an epistemology based on randomness has led to a bivalent epidemiological methodology that dominates medical decision making. In contrast, fuzzy logic, based on twentieth century multi-valued logic, and computational structures that are content addressed and adaptively modified, has advanced a new scientific paradigm for the twenty-first century. Diseases such as stroke involve multiple concomitant causal factors that are difficult to represent using conventional statistical methods. We tested which paradigm best represented this complex multi-causal clinical phenomenon-stroke. We show that the fuzzy logic paradigm better represented clinical complexity in cerebrovascular disease than current probability theory based methodology. We believe this finding is generalizable to all of clinical science since multiple concomitant causal factors are involved in nearly all known pathological processes.

BioStar models of clinical and genomic data for biomedical data warehouse design

PubMed Central

Wang, Liangjiang; Ramanathan, Murali

2008-01-01

Biomedical research is now generating large amounts of data, ranging from clinical test results to microarray gene expression profiles. The scale and complexity of these datasets give rise to substantial challenges in data management and analysis. It is highly desirable that data warehousing and online analytical processing technologies can be applied to biomedical data integration and mining. The major difficulty probably lies in the task of capturing and modelling diverse biological objects and their complex relationships. This paper describes multidimensional data modelling for biomedical data warehouse design. Since the conventional models such as star schema appear to be insufficient for modelling clinical and genomic data, we develop a new model called BioStar schema. The new model can capture the rich semantics of biomedical data and provide greater extensibility for the fast evolution of biological research methodologies. PMID:18048122

Computational Modeling and Treatment Identification in the Myelodysplastic Syndromes.

PubMed

Drusbosky, Leylah M; Cogle, Christopher R

2017-10-01

This review discusses the need for computational modeling in myelodysplastic syndromes (MDS) and early test results. As our evolving understanding of MDS reveals a molecularly complicated disease, the need for sophisticated computer analytics is required to keep track of the number and complex interplay among the molecular abnormalities. Computational modeling and digital drug simulations using whole exome sequencing data input have produced early results showing high accuracy in predicting treatment response to standard of care drugs. Furthermore, the computational MDS models serve as clinically relevant MDS cell lines for pre-clinical assays of investigational agents. MDS is an ideal disease for computational modeling and digital drug simulations. Current research is focused on establishing the prediction value of computational modeling. Future research will test the clinical advantage of computer-informed therapy in MDS.

Evaluation of a Simple in-House Test to Presumptively Differentiate Mycobacterium tuberculosis Complex from Nontuberculous Mycobacteria by Detection of p-Nitrobenzoic Acid Metabolites

PubMed Central

Wang, Guirong; Yu, Xia; Liang, Qian; Chen, Suting; Wilson, Stuart; Huang, Hairong

2013-01-01

The timely differentiation of Mycobacterium tuberculosis complex (MTC) and non-tubercular mycobacterium (NTM) species is urgently needed in patient care since the routine laboratory method is time consuming and cumbersome. An easy and cheap method which can successfully distinguish MTC from NTM was established and evaluated. 38 mycobacterial type and reference strains and 65 clinical isolates representing 10 species of mycobacterium were included in this study. Metabolites of p-nitrobenzoic acid (PNB) reduction were identified using liquid chromatography and tandem mass spectrometry (LC/MS/MS). A spectrophotometric method was developed to detect these metabolites, which was evaluated on a number of MTC and NTM species. All of the tested NTM species and strains reduced PNB to p-aminobenzoic acid (PABA), while none of the MTC strains showed a similar activity. Spectrophotometric detection of PABA had 100% sensitivity and specificity for MTC and NTM differentiation among the type strains and the clinical isolates tested. PABA was identified as one of the metabolites of PNB reduction. All the tested NTM species metabolized PNB to PABA whereas the MTC members lacked this activity. A simple, specific and cost-effective method based on PABA production was established in order to discriminate MTC from NTM from cultured organisms. PMID:24260497

Clinical assessment of pitch perception.

PubMed

Vaerenberg, Bart; Pascu, Alexandru; Del Bo, Luca; Schauwers, Karen; De Ceulaer, Geert; Daemers, Kristin; Coene, Martine; Govaerts, Paul J

2011-07-01

The perception of pitch has recently gained attention. At present, clinical audiologic tests to assess this are hardly available. This article reports on the development of a clinical test using harmonic intonation (HI) and disharmonic intonation (DI). Prospective collection of normative data and pilot study in hearing-impaired subjects. Tertiary referral center. Normative data were collected from 90 normal-hearing subjects recruited from 3 different language backgrounds. The pilot study was conducted on 18 hearing-impaired individuals who were selected into 3 pathologic groups: high-frequency hearing loss (HF), low-frequency hearing loss (LF), and cochlear implant users (CI). Normative data collection and exploratory diagnostics by means of the newly constructed HI/DI tests using intonation patterns to find the just noticeable difference (JND) for pitch discrimination in low-frequency harmonic complex sounds presented in a same-different task. JND for pitch discrimination using HI/DI tests in the hearing population and pathologic groups. Normative data are presented in 5 parameter statistics and box-and-whisker plots showing median JNDs of 2 (HI) and 3 Hz (DI). The results on both tests are statistically abnormal in LF and CI subjects, whereas they are not significantly abnormal in the HF group. The HI and DI tests allow the clinical assessment of low-frequency pitch perception. The data obtained in this study define the normal zone for both tests. Preliminary results indicate possible abnormal TFS perception in some hearing-impaired subjects.

Development of a self-reporting tool to obtain a combined index of severity of fibromyalgia (ICAF).

PubMed

Vallejo, Miguel A; Rivera, Javier; Esteve-Vives, Joaquim

2010-01-07

Fibromyalgia is a syndrome with heterogeneous symptoms. The evaluation in the clinical setting usually fails to cover the complexity of the syndrome. This study aims to determine how different aspects of fibromyalgia are inter-related when measured by means of a self-reporting tool. The objective is to develop a more complete evaluation model adjusted to the complexity and multi-dimensional nature of the syndrome. Application was made of the Fibromyalgia Impact Questionnaire, the Hospital Anxiety and Depression Scale, the Brief Pain Inventory, the Fatigue Assessment Scale, the Health Assessment Questionnaire, the General Health Questionnaire (GHQ-28), the Chronic Pain Coping Inventory, the Arthritis Self-efficacy Scale and the Sleep Quality Scale. An assessment was made, on the basis of clinical interviews, case histories and specific tests, of the patient sociodemographic data, comorbidity, physical exploration and other clinical indexes. An exploratory factor analysis was made, with comparisons of the clinical index scores in extreme groups of patients. The ICAF composed of 59 items was obtained, offering four factors that explain 64% of the variance, and referred to as Emotional Factor (33.7%), Physical-Activity (15%), Active Coping (9%) and Passive Coping (6.3%). A t-test between the extreme scores of these factors in the 301 patients revealed statistically significant differences in occupational status, medically unexplained syndromes, number of tender points, the six-minutes walk test, comorbidity and health care costs. This study offers a tool allowing more complete and rapid evaluation of patients with fibromyalgia. The test intrinsically evaluates the emotional aspects: anxiety and depression, and their impact upon social aspects. It also evaluates patient functional capacity, fatigue, sleep quality, pain, and the way in which the patient copes with the disease. This is achieved by means of a self-assessment questionnaire based on elements from well known tests.

The design and development of a complex multifactorial falls assessment intervention for falls prevention: The Prevention of Falls Injury Trial (PreFIT).

PubMed

Bruce, Julie; Ralhan, Shvaita; Sheridan, Ray; Westacott, Katharine; Withers, Emma; Finnegan, Susanne; Davison, John; Martin, Finbarr C; Lamb, Sarah E

2017-06-01

This paper describes the design and development of a complex multifactorial falls prevention (MFFP) intervention for implementation and testing within the framework of a large UK-based falls prevention randomised controlled trial (RCT). A complex intervention was developed for inclusion within the Prevention of Falls Injury Trial (PreFIT), a multicentre pragmatic RCT. PreFIT aims to compare the clinical and cost-effectiveness of three alternative primary care falls prevention interventions (advice, exercise and MFFP), on outcomes of fractures and falls. Community-dwelling adults, aged 70 years and older, were recruited from primary care in the National Health Service (NHS), England. Development of the PreFIT MFFP intervention was informed by the existing evidence base and clinical guidelines for the assessment and management of falls in older adults. After piloting and modification, the final MFFP intervention includes seven falls risk factors: a detailed falls history interview with consideration of 'red flags'; assessment of balance and gait; vision; medication screen; cardiac screen; feet and footwear screen and home environment assessment. This complex intervention has been fully manualised with clear, documented assessment and treatment pathways for each risk factor. Each risk factor is assessed in every trial participant referred for MFFP. Referral for assessment is based upon a screening survey to identify those with a history of falling or balance problems. Intervention delivery can be adapted to the local setting. This complex falls prevention intervention is currently being tested within the framework of a large clinical trial. This paper adheres to TIDieR and CONSORT recommendations for the comprehensive and explicit reporting of trial interventions. Results from the PreFIT study will be published in due course. The effectiveness and cost-effectiveness of the PreFIT MFFP intervention, compared to advice and exercise, on the prevention of falls and fractures, will be reported at the conclusion of the trial.

The clinical utility of a 30-minute neuropsychological assessment battery in inpatient stroke rehabilitation.

PubMed

Jaywant, Abhishek; Toglia, Joan; Gunning, Faith M; O'Dell, Michael W

2018-07-15

Cognitive assessment is an important component of inpatient stroke rehabilitation. Few studies have empirically evaluated the clinical utility of specific neuropsychological measures in this setting. We investigated the psychometric properties and clinical utility of a 30-minute neuropsychological battery developed by the National Institute of Neurologic Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN). Clinical data were analyzed from 100 individuals with mild-moderate stroke severity on an acute inpatient rehabilitation unit who completed the NINDS-CSN battery at admission. The battery comprised the Symbol-Digit Modalities Test (SDMT), Trail Making Test, Controlled Oral Word Association Test, Animal Naming, and the Hopkins Verbal Learning Test-Revised. We evaluated the battery's distribution of scores, frequency of impaired performance, internal consistency, and ability to predict rehabilitation gain and independence in cognitively-based instrumental activities of daily living (IADL) at discharge. Results indicated that the NINDS-CSN battery was sensitive to cognitive impairment, demonstrated moderately strong internal consistency, and predicted discharge IADL. The SDMT demonstrated the strongest sensitivity to impairment and predictive validity. The NINDS-CSN battery is a clinically useful assessment battery in acute inpatient stroke rehabilitation. Complex attention and processing speed performance may be most informative in predicting amount of rehabilitation gain and IADL functioning at discharge. Copyright © 2018 Elsevier B.V. All rights reserved.

Additional molecular findings in 11p15-associated imprinting disorders: an urgent need for multi-locus testing.

PubMed

Eggermann, Thomas; Heilsberg, Ann-Kathrin; Bens, Susanne; Siebert, Reiner; Beygo, Jasmin; Buiting, Karin; Begemann, Matthias; Soellner, Lukas

2014-07-01

The chromosomal region 11p15 contains two imprinting control regions (ICRs) and is a key player in molecular processes regulated by genomic imprinting. Genomic as well as epigenetic changes affecting 11p15 are associated either with Silver-Russell syndrome (SRS) or Beckwith-Wiedemann syndrome (BWS). In the last years, a growing number of patients affected by imprinting disorders (IDs) have reported carrying the disease-specific 11p15 hypomethylation patterns as well as methylation changes at imprinted loci at other chromosomal sites (multi-locus methylation defects, MLMD). Furthermore, in several patients, molecular alterations (e.g., uniparental disomies, UPDs) additional to the primary epimutations have been reported. To determine the frequency and distribution of mutations and epimutations in patients referred as SRS or BWS for genetic testing, we retrospectively ascertained our routine patient cohort consisting of 711 patients (SRS, n = 571; BWS, n = 140). As this cohort represents the typical cohort in a routine diagnostic lab without clinical preselection, the detection rates were much lower than those reported from clinically characterized cohorts in the literature (SRS, 19.9%; BWS, 28.6%). Among the molecular subgroups known to be predisposed to MLMD, the frequencies corresponded to that in the literature (SRS, 7.1% in ICR1 hypomethylation carriers; BWS, 20.8% in ICR2 hypomethylation patients). In several patients, more than one epigenetic or genetic disturbance could be identified. Our study illustrates that the complex molecular alterations as well as the overlapping and sometimes unusual clinical findings in patients with imprinting disorders (IDs) often make the decision for a specific imprinting disorder test difficult. We therefore suggest to implement molecular assays in routine ID diagnostics which allow the detection of a broad range of (epi)mutation types (epimutations, UPDs, chromosomal imbalances) and cover the clinically most relevant known ID loci because of the following: (a) Multi-locus tests increase the detection rates as they cover numerous loci. (b) Patients with unexpected molecular alterations are detected. (c) The testing of rare imprinting disorders becomes more efficient and quality of molecular diagnosis increases. (d) The tests identify MLMDs. In the future, the detailed characterization of clinical and molecular findings in ID patients will help us to decipher the complex regulation of imprinting and thereby providing the basis for more directed genetic counseling and therapeutic managements in IDs. Molecular disturbances in patients with imprinting disorders are often not restricted to the disease-specific locus but also affect other chromosomal regions. These additional disturbances include methylation defects, uniparental disomies as well as chromosomal imbalances. The identification of these additional alterations is mandatory for a well-directed genetic counseling. Furthermore, these findings help to decipher the complex regulation of imprinting.

Airway persistence by the emerging multi-azole-resistant Rasamsonia argillacea complex in cystic fibrosis.

PubMed

Abdolrasouli, Alireza; Bercusson, Amelia C; Rhodes, Johanna L; Hagen, Ferry; Buil, Jochem B; Tang, Alison Y Y; de Boer, Leonard L; Shah, Anand; Milburn, Andrew J; Elborn, J Stuart; Jones, Andrew L; Meis, Jacques F; Fisher, Matthew C; Schelenz, Silke; Simmonds, Nicholas J; Armstrong-James, Darius

2018-04-27

Infections caused by Rasamsonia argillacea complex have been reported in various clinical settings. Cystic fibrosis (CF) is one of the main underlying conditions. An observational cohort study of CF patients with Rasamsonia in respiratory samples was conducted. Eight isolates from six patients were identified as R. argillacea complex and tested for antifungal susceptibility. All isolates had high MICs to voriconazole and posaconazole and low MECs to echinocandins. Four patients experienced lung function decline in the year preceding first Rasamsonia isolation. This continued in the year following first isolation in three out of four cases. Antifungal therapy was initiated in two patients, to which only one exhibited a clinical response. Three out of six patients died within three years of isolating Rasamsonia. Genotyping suggests that similar genotypes of Rasamsonia can persist in CF airways. Consistent with other fungi in CF, the clinical impact of airway colonization by Rasamsonia is variable. In certain patients, Rasamsonia may be able to drive clinical decline. In others, though a clear impact on lung function may be difficult to determine, the appearance of Rasamsonia acts as a marker of disease severity. In others it does not appear to have an obvious clinical impact on disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Intracellular and non-neuronal targets of voltage-gated potassium channel complex antibodies

PubMed Central

Lang, Bethan; Makuch, Mateusz; Moloney, Teresa; Dettmann, Inga; Mindorf, Swantje; Probst, Christian; Stoecker, Winfried; Buckley, Camilla; Newton, Charles R; Leite, M Isabel; Maddison, Paul; Komorowski, Lars; Adcock, Jane; Vincent, Angela; Waters, Patrick; Irani, Sarosh R

2017-01-01

Objectives Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined. Methods Sera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin (125I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of 125I-αDTX and 125I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2. Results VGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated 125I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical–serological correlations and a limited immunotherapy response. Conclusions Double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies. PMID:28115470

Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice.

PubMed

Castagné, Vincent; Moser, Paul; Roux, Sylvain; Porsolt, Roger D

2011-04-01

The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant-like activity. The behavioral despair and the tail suspension tests are based on the same principle: measurement of the duration of immobility when rodents are exposed to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Antidepressants also increase the latency to immobility, and this additional measure can increase the sensitivity of the behavioral despair test in the mouse for certain classes of antidepressant. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility. © 2011 by John Wiley & Sons, Inc.

Cushing Syndrome in Carney Complex: Clinical, Pathologic, and Molecular Genetic Findings in the 17 Affected Mayo Clinic Patients.

PubMed

Lowe, Kathleen M; Young, William F; Lyssikatos, Charalampos; Stratakis, Constantine A; Carney, J Aidan

2017-02-01

Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder that includes Cushing syndrome (CS). To establish the Mayo Clinic experience with the CS component, including its clinical, laboratory, and pathologic findings, we performed a retrospective search of the patient and pathologic databases of Mayo Clinic in Rochester, MN, for patients with CNC and clinical or laboratory findings of CS. Thirty-seven patients with CNC were identified. Twenty-nine had clinical, pathologic, or laboratory evidence of an adrenocortical disorder. Seventeen had classic CS; 15 underwent bilateral, subtotal, or partial unilateral adrenalectomy, and 2 had no treatment. Pathologically, the glands were normal sized or slightly enlarged with multiple small (1 to 4 mm), brown, black, and yellow micronodules (primary pigmented nodular adrenocortical disease; PPNAD). Three glands each had a mass: a 2 cm adenoma, a 1.5 cm macronodule, and an unencapsulated 1.8 cm myelolipoma. Fourteen of the patients were alive at follow-up, and 3 were deceased; 2 of the latter had PPNAD at autopsy, and the third had PPNAD at surgery. Twelve patients without clinical features of classic CS had abnormal adrenocortical testing results; none developed classic CS during follow-up (mean, 10 y). Autopsy findings in 1 showed bilateral vacuolated cell cortical hyperplasia.

Effects of distance learning on clinical management of LUTS in primary care: a randomised trial.

PubMed

Wolters, René; Wensing, Michel; Klomp, Maarten; Lagro-Jansen, Toine; Weel, Chris van; Grol, Richard

2005-11-01

To determine the effect of a distance learning programme on general practice management of men with lower urinary tract symptoms (LUTS). A cluster randomised controlled trial was performed. General practitioners (GPs) were randomised to a distance learning programme accompanied with educational materials or to a control group only receiving mailed clinical guidelines on LUTS. Clinical management was considered as outcome. Sixty-three GPs registered care management of 187 patients older than 50 years attending the practice because of LUTS. The intervention group showed a lower referral rate to a urologist (OR: 0.08 (95% CI: 0.02-0.40)), but no effect on PSA testing or prescription of medication. PSA testing tended to be requested more frequently by intervention group GPs. Secondary analysis showed patients in the intervention group received more educational materials (OR: 75.6 (95% CI: 13.60-419.90)). The educational programme had impact on clinical management without changing PSA testing. Distance learning is an promising method for continuing education. Activating distance learning packages are a potentially effective method for improving professional performance. Emotional matters as PSA testing probably need a more complex approach.

10-Minute Delayed Recall from the Modified Mini-Mental State Test Predicts Alzheimer’s Disease Pathology

PubMed Central

Lyness, Scott A.; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L.; Chui, Helena C.

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer’s disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0–9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation. PMID:24240637

The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe.

PubMed

Hastings, Ros; de Wert, Guido; Fowler, Brian; Krawczak, Michael; Vermeulen, Eric; Bakker, Egbert; Borry, Pascal; Dondorp, Wybo; Nijsingh, Niels; Barton, David; Schmidtke, Jörg; van El, Carla G; Vermeesch, Joris; Stol, Yrrah; Carmen Howard, Heidi; Cornel, Martina C

2012-09-01

The arrival of new genetic technologies that allow efficient examination of the whole human genome (microarray, next-generation sequencing) will impact upon both laboratories (cytogenetic and molecular genetics in the first instance) and clinical/medical genetic services. The interpretation of analytical results in terms of their clinical relevance and the predicted health status poses a challenge to both laboratory and clinical geneticists, due to the wealth and complexity of the information obtained. There is a need to discuss how to best restructure the genetic services logistically and to determine the clinical utility of genetic testing so that patients can receive appropriate advice and genetic testing. To weigh up the questions and challenges of the new genetic technologies, the European Society of Human Genetics (ESHG) held a series of workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite symposium on the 'Changing landscape of genetic testing', co-organized by the ESHG Genetic Services Quality and Public and Professional Policy Committees. The audience consisted of a mix of geneticists, ethicists, social scientists and lawyers. In this paper, we summarize the discussions during the workshops and present some of the identified ways forward to improve and adapt the genetic services so that patients receive accurate and relevant information. This paper covers ethics, clinical utility, primary care, genetic services and the blurring boundaries between healthcare and research.

10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology.

PubMed

Lyness, Scott A; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L; Chui, Helena C

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation.

Expertise in Clinical Psychology. The Effects of University Training and Practical Experience on Expertise in Clinical Psychology

PubMed Central

Vollmer, Sabine; Spada, Hans; Caspar, Franz; Burri, Salome

2013-01-01

How do university training and subsequent practical experience affect expertise in clinical psychology? To answer this question we developed methods to assess psychological knowledge and the competence to diagnose, construct case conceptualizations, and plan psychotherapeutic treatment: a knowledge test and short case studies in a first study, and a complex, dynamically evolving case study in the second study. In our cross-sectional studies, psychology students, trainees in a certified postgraduate psychotherapist curriculum, and behavior therapists with more than 10 years of experience were tested (100 in total: 20 each of novice, intermediate, and advanced university students, postgraduate trainees, and therapists). Clinical knowledge and competence increased up to the level of trainees but unexpectedly decreased at the level of experienced therapists. We discuss the results against the background of expertise research and the training of clinical psychologists (in Germany). Important factors for the continuing professional development of psychotherapists are proposed. PMID:23543213

Classification of ulnar triangular fibrocartilage complex tears. A treatment algorithm for Palmer type IB tears.

PubMed

Atzei, A; Luchetti, R; Garagnani, L

2017-05-01

The classical definition of 'Palmer Type IB' triangular fibrocartilage complex tear, includes a spectrum of clinical conditions. This review highlights the clinical and arthroscopic criteria that enable us to categorize five classes on a treatment-oriented classification system of triangular fibrocartilage complex peripheral tears. Class 1 lesions represent isolated tears of the distal triangular fibrocartilage complex without distal radio-ulnar joint instability and are amenable to arthroscopic suture. Class 2 tears include rupture of both the distal triangular fibrocartilage complex and proximal attachments of the triangular fibrocartilage complex to the fovea. Class 3 tears constitute isolated ruptures of the proximal attachment of the triangular fibrocartilage complex to the fovea; they are not visible at radio-carpal arthroscopy. Both Class 2 and Class 3 tears are diagnosed with a positive hook test and are typically associated with distal radio-ulnar joint instability. If required, treatment is through reattachment of the distal radio-ulnar ligament insertions to the fovea. Class 4 lesions are irreparable tears due to the size of the defect or to poor tissue quality and, if required, treatment is through distal radio-ulnar ligament reconstruction with tendon graft. Class 5 tears are associated with distal radio-ulnar joint arthritis and can only be treated with salvage procedures. This subdivision of type IB triangular fibrocartilage complex tear provides more insights in the pathomechanics and treatment strategies. II.

Human adaptation and readaptation for Mars mission

NASA Technical Reports Server (NTRS)

Schmitt, Harrison H.

1986-01-01

Human adaptation and readaptation in space appears to involve complex physiological and psychological interactions and adjustments. There is no comprehensive clinical characterization of the symptoms of these interactions, much less a comprehensive examination and testing of appropriate measures to counteract the near and long term adverse consequences. The variety of credible potential countermeasures is great; however, a systematic clinical research program for Shuttle and space station must be implemented as an early part of a Mars Mission strategy.

Intelligent diagnosis of jaundice with dynamic uncertain causality graph model.

PubMed

Hao, Shao-Rui; Geng, Shi-Chao; Fan, Lin-Xiao; Chen, Jia-Jia; Zhang, Qin; Li, Lan-Juan

2017-05-01

Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A "chaining" inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure.

Intelligent diagnosis of jaundice with dynamic uncertain causality graph model*

PubMed Central

Hao, Shao-rui; Geng, Shi-chao; Fan, Lin-xiao; Chen, Jia-jia; Zhang, Qin; Li, Lan-juan

2017-01-01

Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A “chaining” inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure. PMID:28471111

A semantically-aided architecture for a web-based monitoring system for carotid atherosclerosis.

PubMed

Kolias, Vassileios D; Stamou, Giorgos; Golemati, Spyretta; Stoitsis, Giannis; Gkekas, Christos D; Liapis, Christos D; Nikita, Konstantina S

2015-08-01

Carotid atherosclerosis is a multifactorial disease and its clinical diagnosis depends on the evaluation of heterogeneous clinical data, such as imaging exams, biochemical tests and the patient's clinical history. The lack of interoperability between Health Information Systems (HIS) does not allow the physicians to acquire all the necessary data for the diagnostic process. In this paper, a semantically-aided architecture is proposed for a web-based monitoring system for carotid atherosclerosis that is able to gather and unify heterogeneous data with the use of an ontology and to create a common interface for data access enhancing the interoperability of HIS. The architecture is based on an application ontology of carotid atherosclerosis that is used to (a) integrate heterogeneous data sources on the basis of semantic representation and ontological reasoning and (b) access the critical information using SPARQL query rewriting and ontology-based data access services. The architecture was tested over a carotid atherosclerosis dataset consisting of the imaging exams and the clinical profile of 233 patients, using a set of complex queries, constructed by the physicians. The proposed architecture was evaluated with respect to the complexity of the queries that the physicians could make and the retrieval speed. The proposed architecture gave promising results in terms of interoperability, data integration of heterogeneous sources with an ontological way and expanded capabilities of query and retrieval in HIS.

Comparison of two commercial carbapenemase gene confirmatory assays in multiresistant Enterobacteriaceae and Acinetobacter baumannii-complex.

PubMed

Rösner, Stephan; Gehlweiler, Kevin; Küsters, Uta; Kolbert, Mathias; Hübner, Kirsten; Pfennigwerth, Niels; Mack, Dietrich

2018-01-01

Multidrug-resistant Gram-negative bacilli (MDR-GNB) producing carbapenemases are increasing at an alarming speed. Rapid confirmation of carbapenemase type will be an important diagnostic step in clinical microbiology laboratories not only to reduce the risk of transmissions but also for optimising antibiotic therapy in the future. We compared diagnostic reliability of two commercially available molecular assays (Check-Direct CPE vs. AID line probe assay) for detection and typing of carbapenemase genes in 80 well-characterized isolates of MDR-GNB. Respective strains were isolated in various clinical specimens at our clinical microbiology laboratory. The reference standard included confirmation of carbapenemase-production at the molecular level at the German National Reference Laboratory for Multidrug-resistant Gram-negative bacteria (Ruhr-University Bochum, Germany). 53 Enterobacteriaceae and 27 members of the A. baumannii-complex were used in this study. The tested assays appeared highly reliable to confirm carbapenemase-producing Enterobacteriaceae (CPE) with respective sensitivities of 97.7%, but are currently unsuitable for analysis of members of the A. baumannii-complex. Both assays are easy to perform and rapid tools for confirmation and typing of the most common carbapenemase genes in Enterobacteriaceae. Implementation should be possible for any clinical microbiology laboratory with Check-Direct CPE being easier to handle and having less technological requirements.

Assessment of clinical analytical sensitivity and specificity of next-generation sequencing for detection of simple and complex mutations.

PubMed

Chin, Ephrem L H; da Silva, Cristina; Hegde, Madhuri

2013-02-19

Detecting mutations in disease genes by full gene sequence analysis is common in clinical diagnostic laboratories. Sanger dideoxy terminator sequencing allows for rapid development and implementation of sequencing assays in the clinical laboratory, but it has limited throughput, and due to cost constraints, only allows analysis of one or at most a few genes in a patient. Next-generation sequencing (NGS), on the other hand, has evolved rapidly, although to date it has mainly been used for large-scale genome sequencing projects and is beginning to be used in the clinical diagnostic testing. One advantage of NGS is that many genes can be analyzed easily at the same time, allowing for mutation detection when there are many possible causative genes for a specific phenotype. In addition, regions of a gene typically not tested for mutations, like deep intronic and promoter mutations, can also be detected. Here we use 20 previously characterized Sanger-sequenced positive controls in disease-causing genes to demonstrate the utility of NGS in a clinical setting using standard PCR based amplification to assess the analytical sensitivity and specificity of the technology for detecting all previously characterized changes (mutations and benign SNPs). The positive controls chosen for validation range from simple substitution mutations to complex deletion and insertion mutations occurring in autosomal dominant and recessive disorders. The NGS data was 100% concordant with the Sanger sequencing data identifying all 119 previously identified changes in the 20 samples. We have demonstrated that NGS technology is ready to be deployed in clinical laboratories. However, NGS and associated technologies are evolving, and clinical laboratories will need to invest significantly in staff and infrastructure to build the necessary foundation for success.

The Promise of Multi-Omics and Clinical Data Integration to Identify and Target Personalized Healthcare Approaches in Autism Spectrum Disorders

PubMed Central

Higdon, Roger; Earl, Rachel K.; Stanberry, Larissa; Hudac, Caitlin M.; Montague, Elizabeth; Stewart, Elizabeth; Janko, Imre; Choiniere, John; Broomall, William; Kolker, Natali

2015-01-01

Abstract Complex diseases are caused by a combination of genetic and environmental factors, creating a difficult challenge for diagnosis and defining subtypes. This review article describes how distinct disease subtypes can be identified through integration and analysis of clinical and multi-omics data. A broad shift toward molecular subtyping of disease using genetic and omics data has yielded successful results in cancer and other complex diseases. To determine molecular subtypes, patients are first classified by applying clustering methods to different types of omics data, then these results are integrated with clinical data to characterize distinct disease subtypes. An example of this molecular-data-first approach is in research on Autism Spectrum Disorder (ASD), a spectrum of social communication disorders marked by tremendous etiological and phenotypic heterogeneity. In the case of ASD, omics data such as exome sequences and gene and protein expression data are combined with clinical data such as psychometric testing and imaging to enable subtype identification. Novel ASD subtypes have been proposed, such as CHD8, using this molecular subtyping approach. Broader use of molecular subtyping in complex disease research is impeded by data heterogeneity, diversity of standards, and ineffective analysis tools. The future of molecular subtyping for ASD and other complex diseases calls for an integrated resource to identify disease mechanisms, classify new patients, and inform effective treatment options. This in turn will empower and accelerate precision medicine and personalized healthcare. PMID:25831060

Plasma and Plasma Protein Product Transfusion: A Canadian Blood Services Centre for Innovation Symposium.

PubMed

Zeller, Michelle P; Al-Habsi, Khalid S; Golder, Mia; Walsh, Geraldine M; Sheffield, William P

2015-07-01

Plasma obtained via whole blood donation processing or via apheresis technology can either be transfused directly to patients or pooled and fractionated into plasma protein products that are concentrates of 1 or more purified plasma protein. The evidence base supporting clinical efficacy in most of the indications for which plasma is transfused is weak, whereas high-quality evidence supports the efficacy of plasma protein products in at least some of the clinical settings in which they are used. Transfusable plasma utilization remains composed in part of applications that fall outside of clinical practice guidelines. Plasma contains all of the soluble coagulation factors and is frequently transfused in efforts to restore or reinforce patient hemostasis. The biochemical complexities of coagulation have in recent years been rationalized in newer cell-based models that supplement the cascade hypothesis. Efforts to normalize widely used clinical hemostasis screening test values by plasma transfusion are thought to be misplaced, but superior rapid tests have been slow to emerge. The advent of non-vitamin K-dependent oral anticoagulants has brought new challenges to clinical laboratories in plasma testing and to clinicians needing to reverse non-vitamin K-dependent oral anticoagulants urgently. Current plasma-related controversies include prophylactic plasma transfusion before invasive procedures, plasma vs prothrombin complex concentrates for urgent warfarin reversal, and the utility of increased ratios of plasma to red blood cell units transfused in massive transfusion protocols. The first recombinant plasma protein products to reach the clinic were recombinant hemophilia treatment products, and these donor-free equivalents to factors VIII and IX are now being supplemented with novel products whose circulatory half-lives have been increased by chemical modification or genetic fusion. Achieving optimal plasma utilization is an ongoing challenge in the interconnected worlds of transfusable plasma, plasma protein products, and recombinant and engineered replacements. Copyright © 2015 Elsevier Inc. All rights reserved.

Constructional Apraxia in Older Patients with Brain Tumors: Considerations with an Up-To-Date Review of the Literature.

PubMed

Abete Fornara, Giorgia; Di Cristofori, Andrea; Bertani, Giulio Andrea; Carrabba, Giorgio; Zarino, Barbara

2018-06-01

Constructional apraxia (CA) is a neuropsychological impairment of either basic perceptual and motor abilities or executive functions, in the absence of any kind of motor or perceptual deficit. Considering patients with focal brain tumors, CA is common in left or right parietal and parieto-occipital lesions. In neuropsychology, the Rey-Osterrieth Complex Figure Test (ROCFT; or parallel forms) is commonly used for the assessment of CA. This study stems from a clinical observation of a difficulty with CA tests for the majority of older neurosurgical patients without occipitoparietal lesions. Patients were tested at 3 points: before surgery, 3 months after surgery, and 12 months after surgery. Thirty patients (15 meningiomas and 15 glioblastomas) were studied retrospectively. Older patients with focal brain lesions, regardless of the nature of the tumor, performed poorly at CA tests. More than 50% of patients obtained pathologic results at all 3 times considered. Our findings suggest that as CA complex tests involve multiple domains, poor results in copy task may reflect a global cognitive deficit of older patients with tumors, without a specific constructional praxis deficit. CA complex tests (such as the ROCFT) do not give significant informations about visuo-constructional abilities. Copyright © 2018 Elsevier Inc. All rights reserved.

Development and validation of the University of Washington Clinical Assessment of Music Perception test.

PubMed

Kang, Robert; Nimmons, Grace Liu; Drennan, Ward; Longnion, Jeff; Ruffin, Chad; Nie, Kaibao; Won, Jong Ho; Worman, Tina; Yueh, Bevan; Rubinstein, Jay

2009-08-01

Assessment of cochlear implant outcomes centers around speech discrimination. Despite dramatic improvements in speech perception, music perception remains a challenge for most cochlear implant users. No standardized test exists to quantify music perception in a clinically practical manner. This study presents the University of Washington Clinical Assessment of Music Perception (CAMP) test as a reliable and valid music perception test for English-speaking, adult cochlear implant users. Forty-two cochlear implant subjects were recruited from the University of Washington Medical Center cochlear implant program and referred by two implant manufacturers. Ten normal-hearing volunteers were drawn from the University of Washington Medical Center and associated campuses. A computer-driven, self-administered test was developed to examine three specific aspects of music perception: pitch direction discrimination, melody recognition, and timbre recognition. The pitch subtest used an adaptive procedure to determine just-noticeable differences for complex tone pitch direction discrimination within the range of 1 to 12 semitones. The melody and timbre subtests assessed recognition of 12 commonly known melodies played with complex tones in an isochronous manner and eight musical instruments playing an identical five-note sequence, respectively. Testing was repeated for cochlear implant subjects to evaluate test-retest reliability. Normal-hearing volunteers were also tested to demonstrate differences in performance in the two populations. For cochlear implant subjects, pitch direction discrimination just-noticeable differences ranged from 1 to 8.0 semitones (Mean = 3.0, SD = 2.3). Melody and timbre recognition ranged from 0 to 94.4% correct (mean = 25.1, SD = 22.2) and 20.8 to 87.5% (mean = 45.3, SD = 16.2), respectively. Each subtest significantly correlated at least moderately with both Consonant-Nucleus-Consonant (CNC) word recognition scores and spondee recognition thresholds in steady state noise and two-talker babble. Intraclass coefficients demonstrating test-retest correlations for pitch, melody, and timbre were 0.85, 0.92, and 0.69, respectively. Normal-hearing volunteers had a mean pitch direction discrimination threshold of 1.0 semitone, the smallest interval tested, and mean melody and timbre recognition scores of 87.5 and 94.2%, respectively. The CAMP test discriminates a wide range of music perceptual ability in cochlear implant users. Moderate correlations were seen between music test results and both Consonant-Nucleus-Consonant word recognition scores and spondee recognition thresholds in background noise. Test-retest reliability was moderate to strong. The CAMP test provides a reliable and valid metric for a clinically practical, standardized evaluation of music perception in adult cochlear implant users.

Enhancing Clinical Evaluation Skills: Palpation as the Principal Skill

ERIC Educational Resources Information Center

Eberman, Lindsey E.; Finn, Megan E.

2010-01-01

Context: Recognition and evaluation of injuries/illnesses accounts for the greatest percentage (24%) of an athletic trainer's responsibilities as a clinician. When teaching orthopedic evaluation, we often emphasize history taking and special/ligamentous tests to achieve a diagnosis. Because of its complexity and variability, palpation becomes an…

What is an Objective Structured Practical Examination in Anatomy?

ERIC Educational Resources Information Center

Yaqinuddin, Ahmed; Zafar, Muhammad; Ikram, Muhammad Faisal; Ganguly, Paul

2013-01-01

Assessing teaching-learning outcomes in anatomical knowledge is a complex task that requires the evaluation of multiple domains: theoretical, practical, and clinical knowledge. In general, theoretical knowledge is tested by a written examination system constituted by multiple choice questions (MCQs) and/or short answer questions (SAQ). The…

Design of a Tablet Computer App for Facilitation of a Molecular Blood Culture Test in Clinical Microbiology and Preliminary Usability Evaluation

PubMed Central

Pape-Haugaard, Louise; Meltzer, Michelle C; Fuchs, Martin; Schønheyder, Henrik C; Hejlesen, Ole

2016-01-01

Background User mobility is an important aspect of the development of clinical information systems for health care professionals. Mobile phones and tablet computers have obtained widespread use by health care professionals, offering an opportunity for supporting the access to patient information through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular-based diagnostic test used for rapid identification of pathogens in positive blood cultures. To facilitate the workflow of the MuxBCT, a specialized tablet computer app was developed as an accessory to the diagnostic test. The app aims to reduce the complexity of the test by step-by-step guidance of microscopy and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). Objective The objective of the study was to describe the design considerations of the MuxBCT app and the results of a preliminary usability evaluation. Methods The MuxBCT tablet app was developed and set up for use in a clinical microbiology laboratory. A near-live simulation study was conducted in the clinical microbiology laboratory to evaluate the usability of the MuxBCT app. The study was designed to achieve a high degree of realism as participants carried out a scenario representing the context of use for the MuxBCT app. As the MuxBCT was under development, the scenario involved the use of molecular blood culture tests similar to the MuxBCT for identification of microorganisms from positive blood culture samples. The study participants were observed, and their interactions with the app were recorded. After the study, the participants were debriefed to clarify observations. Results Four medical laboratory technicians, for example, representative of end users of the app, participated in the clinical simulation study. Using the MuxBCT app, the study participants successfully identified and reported all microorganisms from the positive blood cultures examined. Three of the four participants reported that they found the app useful, while one study participant reported that she would prefer to make notes on paper and later enter them into the LIS. Conclusions The preliminary usability evaluation results indicate that use of the MuxBCT tablet app can facilitate the workflow of the MuxBCT diagnostic test. PMID:26993432

KRAS Testing and Epidermal Growth Factor Receptor Inhibitor Treatment for Colorectal Cancer in Community Settings

PubMed Central

Webster, Jennifer; Kauffman, Tia L.; Feigelson, Heather Spencer; Pawloski, Pamala A.; Onitilo, Adedayo A.; Potosky, Arnold L.; Cross, Deanna; Meier, Paul R.; Mirabedi, Anousheh S.; Delate, Thomas; Daida, Yihe; Williams, Andrew E.; Alexander, Gwen L.; McCarty, Catherine A.; Honda, Stacey; Kushi, Lawrence H.; Goddard, Katrina A.B.

2013-01-01

Background In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to epidermal growth factor receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. Methods We included 1,188 patients with mCRC diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care. Results Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (p=0.0034), comorbid conditions (p=0.0316), and survival time from diagnosis (p<0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009). Conclusions These findings demonstrate rapid uptake and incorporation of this predictive biomarker into clinical oncology care. Impact In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRC. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the US. PMID:23155138

Clinical perspective of cell-free DNA testing for fetal aneuploidies.

PubMed

Gratacós, Eduard; Nicolaides, Kypros

2014-01-01

Cell-free DNA testing in maternal blood provides the most effective method of screening for trisomy 21, with a reported detection rate of 99% and a false positive rate of less than 0.1%. After many years of research, this method is now commercially available and is carried out in an increasing number of patients, and there is an expanding number of conditions that can be screened for. However, the application of these methods in clinical practice requires a careful analysis. Current first-trimester screening strategies are based on a complex combination of tests, aiming at detecting fetal defects and predicting the risk of main pregnancy complications. It is therefore necessary to define the optimal way of combining cell-free DNA testing with current first-trimester screening methods. In this concise review we describe the basis of cell-free DNA testing and discuss the potential approaches for its implementation in combination with current tests in the first trimester. © 2014 S. Karger AG, Basel.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

PubMed

Celicanin, M; Blaabjerg, M; Maersk-Moller, C; Beniczky, S; Marner, L; Thomsen, C; Bach, F W; Kondziella, D; Andersen, H; Somnier, F; Illes, Z; Pinborg, L H

2017-08-01

The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well. © 2017 EAN.

Perspectives of HER2-targeting in gastric and esophageal cancer.

PubMed

Gerson, James N; Skariah, Sam; Denlinger, Crystal S; Astsaturov, Igor

2017-05-01

The blockade of HER2 signaling has significantly improved the outlook for esophagogastric cancer patients. However, targeting HER2 still remains challenging due to complex biology of this receptor in gastric and esophageal cancers. Areas covered: Here, we review complex HER2 biology, current methods of HER2 testing and tumor heterogeneity of gastroesophageal cancer. Ongoing and completed clinical research data are discussed. Expert opinion: HER2 overexpression is a validated target in gastroesophageal cancer, with therapeutic implications resulting in prolonged survival when inhibited in the front-line setting. With standardized HER2 testing in gastro-esophageal cancer, the ongoing trials are testing newer agents and combinations including combination of anti-HER2 antibodies with immunotherapy. Clonal heterogeneity and emergence of resistance will challenge our approach to treating these patients beyond the frontline settings.

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

Creutzfeldt-Jakob Disease-Like Periodic Sharp Wave Complexes in Voltage-Gated Potassium Channel-Complex Antibodies Encephalitis: A Case Report.

PubMed

Savard, Martin; Irani, Sarosh R; Guillemette, Annie; Gosselin-Lefebvre, Stéphanie; Geschwind, Michael; Jansen, Gerard H; Gould, Peter V; Laforce, Robert

2016-02-01

Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jakob disease. Among available clinical clues to distinguish them, periodic sharp wave complexes, a typical finding in sporadic Creutzfeldt-Jakob disease, have never been reported in association with VGKC-cAbs encephalitis. A 76-year-old man was transferred to a tertiary neurology center with a clinical history of 6-month weight loss, cognitive disturbance, and nonspecific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. Periodic sharp wave complexes every 1 to 2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal positron emission tomography scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal, 0-31), 3 month after the patient deceased. This is the first reported case of VGKC-cAbs encephalitis associated with periodic sharp wave complexes on EEG, which further confuse the differential diagnosis with sporadic Creutzfeldt-Jakob disease. However, the cortical DWI hypersignal without restriction seems to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance because VGKC-cAbs encephalitis is a treatable disease.

Systematic review of safety and tolerability of a complex micronutrient formula used in mental health.

PubMed

Simpson, J Steven A; Crawford, Susan G; Goldstein, Estelle T; Field, Catherine; Burgess, Ellen; Kaplan, Bonnie J

2011-04-18

Theoretically, consumption of complex, multinutrient formulations of vitamins and minerals should be safe, as most preparations contain primarily the nutrients that have been in the human diet for millennia, and at safe levels as defined by the Dietary Reference Intakes. However, the safety profile of commercial formulae may differ from foods because of the amounts and combinations of nutrients they contain. As these complex formulae are being studied and used clinically with increasing frequency, there is a need for direct evaluation of safety and tolerability. All known safety and tolerability data collected on one complex nutrient formula was compiled and evaluated. Data were assembled from all the known published and unpublished studies for the complex formula with the largest amount of published research in mental health. Biological safety data from 144 children and adults were available from six sources: there were no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event (AE) information from 157 children and adults was available from six studies employing the current version of this formula, and only minor, transitory reports of headache and nausea emerged. Only one of the studies permitted a direct comparison between micronutrient treatment and medication: none of the 88 pediatric and adult participants had any clinically meaningful abnormal laboratory values, but tolerability data in the group treated with micronutrients revealed significantly fewer AEs and less weight gain. This compilation of safety and tolerability data is reassuring with respect to the broad spectrum approach that employs complex nutrient formulae as a primary treatment.

Clinical Complexity in Medicine: A Measurement Model of Task and Patient Complexity.

PubMed

Islam, R; Weir, C; Del Fiol, G

2016-01-01

Complexity in medicine needs to be reduced to simple components in a way that is comprehensible to researchers and clinicians. Few studies in the current literature propose a measurement model that addresses both task and patient complexity in medicine. The objective of this paper is to develop an integrated approach to understand and measure clinical complexity by incorporating both task and patient complexity components focusing on the infectious disease domain. The measurement model was adapted and modified for the healthcare domain. Three clinical infectious disease teams were observed, audio-recorded and transcribed. Each team included an infectious diseases expert, one infectious diseases fellow, one physician assistant and one pharmacy resident fellow. The transcripts were parsed and the authors independently coded complexity attributes. This baseline measurement model of clinical complexity was modified in an initial set of coding processes and further validated in a consensus-based iterative process that included several meetings and email discussions by three clinical experts from diverse backgrounds from the Department of Biomedical Informatics at the University of Utah. Inter-rater reliability was calculated using Cohen's kappa. The proposed clinical complexity model consists of two separate components. The first is a clinical task complexity model with 13 clinical complexity-contributing factors and 7 dimensions. The second is the patient complexity model with 11 complexity-contributing factors and 5 dimensions. The measurement model for complexity encompassing both task and patient complexity will be a valuable resource for future researchers and industry to measure and understand complexity in healthcare.

Clinical descriptive measures of shoulder range of motion for a healthy, young and physically active cohort.

PubMed

Vairo, Giampietr L; Duffey, Michele L; Owens, Brett D; Cameron, Kenneth L

2012-09-10

The objective of this innovative research study was to describe clinical shoulder complex range of motion (ROM) measures for a young, healthy, and physically active population. This investigation represents a cross-sectional experiment conducted at a military academy-based sports medicine center. Military cadets with no history of shoulder complex injury were assessed within two months of enrollment in the academy; 548 men (18.8 ± 1.0 yr, 75.2 ± 12.2 kg, 178.3 ± 7.4 cm) and 74 women (18.7 ± 0.9 yr, 63.2 ± 8.9 kg, 165.2 ± 6.9 cm) participated. Descriptive measures included cross-body adduction (CAD), flexion (FLX), external rotation (ER0) with the shoulder complex in adduction and elbow flexed to 90°, internal and external rotation (IR, ER) with the shoulder complex at 90° of abduction and elbow flexed to 90° as well as arc (ARC) of IR-ER using standardized clinical quantification techniques. Bilateral and sex differences were evaluated using dependent and independent t-tests, respectively. Percentiles by arm dominance and sex were also calculated for all ROM measures. Data were normally distributed. Active and passive ROM measures indicated significant bilateral differences (P < 0.05) except for ARC. Sex differences (P < 0.05) were noted for active and passive CAD, FLX and ER0 for the dominant arm as well as active and passive CAD, FLX and ARC for the non-dominant arm. These original data provide descriptive measures for shoulder complex ROM excursions, assisting sports medicine practitioners in potentially identifying clinical deficiencies and functional outcomes following shoulder injury.

Interpretation of genetic testing for lynch syndrome in patients with putative familial colorectal cancer.

PubMed

Rybak, Christina; Hall, Michael J

2011-11-01

Colorectal cancer (CRC) risk assessment involves the evaluation of an individual's personal and family history for characteristics of an inherited susceptibility to develop CRC. Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is the most common cause of hereditary CRC, underlying 2% to 3% of patients with newly diagnosed (incident) CRC. Risk assessment for LS is complex, and the interpretation of the many available tests can be challenging even for the genetics specialist. A move toward universal (reflex) LS screening for mismatch repair in all patients with incident CRC supports the importance of improving the awareness and understanding of LS testing, teaching rational testing approaches, and honing interpretive skills among cancer care providers. This article reviews important clinical features of LS genetic evaluation using 3 pedigree-based case examples from the Fox Chase Cancer Center Gastrointestinal Risk Assessment Clinic.

Blood Tests for People with Severe Learning Disabilities Receiving Dental Treatment under General Anaesthesia.

PubMed

Clough, Stacey; Shehabi, Zahra; Morgan, Claire; Sheppey, Claire

2016-11-01

People with learning disabilities (LDs) have poorer health than their non-disabled peers due to failures in reasonable adjustments. One hundred patients with severe LD and challenging behaviour attended for dental treatment under GA, during which routine blood testing was provided. Communication with general medical practitioners (GMPs) and blood test results were evaluated, showing poor communication with GMPs and significant undiagnosed disease among this group. Blood tests generate similar costs in primary and secondary care but a holistic approach to care under GA reduces expenses brought by lost clinical time and resources due to complex behaviours in an out-patient setting. Clinical relevance: This article discusses a holistic approach to healthcare for people with severe LD, including patient outcomes, financial and resource implications, and offers practical guidance on venepuncture technique, which is relevant to many aspects of both community and hospital dental practice.

Confidentiality, privacy, and security of genetic and genomic test information in electronic health records: points to consider.

PubMed

McGuire, Amy L; Fisher, Rebecca; Cusenza, Paul; Hudson, Kathy; Rothstein, Mark A; McGraw, Deven; Matteson, Stephen; Glaser, John; Henley, Douglas E

2008-07-01

As clinical genetics evolves, and we embark down the path toward more personalized and effective health care, the amount, detail, and complexity of genetic/genomic test information within the electronic health record will increase. This information should be appropriately protected to secure the trust of patients and to support interoperable electronic health information exchange. This article discusses characteristics of genetic/genomic test information, including predictive capability, immutability, and uniqueness, which should be considered when developing policies about information protection. Issues related to "genetic exceptionalism"; i.e., whether genetic/genomic test information should be treated differently from other medical information for purposes of data access and permissible use, are also considered. These discussions can help guide policy that will facilitate the biological and clinical resource development to support the introduction of this information into health care.

Development and validation of an instrument to measure nurse educator perceived confidence in clinical teaching.

PubMed

Nguyen, Van N B; Forbes, Helen; Mohebbi, Mohammadreza; Duke, Maxine

2017-12-01

Teaching nursing in clinical environments is considered complex and multi-faceted. Little is known about the role of the clinical nurse educator, specifically the challenges related to transition from clinician, or in some cases, from newly-graduated nurse to that of clinical nurse educator, as occurs in developing countries. Confidence in the clinical educator role has been associated with successful transition and the development of role competence. There is currently no valid and reliable instrument to measure clinical nurse educator confidence. This study was conducted to develop and psychometrically test an instrument to measure perceived confidence among clinical nurse educators. A multi-phase, multi-setting survey design was used. A total of 468 surveys were distributed, and 363 were returned. Data were analyzed using exploratory and confirmatory factor analyses. The instrument was successfully tested and modified in phase 1, and factorial validity was subsequently confirmed in phase 2. There was strong evidence of internal consistency, reliability, content, and convergent validity of the Clinical Nurse Educator Skill Acquisition Assessment instrument. The resulting instrument is applicable in similar contexts due to its rigorous development and validation process. © 2017 The Authors. Nursing & Health Sciences published by John Wiley & Sons Australia, Ltd.

Genetic testing and genetic counseling in patients with sudden death risk due to heritable arrhythmias.

PubMed

Spoonamore, Katherine G; Ware, Stephanie M

2016-03-01

Sudden cardiac death due to heritable ventricular arrhythmias is an important cause of mortality, especially in young healthy individuals. The identification of the genetic basis of Mendelian diseases associated with arrhythmia has allowed the integration of this information into the diagnosis and clinical management of patients and at-risk family members. The rapid expansion of genetic testing options and the increasing complexity involved in the interpretation of results creates unique opportunities and challenges. There is a need for competency to incorporate genetics into clinical management and to provide appropriate family-based risk assessment and information. In addition, disease-specific genetic knowledge is required to order and correctly interpret and apply genetic testing results. Importantly, genetic diagnosis has a critical role in the risk stratification and clinical management of family members. This review summarizes the approach to genetic counseling and genetic testing for inherited arrhythmias and highlights specific genetic principles that apply to long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

The pursuit of certainty in diagnosing dementia: cognitive testing, childishness and stress in two British memory clinics.

PubMed

Orr, David M R

2010-12-01

By often taking as its focus the experience of illness in itself, medical anthropology has sometimes neglected the meanings that patients may assign to the diagnostic procedures that they are expected to undergo. This paper puts into anthropological perspective the author's experiences working as an assistant psychologist in two British memory clinics for the detection and treatment of dementia, using comments by patients to illustrate the significance that one aspect of these procedures--cognitive testing--had for them. These comments suggest that the meanings that patients construct with regard to such testing are complex and cannot be understood if one persists in seeing it as a neutral diagnostic tool without broader implications. It is argued that a strong association made by many patients between the cognitive tests and their childhood school experiences informs their reactions for better or worse. It is important to acknowledge the implications of this active interpretation of medical procedures if the memory clinic experience is not to become an alienating and infantilising one.

The use of health status questionnaires in the management of chronic obstructive pulmonary disease patients in clinical practice.

PubMed

van der Molen, Thys; Diamant, Zuzana; Kocks, Jan Willem H; Tsiligianni, Ioanna G

2014-08-01

Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.

[The heuristics of reaching a diagnosis].

PubMed

Wainstein, Eduardo

2009-12-01

Making a diagnosis in medicine is a complex process in which many cognitive and psychological issues are involved. After the first encounter with the patient, an unconscious process ensues to suspect the presence of a particular disease. Usually, complementary tests are requested to confirm the clinical suspicion. The interpretation of requested tests can be biased by the clinical diagnosis that was considered in the first encounter with the patient. The awareness of these sources of error is essential in the interpretation of the findings that will eventually lead to a final diagnosis. This article discusses some aspects of the heuristics involved in the adjudication of priory probabilities and provides a brief review of current concepts of the reasoning process.

Personalized prescribing: a new medical model for clinical implementation of psychotropic drugs

PubMed Central

Eap, Chin B.

2016-01-01

The use of pharmacogenetic tests was already being proposed in psychiatry in the early 2000s because genetic factors were known to influence drug pharmacokinetics and pharmacodynamics. However, sufficient levels of evidence to justify routine use have been achieved for only a few tests (eg, major histocompatibility complex, class I, B, allele 1502 [HLA-B*1502] for carbamazepine in epilepsy and bipolar disorders); many findings are too preliminary or, when replicated, of low clinical relevance because of a small effect size. Although drug selection and dose adaptation according to cytochrome P450 genotypes are sound, a large number of patients need to be genotyped in order to prevent one case of severe side effect and/or nonresponse. The decrease in cost for genetic analysis shifts the cost: benefit ratio toward increasing use of pharmacogenetic tests. However, they have to be combined with careful clinical evaluations and other tools (eg, therapeutic drug monitoring and phenotyping) to contribute to the general aim of providing the best care for psychiatric patients. PMID:27757065

Personalized prescribing: a new medical model for clinical implementation of psychotropic drugs.

PubMed

Eap, Chin B

2016-09-01

The use of pharmacogenetic tests was already being proposed in psychiatry in the early 2000s because genetic factors were known to influence drug pharmacokinetics and pharmacodynamics. However, sufficient levels of evidence to justify routine use have been achieved for only a few tests (eg, major histocompatibility complex, class I, B, allele 1502 [HLA-B*1502] for carbamazepine in epilepsy and bipolar disorders); many findings are too preliminary or, when replicated, of low clinical relevance because of a small effect size. Although drug selection and dose adaptation according to cytochrome P450 genotypes are sound, a large number of patients need to be genotyped in order to prevent one case of severe side effect and/or nonresponse. The decrease in cost for genetic analysis shifts the cost: benefit ratio toward increasing use of pharmacogenetic tests. However, they have to be combined with careful clinical evaluations and other tools (eg, therapeutic drug monitoring and phenotyping) to contribute to the general aim of providing the best care for psychiatric patients.

Advancing Translational Research Through the NHLBI Gene Therapy Resource Program (GTRP)

PubMed Central

Benson, Janet; Cornetta, Kenneth; Diggins, Margaret; Johnston, Julie C.; Sepelak, Susan; Wang, Gensheng; Wilson, James M.; Wright, J. Fraser; Skarlatos, Sonia I.

2013-01-01

Abstract Translational research is a lengthy, complex, and necessary endeavor in order to bring basic science discoveries to clinical fruition. The NIH offers several programs to support translational research including an important resource established specifically for gene therapy researchers—the National Heart, Lung, and Blood Institute (NHLBI) Gene Therapy Resource Program (GTRP). This paper reviews the core components of the GTRP and describes how the GTRP provides researchers with resources that are critical to advancing investigational gene therapy products into clinical testing. PMID:23692378

Design of clinical trials for therapeutic cancer vaccines development.

PubMed

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

Colorectal adenomatous polyposis syndromes: Genetic determinism, clinical presentation and recommendations for care.

PubMed

Buecher, Bruno

2016-02-01

Colorectal adenomatous polyposis constitutes a diverse group of disorders with different modes of inheritance. Molecular diagnosis of this condition has become more complex. In fact, somatic mosaicism for APC mutations now appears to be more frequent than previously thought and rare germline alterations of this gene may be implicated in patients tested negative for "classical" APC mutations (point mutations and large genomic rearrangements). Moreover, the knowledge concerning several aspects of the MUTYH-associated polyposis has improved since its first description in 2002 and germline mutations in new genes have recently been implicated in some cases of unexplained adenomatous polyposis. Genetic testing in probands and their relatives should be conducted in the context of pre- and post-test genetic counseling. The recent advent of New Generation Sequencing (NGS) techniques affords the opportunity to rapidly screen patients for a comprehensive panel of colorectal cancer susceptibility genes in a cost-effective fashion. This type of approach will probably replace the classical sequential approach based on clinical presumptive diagnoses in the near future. The risk of colorectal cancer is very high in affected patients in the absence of appropriate care. Clinical management is complex and should be provided in centers with special expertise in these diseases. This review focuses on the various colorectal adenomatous polyposis syndromes with special attention to more innovative and important aspects. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

A New Clinical Pain Knowledge Test for Nurses: Development and Psychometric Evaluation.

PubMed

Bernhofer, Esther I; St Marie, Barbara; Bena, James F

2017-08-01

All nurses care for patients with pain, and pain management knowledge and attitude surveys for nurses have been around since 1987. However, no validated knowledge test exists to measure postlicensure clinicians' knowledge of the core competencies of pain management in current complex patient populations. To develop and test the psychometric properties of an instrument designed to measure pain management knowledge of postlicensure nurses. Psychometric instrument validation. Four large Midwestern U.S. hospitals. Registered nurses employed full time and part time August 2015 to April 2016, aged M = 43.25 years; time as RN, M = 16.13 years. Prospective survey design using e-mail to invite nurses to take an electronic multiple choice pain knowledge test. Content validity of initial 36-item test "very good" (95.1% agreement). Completed tests that met analysis criteria, N = 747. Mean initial test score, 69.4% correct (range 27.8-97.2). After revision/removal of 13 unacceptable questions, mean test score was 50.4% correct (range 8.7-82.6). Initial test item percent difficulty range was 15.2%-98.1%; discrimination values range, 0.03-0.50; final test item percent difficulty range, 17.6%-91.1%, discrimination values range, -0.04 to 1.04. Split-half reliability final test was 0.66. A high decision consistency reliability was identified, with test cut-score of 75%. The final 23-item Clinical Pain Knowledge Test has acceptable discrimination, difficulty, decision consistency, reliability, and validity in the general clinical inpatient nurse population. This instrument will be useful in assessing pain management knowledge of clinical nurses to determine gaps in education, evaluate knowledge after pain management education, and measure research outcomes. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Genetic testing in cardiovascular diseases.

PubMed

Arndt, Anne-Karin; MacRae, Calum A

2014-05-01

The review is designed to outline the major developments in genetic testing in the cardiovascular arena in the past year or so. This is an exciting time in genetic testing as whole exome and whole genome approaches finally reach the clinic. These new approaches offer insight into disease causation in families in which this might previously have been inaccessible, and also bring a wide range of interpretative challenges. Among the most significant recent findings has been the extent of physiologic rare coding variation in the human genome. New disease genes have been identified through whole exome studies in neonatal arrhythmia, congenital heart disease and coronary artery disease that were simply inaccessible with other techniques. This has not only shed light on the challenges of genetic testing at this scale, but has also sharply defined the limits of prior gene-panel focused testing. As novel therapies targeting specific genetic subsets of disease become available, genetic testing will become a part of routine clinical care. The pace of change in sequencing technologies has begun to transform clinical medicine, and cardiovascular disease is no exception. The complexity of such studies emphasizes the importance of real-time communication between the genetics laboratory and genetically informed clinicians. New efforts in data and knowledge management will be central to the continued advancement of genetic testing.

Clinical education in nursing: rethinking learning in practice settings.

PubMed

Ironside, Pamela M; McNelis, Angela M; Ebright, Patricia

2014-01-01

Clinical education is a time- and resource-intensive aspect of contemporary nursing programs. Despite widespread agreement in the discipline about the centrality of clinical experiences to learning nursing, little is known about if and how current clinical experiences contribute to students' learning and readiness for practice. Before large-scale studies testing specific educational interventionals can be conducted, it is important to understand what currently occurs during clinical experiences. This study, funded by the National Council of State Boards of Nursing, examined the nature of contemporary clinical education by describing students' and faculty's experiences at three geographically diverse universities in the United States. Findings suggest that teachers' and students' focus on task completion persists and often overshadows the more complex aspects of learning nursing practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C

PubMed Central

Wilson, Eleanor M.; Rosenthal, Elana S.; Kattakuzhy, Sarah; Tang, Lydia

2016-01-01

SUMMARY Directly acting antiviral (DAA) combination therapies for chronic hepatitis C virus (HCV) infection are highly effective, but treatment decisions remain complex. Laboratory testing is important to evaluate a range of viral, host, and pharmacological factors when considering HCV treatment, and patients must be monitored during and after therapy for safety and to assess the viral response. In this review, we discuss the laboratory tests relevant for the treatment of HCV infection in the era of DAA therapy, grouped according to viral and host factors. PMID:27795306

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.

Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR.

PubMed

Araújo, Cristina P; Osório, Ana Luiza A R; Jorge, Klaudia S G; Ramos, Carlos A N; Souza Filho, Antonio F; Vidal, Carlos E S; Vargas, Agueda P C; Roxo, Eliana; Rocha, Adalgiza S; Suffys, Philip N; Fonseca, Antônio A; Silva, Marcio R; Barbosa Neto, José D; Cerqueira, Valíria D; Araújo, Flábio R

2014-01-01

Post-mortem bacterial culture and specific biochemical tests are currently performed to characterize the etiologic agent of bovine tuberculosis. Cultures take up to 90 days to develop. A diagnosis by molecular tests such as PCR can provide fast and reliable results while significantly decreasing the time of confirmation. In the present study, a nested-PCR system, targeting rv2807, with conventional PCR followed by real-time PCR, was developed to detect Mycobacterium tuberculosis complex (MTC) organisms directly from bovine and bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other Actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. Regarding the analytical sensitivity, DNA of the M. bovis AN5 strain was detected up to 1.5 pg by nested-PCR, whereas DNA of M. tuberculosis H37Rv strain was detected up to 6.1 pg. The nested-PCR system showed 100% analytical specificity for MTC when tested with DNA of reference strains of non-tuberculous mycobacteria and closely-related Actinomycetales. A clinical sensitivity level of 76.7% was detected with tissues samples positive for MTC by means of the culture and conventional PCR. A clinical specificity of 100% was detected with DNA from tissue samples of cattle with negative results in the comparative intradermal tuberculin test. These cattle exhibited no visible lesions and were negative in the culture for MTC. The use of the nested-PCR assay to detect M. tuberculosis complex in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis.

Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR

PubMed Central

Araújo, Cristina P.; Osório, Ana Luiza A.R.; Jorge, Klaudia S.G.; Ramos, Carlos A.N.; Souza Filho, Antonio F.; Vidal, Carlos E.S.; Vargas, Agueda P.C.; Roxo, Eliana; Rocha, Adalgiza S.; Suffys, Philip N.; Fonseca, Antônio A.; Silva, Marcio R.; Barbosa Neto, José D.; Cerqueira, Valíria D.; Araújo, Flábio R.

2014-01-01

Post-mortem bacterial culture and specific biochemical tests are currently performed to characterize the etiologic agent of bovine tuberculosis. Cultures take up to 90 days to develop. A diagnosis by molecular tests such as PCR can provide fast and reliable results while significantly decreasing the time of confirmation. In the present study, a nested-PCR system, targeting rv2807, with conventional PCR followed by real-time PCR, was developed to detect Mycobacterium tuberculosis complex (MTC) organisms directly from bovine and bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other Actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. Regarding the analytical sensitivity, DNA of the M. bovis AN5 strain was detected up to 1.5 pg by nested-PCR, whereas DNA of M. tuberculosis H37Rv strain was detected up to 6.1 pg. The nested-PCR system showed 100% analytical specificity for MTC when tested with DNA of reference strains of non-tuberculous mycobacteria and closely-related Actinomycetales. A clinical sensitivity level of 76.7% was detected with tissues samples positive for MTC by means of the culture and conventional PCR. A clinical specificity of 100% was detected with DNA from tissue samples of cattle with negative results in the comparative intradermal tuberculin test. These cattle exhibited no visible lesions and were negative in the culture for MTC. The use of the nested-PCR assay to detect M. tuberculosis complex in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis. PMID:25242951

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.

Nonclinical safety testing of biopharmaceuticals--Addressing current challenges of these novel and emerging therapies.

PubMed

Brennan, Frank R; Baumann, Andreas; Blaich, Guenter; de Haan, Lolke; Fagg, Rajni; Kiessling, Andrea; Kronenberg, Sven; Locher, Mathias; Milton, Mark; Tibbitts, Jay; Ulrich, Peter; Weir, Lucinda

2015-10-01

Non-clinical safety testing of biopharmaceuticals can present significant challenges to human risk assessment with these often innovative and complex drugs. Hot Topics in this field were discussed recently at the 4th Annual European Biosafe General Membership meeting. In this feature article, the presentations and subsequent discussions from the main sessions are summarized. The topics covered include: (i) wanted versus unwanted immune activation, (ii) bi-specific protein scaffolds, (iii) use of Pharmacokinetic (PK)/Pharmacodynamic (PD) data to impact/optimize toxicology study design, (iv) cytokine release and challenges to human translation (v) safety testing of cell and gene therapies including chimeric antigen receptor T (CAR-T) cells and retroviral vectors and (vi) biopharmaceutical development strategies encompassing a range of diverse topics including optimizing entry of monoclonal antibodies (mAbs) into the brain, safety testing of therapeutic vaccines, non-clinical testing of biosimilars, infection in toxicology studies with immunomodulators and challenges to human risk assessment, maternal and infant anti-drug antibody (ADA) development and impact in non-human primate (NHP) developmental toxicity studies, and a summary of an NC3Rs workshop on the future vision for non-clinical safety assessment of biopharmaceuticals. Copyright © 2015 Elsevier Inc. All rights reserved.

Atherosclerotic renal artery stenosis: epidemiology, cardiovascular outcomes, and clinical prediction rules.

PubMed

Zoccali, Carmine; Mallamaci, Francesca; Finocchiaro, Pietro

2002-11-01

Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.

Development and psychometric testing of Holistic Clinical Assessment Tool (HCAT) for undergraduate nursing students.

PubMed

Wu, Xi Vivien; Enskär, Karin; Pua, Lay Hoon; Heng, Doreen Gek Noi; Wang, Wenru

2016-09-22

A major focus in nursing education is on the judgement of clinical performance, and it is a complex process due to the diverse nature of nursing practice. A holistic approach in assessment of competency is advocated. Difficulties in the development of valid and reliable assessment measures in nursing competency have resulted in the development of assessment instruments with an increase in face and content validity, but few studies have tested these instruments psychometrically. It is essential to develop a holistic assessment tool to meet the needs of the clinical education. The study aims to develop a Holistic Clinical Assessment Tool (HCAT) and test its psychometric properties. The HCAT was developed based on the systematic literature review and the findings of qualitative studies. An expert panel was invited to evaluate the content validity of the tool. A total of 130 final-year nursing undergraduate students were recruited to evaluate the psychometric properties (i.e. factor structure, internal consistency and test-retest reliability) of the tool. The HCAT has good content validity with content validity index of .979. The exploratory factor analysis reveals a four-factor structure of the tool. The internal consistency and test-retest reliability of the HCAT are satisfactory with Cronbach alpha ranging from .789 to .965 and Intraclass Correlation Coefficient ranging from .881 to .979 for the four subscales and total scale. HCAT has the potential to be used as a valid measure to evaluate clinical competence in nursing students, and provide specific and ongoing feedback to enhance the holistic clinical learning experience. In addition, HCAT functions as a tool for self-reflection, peer-assessment and guides preceptors in clinical teaching and assessment.

Is overestimation of body size associated with neuropsychological weaknesses in anorexia nervosa?

PubMed

Øverås, Maria; Kapstad, Hilde; Brunborg, Cathrine; Landrø, Nils Inge; Rø, Øyvind

2017-03-01

Recent research indicates some evidence of neuropsychological weaknesses in visuospatial memory, central coherence and set-shifting in adults with anorexia nervosa (AN). The growing interest in neuropsychological functioning of patients with AN is based upon the assumption that neuropsychological weaknesses contribute to the clinical features of the illness. However, due to a paucity of research on the connection between neuropsychological difficulties and the clinical features of AN, this link remains hypothetical. The main objective of this study was to explore the association between specific areas of neuropsychological functioning and body size estimation in patients with AN and healthy controls. The sample consisted of 36 women diagnosed with AN and 34 healthy female controls. Participants were administered the continuous visual memory test and the recall trials of Rey Complex Figure Test to assess visual memory. Central coherence was assessed using the copy trial of Rey Complex Figure Test, and the Wisconsin Card Sorting Test was used to assess set-shifting. Body size estimation was assessed with a computerized morphing programme. The analyses showed no significant correlations between any of the neuropsychological measures and body size estimation. The results suggest that there is no association between these areas of neuropsychological difficulties and body size estimation among patients with AN. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

The relationship between immediate relevant basic science knowledge and clinical knowledge: physiology knowledge and transthoracic echocardiography image interpretation.

PubMed

Nielsen, Dorte Guldbrand; Gotzsche, Ole; Sonne, Ole; Eika, Berit

2012-10-01

Two major views on the relationship between basic science knowledge and clinical knowledge stand out; the Two-world view seeing basic science and clinical science as two separate knowledge bases and the encapsulated knowledge view stating that basic science knowledge plays an overt role being encapsulated in the clinical knowledge. However, resent research has implied that a more complex relationship between the two knowledge bases exists. In this study, we explore the relationship between immediate relevant basic science (physiology) and clinical knowledge within a specific domain of medicine (echocardiography). Twenty eight medical students in their 3rd year and 45 physicians (15 interns, 15 cardiology residents and 15 cardiology consultants) took a multiple-choice test of physiology knowledge. The physicians also viewed images of a transthoracic echocardiography (TTE) examination and completed a checklist of possible pathologies found. A total score for each participant was calculated for the physiology test, and for all physicians also for the TTE checklist. Consultants scored significantly higher on the physiology test than did medical students and interns. A significant correlation between physiology test scores and TTE checklist scores was found for the cardiology residents only. Basic science knowledge of immediate relevance for daily clinical work expands with increased work experience within a specific domain. Consultants showed no relationship between physiology knowledge and TTE interpretation indicating that experts do not use basic science knowledge in routine daily practice, but knowledge of immediate relevance remains ready for use.

The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe

PubMed Central

Hastings, Ros; de Wert, Guido; Fowler, Brian; Krawczak, Michael; Vermeulen, Eric; Bakker, Egbert; Borry, Pascal; Dondorp, Wybo; Nijsingh, Niels; Barton, David; Schmidtke, Jörg; van El, Carla G; Vermeesch, Joris; Stol, Yrrah; Carmen Howard, Heidi; Cornel, Martina C

2012-01-01

The arrival of new genetic technologies that allow efficient examination of the whole human genome (microarray, next-generation sequencing) will impact upon both laboratories (cytogenetic and molecular genetics in the first instance) and clinical/medical genetic services. The interpretation of analytical results in terms of their clinical relevance and the predicted health status poses a challenge to both laboratory and clinical geneticists, due to the wealth and complexity of the information obtained. There is a need to discuss how to best restructure the genetic services logistically and to determine the clinical utility of genetic testing so that patients can receive appropriate advice and genetic testing. To weigh up the questions and challenges of the new genetic technologies, the European Society of Human Genetics (ESHG) held a series of workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite symposium on the ‘Changing landscape of genetic testing', co-organized by the ESHG Genetic Services Quality and Public and Professional Policy Committees. The audience consisted of a mix of geneticists, ethicists, social scientists and lawyers. In this paper, we summarize the discussions during the workshops and present some of the identified ways forward to improve and adapt the genetic services so that patients receive accurate and relevant information. This paper covers ethics, clinical utility, primary care, genetic services and the blurring boundaries between healthcare and research. PMID:22453292

Multispectral imaging burn wound tissue classification system: a comparison of test accuracies between several common machine learning algorithms

NASA Astrophysics Data System (ADS)

Squiers, John J.; Li, Weizhi; King, Darlene R.; Mo, Weirong; Zhang, Xu; Lu, Yang; Sellke, Eric W.; Fan, Wensheng; DiMaio, J. Michael; Thatcher, Jeffrey E.

2016-03-01

The clinical judgment of expert burn surgeons is currently the standard on which diagnostic and therapeutic decisionmaking regarding burn injuries is based. Multispectral imaging (MSI) has the potential to increase the accuracy of burn depth assessment and the intraoperative identification of viable wound bed during surgical debridement of burn injuries. A highly accurate classification model must be developed using machine-learning techniques in order to translate MSI data into clinically-relevant information. An animal burn model was developed to build an MSI training database and to study the burn tissue classification ability of several models trained via common machine-learning algorithms. The algorithms tested, from least to most complex, were: K-nearest neighbors (KNN), decision tree (DT), linear discriminant analysis (LDA), weighted linear discriminant analysis (W-LDA), quadratic discriminant analysis (QDA), ensemble linear discriminant analysis (EN-LDA), ensemble K-nearest neighbors (EN-KNN), and ensemble decision tree (EN-DT). After the ground-truth database of six tissue types (healthy skin, wound bed, blood, hyperemia, partial injury, full injury) was generated by histopathological analysis, we used 10-fold cross validation to compare the algorithms' performances based on their accuracies in classifying data against the ground truth, and each algorithm was tested 100 times. The mean test accuracy of the algorithms were KNN 68.3%, DT 61.5%, LDA 70.5%, W-LDA 68.1%, QDA 68.9%, EN-LDA 56.8%, EN-KNN 49.7%, and EN-DT 36.5%. LDA had the highest test accuracy, reflecting the bias-variance tradeoff over the range of complexities inherent to the algorithms tested. Several algorithms were able to match the current standard in burn tissue classification, the clinical judgment of expert burn surgeons. These results will guide further development of an MSI burn tissue classification system. Given that there are few surgeons and facilities specializing in burn care, this technology may improve the standard of burn care for patients without access to specialized facilities.

The use of computed tomography scans and the Bender Gestalt Test in the assessment of competency to stand trial and criminal responsibility in the field of mental health and law.

PubMed

Mosotho, Nathaniel Lehlohonolo; Timile, Ino; Joubert, Gina

computed tomography and the Bender Gestalt Test are some of the tests used routinely for the assessment of alleged offenders referred under Sections 77 and 78 of the Criminal Procedure Act 51 of 1977. An exploratory retrospective study was conducted at the Free State Psychiatric Complex. The aim of this study was to identify the extent to which the Bender Gestalt Test results and the computed tomography scans are associated with outcomes in the assessment of competency to stand trial and criminal responsibility in individuals referred to the Free State Psychiatric Complex (FSPC) observation unit. This was a cross-sectional study and the entire population of patients admitted in 2013 was included in the study. The clinical and demographic data were obtained from patient files. The majority of participants were black, males, single and unemployed. The most common diagnosis was schizophrenia. The current study showed no statistically significant association between the Bender Gestalt Test Hain's scores and the outcome of criminal responsibility and competency to stand trial. Similarly, the study also showed no statistically significant association between the presence of a brain lesion and the outcome of criminal responsibility and competency to stand trial. It was also concluded that as CT scans are expensive, patients should be referred for that service only when there is a clear clinical indication to do so. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rapid molecular assays for detection of tuberculosis.

PubMed

Eddabra, Rkia; Ait Benhassou, Hassan

2018-01-01

Tuberculosis (TB) is an infectious disease that remains an important public health problem at the global level. It is one of the main causes of morbidity and mortality, due to the emergence of antibiotic resistant Mycobacterium strains and HIV co-infection. Over the past decade, important progress has been made for better control of the disease. While microscopy and culture continue to be indispensible for laboratory diagnosis of tuberculosis, the range of several molecular diagnostic tests, including the nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have expanded tremendously. They are becoming more accessible not only for detection and identification of Mycobacterium tuberculosis complex in clinical specimens, but now extend to diagnosing multi-drug resistant strains. Molecular diagnostic tests provide timely results useful for high-quality patient care, low contamination risk, and ease of performance and speed. This review focuses on the current diagnostic tests in use, including emerging technologies used for detection of tuberculosis in clinical specimens. The sensitivity and specificity of these tests have also been taken into consideration.

Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

PubMed

Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

2018-06-01

To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD, heart failure, stroke and hip fracture are infrequent in primary care and represent a minority among patients in need of coordinated community health care. In primary care, the low rate of receiving patients discharged from hospitals of major chronic diseases hampers maintenance of required specific skills, thus constricting the transfer of tasks to primary care. Generic clinical pathways are suggested to be more feasible than disease-specific pathways for most patients with complex needs.

Prenatal Testing for Adult-Onset Conditions: the Position of the National Society of Genetic Counselors.

PubMed

Hercher, Laura; Uhlmann, Wendy R; Hoffman, Erin P; Gustafson, Shanna; Chen, Kelly M

2016-12-01

Advances in genetic testing and the availability of such testing in pregnancy allows prospective parents to test their future child for adult-onset conditions. This ability raises several complex ethical issues. Prospective parents have reproductive rights to obtain information about their fetus. This information may or may not alter pregnancy management. These rights can be in conflict with the rights of the future individual, who will be denied the right to elect or decline testing. This paper highlights the complexity of these issues, details discussions that went into the National Society of Genetic Counselors (NSGC) Public Policy Task Force's development of the Prenatal testing for Adult-Onset Conditions position statement adopted in November 2014, and cites relevant literature on this topic through December 2015. Issues addressed include parental rights and autonomy, rights of the future child, the right not to know, possible adverse effects on childhood and the need for genetic counseling. This paper will serve as a reference to genetic counselors and healthcare professionals when faced with this situation in clinical practice.

Implementation of personalized medicine in Central-Eastern Europe: pitfalls and potentials based on citizen's attitude.

PubMed

Balicza, Peter; Terebessy, Andras; Grosz, Zoltan; Varga, Noemi Agnes; Gal, Aniko; Fekete, Balint Andras; Molnar, Maria Judit

2018-03-01

Next-generation sequencing is increasingly utilized worldwide as a research and diagnostic tool and is anticipated to be implemented into everyday clinical practice. Since Central-Eastern European attitude toward genetic testing, especially broad genetic testing, is not well known, we performed a survey on this issue among Hungarian participants. A self-administered questionnaire was distributed among patients and patient relatives at our neurogenetic outpatient clinic. Members of the general population were also recruited via public media. We used chi-square testing and binary logistic regression to examine factors influencing attitude. We identified a mixed attitude toward genetic testing. Access to physician consultation positively influenced attitude. A higher self-determined genetic familiarity score associated with higher perceived genetic influence score, which in turn associated with greater willingness to participate in genetic testing. Medical professionals constituted a skeptical group. We think that given the controversies and complexities of the next-generation sequencing field, the optimal clinical translation of NGS data should be performed in institutions which have the unique capability to provide interprofessional health education, transformative biomedical research, and crucial patient care. With optimization of the clinical translational process, improvement of genetic literacy may increase patient engagement and empowerment. The paper highlights that in countries with relatively low-genetic literacy, a special strategy is needed to enhance the implementation of personalized medicine.

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications.

PubMed

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

: Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype-phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, 'real-world' experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines.

Contemporary genetic testing in inherited cardiac disease: tools, ethical issues, and clinical applications

PubMed Central

Girolami, Francesca; Frisso, Giulia; Benelli, Matteo; Crotti, Lia; Iascone, Maria; Mango, Ruggiero; Mazzaccara, Cristina; Pilichou, Kalliope; Arbustini, Eloisa; Tomberli, Benedetta; Limongelli, Giuseppe; Basso, Cristina; Olivotto, Iacopo

2018-01-01

Inherited cardiac diseases comprise a wide and heterogeneous spectrum of diseases of the heart, including the cardiomyopathies and the arrhythmic diseases in structurally normal hearts, that is, channelopathies. With a combined estimated prevalence of 3% in the general population, these conditions represent a relevant epidemiological entity worldwide, and are a major cause of cardiac morbidity and mortality in the young. The extraordinary progress achieved in molecular genetics over the last three decades has unveiled the complex molecular basis of many familial cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. Although genotype–phenotype correlations are generally unpredictable, a precise molecular diagnosis can help predict prognosis in specific patient subsets and may guide management. In clinically unaffected relatives, genetic cascade testing is recommended, after the initial identification of a pathogenic variation, with the aim of identifying asymptomatic relatives who might be at risk of disease-related complications, including unexpected sudden cardiac death. Future implications include the identification of novel therapeutic targets and development of tailored treatments including gene therapy. This document reflects the multidisciplinary, ‘real-world’ experience required when implementing genetic testing in cardiomyopathies and arrhythmic syndromes, along the recommendations of various guidelines. PMID:29176389

Validation of Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection.

PubMed

Schlaberg, Robert; Chiu, Charles Y; Miller, Steve; Procop, Gary W; Weinstock, George

2017-06-01

- Metagenomic sequencing can be used for detection of any pathogens using unbiased, shotgun next-generation sequencing (NGS), without the need for sequence-specific amplification. Proof-of-concept has been demonstrated in infectious disease outbreaks of unknown causes and in patients with suspected infections but negative results for conventional tests. Metagenomic NGS tests hold great promise to improve infectious disease diagnostics, especially in immunocompromised and critically ill patients. - To discuss challenges and provide example solutions for validating metagenomic pathogen detection tests in clinical laboratories. A summary of current regulatory requirements, largely based on prior guidance for NGS testing in constitutional genetics and oncology, is provided. - Examples from 2 separate validation studies are provided for steps from assay design, and validation of wet bench and bioinformatics protocols, to quality control and assurance. - Although laboratory and data analysis workflows are still complex, metagenomic NGS tests for infectious diseases are increasingly being validated in clinical laboratories. Many parallels exist to NGS tests in other fields. Nevertheless, specimen preparation, rapidly evolving data analysis algorithms, and incomplete reference sequence databases are idiosyncratic to the field of microbiology and often overlooked.

Incidence and clinical vital parameters in primary ketosis of Murrah buffaloes

PubMed Central

Kumar, Ankit; Sindhu, Neelesh; Kumar, Parmod; Kumar, Tarun; Charaya, Gaurav; Surbhi; Jain, V. K.; Sridhar

2015-01-01

Aim: The present study was undertaken to ascertain the incidence and clinical vital parameters in cases of primary ketosis in Murrah buffaloes brought to teaching veterinary clinical complex, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar and from adjoining villages of the district Hisar, Haryana, India. Materials and Methods: The investigation was conducted on 24 clinical cases (out of total 145 screened) of primary ketosis. The diagnosis was confirmed on the basis of clinical signs and significantly positive two tests for ketone bodies in urine (Rothera’s and Keto-Diastix strip test). Data collected were statistically analyzed using independent Student’s t-test. Results: Overall incidence of disease in these areas was found to be 16.55% and all the animals were recently parturited (mean: 1.42±0.14 month), on an average in their third lactation (mean: 2.38±0.30) and exhibited clinical signs such as selective anorexia (refusal to feed on concentrate diet), drastic reduction in milk yield (mean: 64.4±5.35%), ketotic odor from urine, breath, and milk and rapid loss of body condition. All the clinical vital parameters in ketotic buffaloes (body temperature, heart rate, respiration rate, and rumen movements) were within normal range. Conclusion: Primary ketosis in Murrah buffaloes was the most common seen in the third lactation, within the first 2 months after parturition with characteristics clinical signs and no variability in vital parameters. The disease has severe effect on the production status of affected animal. PMID:27047203

Clinical skills temporal degradation assessment in undergraduate medical education.

PubMed

Fisher, Joseph; Viscusi, Rebecca; Ratesic, Adam; Johnstone, Cameron; Kelley, Ross; Tegethoff, Angela M; Bates, Jessica; Situ-Lacasse, Elaine H; Adamas-Rappaport, William J; Amini, Richard

2018-01-01

Medical students' ability to learn clinical procedures and competently apply these skills is an essential component of medical education. Complex skills with limited opportunity for practice have been shown to degrade without continued refresher training. To our knowledge there is no evidence that objectively evaluates temporal degradation of clinical skills in undergraduate medical education. The purpose of this study was to evaluate temporal retention of clinical skills among third year medical students. This was a cross-sectional study conducted at four separate time intervals in the cadaver laboratory at a public medical school. Forty-five novice third year medical students were evaluated for retention of skills in the following three procedures: pigtail thoracostomy, femoral line placement, and endotracheal intubation. Prior to the start of third-year medical clerkships, medical students participated in a two-hour didactic session designed to teach clinically relevant materials including the procedures. Prior to the start of their respective surgery clerkships, students were asked to perform the same three procedures and were evaluated by trained emergency medicine and surgery faculty for retention rates, using three validated checklists. Students were then reassessed at six week intervals in four separate groups based on the start date of their respective surgical clerkships. We compared the evaluation results between students tested one week after training and those tested at three later dates for statistically significant differences in score distribution using a one-tailed Wilcoxon Mann-Whitney U-test for non-parametric rank-sum analysis. Retention rates were shown to have a statistically significant decline between six and 12 weeks for all three procedural skills. In the instruction of medical students, skill degradation should be considered when teaching complex technical skills. Based on the statistically significant decline in procedural skills noted in our investigation, instructors should consider administering a refresher course between six and twelve weeks from initial training.

Executive decision-making in the domestic sheep.

PubMed

Morton, A Jennifer; Avanzo, Laura

2011-01-31

Two new large animal models of Huntington's disease (HD) have been developed recently, an old world monkey (macaque) and a sheep. Macaques, with their large brains and complex repertoire of behaviors are the 'gold-standard' laboratory animals for testing cognitive function, but there are many practical and ethical issues that must be resolved before HD macaques can be used for pre-clinical research. By contrast, despite their comparable brain size, sheep do not enjoy a reputation for intelligence, and are not used for pre-clinical cognitive testing. Given that cognitive decline is a major therapeutic target in HD, the feasibility of testing cognitive function in sheep must be explored if they are to be considered seriously as models of HD. Here we tested the ability of sheep to perform tests of executive function (discrimination learning, reversal learning and attentional set-shifting). Significantly, we found that not only could sheep perform discrimination learning and reversals, but they could also perform the intradimensional (ID) and extradimensional (ED) set-shifting tasks that are sensitive tests of cognitive dysfunction in humans. Their performance on the ID/ED shifts mirrored that seen in humans and macaques, with significantly more errors to reach criterion in the ED than the ID shift. Thus, sheep can perform 'executive' cognitive tasks that are an important part of the primate behavioral repertoire, but which have never been shown previously to exist in any other large animal. Sheep have great potential, not only for use as a large animal model of HD, but also for studying cognitive function and the evolution of complex behaviours in normal animals.

Executive Decision-Making in the Domestic Sheep

PubMed Central

Morton, A. Jennifer; Avanzo, Laura

2011-01-01

Two new large animal models of Huntington's disease (HD) have been developed recently, an old world monkey (macaque) and a sheep. Macaques, with their large brains and complex repertoire of behaviors are the ‘gold-standard’ laboratory animals for testing cognitive function, but there are many practical and ethical issues that must be resolved before HD macaques can be used for pre-clinical research. By contrast, despite their comparable brain size, sheep do not enjoy a reputation for intelligence, and are not used for pre-clinical cognitive testing. Given that cognitive decline is a major therapeutic target in HD, the feasibility of testing cognitive function in sheep must be explored if they are to be considered seriously as models of HD. Here we tested the ability of sheep to perform tests of executive function (discrimination learning, reversal learning and attentional set-shifting). Significantly, we found that not only could sheep perform discrimination learning and reversals, but they could also perform the intradimensional (ID) and extradimensional (ED) set-shifting tasks that are sensitive tests of cognitive dysfunction in humans. Their performance on the ID/ED shifts mirrored that seen in humans and macaques, with significantly more errors to reach criterion in the ED than the ID shift. Thus, sheep can perform ‘executive’ cognitive tasks that are an important part of the primate behavioral repertoire, but which have never been shown previously to exist in any other large animal. Sheep have great potential, not only for use as a large animal model of HD, but also for studying cognitive function and the evolution of complex behaviours in normal animals. PMID:21305061

Heuristics in Managing Complex Clinical Decision Tasks in Experts’ Decision Making

PubMed Central

Islam, Roosan; Weir, Charlene; Del Fiol, Guilherme

2016-01-01

Background Clinical decision support is a tool to help experts make optimal and efficient decisions. However, little is known about the high level of abstractions in the thinking process for the experts. Objective The objective of the study is to understand how clinicians manage complexity while dealing with complex clinical decision tasks. Method After approval from the Institutional Review Board (IRB), three clinical experts were interviewed the transcripts from these interviews were analyzed. Results We found five broad categories of strategies by experts for managing complex clinical decision tasks: decision conflict, mental projection, decision trade-offs, managing uncertainty and generating rule of thumb. Conclusion Complexity is created by decision conflicts, mental projection, limited options and treatment uncertainty. Experts cope with complexity in a variety of ways, including using efficient and fast decision strategies to simplify complex decision tasks, mentally simulating outcomes and focusing on only the most relevant information. Application Understanding complex decision making processes can help design allocation based on the complexity of task for clinical decision support design. PMID:27275019

Heuristics in Managing Complex Clinical Decision Tasks in Experts' Decision Making.

PubMed

Islam, Roosan; Weir, Charlene; Del Fiol, Guilherme

2014-09-01

Clinical decision support is a tool to help experts make optimal and efficient decisions. However, little is known about the high level of abstractions in the thinking process for the experts. The objective of the study is to understand how clinicians manage complexity while dealing with complex clinical decision tasks. After approval from the Institutional Review Board (IRB), three clinical experts were interviewed the transcripts from these interviews were analyzed. We found five broad categories of strategies by experts for managing complex clinical decision tasks: decision conflict, mental projection, decision trade-offs, managing uncertainty and generating rule of thumb. Complexity is created by decision conflicts, mental projection, limited options and treatment uncertainty. Experts cope with complexity in a variety of ways, including using efficient and fast decision strategies to simplify complex decision tasks, mentally simulating outcomes and focusing on only the most relevant information. Understanding complex decision making processes can help design allocation based on the complexity of task for clinical decision support design.

Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA.

PubMed

Yang, Xian; Han, Rui; Guo, Yike; Bradley, Jeremy; Cox, Benita; Dickinson, Robert; Kitney, Richard

2012-01-01

Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting hospitals to effectively manage time and resources in clinical pathway.

Molecular methods for pathogen and microbial community detection and characterization: current and potential application in diagnostic microbiology.

PubMed

Sibley, Christopher D; Peirano, Gisele; Church, Deirdre L

2012-04-01

Clinical microbiology laboratories worldwide have historically relied on phenotypic methods (i.e., culture and biochemical tests) for detection, identification and characterization of virulence traits (e.g., antibiotic resistance genes, toxins) of human pathogens. However, limitations to implementation of molecular methods for human infectious diseases testing are being rapidly overcome allowing for the clinical evaluation and implementation of diverse technologies with expanding diagnostic capabilities. The advantages and limitation of molecular techniques including real-time polymerase chain reaction, partial or whole genome sequencing, molecular typing, microarrays, broad-range PCR and multiplexing will be discussed. Finally, terminal restriction fragment length polymorphism (T-RFLP) and deep sequencing are introduced as technologies at the clinical interface with the potential to dramatically enhance our ability to diagnose infectious diseases and better define the epidemiology and microbial ecology of a wide range of complex infections. Copyright © 2012 Elsevier B.V. All rights reserved.

Modelling clinical systemic lupus erythematosus: similarities, differences and success stories

PubMed Central

Celhar, Teja

2017-01-01

Abstract Mouse models of SLE have been indispensable tools to study disease pathogenesis, to identify genetic susceptibility loci and targets for drug development, and for preclinical testing of novel therapeutics. Recent insights into immunological mechanisms of disease progression have boosted a revival in SLE drug development. Despite promising results in mouse studies, many novel drugs have failed to meet clinical end points. This is probably because of the complexity of the disease, which is driven by polygenic predisposition and diverse environmental factors, resulting in a heterogeneous clinical presentation. Each mouse model recapitulates limited aspects of lupus, especially in terms of the mechanism underlying disease progression. The main mouse models have been fairly successful for the evaluation of broad-acting immunosuppressants. However, the advent of targeted therapeutics calls for a selection of the most appropriate model(s) for testing and, ultimately, identification of patients who will be most likely to respond. PMID:28013204

Rewards of bridging the divide between measurement and clinical theory: demonstration of a bifactor model for the Brief Symptom Inventory.

PubMed

Thomas, Michael L

2012-03-01

There is growing evidence that psychiatric disorders maintain hierarchical associations where general and domain-specific factors play prominent roles (see D. Watson, 2005). Standard, unidimensional measurement models can fail to capture the meaningful nuances of such complex latent variable structures. The present study examined the ability of the multidimensional item response theory bifactor model (see R. D. Gibbons & D. R. Hedeker, 1992) to improve construct validity by serving as a bridge between measurement and clinical theories. Archival data consisting of 688 outpatients' psychiatric diagnoses and item-level responses to the Brief Symptom Inventory (BSI; L. R. Derogatis, 1993) were extracted from files at a university mental health clinic. The bifactor model demonstrated superior fit for the internal structure of the BSI and improved overall diagnostic accuracy in the sample (73%) compared with unidimensional (61%) and oblique simple structure (65%) models. Consistent with clinical theory, multiple sources of item variance were drawn from individual test items. Test developers and clinical researchers are encouraged to consider model-based measurement in the assessment of psychiatric distress.

Progress with the use of monoclonal antibodies for the treatment of systemic lupus erythematosus.

PubMed

Jordan, Natasha; Lutalo, Pamela Mk; D'Cruz, David P

2015-01-01

In recent years, significant progress has been made in the use of monoclonal antibodies in the treatment of systemic lupus erythematosus (SLE). Advances in our understanding of the complexity of SLE immunopathogenesis have led to the testing of several biologic agents in clinical trials. Monoclonal therapies currently emerging or under development include B-cell depletion therapies, agents targeting B-cell survival factors, blockade of T-cell co-stimulation and anticytokine therapies. Issues remain, however, regarding clinical trial design and outcome measures in SLE which need to be addressed to optimize translation of these promising therapies into clinical practice.

Systematic review of safety and tolerability of a complex micronutrient formula used in mental health

PubMed Central

2011-01-01

Background Theoretically, consumption of complex, multinutrient formulations of vitamins and minerals should be safe, as most preparations contain primarily the nutrients that have been in the human diet for millennia, and at safe levels as defined by the Dietary Reference Intakes. However, the safety profile of commercial formulae may differ from foods because of the amounts and combinations of nutrients they contain. As these complex formulae are being studied and used clinically with increasing frequency, there is a need for direct evaluation of safety and tolerability. Methods All known safety and tolerability data collected on one complex nutrient formula was compiled and evaluated. Results Data were assembled from all the known published and unpublished studies for the complex formula with the largest amount of published research in mental health. Biological safety data from 144 children and adults were available from six sources: there were no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event (AE) information from 157 children and adults was available from six studies employing the current version of this formula, and only minor, transitory reports of headache and nausea emerged. Only one of the studies permitted a direct comparison between micronutrient treatment and medication: none of the 88 pediatric and adult participants had any clinically meaningful abnormal laboratory values, but tolerability data in the group treated with micronutrients revealed significantly fewer AEs and less weight gain. Conclusions This compilation of safety and tolerability data is reassuring with respect to the broad spectrum approach that employs complex nutrient formulae as a primary treatment. PMID:21501484

The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle.

PubMed

Brautbar, Ariel; Wang, Jing; Abdenur, Jose E; Chang, Richard C; Thomas, Janet A; Grebe, Theresa A; Lim, Cynthia; Weng, Shao-Wen; Graham, Brett H; Wong, Lee-Jun

2008-08-01

The mitochondrial 13513G>A (D393N) mutation in the ND5 subunit of the respiratory chain complex I was initially described in association with MELAS syndrome. Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disease. The mutation was found in a total of 5 patients. An additional patient who had clinical presentation consistent with a Leigh-like phenotype but with a normal brain MRI was added to the cohort. None of an additional 88 patients meeting MELAS disease criteria, nor 56 patients with respiratory chain deficiency screened for the 13513G>A were found positive for the mutation. The most frequent clinical manifestations in our patients were hypotonia, ocular and cerebellar involvement. Low mutation heteroplasmy in the range of 20-40% was observed in all 6 patients. This observation is consistent with the previously reported low heteroplasmy of this mutation in some patients with the 13513G>A mutation and complex I deficiency. However, normal complex I activity was observed in two patients in our cohort. As most patients with Leigh-like disease and the 13513G>A mutation have been described with complex I deficiency, this report adds to the previously reported subset of patients with normal respiratory complex function. We conclude that in any patient with Leigh or Leigh-like disease, testing for the 13513G>A mutation is clinically relevant and low mutant loads in blood or muscle may be considered pathogenic, in the presence of normal respiratory chain enzyme activities.

'Battling my biology': psychological effects of genetic testing for risk of weight gain.

PubMed

Meisel, S F; Wardle, J

2014-04-01

The availability of genetic tests for multifactorial conditions such as obesity raises concerns that higher-risk results could lead to fatalistic reactions or lower-risk results to complacency. No study has investigated the effects of genetic test feedback for the risk of obesity in non-clinical samples. The present study explored psychological and behavioral reactions to genetic test feedback for a weight related gene (FTO) in a volunteer sample (n = 18) using semi-structured interviews. Respondents perceived the gene test result as scientifically objective; removing some of the emotion attached to the issue of weight control. Those who were struggling with weight control reported relief of self-blame. There was no evidence for either complacency or fatalism; all respondents emphasized the importance of lifestyle choices in long-term weight management, although they recognized the role of both genes and environment. Regardless of the test result, respondents evaluated the testing positively and found it motivating and informative. Genetic test feedback for risk of weight gain may offer psychological benefits beyond its objectively limited clinical utility. As the role of genetic counselors is likely to expand, awareness of reasons for genetic testing for common, complex conditions and reactions to the test result is important.

Evaluating Device Design and Cleanability of Orthopedic Device Models Contaminated with a Clinically Relevant Bone Test Soil.

PubMed

Lucas, Anne D; Nagaraja, Srinidhi; Gordon, Edward A; Hitchins, Victoria M

2015-01-01

Reusable medical devices need to be cleaned prior to disinfection or sterilization and subsequent use to prevent infections. The cleanability of medical devices depends in part on the design of the device. This study examined how models of orthopedic medical devices of increasing complexity retain calcium phosphate bone cement, a relevant test soil for these devices. The dye Alizarin Red S and micro-computed tomography (μCT) were used to assess the amount and location of bone cement debris in a series of model orthopedic devices. Testing was performed after soiling and cleaning once, and soiling and cleaning 10 times. The color change of the dye after reacting with the bone cement was useful for indicating the presence of bone cement in these models. High-resolution μCT analysis provided the volume and location of the bone cement. Models that were more complex retained significantly more bone debris than simpler designs. Model devices repeatedly soiled and cleaned 10 times retained significantly more bone debris than those soiled and cleaned once. Significantly more bone cement was retained in the more complex lumen structures. This information may be useful in designing reusable orthopedic devices, and other complex medical devices with lumens.

Rey Figure Test with recognition trial: normative data for Lebanese adults.

PubMed

Darwish, Hala; Zeinoun, Pia; Farran, Natali; Fares, Souha

2018-06-12

This study aimed to provide normative data for four trials of the Rey figure Test - a complex design used to assess visuoconstructional abilities, aspects of visual memory, and aspects of executive functioning. Despite its frequent clinical and research use in the Arab region, published studies regarding the measures' adaptation or normative data remain absent. We administered the Rey figure on a convenience sample of Lebanese (n = 254) aged 30 years to 99. We examined the impact of relevant demographics, and found that age, gender, and years of education impacted scores, and norms were derived based on these variables. Such normative data for the Rey figure enhance its practicality and psychometric adequacy for use in research and clinical settings in Lebanon.

Supervising international students in clinical placements: perceptions of experiences and factors influencing competency development.

PubMed

Attrill, Stacie; Lincoln, Michelle; McAllister, Sue

2016-07-16

Health professional education programs attract students from around the world and clinical supervisors frequently report that international students find learning in clinical placement contexts particularly challenging. In existing literature clinical supervisors, who support international students on placement have identified concerns about their communication and interactions within clinical environments. However, clinical supervisors' perspectives about their experiences with international students on placement and the strategies they utilise to facilitate international student learning have not been described. As a result we have little insight into the nature of these concerns and what clinical supervisors do to support international students' competency development. Five focus group interviews were conducted with twenty Speech-Language Pathology clinical supervisors, recruited from 2 Australian universities. Interview data were analysed thematically. Themes identified were interpreted using cognitive load and sociocultural learning theories to enhance understanding of the findings. Four themes were identified: 'Complex teaching and learning relationships', 'Conceptions of students as learners'; Student communication skills for professional practice', and 'Positive mutual learning relationships'. Findings indicated that clinical supervisors felt positive about supporting international students in clinical placements and experienced mutual learning benefits. However, they also identified factors inherent to international students and the placement environment that added to workload, and made facilitating student learning complex. Clinical supervisors described strategies they used to support international students' cultural adjustment and learning, but communication skills were reported to be difficult to facilitate within the constraints of placements. Future research should address the urgent need to develop and test strategies for improving international students' learning in clinical settings.

Pharmacogenetic testing, informed consent and the problem of secondary information.

PubMed

Netzer, Christian; Biller-Andorno, Nikola

2004-08-01

Numerous benefits for patients have been predicted if prescribing decisions were routinely accompanied by pharmacogenetic testing. So far, little attention has been paid to the possibility that the routine application of this new technology could result in considerable harm to patients. This article emphasises that pharmacogenetic testing shares both the opportunities and the pitfalls with 'conventional' disease-genetic testing. It demonstrates that performing pharmacogenetic tests as well as interpreting the results are extraordinarily complex issues requiring a high level of expertise. It further argues that pharmacogenetic testing can have a huge impact on clinical decisions and may influence the therapeutic strategy as well as the clinical monitoring of a patient. This view challenges the predominant paradigm that pharmacogenetic testing will predict patients' responses to medicines, but that it will not provide any other significant disease-specific predictive information about the patient or family members. The article also questions published proposals to reduce the consent procedure for pharmacogenetic testing to a simple statement that the physician wishes to test a sample of the patient's DNA to see if a drug will be safe or whether it will work, and presents an alternative model that is better suited to protect patient's interests and to obtain meaningful informed consent. The paper concludes by outlining conditions for the application of pharmacogenetic testing in clinical practice in a way that can make full use of its potential benefits while minimising possible harm to patients and their families.

Arden Syntax Clinical Foundation Framework for Event Monitoring in Intensive Care Units: Report on a Pilot Study.

PubMed

de Bruin, Jeroen S; Zeckl, Julia; Adlassnig, Katharina; Blacky, Alexander; Koller, Walter; Rappelsberger, Andrea; Adlassnig, Klaus-Peter

2017-01-01

The creation of clinical decision support systems has received a strong impulse over the last years, but their integration into a clinical routine has lagged behind, partly due to a lack of interoperability and trust by physicians. We report on the implementation of a clinical foundation framework in Arden Syntax, comprising knowledge units for (a) preprocessing raw clinical data, (b) the determination of single clinical concepts, and (c) more complex medical knowledge, which can be modeled through the composition and configuration of knowledge units in this framework. Thus, it can be tailored to clinical institutions or patients' caregivers. In the present version, we integrated knowledge units for several infection-related clinical concepts into the framework and developed a clinical event monitoring system over the framework that employs three different scenarios for monitoring clinical signs of bloodstream infection. The clinical event monitoring system was tested using data from intensive care units at Vienna General Hospital, Austria.

The 48-Pictures Test: a two-alternative forced-choice recognition test for the detection of malingering.

PubMed

Chouinard, M J; Rouleau, I

1997-11-01

We tested the validity of the 48-Pictures Test, a 2-alternative forced-choice recognition test, in detecting exaggerated memory impairments. This test maximizes subjective difficulty, through a large number of stimuli and shows minimal objective difficulty. We compared 17 suspected malingerers to 39 patients with memory impairments (6 amnesic, 15 frontal lobe dysfunctions, 18 other etiologies), and 17 normal adults instructed to simulate malingering on three memory tests: the 48-Pictures Test, the Rey Auditory Verbal Learning Test (RAVLT), and the Rey Complex Figure Test (RCFT). On the 48-Pictures Test, the clinical groups showed good recognition performance (amnesics: 85%; frontal dysfunction: 94%; other memory impairments: 97%), whereas the two simulator groups showed a poor performance (suspected malingerers: 62% correct; volunteer simulators 68% correct). The two other tests did not show a high degree of discrimination between the clinical groups and the simulator groups, except in 2 measures: the 2 simulator groups tended to show a performance decrement from the last recall trial to immediate recognition of the RAVLT and also performed better than the clinical groups on the immediate recall of the RCFT. A discriminant analysis with the latter 2 measures and the 48-Pictures Test correctly classified 96% of the participants. These results suggest that the 48-Pictures Test is a useful tool for the detection of possible simulated memory impairment and that when combined to the RAVLT recall-recognition difference score and to the immediate recall score on the RCFT can provide strong evidence of exaggerated memory impairment.

Product-evaluation registry of Meriva®, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis.

PubMed

Belcaro, G; Cesarone, M R; Dugall, M; Pellegrini, L; Ledda, A; Grossi, M G; Togni, S; Appendino, G

2010-06-01

A proprietary complex of curcumin with soy phosphatidylcholine (Meriva®, Indena SpA) was evaluated in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to 200 mg curcumin per diem. OA signs/symptoms were evaluated by the WOMAC scores. Mobility was studied by walking performance (treadmill), and inflammatory status was assessed by measurements of C-reactive protein (CRP). After three months of treatment, the global WOMAC score decreased by 58% (P<0.05), walking distance in the treadmill test was prolonged from 76 m to 332 m (P<0.05), and CRP levels decreased from 168 +/- 18 to 11.3 +/-. 4.1 mg/L in the subpopulation with high CRP. In comparison, the control group experienced only a modest improvement in these parameters (2% in the WOMAC score, from 82 m to 129 m in the treadmill test, and from 175 +/- 12.3 to 112 +/- 22.2 mg/L in the CRP plasma concentration), while the treatment costs (use of anti-inflammatory drugs, treatment and hospitalization) were reduced significantly in the treatment group. These results show that Meriva® is clinically effective in the management and treatment of osteoarthritis and suggest that the increased stability and better absorption of curcumin induced by complexation with phospholipids have clinical relevance, setting the stage for larger and more prolonged studies.

In vitro effects of citrus oils against Mycobacterium tuberculosis and non-tuberculous Mycobacteria of clinical importance.

PubMed

Crandall, Philip G; Ricke, Steven C; O'Bryan, Corliss A; Parrish, Nicole M

2012-01-01

We evaluated the in vitro activity of citrus oils against Mycobacterium tuberculosis and other non-tuberculous Mycobacterium species. Citrus essential oils were tested against a variety of Mycobacterium species and strains using the BACTEC radiometric growth system. Cold pressed terpeneless Valencia oil (CPT) was further tested using the Wayne model of in vitro latency. Exposure of M. tuberculosis and M. bovis BCG to 0.025 % cold pressed terpeneless Valencia orange oil (CPT) resulted in a 3-log decrease in viable counts versus corresponding controls. Inhibition of various clinical isolates of the M. avium complex and M. abscessus ranged from 2.5 to 5.2-logs. Some species/strains were completely inhibited in the presence of CPT including one isolate each of the following: the M. avium complex, M. chelonae and M. avium subsp. paratuberculosis. CPT also inhibited the growth of BCG more than 99 % in an in vitro model of latency which mimics anaerobic dormancy thought to occur in vivo. The activity of CPT against drug-resistant strains of the M. avium complex and M. abscessus suggest that the mechanism of action for CPT is different than that of currently available drugs. Inhibition of latently adapted bacilli offers promise for treatment of latent infections of MTB. These results suggest that the antimycobacterial properties of CPT warrant further study to elucidate the specific mechanism of action and clarify the spectrum of activity.

The relationship between psychological distress and baseline sports-related concussion testing.

PubMed

Bailey, Christopher M; Samples, Hillary L; Broshek, Donna K; Freeman, Jason R; Barth, Jeffrey T

2010-07-01

This study examined the effect of psychological distress on neurocognitive performance measured during baseline concussion testing. Archival data were utilized to examine correlations between personality testing and computerized baseline concussion testing. Significantly correlated personality measures were entered into linear regression analyses, predicting baseline concussion testing performance. Suicidal ideation was examined categorically. Athletes underwent testing and screening at a university athletic training facility. Participants included 47 collegiate football players 17 to 19 years old, the majority of whom were in their first year of college. Participants were administered the Concussion Resolution Index (CRI), an internet-based neurocognitive test designed to monitor and manage both at-risk and concussed athletes. Participants took the Personality Assessment Inventory (PAI), a self-administered inventory designed to measure clinical syndromes, treatment considerations, and interpersonal style. Scales and subscales from the PAI were utilized to determine the influence psychological distress had on the CRI indices: simple reaction time, complex reaction time, and processing speed. Analyses revealed several significant correlations among aspects of somatic concern, depression, anxiety, substance abuse, and suicidal ideation and CRI performance, each with at least a moderate effect. When entered into a linear regression, the block of combined psychological symptoms accounted for a significant amount of baseline CRI performance, with moderate to large effects (r = 0.23-0.30). When examined categorically, participants with suicidal ideation showed significantly slower simple reaction time and complex reaction time, with a similar trend on processing speed. Given the possibility of obscured concussion deficits after injury, implications for premature return to play, and the need to target psychological distress outright, these findings heighten the clinical importance of screening for psychological distress during baseline and post-injury concussion evaluations.

Interim analysis: A rational approach of decision making in clinical trial.

PubMed

Kumar, Amal; Chakraborty, Bhaswat S

2016-01-01

Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

Genetic horoscopes: is it all in the genes? Points for regulatory control of direct-to-consumer genetic testing

PubMed Central

Patch, Christine; Sequeiros, Jorge; Cornel, Martina C

2009-01-01

The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and the appropriate regulatory and policy response. How these concerns are interpreted and addressed is an ongoing debate. If the possibility of using the discoveries from genomic science to improve health is to be realised without losing public confidence, then improvements in the evaluation and mechanisms for control of supply of tests may be as important as the science itself. PMID:19259126

Genetic horoscopes: is it all in the genes? Points for regulatory control of direct-to-consumer genetic testing.

PubMed

Patch, Christine; Sequeiros, Jorge; Cornel, Martina C

2009-07-01

The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and the appropriate regulatory and policy response. How these concerns are interpreted and addressed is an ongoing debate. If the possibility of using the discoveries from genomic science to improve health is to be realised without losing public confidence, then improvements in the evaluation and mechanisms for control of supply of tests may be as important as the science itself.

Development of a Self-Management Theory-Guided Discharge Intervention for Parents of Hospitalized Children.

PubMed

Sawin, Kathleen J; Weiss, Marianne E; Johnson, Norah; Gralton, Karen; Malin, Shelly; Klingbeil, Carol; Lerret, Stacee M; Thompson, Jamie J; Zimmanck, Kim; Kaul, Molly; Schiffman, Rachel F

2017-03-01

Parents of hospitalized children, especially parents of children with complex and chronic health conditions, report not being adequately prepared for self-management of their child's care at home after discharge. No theory-based discharge intervention exists to guide pediatric nurses' preparation of parents for discharge. To develop a theory-based conversation guide to optimize nurses' preparation of parents for discharge and self-management of their child at home following hospitalization. Two frameworks and one method influenced the development of the intervention: the Individual and Family Self-Management Theory, Tanner's Model of Clinical Judgment, and the Teach-Back method. A team of nurse scientists, nursing leaders, nurse administrators, and clinical nurses developed and field tested the electronic version of a nine-domain conversation guide for use in acute care pediatric hospitals. The theory-based intervention operationalized self-management concepts, added components of nursing clinical judgment, and integrated the Teach-Back method. Development of a theory-based intervention, the translation of theoretical knowledge to clinical innovation, is an important step toward testing the effectiveness of the theory in guiding clinical practice. Clinical nurses will establish the practice relevance through future use and refinement of the intervention. © 2017 Sigma Theta Tau International.

Normalization methods in time series of platelet function assays

PubMed Central

Van Poucke, Sven; Zhang, Zhongheng; Roest, Mark; Vukicevic, Milan; Beran, Maud; Lauwereins, Bart; Zheng, Ming-Hua; Henskens, Yvonne; Lancé, Marcus; Marcus, Abraham

2016-01-01

Abstract Platelet function can be quantitatively assessed by specific assays such as light-transmission aggregometry, multiple-electrode aggregometry measuring the response to adenosine diphosphate (ADP), arachidonic acid, collagen, and thrombin-receptor activating peptide and viscoelastic tests such as rotational thromboelastometry (ROTEM). The task of extracting meaningful statistical and clinical information from high-dimensional data spaces in temporal multivariate clinical data represented in multivariate time series is complex. Building insightful visualizations for multivariate time series demands adequate usage of normalization techniques. In this article, various methods for data normalization (z-transformation, range transformation, proportion transformation, and interquartile range) are presented and visualized discussing the most suited approach for platelet function data series. Normalization was calculated per assay (test) for all time points and per time point for all tests. Interquartile range, range transformation, and z-transformation demonstrated the correlation as calculated by the Spearman correlation test, when normalized per assay (test) for all time points. When normalizing per time point for all tests, no correlation could be abstracted from the charts as was the case when using all data as 1 dataset for normalization. PMID:27428217

Disseminated Infection by Mycobacterium sherrisii and Histoplasma capsulatum in an African HIV-Infected Patient

PubMed Central

Taján, Juan; Espasa, Mateu; Sala, Montserrat; Navarro, Marta; Font, Bernat; González-Martín, Julián; Segura, Ferran

2013-01-01

Mycobacterium sherrisii is a new species of opportunistic, slow-growing, non-tuberculous Mycobacterium closely related to Mycobacterium simiae that can currently be identified with the sequence of 16S rARN gene and the heat-shock protein 65. Few cases of patients infected by this Mycobacterium have been reported and all of them were associated with human immunodeficiency virus or other immunosuppressive conditions. Clinical management is complex, because there is not a clear correlation between the in vitro antibiotic susceptibility testing and the patient's clinical outcome. PMID:23419367

[Post-partum posterior reversible encephalopathy syndrome].

PubMed

Aaen, Anne Albers; Jeppesen, Jørgen; Obaid, Hayder; Bülow, Hans Henrik

2015-11-23

Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with vasogenic subcortical oedema caused by hypertension. Oedema is often seen on magnetic resonance imaging. The wide clinical spectrum ranges from headaches to vision loss and even death. Early diagnosis and treatment is important for the reversibility of the condition. In this case report we emphasize the importance of blood pressure control in a post-partum woman, who had a rather complicated pregnancy. The symptoms of PRES were not recognized immediately because of failure to use and acknowledge a blood pressure test.

Clinical Applications for EPs in the ICU.

PubMed

Koenig, Matthew A; Kaplan, Peter W

2015-12-01

In critically ill patients, evoked potential (EP) testing is an important tool for measuring neurologic function, signal transmission, and secondary processing of sensory information in real time. Evoked potential measures conduction along the peripheral and central sensory pathways with longer-latency potentials representing more complex thalamocortical and intracortical processing. In critically ill patients with limited neurologic exams, EP provides a window into brain function and the potential for recovery of consciousness. The most common EP modalities in clinical use in the intensive care unit include somatosensory evoked potentials, brainstem auditory EPs, and cortical event-related potentials. The primary indications for EP in critically ill patients are prognostication in anoxic-ischemic or traumatic coma, monitoring for neurologic improvement or decline, and confirmation of brain death. Somatosensory evoked potentials had become an important prognostic tool for coma recovery, especially in comatose survivors of cardiac arrest. In this population, the bilateral absence of cortical somatosensory evoked potentials has nearly 100% specificity for death or persistent vegetative state. Historically, EP has been regarded as a negative prognostic test, that is, the absence of cortical potentials is associated with poor outcomes while the presence cortical potentials are prognostically indeterminate. In recent studies, the presence of middle-latency and long-latency potentials as well as the amplitude of cortical potentials is more specific for good outcomes. Event-related potentials, particularly mismatch negativity of complex auditory patterns, is emerging as an important positive prognostic test in patients under comatose. Multimodality predictive algorithms that combine somatosensory evoked potentials, event-related potentials, and clinical and radiographic factors are gaining favor for coma prognostication.

Evaluation of Genotypic and Phenotypic Protease Virulence Tests for Dichelobacter nodosus Infection in Sheep

PubMed Central

McPherson, Andrew S.; Dhungyel, Om P.

2017-01-01

ABSTRACT Dichelobacter nodosus is a fastidious, strictly anaerobic bacterium, an obligate parasite of the ruminant hoof, and the essential causative agent of virulent ovine footrot. The clinical disease results from a complex interplay between the pathogen, the environment, and the host. Sheep flocks diagnosed with virulent but not benign footrot in Australia may be quarantined and required to undergo a compulsory eradication program, with costs met by the farmer. Virulence of D. nodosus at least partially depends on the elaboration of a protease encoded by aprV2 and manifests as elastase activity. Laboratory virulence tests are used to assist diagnosis because clinical differentiation of virulent and benign footrot can be challenging during the early stages of disease or when the disease is not fully expressed due to unfavorable pasture conditions. Using samples collected from foot lesions from 960 sheep from 40 flocks in four different geographic regions, we evaluated the analytical characteristics of qPCR tests for the protease gene alleles aprV2 and aprB2, and compared these with results from phenotypic protease (elastase and gelatin gel) tests. There was a low level of agreement between clinical diagnosis and quantitative PCR (qPCR) test outcomes at both the flock and sample levels and poor agreement between qPCR test outcomes and the results of phenotypic virulence tests. The diagnostic specificity of the qPCR test was low at both the flock and individual swab levels (31.3% and 18.8%, respectively). By contrast, agreement between the elastase test and clinical diagnosis was high at both the flock level (diagnostic sensitivity [DSe], 100%; diagnostic specificity [DSp], 78.6%) and the isolate level (DSe, 69.5%; DSp, 80.5%). PMID:28202796

Evaluation of Genotypic and Phenotypic Protease Virulence Tests for Dichelobacter nodosus Infection in Sheep.

PubMed

McPherson, Andrew S; Dhungyel, Om P; Whittington, Richard J

2017-05-01

Dichelobacter nodosus is a fastidious, strictly anaerobic bacterium, an obligate parasite of the ruminant hoof, and the essential causative agent of virulent ovine footrot. The clinical disease results from a complex interplay between the pathogen, the environment, and the host. Sheep flocks diagnosed with virulent but not benign footrot in Australia may be quarantined and required to undergo a compulsory eradication program, with costs met by the farmer. Virulence of D. nodosus at least partially depends on the elaboration of a protease encoded by aprV2 and manifests as elastase activity. Laboratory virulence tests are used to assist diagnosis because clinical differentiation of virulent and benign footrot can be challenging during the early stages of disease or when the disease is not fully expressed due to unfavorable pasture conditions. Using samples collected from foot lesions from 960 sheep from 40 flocks in four different geographic regions, we evaluated the analytical characteristics of qPCR tests for the protease gene alleles aprV2 and aprB2 , and compared these with results from phenotypic protease (elastase and gelatin gel) tests. There was a low level of agreement between clinical diagnosis and quantitative PCR (qPCR) test outcomes at both the flock and sample levels and poor agreement between qPCR test outcomes and the results of phenotypic virulence tests. The diagnostic specificity of the qPCR test was low at both the flock and individual swab levels (31.3% and 18.8%, respectively). By contrast, agreement between the elastase test and clinical diagnosis was high at both the flock level (diagnostic sensitivity [DSe], 100%; diagnostic specificity [DSp], 78.6%) and the isolate level (DSe, 69.5%; DSp, 80.5%). Copyright © 2017 McPherson et al.

Mitochondrial reactive oxygen species and complex II levels are associated with the outcome of hepatocellular carcinoma

PubMed Central

WU, JIANHUA; ZHAO, FEI; ZHAO, YUFEI; GUO, ZHANJUN

2015-01-01

In the present study, two oxidative stress parameters, reactive oxygen species (ROS) and mitochondrial respiratory complex II, were evaluated in the mitochondria of hepatocellular carcinoma (HCC) cells to determine the association between these parameters and the carcinogenesis and clinical outcome of HCC. High levels of ROS and low levels of complex II were found to be associated with reduced post-operative survival in HCC patients using the log-rank test. Furthermore, multivariate analysis confirmed that the levels of ROS [relative risk (RR)=2.867; 95% confidence interval (CI), 1.062–7.737; P=0.038] and complex II (RR=5.422; 95% CI, 1.273–23.088; P=0.022) were independent predictors for the survival of patients with HCC. Therefore, the analysis of ROS and complex II levels may provide a useful research and therapeutic tool for the prediction of HCC prognosis and treatment. PMID:26622849

What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy?

PubMed

de Leon, Jose; Spina, Edoardo

2016-01-01

This editorial considers two questions in psychopharmacotherapy: 1) What is needed to market pharmacogenetic tests in the US, since the US appears to lead other countries? and 2) What is needed for US-marketed pharmacogenetic tests to be incorporated by prescribers into long-term practice? US marketing of pharmacogenetic tests requires 1) understanding the pharmacological complexity of drug response, 2) modifying the oversight of non-FDA regulatory agencies, 3) clarifying the FDA's role and 4) promoting innovative marketing. The incorporation of pharmacogenetic tests into long-term practice requires 1) not jeopardizing pharmacogenetic testing by short-sighted marketing of non-validated tests, 2) educating prescribers about benefits, 3) educating patients about limitations and 4) considering the differences between isolated testing and generalized testing incorporating big data.

Efficacy of an evidence-based clinical decision support in primary care practices: a randomized clinical trial.

PubMed

McGinn, Thomas G; McCullagh, Lauren; Kannry, Joseph; Knaus, Megan; Sofianou, Anastasia; Wisnivesky, Juan P; Mann, Devin M

2013-09-23

There is consensus that incorporating clinical decision support into electronic health records will improve quality of care, contain costs, and reduce overtreatment, but this potential has yet to be demonstrated in clinical trials. To assess the influence of a customized evidence-based clinical decision support tool on the management of respiratory tract infections and on the effectiveness of integrating evidence at the point of care. In a randomized clinical trial, we implemented 2 well-validated integrated clinical prediction rules, namely, the Walsh rule for streptococcal pharyngitis and the Heckerling rule for pneumonia. INTERVENTIONS AND MAIN OUTCOMES AND MEASURES: The intervention group had access to the integrated clinical prediction rule tool and chose whether to complete risk score calculators, order medications, and generate progress notes to assist with complex decision making at the point of care. The intervention group completed the integrated clinical prediction rule tool in 57.5% of visits. Providers in the intervention group were significantly less likely to order antibiotics than the control group (age-adjusted relative risk, 0.74; 95% CI, 0.60-0.92). The absolute risk of the intervention was 9.2%, and the number needed to treat was 10.8. The intervention group was significantly less likely to order rapid streptococcal tests compared with the control group (relative risk, 0.75; 95% CI, 0.58-0.97; P= .03). The integrated clinical prediction rule process for integrating complex evidence-based clinical decision report tools is of relevant importance for national initiatives, such as Meaningful Use. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01386047.

Current Landscape and New Paradigms of Proficiency Testing and External Quality Assessment for Molecular Genetics

PubMed Central

Kalman, Lisa V.; Lubin, Ira M.; Barker, Shannon; du Sart, Desiree; Elles, Rob; Grody, Wayne W.; Pazzagli, Mario; Richards, Sue; Schrijver, Iris; Zehnbauer, Barbara

2015-01-01

Context Participation in proficiency testing (PT) or external quality assessment (EQA) programs allows the assessment and comparison of test performance among different clinical laboratories and technologies. In addition to the approximately 2300 tests for individual genetic disorders, recent advances in technology have enabled the development of clinical tests which quickly and economically analyze the entire human genome. New PT/EQA approaches are needed to ensure the continued quality of these complex tests. Objective To review the availability and scope of PT/EQA for molecular genetic testing for inherited conditions in Europe, Australasia and the United States; to evaluate the successes and demonstrated value of available PT/EQA programs; and to examine the challenges to the provision of comprehensive PT/EQA posed by new laboratory practices and methodologies. Data Sources The available literature on this topic was reviewed and supplemented with personal experiences of several PT/EQA providers. Conclusions PT/EQA schemes are available for common genetic disorders tested in many clinical laboratories, but are not available for most genetic tests offered by only one or a few laboratories. Provision of broad, method-based PT schemes, such as DNA sequencing, would allow assessment of a large number of tests for which formal PT is not currently available. Participation in PT/EQA improves the quality of testing by identifying inaccuracies that laboratories can trace to errors in the testing process. Areas of research and development to ensure that PT/EQA programs can meet the needs of new and evolving genetic tests and technologies are identified and discussed. PMID:23808472

Genetic testing for patients with renal disease: procedures, pitfalls, and ethical considerations.

PubMed

Korf, B R

1999-07-01

The Human Genome Project is rapidly producing insights into the molecular basis of human genetic disorders. The most immediate clinical benefit is the advent of new diagnostic methods. Molecular diagnostic tools are available for several genetic renal disorders and are in development for many more. Two general approaches to molecular diagnosis are linkage-based testing and direct mutation detection. The former is used when the gene has not been cloned but has been mapped in relation to polymorphic loci. Linkage-based testing is also helpful when a large diversity of mutations makes direct detection difficult. Limitations include the need to study multiple family members, the need for informative polymorphisms, and genetic heterogeneity. Direct mutation detection is limited by genetic heterogeneity and the need to distinguish nonpathogenic allelic variants from pathogenic mutations. Molecular testing raises a number of complex ethical issues, including those associated with prenatal or presymptomatic diagnosis. In addition, there are concerns about informed consent, privacy, genetic discrimination, and technology transfer for newly developed tests. Health professionals need to be aware of the technical and ethical implications of these new methods of testing, as well as the complexities in test interpretation, as molecular approaches are increasingly integrated into medical practice.

Mobility Lab to Assess Balance and Gait with Synchronized Body-worn Sensors

PubMed Central

Mancini, Martina; King, Laurie; Salarian, Arash; Holmstrom, Lars; McNames, James; Horak, Fay B

2014-01-01

This paper is a commentary to introduce how rehabilitation professionals can use a new, body-worn sensor system to obtain objective measures of balance and gait. Current assessments of balance and gait in clinical rehabilitation are largely limited to subjective scales, simple stop-watch measures, or complex, expensive machines not practical or largely available. Although accelerometers and gyroscopes have been shown to accurately quantify many aspects of gait and balance kinematics, only recently a comprehensive, portable system has become available for clinicians. By measuring body motion during tests that clinicians are already performing, such as the Timed Up and Go test (TUG) and the Clinical Test of Sensory Integration for Balance (CITSIB), the additional time for assessment is minimal. By providing instant analysis of balance and gait and comparing a patient’s performance to age-matched control values, therapists receive an objective, sensitive screening profile of balance and gait strategies. This motion screening profile can be used to identify mild abnormalities not obvious with traditional clinical testing, measure small changes due to rehabilitation, and design customized rehabilitation programs for each individual’s specific balance and gait deficits. PMID:24955286

High sensitivity and specificity of a new functional flow cytometry assay for clinically significant heparin-induced thrombocytopenia antibodies.

PubMed

Garritsen, H S; Probst-Kepper, M; Legath, N; Eberl, W; Samaniego, S; Woudenberg, J; Schuitemaker, J H N; Kroll, H; Gurney, D A; Moore, G W; Zehnder, J L

2014-04-01

Heparin-induced thrombocytopenia (HIT) is a life-threatening condition, in which the anticoagulant heparin, platelet factor 4 (PF4), and platelet-activating antibodies form complexes with prothrombotic properties. Laboratory tests to support clinical diagnosis are subdivided into functional, platelet activation assays, which lack standardization, or immunological assays, which have moderate specificity toward HIT. In this study, clinical performance of HITAlert, a novel in vitro diagnostic (IVD) registered platelet activation assay, was tested in a large cohort of HIT-suspected patients and compared with immunological assays. From 346 HIT-suspected patients (single center), clinical data including 4T pretest probability results, citrated platelet-poor plasmas, and sera were collected, allowing direct comparison of clinical observations with HITAlert results. HITAlert performance was compared with PF4 IgG ELISA (246 patients, three centers) and PF4 PaGIA (298 patients, single center). HITAlert showed high sensitivity (88.2%) and specificity (99.1%) when compared with clinical diagnosis. Agreement of HITAlert with PF4 ELISA- and PF4 PaGIA-positive patients is low (52.7 and 23.2%, respectively), while agreement with PF4 IgG ELISA- and PF4 PaGIA-negative patients is very high (98.1 and 99.1%, respectively). HITAlert performance is excellent when compared with clinical HIT diagnosis, making it a suitable assay for rapid testing of platelet activation due to anticoagulant therapy. © 2013 John Wiley & Sons Ltd.

Complex patterns of abnormal heartbeats

NASA Technical Reports Server (NTRS)

Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

2002-01-01

Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease: The PReVaiL randomized clinical trial.

PubMed

Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars; Jakobsen, Janus Christian; Zoffmann, Vibeke; Dideriksen, Kasper; Kruse, Anne; Mikkelsen, Ulla Ramer; Wetterslev, Jørn

2016-10-15

To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. Randomized clinical trial. Denmark. A total of 158 adolescents aged 13-16years with no physical activity restrictions after repaired complex congenital heart disease. PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. The primary outcome was maximal oxygen uptake (VO2 peak) at 52weeks after randomization. The secondary outcome was physical activity. Exploratory outcomes were generic and disease-specific questionnaires. In the intervention group, 58 patients (72%) completed the final test, but of those, only 46 (57%) fulfilled the compliance criteria of using the eHealth application for at least 2 consecutive weeks. In the control group, 61 patients (79%) completed both exercise tests. Adjusted for baseline values, the difference between the intervention group and the control group in mean VO2 peak at 1year was -0.65ml·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. Adding a tailored eHealth intervention to health education and individual counseling did not affect outcomes among adolescents with congenital heart disease. Our results do not support the use of this eHealth intervention in adolescents with complex congenital heart disease. Clinical trials.gov identifier: NCT01189981. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society.

PubMed

Sassi, Roberto; Cerutti, Sergio; Lombardi, Federico; Malik, Marek; Huikuri, Heikki V; Peng, Chung-Kang; Schmidt, Georg; Yamamoto, Yoshiharu

2015-09-01

Following the publication of the Task Force document on heart rate variability (HRV) in 1996, a number of articles have been published to describe new HRV methodologies and their application in different physiological and clinical studies. This document presents a critical review of the new methods. A particular attention has been paid to methodologies that have not been reported in the 1996 standardization document but have been more recently tested in sufficiently sized populations. The following methods were considered: Long-range correlation and fractal analysis; Short-term complexity; Entropy and regularity; and Nonlinear dynamical systems and chaotic behaviour. For each of these methods, technical aspects, clinical achievements, and suggestions for clinical application were reviewed. While the novel approaches have contributed in the technical understanding of the signal character of HRV, their success in developing new clinical tools, such as those for the identification of high-risk patients, has been rather limited. Available results obtained in selected populations of patients by specialized laboratories are nevertheless of interest but new prospective studies are needed. The investigation of new parameters, descriptive of the complex regulation mechanisms of heart rate, has to be encouraged because not all information in the HRV signal is captured by traditional methods. The new technologies thus could provide after proper validation, additional physiological, and clinical meaning. Multidisciplinary dialogue and specialized courses in the combination of clinical cardiology and complex signal processing methods seem warranted for further advances in studies of cardiac oscillations and in the understanding normal and abnormal cardiac control processes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Molecular diagnostics of lung cancer in the clinic.

PubMed

Sholl, Lynette

2017-10-01

According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor ( EGFR ) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively. Besides these, a number of other biomarkers are under clinical investigation as predictors of response to targeted therapies, including BRAF , ERBB2 , MET splice mutations and amplification, and RET rearrangements. Successful testing for this complex array of molecular targets demands careful coordination between proceduralists, pathologists and molecular laboratories to ensure proper tumor tissue handling following biopsy as well as judicious use of diagnostic immunohistochemistry. Even so, sample failure rates due to inadequate tumor tissue are high in practice, particularly when using sequential testing methods. Use of next generation sequencing (NGS) in clinical practice can enable detection of multiple targets and multiple alteration types (mutation, gene copy change, and rearrangement) simultaneously even with small amounts of input nucleic acids, thus increasing molecular testing success rates. In patients with an established lung cancer diagnosis but with prohibitively limited amounts of tumor tissue or who are experiencing relapse, analyses of circulating tumor DNA (ctDNA) from the plasma can serve as an alternate testing substrate, however the more limited clinical sensitivity of this approach must be taken into account. This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies.

Molecular diagnostics of lung cancer in the clinic

PubMed Central

2017-01-01

According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively. Besides these, a number of other biomarkers are under clinical investigation as predictors of response to targeted therapies, including BRAF, ERBB2, MET splice mutations and amplification, and RET rearrangements. Successful testing for this complex array of molecular targets demands careful coordination between proceduralists, pathologists and molecular laboratories to ensure proper tumor tissue handling following biopsy as well as judicious use of diagnostic immunohistochemistry. Even so, sample failure rates due to inadequate tumor tissue are high in practice, particularly when using sequential testing methods. Use of next generation sequencing (NGS) in clinical practice can enable detection of multiple targets and multiple alteration types (mutation, gene copy change, and rearrangement) simultaneously even with small amounts of input nucleic acids, thus increasing molecular testing success rates. In patients with an established lung cancer diagnosis but with prohibitively limited amounts of tumor tissue or who are experiencing relapse, analyses of circulating tumor DNA (ctDNA) from the plasma can serve as an alternate testing substrate, however the more limited clinical sensitivity of this approach must be taken into account. This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies. PMID:29114472

Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: a propensity score analysis.

PubMed

Fernández-Ruiz, Mario; Aguado, José María; Almirante, Benito; Lora-Pablos, David; Padilla, Belén; Puig-Asensio, Mireia; Montejo, Miguel; García-Rodríguez, Julio; Pemán, Javier; Ruiz Pérez de Pipaón, Maite; Cuenca-Estrella, Manuel

2014-05-01

Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.

Feasibility of the music therapy assessment tool for awareness in disorders of consciousness (MATADOC) for use with pediatric populations.

PubMed

Magee, Wendy L; Ghetti, Claire M; Moyer, Alvin

2015-01-01

Measuring responsiveness to gain accurate diagnosis in populations with disorders of consciousness (DOC) is of central concern because these patients have such complex clinical presentations. Due to the uncertainty of accuracy for both behavioral and neurophysiological measures in DOC, combined assessment approaches are recommended. A number of standardized behavioral measures can be used with adults with DOC with minor to moderate reservations relating to the measures' psychometric properties and clinical applicability. However, no measures have been standardized for use with pediatric DOC populations. When adapting adult measures for children, confounding factors include developmental considerations for language-based items included in all DOC measures. Given the lack of pediatric DOC measures, there is a pressing need for measures that are sensitive to the complex clinical presentations typical of DOC and that can accommodate the developmental levels of pediatric populations. The music therapy assessment tool for awareness in disorders of consciousness (MATADOC) is a music-based measure that has been standardized for adults with DOC. Given its emphasis on non-language based sensory stimuli, it is well-suited to pediatric populations spanning developmental stages. In a pre-pilot exploratory study, we examined the clinical utility of this measure and explored trends for test-retest and inter-rater agreement as well as its performance against external reference standards. In several cases, MATADOC items in the visual and auditory domains produced outcomes suggestive of higher level functioning when compared to outcomes provided by other DOC measures. Preliminary findings suggest that the MATADOC provides a useful protocol and measure for behavioral assessment and clinical treatment planning with pediatric DOC. Further research with a larger sample is warranted to test a version of the MATADOC that is refined to meet developmental needs of pediatric DOC populations.

Developing integrated clinical reasoning competencies in dental students using scaffolded case-based learning - empirical evidence.

PubMed

Postma, T C; White, J G

2016-08-01

This study provides empirical evidence of the development of integrated clinical reasoning in the discipline-based School of Dentistry, University of Pretoria, South Africa. Students were exposed to case-based learning in comprehensive patient care (CPC) in the preclinical year of study, scaffolded by means of the four-component instructional design model for complex learning. Progress test scores of third- to fifth-year dental students, who received case-based teaching and learning in the third year (2009-2011), were compared to the scores of preceding fourth- and fifth-year cohorts. These fourth- and fifth-year cohorts received content-based teaching concurrently with their clinical training in CPC. The progress test consisted of a complex case study and 32 MCQs on tracer conditions. Students had to gather the necessary information and had to make diagnostic and treatment-planning decisions. Preclinical students who participated in the case-based teaching and learning achieved similar scores compared to final-year students who received lecture-based teaching and learning. Final-year students who participated in the case-based learning made three more correct clinical decisions per student, compared to those who received content-based teaching. Students struggled more with treatment-planning than with diagnostic decisions. The scaffolded case-based learning appears to contribute to accurate clinical decisions when compared to lecture-based teaching. It is suggested that the development of integrated reasoning competencies starts as early as possible in a dental curriculum, perhaps even in the preclinical year of study. Treatment-planning should receive particular attention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Feasibility of the music therapy assessment tool for awareness in disorders of consciousness (MATADOC) for use with pediatric populations

PubMed Central

Magee, Wendy L.; Ghetti, Claire M.; Moyer, Alvin

2015-01-01

Measuring responsiveness to gain accurate diagnosis in populations with disorders of consciousness (DOC) is of central concern because these patients have such complex clinical presentations. Due to the uncertainty of accuracy for both behavioral and neurophysiological measures in DOC, combined assessment approaches are recommended. A number of standardized behavioral measures can be used with adults with DOC with minor to moderate reservations relating to the measures’ psychometric properties and clinical applicability. However, no measures have been standardized for use with pediatric DOC populations. When adapting adult measures for children, confounding factors include developmental considerations for language-based items included in all DOC measures. Given the lack of pediatric DOC measures, there is a pressing need for measures that are sensitive to the complex clinical presentations typical of DOC and that can accommodate the developmental levels of pediatric populations. The music therapy assessment tool for awareness in disorders of consciousness (MATADOC) is a music-based measure that has been standardized for adults with DOC. Given its emphasis on non-language based sensory stimuli, it is well-suited to pediatric populations spanning developmental stages. In a pre-pilot exploratory study, we examined the clinical utility of this measure and explored trends for test-retest and inter-rater agreement as well as its performance against external reference standards. In several cases, MATADOC items in the visual and auditory domains produced outcomes suggestive of higher level functioning when compared to outcomes provided by other DOC measures. Preliminary findings suggest that the MATADOC provides a useful protocol and measure for behavioral assessment and clinical treatment planning with pediatric DOC. Further research with a larger sample is warranted to test a version of the MATADOC that is refined to meet developmental needs of pediatric DOC populations. PMID:26074850

Developing a case mix classification for child and adolescent mental health services: the influence of presenting problems, complexity factors and service providers on number of appointments.

PubMed

Martin, Peter; Davies, Roger; Macdougall, Amy; Ritchie, Benjamin; Vostanis, Panos; Whale, Andy; Wolpert, Miranda

2017-09-01

Case-mix classification is a focus of international attention in considering how best to manage and fund services, by providing a basis for fairer comparison of resource utilization. Yet there is little evidence of the best ways to establish case mix for child and adolescent mental health services (CAMHS). To develop a case mix classification for CAMHS that is clinically meaningful and predictive of number of appointments attended and to investigate the influence of presenting problems, context and complexity factors and provider variation. We analysed 4573 completed episodes of outpatient care from 11 English CAMHS. Cluster analysis, regression trees and a conceptual classification based on clinical best practice guidelines were compared regarding their ability to predict number of appointments, using mixed effects negative binomial regression. The conceptual classification is clinically meaningful and did as well as data-driven classifications in accounting for number of appointments. There was little evidence for effects of complexity or context factors, with the possible exception of school attendance problems. Substantial variation in resource provision between providers was not explained well by case mix. The conceptually-derived classification merits further testing and development in the context of collaborative decision making.

[Pilot tests using molecular diagnostic assay cervicovaginal infection during pregnancy].

PubMed

Beltrán-Montoya, J; Escudero-Gontes, S; Martínez-Huerta, N E; Ávila-Vergara, M A; Morales-Hernández, V; Canchola-Sotelo, C; Palacios-González, B; Vadillo-Ortega, F

2016-08-01

The prevalence of cervicovaginal infections during pregnancy has been associated with adverse perinatal outcomes however, the actual approach used for diagnosis is not effective. The aim of this study was to compare the diagnosis of vaginal infections in pregnant women using clinical, molecular diagnostic and traditional microbiological culture in a pilot study, to determine the prevalence and association with the development of preterm labor. We performed a nested cross-sectional study composed by 54 women in a cohort of pregnant women in Mexico City. Cervicovaginal infections were evaluated by clinical methods, microbiology culture and a commercially available molecular biology test. Prevalence of cervicovaginal infections during pregnancy was estimated between 28% and 50% according to methodologies. Considering the clinical diagnosis of preterm labor as the gold standard, all diagnostic tests were poor as predictors of preterm labor. Traditional approaches to establish the significance of cervicovaginal infection in pregnancy are exhausted, so be sought new ways to understand this complex relationship. Meanwhile it is recommended to continue to use traditional methods to identify infections during pregnancy in both knowledge of new methods aimed at understanding these relationships are sophisticated.

Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene.

PubMed

Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena

2018-02-01

Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for molecular genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation event combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.

Genetics, Genomics and Cancer Risk Assessment: State of the art and future directions in the era of personalized medicine

PubMed Central

Weitzel, Jeffrey N.; Blazer, Kathleen R.; MacDonald, Deborah J.; Culver, Julie O.; Offit, Kenneth

2012-01-01

Scientific and technologic advances are revolutionizing our approach to genetic cancer risk assessment, cancer screening and prevention, and targeted therapy, fulfilling the promise of personalized medicine. In this monograph we review the evolution of scientific discovery in cancer genetics and genomics, and describe current approaches, benefits and barriers to the translation of this information to the practice of preventive medicine. Summaries of known hereditary cancer syndromes and highly penetrant genes are provided and contrasted with recently-discovered genomic variants associated with modest increases in cancer risk. We describe the scope of knowledge, tools, and expertise required for the translation of complex genetic and genomic test information into clinical practice. The challenges of genomic counseling include the need for genetics and genomics professional education and multidisciplinary team training, the need for evidence-based information regarding the clinical utility of testing for genomic variants, the potential dangers posed by premature marketing of first-generation genomic profiles, and the need for new clinical models to improve access to and responsible communication of complex disease-risk information. We conclude that given the experiences and lessons learned in the genetics era, the multidisciplinary model of genetic cancer risk assessment and management will serve as a solid foundation to support the integration of personalized genomic information into the practice of cancer medicine. PMID:21858794

Composite Configuration Interventional Therapy Robot for the Microwave Ablation of Liver Tumors

NASA Astrophysics Data System (ADS)

Cao, Ying-Yu; Xue, Long; Qi, Bo-Jin; Jiang, Li-Pei; Deng, Shuang-Cheng; Liang, Ping; Liu, Jia

2017-11-01

The existing interventional therapy robots for the microwave ablation of liver tumors have a poor clinical applicability with a large volume, low positioning speed and complex automatic navigation control. To solve above problems, a composite configuration interventional therapy robot with passive and active joints is developed. The design of composite configuration reduces the size of the robot under the premise of a wide range of movement, and the robot with composite configuration can realizes rapid positioning with operation safety. The cumulative error of positioning is eliminated and the control complexity is reduced by decoupling active parts. The navigation algorithms for the robot are proposed based on solution of the inverse kinematics and geometric analysis. A simulation clinical test method is designed for the robot, and the functions of the robot and the navigation algorithms are verified by the test method. The mean error of navigation is 1.488 mm and the maximum error is 2.056 mm, and the positioning time for the ablation needle is in 10 s. The experimental results show that the designed robot can meet the clinical requirements for the microwave ablation of liver tumors. The composite configuration is proposed in development of the interventional therapy robot for the microwave ablation of liver tumors, which provides a new idea for the structural design of medical robots.

Company Profile: GenesFX Health Pty Ltd.

PubMed

Sheffield, Leslie J; Rogers, Edith

2011-07-01

GenesFX Health (Melbourne, Australia) is providing genetic testing with clinical interpretation to personalize how people take medications. The company's aim is to achieve the best health outcomes for patients by ensuring that the way they metabolize medications is included when doctors prescribe them medication. This would be achieved by introducing pharmacogenomics into medical practice to provide more informed prescribing, reduce side effects and create maximum efficacy of medications. Through the use of GenesFX Health innovative genetic test, DNAdose ® , GenesFX Health is able to analyze the profile of a patient's genetic variation and maps this to the optimum drug and dosage for a specific treatment. The company's focus on the interpretation of genetic test results has led to the development of a Pharmacogenomic Database and Pharmacogenomic Interpretation System, which allows the team to communicate complex genetic test results in a meaningful way to doctors. There is a significant opportunity to expand GenesFX Health current model of delivering pharmacogenomic tests, by partnering with other laboratories around the world, making pharmacogenomics more accessible and clinically useful. Doctors using the service have welcomed the clinical guidance. Patients have felt relieved and empowered by understanding why they have adverse reactions to medications, and which medications and doses are most suited to them.

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.

Joint stability characteristics of the ankle complex in female athletes with histories of lateral ankle sprain, part II: clinical experience using arthrometric measurement.

PubMed

Kovaleski, John E; Heitman, Robert J; Gurchiek, Larry R; Hollis, J M; Liu, Wei; Pearsall, Albert W

2014-01-01

This is part II of a 2-part series discussing stability characteristics of the ankle complex. In part I, we used a cadaver model to examine the effects of sectioning the lateral ankle ligaments on anterior and inversion motion and stiffness of the ankle complex. In part II, we wanted to build on and apply these findings to the clinical assessment of ankle-complex motion and stiffness in a group of athletes with a history of unilateral ankle sprain. To examine ankle-complex motion and stiffness in a group of athletes with reported history of lateral ankle sprain. Cross-sectional study. University research laboratory. Twenty-five female college athletes (age = 19.4 ± 1.4 years, height = 170.2 ± 7.4 cm, mass = 67.3 ± 10.0 kg) with histories of unilateral ankle sprain. All ankles underwent loading with an ankle arthrometer. Ankles were tested bilaterally. The dependent variables were anterior displacement, anterior end-range stiffness, inversion rotation, and inversion end-range stiffness. Anterior displacement of the ankle complex did not differ between the uninjured and sprained ankles (P = .37), whereas ankle-complex rotation was greater for the sprained ankles (P = .03). The sprained ankles had less anterior and inversion end-range stiffness than the uninjured ankles (P < .01). Changes in ankle-complex laxity and end-range stiffness were detected in ankles with histories of sprain. These results indicate the presence of altered mechanical characteristics in the soft tissues of the sprained ankles.

The Association of Clinic-Based Mobility Tasks and Measures of Community Performance and Risk.

PubMed

Callisaya, Michele L; Verghese, Joe

2018-01-10

Gait speed is recognized as an important predictor of adverse outcomes in older people. However, it is unknown whether other more complex mobility tasks are better predictors of such outcomes. To examine a range of clinic-based mobility tests and determine which were most strongly associated with measures of community performance and risk (CP&R). Cross-sectional study. Central Control Mobility and Aging Study, Westchester County, New York. Aged ≥65 years (n = 424). Clinic-based mobility measures included gait speed measured during normal and dual-task conditions, the Floor Maze Immediate and Delay tasks, and stair ascending and descending. CP&R measures were self-reported by the use of standardized questionnaires and classified into measures of performance (distance walked, travel outside one's home [life space], activities of daily living, and participation in cognitive leisure activities) or risk (balance confidence, fear of falling, and past falls). Linear and logistic regression were used to examine associations between the clinic-based mobility measures and CP&R measures adjusting for covariates. The mean age of the sample was 77.8 (SD 6.4) years, and 55.2% (n = 234) were female. In final models, faster normal walking speed was most strongly associated with 5 of the 7 community measures (greater distance walked, greater life space, better activities of daily living function, higher balance confidence, and less fear of falling; all P < .05). More complex tasks (walking while talking and maze immediate) were associated with cognitive leisure activity (P < .05), and ascending stairs was the only measure associated with a history of falls (P < .05). Normal walking speed is a simple and inexpensive clinic-based mobility test that is associated with a wide range of CP&R measures. In addition, poorer performance ascending stairs may assist in identifying those at risk of falls. Poorer performance in more complex mobility tasks (walking while talking and maze immediate) may suggest inability to participate in cognitive leisure activities. III. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios.

PubMed

Esteves, Sandro C; Agarwal, Ashok; Cho, Chak-Lam; Majzoub, Ahmad

2017-09-01

Sperm DNA fragmentation (SDF) is recognized as a leading cause of male infertility because it can impair the paternal genome through distinct pathophysiological mechanisms. Current evidence supports SDF as a major factor in the pathophysiology of several conditions, including varicocele, unexplained infertility, assisted reproductive technology failure, and environmental lifestyle factors, although the mechanisms involved have not been fully described yet. Measurement of the levels of DNA fragmentation in semen provides valuable information on the integrity of paternal chromatin and may guide therapeutic strategies. A recently published clinical practice guideline (CPG) highlighted how to use the information provided by SDF testing in daily practice, which triggered a series of commentaries by leading infertility experts. These commentaries contained an abundance of information and conflicting views about the clinical utility of SDF testing, which underline the complex nature of SDF. A search of papers published in response to the CPG entitled "Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios" was performed within the Translational Andrology and Urology ( TAU ) website (http://tau.amegroups.com/). The start and end dates for the search were May 2017 and August 2017, respectively. Each commentary meeting our inclusion criteria was rated as "supportive without reservation", "supportive with reservation", "not supportive" or "neutral". We recorded whether articles discussed either SDF characteristics as a laboratory test method or clinical scenarios, or both. Subsequently, we extracted the particulars from each commentary and utilized the 'Strengths-Weaknesses-Opportunities-Threats' (SWOT) analysis to understand the perceived advantages and drawbacks of SDF as a specialized sperm function method in clinical practice. Fifty-eight fertility experts from six continents and twenty-two countries contributed commentaries. Overall, participants (87.9%; n=51) were supportive of the recommendations provided by the CPG on the utility of SDF testing based on clinical scenarios. The majority of participants made explicit remarks about both the clinical scenarios and SDF assays' characteristics. Among 'not supportive' and 'supportive with reservation' participants, 75% (n=30/40) and 77.5% (n=31/40) expressed concerns related to technical limitations of SDF testing methods and clinical utility of the test in one or more clinical scenarios discussed in the CPG, respectively. The SWOT analysis revealed that the CPG provides a reasonable evidence-based proposal for integration of SDF testing in the routine daily practice. It also uncovered gaps of knowledge and threats limiting the widespread application of SDF in everyday practice, thus allowing the identification of opportunities to further refine SDF testing and its clinical utility. The understanding of the role of SDF in male infertility requires an in-depth analysis of the multifactorial pathophysiological processes and the theories involved. The SWOT analysis allowed an objective evaluation of CPG on the clinical utility of SDF testing based on clinical scenarios and its accompanying commentaries written by global experts in all possible angles. Implementation of SDF testing in the clinic may not only increase the outcome of ART but more importantly improve the health of both fathers to be and resulting offspring.

The objective structured clinical examination revisited for postgraduate trainees in general practice.

PubMed

Schoenmakers, Birgitte; Wens, Johan

2014-03-04

To investigate if the psychometric qualities of an OSCE consisting of more complex simulated patient encounters remain valid and reliable in the assessment of postgraduate trainees in general practice. In this intervention study without control group, the traditional OSCE was formally replaced by the new, complex version. The study population was composed by all postgraduate trainees (second and third phase) in general practice during the ongoing academic year. Data were handled and collected as part of the formal assessment program. Univariate analyses, the variance of scores and multivariate analyses were performed to assess the test qualities. A total of 340 students participated. Average final scores were slightly higher for third-phase students (t-test, p =0.05). Overall test scores were equally distributed on station level, circuit level and phase level. A multiple regression analysis revealed that test scores were dependent on the stations and circuits, but not on the master phase. In a changing learning environment, assessment and evaluation strategies require reorientation. The reliability and validity of the OSCE remain subject to discussion. In particular, when it comes to content and design, the traditional OSCE might underestimate the performance level of postgraduate trainees in general practice. A reshaping of this OSCE to a more sophisticated design with more complex patient encounters appears to restore the validity of the test results.

Influence of cognitive function on quality of life in anorexia nervosa patients.

PubMed

Hamatani, Sayo; Tomotake, Masahito; Takeda, Tomoya; Kameoka, Naomi; Kawabata, Masashi; Kubo, Hiroko; Tada, Yukio; Tomioka, Yukiko; Watanabe, Shinya; Inoshita, Masatoshi; Kinoshita, Makoto; Ohta, Masashi; Ohmori, Tetsuro

2017-05-01

The purpose of this study was to elucidate determinants of quality of life (QOL) in anorexia nervosa (AN) patients. Twenty-one female patients with AN participated in the study. QOL was assessed with the 36-Item Short Form Health Survey (SF-36), and cognitive function was evaluated using the Wisconsin Card Sorting Test Keio version, the Rey Complex Figure Test, and the Social Cognition Screening Questionnaire. Clinical symptoms were evaluated with the Beck Depression Inventory-II, the State-Trait Anxiety Inventory-Form JYZ (STAI-JYZ), and the Maudsley Obsessive Compulsive Inventory. The Difficulty Maintaining Set score of the Wisconsin Card Sorting Test Keio version was negatively correlated to the SF-36 Physical Component Summary. Scores of the Beck Depression Inventory-II and the STAI-JYZ State and Trait were negatively correlated to the SF-36 Mental Component Summary (MCS), and the Central Coherence Index 30-min Delayed Recall score of the Rey Complex Figure Test was positively correlated with the MCS. Stepwise regression analysis showed that the Difficulty Maintaining Set score was an independent predictor of the Physical Component Summary and scores for Central Coherence Index 30-min Delayed Recall and the STAI-JYZ Trait-predicted MCS. These results suggest that not only trait anxiety but also poor central coherence and impaired ability to maintain new rule worsen AN patients' QOL. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

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.

Overcoming regulatory and economic challenges facing pharmacogenomics.

PubMed

Cohen, Joshua P

2012-09-15

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of a novel, multilayered presentation format for clinical practice guidelines.

PubMed

Kristiansen, Annette; Brandt, Linn; Alonso-Coello, Pablo; Agoritsas, Thomas; Akl, Elie A; Conboy, Tara; Elbarbary, Mahmoud; Ferwana, Mazen; Medani, Wedad; Murad, Mohammad Hassan; Rigau, David; Rosenbaum, Sarah; Spencer, Frederick A; Treweek, Shaun; Guyatt, Gordon; Vandvik, Per Olav

2015-03-01

Bridging the gap between clinical research and everyday health-care practice requires effective communication strategies. To address current shortcomings in conveying practice recommendations and supporting evidence, we are creating and testing presentation formats for clinical practice guidelines (CPGs). We carried out multiple cycles of brainstorming and sketching, developing a prototype. Physicians participating in the user testing viewed CPG formats linked to clinical scenarios and engaged in semistructured interviews applying a think-aloud method for exploring important aspects of user experience. We developed a multilayered presentation format that allows clinicians to successively view more in-depth information. Starting with the recommendations, clinicians can, on demand, access a rationale and a key information section containing statements on quality of the evidence, balance between desirable and undesirable consequences, values and preferences, and resource considerations. We collected feedback from 27 stakeholders and performed user testing with 47 practicing physicians from six countries. Advisory group feedback and user testing of the first version revealed problems with conceptual understanding of underlying CPG methodology, as well as difficulties with the complexity of the layout and content. Extensive revisions made before the second round of user testing resulted in most participants expressing overall satisfaction with the final presentation format. We have developed an electronic, multilayered, CPG format that enhances the usability of CPGs for frontline clinicians. We have implemented the format in electronic guideline tools that guideline organizations can now use when authoring and publishing their guidelines.

Simplifying the complexity surrounding ICU work processes--identifying the scope for information management in ICU settings.

PubMed

Munir, Samina K; Kay, Stephen

2005-08-01

A multi-site study, conducted in two English and two Danish intensive care units, investigates the complexity of work processes in intensive care, and the implications of this complexity for information management with regards to clinical information systems. Data were collected via observations, shadowing of clinical staff, interviews and questionnaires. The construction of role activity diagrams enabled the capture of critical care work processes. Upon analysing these diagrams, it was found that intensive care work processes consist of 'simplified-complexity', these processes are changed with the introduction of information systems for the everyday use and management of all clinical information. The prevailing notion of complexity surrounding critical care clinical work processes was refuted and found to be misleading; in reality, it is not the work processes that cause the complexity, the complexity is rooted in the way in which clinical information is used and managed. This study emphasises that the potential for clinical information systems that consider integrating all clinical information requirements is not only immense but also very plausible.

A Pilot Study to Evaluate Effectiveness of INR Self-Testing in Elderly Patients.

PubMed

Pogge, Elizabeth

2015-12-01

To determine if international normalized ratio (INR) patient self-testing (PST) resulted in an increased time in therapeutic range (TTR) in an elderly population when compared with clinic testing over a six-month period. A pilot study and retrospective chart review from August 2010 to August 2014. Ambulatory, anticoagulation clinic with two locations in Sun City West and Peoria, Arizona. Of 91 patients, the data of 20 patients who were 65 years of age or older and had at least six months of pre- and post-PST INR data were extracted and analyzed. The primary outcome evaluated improvement of TTR during post-PST in elderly patients compared with clinic management over a six-month period. Secondary outcomes assessed patients' satisfaction with PST and identified barriers to PST. The post-PST mean TTR significantly increased to 73% from 63.6% for the first six months of PST (P = 0.04). Participants were satisfied with PST, with an average score ranging from 4.6 to 5 on a Likert scale of 1 to 5 on 10 satisfaction survey questions. Cost was identified as the most common barrier to PST, with 43% of patients not participating in PST because of financial burden. With appropriate screening and training, PST is associated with improved TTRs and higher patient satisfaction in elderly patients when compared with clinic testing. Barriers identified to PST include cost, the complex process, and noncompliance.

A highly stable l-alanine-based mono(aquated) Mn(ii) complex as a T1-weighted MRI contrast agent.

PubMed

Khannam, Mahmuda; Weyhermüller, Thomas; Goswami, Upashi; Mukherjee, Chandan

2017-08-08

The synthesized lithium (S)-6,6'-(1-carboxyethylazanediyl)bis(methylene)dipicolinate (Li 3 cbda) is a new chiral, alanine-based ligand bearing two picolinate functionalities. The trianionic form of the ligand [(cbda) 3- ] constitutes a seven-coordinate, water-soluble, pentagonal bipyramidal Mn(ii) complex (1). The structural analysis reveals the presence of a water coordinating site in the complex. The complex is thermodynamically very stable, and the stability is not affected by the presence of physiological anions (HCO 3 - , PO 4 3- , and F - ). The pH of the medium exerts a small effect on the stability of the complex. The r 1 relaxivity of 3.02 mM -1 s -1 is exhibited by the complex at 1.41 T, pH ∼7.4, and 25 °C. Phantom images obtained via a clinical MRI BRIVO MR355 system established concentration-dependent signal enhancement by the complex. The cytotoxicity test confirmed complex 1 as a biocompatible potential T 1 -weighted MRI contrast agent.

Enhanced visual performance in obsessive compulsive personality disorder.

PubMed

Ansari, Zohreh; Fadardi, Javad Salehi

2016-12-01

Visual performance is considered as commanding modality in human perception. We tested whether Obsessive-compulsive personality disorder (OCPD) people do differently in visual performance tasks than people without OCPD. One hundred ten students of Ferdowsi University of Mashhad and non-student participants were tested by Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II), among whom 18 (mean age = 29.55; SD = 5.26; 84% female) met the criteria for OCPD classification; controls were 20 persons (mean age = 27.85; SD = 5.26; female = 84%), who did not met the OCPD criteria. Both groups were tested on a modified Flicker task for two dimensions of visual performance (i.e., visual acuity: detecting the location of change, complexity, and size; and visual contrast sensitivity). The OCPD group had responded more accurately on pairs related to size, complexity, and contrast, but spent more time to detect a change on pairs related to complexity and contrast. The OCPD individuals seem to have more accurate visual performance than non-OCPD controls. The findings support the relationship between personality characteristics and visual performance within the framework of top-down processing model. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Pre- and postoperative evaluation of patients with lumbosacral disc herniation by neurophysiological and clinical assessment.

PubMed

Wojtysiak, Magdalena; Huber, Juliusz; Wiertel-Krawczuk, Agnieszka; Szymankiewicz-Szukała, Agnieszka; Moskal, Jakub; Janicki, Jacek

2014-10-01

The application of complex neurophysiological examination including motor evoked potentials (MEP) for pre- and postoperative evaluation of patients experiencing acute sciatica. The assessment of sensitivity and specificity of needle electromyography, MEP, and H-reflex examinations. The comparative analysis of preoperative and postoperative neurophysiological examination. In spite of the fact that complex neurophysiological diagnostic tools seem to be important for interpretation of incompatible results of neuroimaging and clinical examination, especially in the patients qualified for surgical treatment, their application has never been completely analyzed and documented. Pre- and postoperative electromyography, electroneurography, F-waves, H-reflex, and MEP examination were performed in 23 patients with confirmed disc-root conflict at lumbosacral spine. Clinical evaluation included examination of sensory perception for L5-S1 dermatomes, muscles strength with Lovett's scale, deep tendon reflexes, pain intensity with visual analogue scale, and straight leg raising test. Sensitivity of electromyography at rest and MEP examination for evaluation of L5-S1 roots injury was 22% to 63% and 31% to 56% whereas specificity was 71% to 83% and 57% to 86%, respectively. H-reflex sensitivity and specificity for evaluation of S1 root injury were 56% and 67%, respectively. A significant improvement of root latency parameter in postoperative MEP studies as compared with preoperative was recorded for L5 (P = 0.039) and S1 root's levels (P = 0.05). The analysis of the results from neurophysiological tests together with neuroimaging and clinical examination allow for a precise preoperative indication of the lumbosacral roots injury and accurate postoperative evaluation of patients experiencing sciatica. 3.

Dyspepsia treatment with Al compounds widely used in clinical practice — an animal model approach

NASA Astrophysics Data System (ADS)

Pinheiro, T.; Canena, J.; Reis, J.; Santos, A. M.; Pinto, A. S.; Quina, M. G.; Reis, M. A.; Alves, L. C.

1996-04-01

The potential toxic effects of Al to organs and tissues used in drugs commonly applied in dyspepsia as therapeutic, have been studied. Brain, liver, kidney and serum samples obtained from Wistar rats treated with two commercial Al complexes were studied and compared with equivalent samples collected from healthy animals receiving a placebo. The major alterations found, connected with the persistent intake of medicaments based on Al compounds, are relative to the accumulation of Al in liver and kidney. Also, the Al levels increase in brain and serum of rats supplemented with one of the Al complexes used. In the liver and kidney samples analyzed alterations in the Cu and Zn content levels were observed. Furthermore, a tendency to the decrease of Fe content in kidney and an increase of the Mn levels in brain is observed. The elemental alterations found are probably related to the intake of the drugs tested and are dependent on the type of the Al complex administered. The results obtained suggest that the long term use of these medicaments in the clinical practice should be thought over.

Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer's disease.

PubMed

Hirni, Daniela I; Kivisaari, Sasa L; Monsch, Andreas U; Taylor, Kirsten I

2013-04-01

Alzheimer's disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transforming clinical microbiology with bacterial genome sequencing.

PubMed

Didelot, Xavier; Bowden, Rory; Wilson, Daniel J; Peto, Tim E A; Crook, Derrick W

2012-09-01

Whole-genome sequencing of bacteria has recently emerged as a cost-effective and convenient approach for addressing many microbiological questions. Here, we review the current status of clinical microbiology and how it has already begun to be transformed by using next-generation sequencing. We focus on three essential tasks: identifying the species of an isolate, testing its properties, such as resistance to antibiotics and virulence, and monitoring the emergence and spread of bacterial pathogens. We predict that the application of next-generation sequencing will soon be sufficiently fast, accurate and cheap to be used in routine clinical microbiology practice, where it could replace many complex current techniques with a single, more efficient workflow.

Transforming clinical microbiology with bacterial genome sequencing

PubMed Central

2016-01-01

Whole genome sequencing of bacteria has recently emerged as a cost-effective and convenient approach for addressing many microbiological questions. Here we review the current status of clinical microbiology and how it has already begun to be transformed by the use of next-generation sequencing. We focus on three essential tasks: identifying the species of an isolate, testing its properties such as resistance to antibiotics and virulence, and monitoring the emergence and spread of bacterial pathogens. The application of next-generation sequencing will soon be sufficiently fast, accurate and cheap to be used in routine clinical microbiology practice, where it could replace many complex current techniques with a single, more efficient workflow. PMID:22868263

Current methodological issues in the economic assessment of personalized medicine.

PubMed

Annemans, Lieven; Redekop, Ken; Payne, Katherine

2013-01-01

There is a need for methodological scrutiny in the economic assessment of personalized medicine. In this article, we present a list of 10 specific issues that we argue pose specific methodological challenges that require careful consideration when designing and conducting robust model-based economic evaluations in the context of personalized medicine. Key issues are related to the correct framing of the research question, interpretation of test results, data collection of medical management options after obtaining test results, and expressing the value of tests. The need to formulate the research question clearly and be explicit and specific about the technology being evaluated is essential because various test kits can have the same purpose and yet differ in predictive value, costs, and relevance to practice and patient populations. The correct reporting of sensitivity/specificity, and especially the false negatives and false positives (which are population dependent), of the investigated tests is also considered as a key element. This requires additional structural complexity to establish the relationship between the test result and the consecutive treatment changes and outcomes. This process involves translating the test characteristics into clinical utility, and therefore outlining the clinical and economic consequences of true and false positives and true and false negatives. Information on treatment patterns and on their costs and outcomes, however, is often lacking, especially for false-positive and false-negative test results. The analysis can even become very complex if different tests are combined or sequentially used. This potential complexity can be handled by explicitly showing how these tests are going to be used in practice and then working with the combined sensitivities and specificities of the tests. Each of these issues leads to a higher degree of uncertainty in economic models designed to assess the added value of personalized medicine compared with their simple pharmaceutical counterparts. To some extent, these problems can be overcome by performing early population-level simulations, which can lead to the identification and collection of data on critical input parameters. Finally, it is important to understand that a test strategy does not necessarily lead to more quality-adjusted life-years (QALYs). It is possible that the test will lead to not only fewer QALYs but also fewer costs, which can be defined as "decremental" cost per QALYs. Different decision criteria are needed to interpret such results. © 2013 Published by Elsevier Inc. on behalf of International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

The geometric preference subtype in ASD: identifying a consistent, early-emerging phenomenon through eye tracking.

PubMed

Moore, Adrienne; Wozniak, Madeline; Yousef, Andrew; Barnes, Cindy Carter; Cha, Debra; Courchesne, Eric; Pierce, Karen

2018-01-01

The wide range of ability and disability in ASD creates a need for tools that parse the phenotypic heterogeneity into meaningful subtypes. Using eye tracking, our past studies revealed that when presented with social and geometric images, a subset of ASD toddlers preferred viewing geometric images, and these toddlers also had greater symptom severity than ASD toddlers with greater social attention. This study tests whether this "GeoPref test" effect would generalize across different social stimuli. Two hundred and twenty-seven toddlers (76 ASD) watched a 90-s video, the Complex Social GeoPref test, of dynamic geometric images paired with social images of children interacting and moving. Proportion of visual fixation time and number of saccades per second to both images were calculated. To allow for cross-paradigm comparisons, a subset of 126 toddlers also participated in the original GeoPref test. Measures of cognitive and social functioning (MSEL, ADOS, VABS) were collected and related to eye tracking data. To examine utility as a diagnostic indicator to detect ASD toddlers, validation statistics (e.g., sensitivity, specificity, ROC, AUC) were calculated for the Complex Social GeoPref test alone and when combined with the original GeoPref test. ASD toddlers spent a significantly greater amount of time viewing geometric images than any other diagnostic group. Fixation patterns from ASD toddlers who participated in both tests revealed a significant correlation, supporting the idea that these tests identify a phenotypically meaningful ASD subgroup. Combined use of both original and Complex Social GeoPref tests identified a subgroup of about 1 in 3 ASD toddlers from the "GeoPref" subtype (sensitivity 35%, specificity 94%, AUC 0.75.) Replicating our previous studies, more time looking at geometric images was associated with significantly greater ADOS symptom severity. Regardless of the complexity of the social images used (low in the original GeoPref test vs high in the new Complex Social GeoPref test), eye tracking of toddlers can accurately identify a specific ASD "GeoPref" subtype with elevated symptom severity. The GeoPref tests are predictive of ASD at the individual subject level and thus potentially useful for various clinical applications (e.g., early identification, prognosis, or development of subtype-specific treatments).

Clinical trial tests drug for tumors associated with Krebs-cycle dysfunction | Center for Cancer Research

Cancer.gov

The Krebs cycle is part of the complex process where cells turn food into energy. One of the elements of the Krebs cycle is succinate dehydrogenase (SDH). Loss of SDH activity in cells has been linked to tumor formation. This new trial is studying guadecitabine for tumors associated with Krebs cycle dysfunction. Learn more...

Robotics: a way to link the "islands of automation".

PubMed

O'Bryan, D

1994-01-01

This article looks at what the natural evolution of robots can do for the clinical testing industry, from performing simple functions to becoming the prime labor force of the clinical laboratory. Until now, robots have been applied to instrument processes as somewhat of an upgrade to accomplish a variety of laboratory tasks. Over the next 10 years, however, robotics development will respond to the internal and external influences expected to challenge the industry. A limited supply of human workers and the increased demands of testing volumes and cost-effectiveness will herald a new phase of robotics to link, as well as develop, technological capabilities. Since science fiction was invented, robots have teased the imagination-alternately as mindless automatons or as clones of their inventors endowed with minds of their own. The appeal in the first case was the seemingly infinite capacity for performing menial tasks too boring, complex, or dangerous for mankind. The appeal in the second was the fantasy of artificial intelligence. In both cases, the fictional concept has become reality--and, by the 21st century, should even be commonplace. Financial encouragement of robotics development might even be a mission for laboratories themselves, as they prepare for potential competition from even more complex technology.

Saccade and cognitive impairment associated with kava intoxication.

PubMed

Cairney, Sheree; Maruff, Paul; Clough, Alan R; Collie, Alex; Currie, Jon; Currie, Bart J

2003-10-01

Kava is an extract from the Piper methysticum Forst. f. plant that has social and spiritual importance in Pacific islands societies. Herbal remedies that contain kava are used for the psychiatric treatment of anxiety and insomnia. Laboratory studies have found only subtle, if any, changes on cognitive or motor functions from the acute effects of consuming small clinical doses of kava products. Intoxication from recreational doses of kava has not been studied. The performance of individuals intoxicated from drinking kava (n=11) was compared with a control group (n=17) using saccade and cognitive tests. On average, intoxicated individuals had consumed 205 g of kava powder each (approximately 150 times clinical doses) in a group session that went for 14.4 h and ended 8 h prior to testing. Intoxicated kava drinkers showed ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task that only became evident as the task complexity increased. Kava intoxication is characterized by specific abnormalities of movement coordination and visual attention but normal performance of complex cognitive functions. Saccade abnormalities suggest disruption of cerebellar and GABAergic functions. Copyright 2003 John Wiley & Sons, Ltd.

Childhood Acute Myeloid Leukaemia

PubMed Central

Rubnitz, Jeffrey E.; Inaba, Hiroto

2012-01-01

Summary Although acute myeloid leukaemia (AML) has long been recognized for its morphological and cytogenetic heterogeneity, recent high-resolution genomic profiling has demonstrated a complexity even greater than previously imagined. This complexity can be seen in the number and diversity of genetic alterations, epigenetic modifications, and characteristics of the leukaemic stem cells. The broad range of abnormalities across different AML subtypes suggests that improvements in clinical outcome will require the development of targeted therapies for each subtype of disease and the design of novel clinical trials to test these strategies. It is highly unlikely that further gains in long-term survival rates will be possible by mere intensification of conventional chemotherapy. In this review, we summarize recent studies that provide new insight into the genetics and biology of AML, discuss risk stratification and therapy for this disease, and profile some of the therapeutic agents currently under investigation. PMID:22966788

[Critical reflexion on quality improvement and networking].

PubMed

Adler, R

2012-06-06

Qualitiy-control and networking are two issues of debate in modern medicine. The origin of these terms is not to be found in medicine, but rather in industry. However their naive transfer to the field of medicine causes damage. It is relatively easy to test industrial products for their quality. Dealing with meaningful medical problems is far too complex. Simple data such as blood pressure, HbA1c, etc. may be assessed. The only means of quality-control of complex medical situations and actions are ward rounds by attending physicians, case presentations at staff meetings, etc. Issues of clinical quality-control are discussed on the basis of the history of an aged couple. Furthermore a personal clinical experience illustrates how doctors create a useful network with other physicians and how they eliminate "useless" colleagues from their network. Economists should have no influence or impact whatsoever on the quality-control and networking of physicians.

Ground Truth Creation for Complex Clinical NLP Tasks - an Iterative Vetting Approach and Lessons Learned.

PubMed

Liang, Jennifer J; Tsou, Ching-Huei; Devarakonda, Murthy V

2017-01-01

Natural language processing (NLP) holds the promise of effectively analyzing patient record data to reduce cognitive load on physicians and clinicians in patient care, clinical research, and hospital operations management. A critical need in developing such methods is the "ground truth" dataset needed for training and testing the algorithms. Beyond localizable, relatively simple tasks, ground truth creation is a significant challenge because medical experts, just as physicians in patient care, have to assimilate vast amounts of data in EHR systems. To mitigate potential inaccuracies of the cognitive challenges, we present an iterative vetting approach for creating the ground truth for complex NLP tasks. In this paper, we present the methodology, and report on its use for an automated problem list generation task, its effect on the ground truth quality and system accuracy, and lessons learned from the effort.

Algodystrophy: complex regional pain syndrome and incomplete forms

PubMed Central

Giannotti, Stefano; Bottai, Vanna; Dell’Osso, Giacomo; Bugelli, Giulia; Celli, Fabio; Cazzella, Niki; Guido, Giulio

2016-01-01

Summary The algodystrophy, also known as complex regional pain syndrome (CRPS), is a painful disease characterized by erythema, edema, functional impairment, sensory and vasomotor disturbance. The diagnosis of CRPS is based solely on clinical signs and symptoms, and for exclusion compared to other forms of chronic pain. There is not a specific diagnostic procedure; careful clinical evaluation and additional test should lead to an accurate diagnosis. There are similar forms of chronic pain known as bone marrow edema syndrome, in which is absent the history of trauma or triggering events and the skin dystrophic changes and vasomotor alterations. These incomplete forms are self-limited, and surgical treatment is generally not needed. It is still controversial, if these forms represent a distinct self-limiting entity or an incomplete variant of CRPS. In painful unexplained conditions such as frozen shoulder, post-operative stiff shoulder or painful knee prosthesis, the algodystrophy, especially in its incomplete forms, could represent the cause. PMID:27252736

Global issues in drug development for Alzheimer's disease.

PubMed

Doody, Rachelle S; Cole, Patricia E; Miller, David S; Siemers, Eric; Black, Ronald; Feldman, Howard; Schindler, Rachel; Graham, Stephen; Heath, Theresa; Khachaturian, Ara S; Evans, Rebecca; Carrillo, Maria C

2011-03-01

The number of clinical trials for Alzheimer's disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer's Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer's disease. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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.

Downsizing genomic medicine: approaching the ethical complexity of whole-genome sequencing by starting small.

PubMed

Sharp, Richard R

2011-03-01

As we look to a time when whole-genome sequencing is integrated into patient care, it is possible to anticipate a number of ethical challenges that will need to be addressed. The most intractable of these concern informed consent and the responsible management of very large amounts of genetic information. Given the range of possible findings, it remains unclear to what extent it will be possible to obtain meaningful patient consent to genomic testing. Equally unclear is how clinicians will disseminate the enormous volume of genetic information produced by whole-genome sequencing. Toward developing practical strategies for managing these ethical challenges, we propose a research agenda that approaches multiplexed forms of clinical genetic testing as natural laboratories in which to develop best practices for managing the ethical complexities of genomic medicine.

"Think aloud" and "Near live" usability testing of two complex clinical decision support tools.

PubMed

Richardson, Safiya; Mishuris, Rebecca; O'Connell, Alexander; Feldstein, David; Hess, Rachel; Smith, Paul; McCullagh, Lauren; McGinn, Thomas; Mann, Devin

2017-10-01

Low provider adoption continues to be a significant barrier to realizing the potential of clinical decision support. "Think Aloud" and "Near Live" usability testing were conducted on two clinical decision support tools. Each was composed of an alert, a clinical prediction rule which estimated risk of either group A Streptococcus pharyngitis or pneumonia and an automatic order set based on risk. The objective of this study was to further understanding of the facilitators of usability and to evaluate the types of additional information gained from proceeding to "Near Live" testing after completing "Think Aloud". This was a qualitative observational study conducted at a large academic health care system with 12 primary care providers. During "Think Aloud" testing, participants were provided with written clinical scenarios and asked to verbalize their thought process while interacting with the tool. During "Near Live" testing participants interacted with a mock patient. Morae usability software was used to record full screen capture and audio during every session. Participant comments were placed into coding categories and analyzed for generalizable themes. Themes were compared across usability methods. "Think Aloud" and "Near Live" usability testing generated similar themes under the coding categories visibility, workflow, content, understand-ability and navigation. However, they generated significantly different themes under the coding categories usability, practical usefulness and medical usefulness. During both types of testing participants found the tool easier to use when important text was distinct in its appearance, alerts were passive and appropriately timed, content was up to date, language was clear and simple, and each component of the tool included obvious indicators of next steps. Participant comments reflected higher expectations for usability and usefulness during "Near Live" testing. For example, visit aids, such as automatically generated order sets, were felt to be less useful during "Near-Live" testing because they would not be all inclusive for the visit. These complementary types of usability testing generated unique and generalizable insights. Feedback during "Think Aloud" testing primarily helped to improve the tools' ease of use. The additional feedback from "Near Live" testing, which mimics a real clinical encounter, was helpful for eliciting key barriers and facilitators to provider workflow and adoption. Copyright © 2017 Elsevier B.V. All rights reserved.

The ideal laboratory information system.

PubMed

Sepulveda, Jorge L; Young, Donald S

2013-08-01

Laboratory information systems (LIS) are critical components of the operation of clinical laboratories. However, the functionalities of LIS have lagged significantly behind the capacities of current hardware and software technologies, while the complexity of the information produced by clinical laboratories has been increasing over time and will soon undergo rapid expansion with the use of new, high-throughput and high-dimensionality laboratory tests. In the broadest sense, LIS are essential to manage the flow of information between health care providers, patients, and laboratories and should be designed to optimize not only laboratory operations but also personalized clinical care. To list suggestions for designing LIS with the goal of optimizing the operation of clinical laboratories while improving clinical care by intelligent management of laboratory information. Literature review, interviews with laboratory users, and personal experience and opinion. Laboratory information systems can improve laboratory operations and improve patient care. Specific suggestions for improving the function of LIS are listed under the following sections: (1) Information Security, (2) Test Ordering, (3) Specimen Collection, Accessioning, and Processing, (4) Analytic Phase, (5) Result Entry and Validation, (6) Result Reporting, (7) Notification Management, (8) Data Mining and Cross-sectional Reports, (9) Method Validation, (10) Quality Management, (11) Administrative and Financial Issues, and (12) Other Operational Issues.

An integrated clinical and genomic information system for cancer precision medicine.

PubMed

Jang, Yeongjun; Choi, Taekjin; Kim, Jongho; Park, Jisub; Seo, Jihae; Kim, Sangok; Kwon, Yeajee; Lee, Seungjae; Lee, Sanghyuk

2018-04-20

Increasing affordability of next-generation sequencing (NGS) has created an opportunity for realizing genomically-informed personalized cancer therapy as a path to precision oncology. However, the complex nature of genomic information presents a huge challenge for clinicians in interpreting the patient's genomic alterations and selecting the optimum approved or investigational therapy. An elaborate and practical information system is urgently needed to support clinical decision as well as to test clinical hypotheses quickly. Here, we present an integrated clinical and genomic information system (CGIS) based on NGS data analyses. Major components include modules for handling clinical data, NGS data processing, variant annotation and prioritization, drug-target-pathway analysis, and population cohort explorer. We built a comprehensive knowledgebase of genes, variants, drugs by collecting annotated information from public and in-house resources. Structured reports for molecular pathology are generated using standardized terminology in order to help clinicians interpret genomic variants and utilize them for targeted cancer therapy. We also implemented many features useful for testing hypotheses to develop prognostic markers from mutation and gene expression data. Our CGIS software is an attempt to provide useful information for both clinicians and scientists who want to explore genomic information for precision oncology.

Clinical-decision support based on medical literature: A complex network approach

NASA Astrophysics Data System (ADS)

Jiang, Jingchi; Zheng, Jichuan; Zhao, Chao; Su, Jia; Guan, Yi; Yu, Qiubin

2016-10-01

In making clinical decisions, clinicians often review medical literature to ensure the reliability of diagnosis, test, and treatment because the medical literature can answer clinical questions and assist clinicians making clinical decisions. Therefore, finding the appropriate literature is a critical problem for clinical-decision support (CDS). First, the present study employs search engines to retrieve relevant literature about patient records. However, the result of the traditional method is usually unsatisfactory. To improve the relevance of the retrieval result, a medical literature network (MLN) based on these retrieved papers is constructed. Then, we show that this MLN has small-world and scale-free properties of a complex network. According to the structural characteristics of the MLN, we adopt two methods to further identify the potential relevant literature in addition to the retrieved literature. By integrating these potential papers into the MLN, a more comprehensive MLN is built to answer the question of actual patient records. Furthermore, we propose a re-ranking model to sort all papers by relevance. We experimentally find that the re-ranking model can improve the normalized discounted cumulative gain of the results. As participants of the Text Retrieval Conference 2015, our clinical-decision method based on the MLN also yields higher scores than the medians in most topics and achieves the best scores for topics: #11 and #12. These research results indicate that our study can be used to effectively assist clinicians in making clinical decisions, and the MLN can facilitate the investigation of CDS.

Anticoagulant treatment of medical patients with complex clinical conditions.

PubMed

Ruiz-Ruiz, F; Medrano, F J; Santos-Lozano, J M; Rodríguez-Torres, P; Navarro-Puerto, A; Calderón, E J

2018-06-12

There is scarce available information on the treatment or prophylaxis with anticoagulant drugs of outpatients with medical diseases and complex clinical conditions. There are no clinical practice guidelines and/or specific recommendations for this patient subgroup, which are frequently treated by internists. Complex clinical conditions are those in which, due to comorbidity, age, vital prognosis or multiple treatment with drugs, a clinical situation arises of disease-disease, disease-drug or drug-drug interactions that is not included within the scenarios that commonly generate the scientific evidence. The objective of this narrative review is collecting and adapting of the clinical guidelines recommendations and systematic reviews to complex clinical conditions, in which the direct application of recommendations based on studies that do not include patients with this complexity and comorbidity could be problematic. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Client satisfaction with reproductive health-care quality: integrating business approaches to modeling and measurement.

PubMed

Alden, Dana L; Do, Mai Hoa; Bhawuk, Dharm

2004-12-01

Health-care managers are increasingly interested in client perceptions of clinic service quality and satisfaction. While tremendous progress has occurred, additional perspectives on the conceptualization, modeling and measurement of these constructs may further assist health-care managers seeking to provide high-quality care. To that end, this study draws on theories from business and health to develop an integrated model featuring antecedents to and consequences of reproductive health-care client satisfaction. In addition to developing a new model, this study contributes by testing how well Western-based theories of client satisfaction hold in a developing, Asian country. Applied to urban, reproductive health clinic users in Hanoi, Vietnam, test results suggest that hypothesized antecedents such as pre-visit expectations, perceived clinic performance and how much performance exceeds expectations impact client satisfaction. However, the relative importance of these predictors appears to vary depending on a client's level of service-related experience. Finally, higher levels of client satisfaction are positively related to future clinic use intentions. This study demonstrates the value of: (1) incorporating theoretical perspectives from multiple disciplines to model processes underlying health-care satisfaction and (2) field testing those models before implementation. It also furthers research designed to provide health-care managers with actionable measures of the complex processes related to their clients' satisfaction.

Capacity, consent, and mental health legislation: time for a new standard?

PubMed

O'Brien, Anthony J

2010-01-01

Recent international reforms in mental health legislation have introduced a capacity test as a criterion for civil commitment. There are proposals that a common test of incapacity should apply in both mental and physical health under a single legislative framework for all cases in which the normally accepted standard of informed consent for treatment is not met. Capacity is a complex concept, but can be reliably assessed in clinical practice. Nurses need to be involved in the policy debate about capacity and consent in mental health care.

Organometallic iron complexes as potential cancer therapeutics.

PubMed

Mojžišová, Gabriela; Mojžiš, Ján; Vašková, Janka

2014-01-01

Metal-containing drugs have long been used for medicinal purposes in more or less empirical way. The potential of these anticancer agents has only been fully realised and explored since the discovery of the biological activity of cisplatin. Cisplatin and carboplatin have been two of the most successful anti-cancer agents ever developed, and are currently used to treat ovarian, lung and testicular cancers. They share certain side effects, so their clinical use is severely limited by dose-limiting toxicity. Inherent or acquired resistance is a second problem often associated with platinum-based drugs, with further limits of their clinical use. These problems have prompted chemists to employ different strategies in development of the new metal-based anticancer agents with different mechanisms of action. There are various metal complexes still under development and investigation for the future cancer treatment use. In the search for novel bio-organometallic molecules, iron containing anti-tumoral agents are enjoying an increasing interest and appear very promising as the potential drug candidates. Iron, as an essential cofactor in a number of enzymes and physiological processes, may be less toxic than non essential metals, such as platinum. Up to now, some of iron complexes have been tested as cytotoxic agents and found to be endowed with an antitumor activity in several in vitro tests (on cultured cancer cell lines) and few in vivo experiments (e. g. on Ehrlich's ascites carcinoma). Although the precise molecular mechanism is yet to be defined, a number of observations suggest that the reactive oxygen species can play important role in iron-induced cytotoxicty. This review covers some relevant examples of research on the novel iron complexes.

Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens

PubMed Central

Hacohen, Yael; Wright, Sukhvir; Waters, Patrick; Agrawal, Shakti; Carr, Lucinda; Cross, Helen; De Sousa, Carlos; DeVile, Catherine; Fallon, Penny; Gupta, Rajat; Hedderly, Tammy; Hughes, Elaine; Kerr, Tim; Lascelles, Karine; Lin, Jean-Pierre; Philip, Sunny; Pohl, Keith; Prabahkar, Prab; Smith, Martin; Williams, Ruth; Clarke, Antonia; Hemingway, Cheryl; Wassmer, Evangeline; Vincent, Angela; Lim, Ming J

2013-01-01

Objective To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens. Method Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007–2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase. Results Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect. Conclusions Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future. PMID:23175854

QALMA: A computational toolkit for the analysis of quality protocols for medical linear accelerators in radiation therapy

NASA Astrophysics Data System (ADS)

Rahman, Md Mushfiqur; Lei, Yu; Kalantzis, Georgios

2018-01-01

Quality Assurance (QA) for medical linear accelerator (linac) is one of the primary concerns in external beam radiation Therapy. Continued advancements in clinical accelerators and computer control technology make the QA procedures more complex and time consuming which often, adequate software accompanied with specific phantoms is required. To ameliorate that matter, we introduce QALMA (Quality Assurance for Linac with MATLAB), a MALAB toolkit which aims to simplify the quantitative analysis of QA for linac which includes Star-Shot analysis, Picket Fence test, Winston-Lutz test, Multileaf Collimator (MLC) log file analysis and verification of light & radiation field coincidence test.

Sigma metrics used to assess analytical quality of clinical chemistry assays: importance of the allowable total error (TEa) target.

PubMed

Hens, Koen; Berth, Mario; Armbruster, Dave; Westgard, Sten

2014-07-01

Six Sigma metrics were used to assess the analytical quality of automated clinical chemistry and immunoassay tests in a large Belgian clinical laboratory and to explore the importance of the source used for estimation of the allowable total error. Clinical laboratories are continually challenged to maintain analytical quality. However, it is difficult to measure assay quality objectively and quantitatively. The Sigma metric is a single number that estimates quality based on the traditional parameters used in the clinical laboratory: allowable total error (TEa), precision and bias. In this study, Sigma metrics were calculated for 41 clinical chemistry assays for serum and urine on five ARCHITECT c16000 chemistry analyzers. Controls at two analyte concentrations were tested and Sigma metrics were calculated using three different TEa targets (Ricos biological variability, CLIA, and RiliBÄK). Sigma metrics varied with analyte concentration, the TEa target, and between/among analyzers. Sigma values identified those assays that are analytically robust and require minimal quality control rules and those that exhibit more variability and require more complex rules. The analyzer to analyzer variability was assessed on the basis of Sigma metrics. Six Sigma is a more efficient way to control quality, but the lack of TEa targets for many analytes and the sometimes inconsistent TEa targets from different sources are important variables for the interpretation and the application of Sigma metrics in a routine clinical laboratory. Sigma metrics are a valuable means of comparing the analytical quality of two or more analyzers to ensure the comparability of patient test results.

The analytical validation of the Oncotype DX Recurrence Score assay

PubMed Central

Baehner, Frederick L

2016-01-01

In vitro diagnostic multivariate index assays are highly complex molecular assays that can provide clinically actionable information regarding the underlying tumour biology and facilitate personalised treatment. These assays are only useful in clinical practice if all of the following are established: analytical validation (i.e., how accurately/reliably the assay measures the molecular characteristics), clinical validation (i.e., how consistently/accurately the test detects/predicts the outcomes of interest), and clinical utility (i.e., how likely the test is to significantly improve patient outcomes). In considering the use of these assays, clinicians often focus primarily on the clinical validity/utility; however, the analytical validity of an assay (e.g., its accuracy, reproducibility, and standardisation) should also be evaluated and carefully considered. This review focuses on the rigorous analytical validation and performance of the Oncotype DX® Breast Cancer Assay, which is performed at the Central Clinical Reference Laboratory of Genomic Health, Inc. The assay process includes tumour tissue enrichment (if needed), RNA extraction, gene expression quantitation (using a gene panel consisting of 16 cancer genes plus 5 reference genes and quantitative real-time RT-PCR), and an automated computer algorithm to produce a Recurrence Score® result (scale: 0–100). This review presents evidence showing that the Recurrence Score result reported for each patient falls within a tight clinically relevant confidence interval. Specifically, the review discusses how the development of the assay was designed to optimise assay performance, presents data supporting its analytical validity, and describes the quality control and assurance programmes that ensure optimal test performance over time. PMID:27729940

The analytical validation of the Oncotype DX Recurrence Score assay.

PubMed

Baehner, Frederick L

2016-01-01

In vitro diagnostic multivariate index assays are highly complex molecular assays that can provide clinically actionable information regarding the underlying tumour biology and facilitate personalised treatment. These assays are only useful in clinical practice if all of the following are established: analytical validation (i.e., how accurately/reliably the assay measures the molecular characteristics), clinical validation (i.e., how consistently/accurately the test detects/predicts the outcomes of interest), and clinical utility (i.e., how likely the test is to significantly improve patient outcomes). In considering the use of these assays, clinicians often focus primarily on the clinical validity/utility; however, the analytical validity of an assay (e.g., its accuracy, reproducibility, and standardisation) should also be evaluated and carefully considered. This review focuses on the rigorous analytical validation and performance of the Oncotype DX ® Breast Cancer Assay, which is performed at the Central Clinical Reference Laboratory of Genomic Health, Inc. The assay process includes tumour tissue enrichment (if needed), RNA extraction, gene expression quantitation (using a gene panel consisting of 16 cancer genes plus 5 reference genes and quantitative real-time RT-PCR), and an automated computer algorithm to produce a Recurrence Score ® result (scale: 0-100). This review presents evidence showing that the Recurrence Score result reported for each patient falls within a tight clinically relevant confidence interval. Specifically, the review discusses how the development of the assay was designed to optimise assay performance, presents data supporting its analytical validity, and describes the quality control and assurance programmes that ensure optimal test performance over time.

Canadian Health Measures Survey pre-test: design, methods, results.

PubMed

Tremblay, Mark; Langlois, Renée; Bryan, Shirley; Esliger, Dale; Patterson, Julienne

2007-01-01

The Canadian Health Measures Survey (CHMS) pre-test was conducted to provide information about the challenges and costs associated with administering a physical health measures survey in Canada. To achieve the specific objectives of the pre-test, protocols were developed and tested, and methods for household interviewing and clinic testing were designed and revised. The cost, logistics and suitability of using fixed sites for the CHMS were assessed. Although data collection, transfer and storage procedures are complex, the pre-test experience confirmed Statistics Canada's ability to conduct a direct health measures survey and the willingness of Canadians to participate in such a health survey. Many operational and logistical procedures worked well and, with minor modifications, are being employed in the main survey. Fixed sites were problematic, and survey costs were higher than expected.

Dissecting Complex Diseases in Complex Populations

PubMed Central

Choudhry, Shweta; Seibold, Max A.; Borrell, Luisa N.; Tang, Hua; Serebrisky, Denise; Chapela, Rocio; Rodriguez-Santana, José R.; Avila, Pedro C.; Ziv, Elad; Rodriguez-Cintron, William; Risch, Neil J.; Burchard, Esteban González

2007-01-01

Asthma is a common but complex respiratory ailment; current data indicate that interaction of genetic and environmental factors lead to its clinical expression. In the United States, asthma prevalence, morbidity, and mortality vary widely among different Latino ethnic groups. The prevalence of asthma is highest in Puerto Ricans, intermediate in Dominicans and Cubans, and lowest in Mexicans and Central Americans. Independently, known socioeconomic, environmental, and genetic differences do not fully account for this observation. One potential explanation is that there may be unique and ethnic-specific gene–environment interactions that can differentially modify risk for asthma in Latino ethnic groups. These gene–environment interactions can be tested using genetic ancestry as a surrogate for genetic risk factors. Latinos are admixed and share varying proportions of African, Native American, and European ancestry. Most Latinos are unaware of their precise ancestry and report their ancestry based on the national origin of their family and their physical appearance. The unavailability of precise ancestry and the genetic complexity among Latinos may complicate asthma research studies in this population. On the other hand, precisely because of this rich mixture of ancestry, Latinos present a unique opportunity to disentangle the clinical, social, environmental, and genetic underpinnings of population differences in asthma prevalence, severity, and bronchodilator drug responsiveness. PMID:17607004

Unexplained high thyroid stimulating hormone: a "BIG" problem.

PubMed

Mendoza, Heidi; Connacher, Alan; Srivastava, Rajeev

2009-01-01

Macro-hormones and macro-enzymes are high molecular weight conjugates of hormones or enzymes, respectively, often with immunoglobulins. These are referred to as macromolecular complexes, and may cause artefactually elevated biochemical tests results. Macro enzymes of the most commonly measured serum enzymes have been identified and are recognised as a source of elevated measurements that may cause diagnostic confusion; macro-creatine kinase and macro-amylase are the two better known macro-enzymes in clinical practice. Literature on macro-hormones is largely restricted to macro-prolactin. We present a case of a clinically euthyroid patient, who had persistently elevated thyroid stimulating hormone (TSH) but free thyroxine within the reference limits. She underwent repeated thyroid investigations and thyroid hormone interference studies, until macro-TSH was identified as the most likely cause of unexplained elevated TSH. Following the identification and characterisation of this biochemical abnormality, she is no longer subject to repeated blood tests for assessment of thyroid function; the patient currently remains clinically euthyroid.

Promoting the self-regulation of clinical reasoning skills in nursing students.

PubMed

Kuiper, R; Pesut, D; Kautz, D

2009-10-02

The purpose of this paper is to describe the research surrounding the theories and models the authors united to describe the essential components of clinical reasoning in nursing practice education. The research was conducted with nursing students in health care settings through the application of teaching and learning strategies with the Self-Regulated Learning Model (SRL) and the Outcome-Present-State-Test (OPT) Model of Reflective Clinical Reasoning. Standardized nursing languages provided the content and clinical vocabulary for the clinical reasoning task. This descriptive study described the application of the OPT model of clinical reasoning, use of nursing language content, and reflective journals based on the SRL model with 66 undergraduate nursing students over an 8 month period of time. The study tested the idea that self-regulation of clinical reasoning skills can be developed using self-regulation theory and the OPT model. This research supports a framework for effective teaching and learning methods to promote and document learner progress in mastering clinical reasoning skills. Self-regulated Learning strategies coupled with the OPT model suggest benefits of self-observation and self-monitoring during clinical reasoning activities, and pinpoints where guidance is needed for the development of cognitive and metacognitive awareness. Thinking and reasoning about the complexities of patient care needs requires attention to the content, processes and outcomes that make a nursing care difference. These principles and concepts are valuable to clinical decision making for nurses globally as they deal with local, regional, national and international health care issues.

Advanced Multi-Axis Spine Testing: Clinical Relevance and Research Recommendations

PubMed Central

Holsgrove, Timothy P.; Nayak, Nikhil R.; Welch, William C.

2015-01-01

Back pain and spinal degeneration affect a large proportion of the general population. The economic burden of spinal degeneration is significant, and the treatment of spinal degeneration represents a large proportion of healthcare costs. However, spinal surgery does not always provide improved clinical outcomes compared to non-surgical alternatives, and modern interventions, such as total disc replacement, may not offer clinically relevant improvements over more established procedures. Although psychological and socioeconomic factors play an important role in the development and response to back pain, the variation in clinical success is also related to the complexity of the spine, and the multi-faceted manner by which spinal degeneration often occurs. The successful surgical treatment of degenerative spinal conditions requires collaboration between surgeons, engineers, and scientists in order to provide a multi-disciplinary approach to managing the complete condition. In this review, we provide relevant background from both the clinical and the basic research perspectives, which is synthesized into several examples and recommendations for consideration in increasing translational research between communities with the goal of providing improved knowledge and care. Current clinical imaging, and multi-axis testing machines, offer great promise for future research by combining invivo kinematics and loading with in-vitro testing in six degrees of freedom to offer more accurate predictions of the performance of new spinal instrumentation. Upon synthesis of the literature, it is recommended that in-vitro tests strive to recreate as many aspects of the in-vivo environment as possible, and that a physiological preload is a critical factor in assessing spinal biomechanics in the laboratory. A greater link between surgical procedures, and the outcomes in all three anatomical planes should be considered in both the in-vivo and in-vitro settings, to provide data relevant to quality of motion, and stability. PMID:26273552

Service and Education: The Association Between Workload, Patient Complexity, and Teaching on Internal Medicine Inpatient Services.

PubMed

Ratcliffe, Temple A; Crabtree, Meghan A; Palmer, Raymond F; Pugh, Jacqueline A; Lanham, Holly J; Leykum, Luci K

2018-04-01

Attending rounds remain the primary venue for formal teaching and learning at academic medical centers. Little is known about the effect of increasing clinical demands on teaching during attending rounds. To explore the relationships among teaching time, teaching topics, clinical workload, and patient complexity variables. Observational study of medicine teaching teams from September 2008 through August 2014. Teams at two large teaching hospitals associated with a single medical school were observed for periods of 2 to 4 weeks. Twelve medicine teaching teams consisting of one attending, one second- or third-year resident, two to three interns, and two to three medical students. The study examined relationships between patient complexity (comorbidities, complications) and clinical workload variables (census, turnover) with educational measures. Teams were clustered based on clinical workload and patient complexity. Educational measures of interest were time spent teaching and number of teaching topics. Data were analyzed both at the daily observation level and across a given patient's admission. We observed 12 teams, 1994 discussions (approximately 373 h of rounds) of 563 patients over 244 observation days. Teams clustered into three groups: low patient complexity/high clinical workload, average patient complexity/low clinical workload, and high patient complexity/high clinical workload. Modest associations for team, patient complexity, and clinical workload variables were noted with total time spent teaching (9.1% of the variance in time spent teaching during a patient's admission; F[8,549] = 6.90, p < 0.001) and number of teaching topics (16% of the variance in the total number of teaching topics during a patient's admission; F[8,548] = 14.18, p < 0.001). Clinical workload and patient complexity characteristics among teams were only modestly associated with total teaching time and teaching topics.

Development of method for quantifying essential tremor using a small optical device.

PubMed

Chen, Kai-Hsiang; Lin, Po-Chieh; Chen, Yu-Jung; Yang, Bing-Shiang; Lin, Chin-Hsien

2016-06-15

Clinical assessment scales are the most common means used by physicians to assess tremor severity. Some scientific tools that may be able to replace these scales to objectively assess the severity, such as accelerometers, digital tablets, electromyography (EMG) measurement devices, and motion capture cameras, are currently available. However, most of the operational modes of these tools are relatively complex or are only able to capture part of the clinical information; furthermore, using these tools is sometimes time consuming. Currently, there is no tool available for automatically quantifying tremor severity in clinical environments. We aimed to develop a rapid, objective, and quantitative system for measuring the severity of finger tremor using a small portable optical device (Leap Motion). A single test took 15s to conduct, and three algorithms were proposed to quantify the severity of finger tremor. The system was tested with four patients diagnosed with essential tremor. The proposed algorithms were able to quantify different characteristics of tremor in clinical environments, and could be used as references for future clinical assessments. A portable, easy-to-use, small-sized, and noncontact device (Leap Motion) was used to clinically detect and record finger movement, and three algorithms were proposed to describe tremor amplitudes. Copyright © 2016 Elsevier B.V. All rights reserved.

Joint Stability Characteristics of the Ankle Complex in Female Athletes With Histories of Lateral Ankle Sprain, Part II: Clinical Experience Using Arthrometric Measurement

PubMed Central

Kovaleski, John E.; Heitman, Robert J.; Gurchiek, Larry R.; Hollis, J. M.; Liu, Wei; IV, Albert W. Pearsall

2014-01-01

Context: This is part II of a 2-part series discussing stability characteristics of the ankle complex. In part I, we used a cadaver model to examine the effects of sectioning the lateral ankle ligaments on anterior and inversion motion and stiffness of the ankle complex. In part II, we wanted to build on and apply these findings to the clinical assessment of ankle-complex motion and stiffness in a group of athletes with a history of unilateral ankle sprain. Objective: To examine ankle-complex motion and stiffness in a group of athletes with reported history of lateral ankle sprain. Design: Cross-sectional study. Setting: University research laboratory. Patients or Other Participants: Twenty-five female college athletes (age = 19.4 ± 1.4 years, height = 170.2 ± 7.4 cm, mass = 67.3 ± 10.0 kg) with histories of unilateral ankle sprain. Intervention(s): All ankles underwent loading with an ankle arthrometer. Ankles were tested bilaterally. Main Outcome Measure(s): The dependent variables were anterior displacement, anterior end-range stiffness, inversion rotation, and inversion end-range stiffness. Results: Anterior displacement of the ankle complex did not differ between the uninjured and sprained ankles (P = .37), whereas ankle-complex rotation was greater for the sprained ankles (P = .03). The sprained ankles had less anterior and inversion end-range stiffness than the uninjured ankles (P < .01). Conclusions: Changes in ankle-complex laxity and end-range stiffness were detected in ankles with histories of sprain. These results indicate the presence of altered mechanical characteristics in the soft tissues of the sprained ankles. PMID:24568223

A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios

PubMed Central

Agarwal, Ashok; Cho, Chak-Lam; Majzoub, Ahmad

2017-01-01

Background Sperm DNA fragmentation (SDF) is recognized as a leading cause of male infertility because it can impair the paternal genome through distinct pathophysiological mechanisms. Current evidence supports SDF as a major factor in the pathophysiology of several conditions, including varicocele, unexplained infertility, assisted reproductive technology failure, and environmental lifestyle factors, although the mechanisms involved have not been fully described yet. Measurement of the levels of DNA fragmentation in semen provides valuable information on the integrity of paternal chromatin and may guide therapeutic strategies. A recently published clinical practice guideline (CPG) highlighted how to use the information provided by SDF testing in daily practice, which triggered a series of commentaries by leading infertility experts. These commentaries contained an abundance of information and conflicting views about the clinical utility of SDF testing, which underline the complex nature of SDF. Methods A search of papers published in response to the CPG entitled “Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios” was performed within the Translational Andrology and Urology (TAU) website (http://tau.amegroups.com/). The start and end dates for the search were May 2017 and August 2017, respectively. Each commentary meeting our inclusion criteria was rated as “supportive without reservation”, “supportive with reservation”, “not supportive” or “neutral”. We recorded whether articles discussed either SDF characteristics as a laboratory test method or clinical scenarios, or both. Subsequently, we extracted the particulars from each commentary and utilized the ‘Strengths-Weaknesses-Opportunities-Threats’ (SWOT) analysis to understand the perceived advantages and drawbacks of SDF as a specialized sperm function method in clinical practice. Results Fifty-eight fertility experts from six continents and twenty-two countries contributed commentaries. Overall, participants (87.9%; n=51) were supportive of the recommendations provided by the CPG on the utility of SDF testing based on clinical scenarios. The majority of participants made explicit remarks about both the clinical scenarios and SDF assays’ characteristics. Among ‘not supportive’ and ‘supportive with reservation’ participants, 75% (n=30/40) and 77.5% (n=31/40) expressed concerns related to technical limitations of SDF testing methods and clinical utility of the test in one or more clinical scenarios discussed in the CPG, respectively. The SWOT analysis revealed that the CPG provides a reasonable evidence-based proposal for integration of SDF testing in the routine daily practice. It also uncovered gaps of knowledge and threats limiting the widespread application of SDF in everyday practice, thus allowing the identification of opportunities to further refine SDF testing and its clinical utility. Conclusions The understanding of the role of SDF in male infertility requires an in-depth analysis of the multifactorial pathophysiological processes and the theories involved. The SWOT analysis allowed an objective evaluation of CPG on the clinical utility of SDF testing based on clinical scenarios and its accompanying commentaries written by global experts in all possible angles. Implementation of SDF testing in the clinic may not only increase the outcome of ART but more importantly improve the health of both fathers to be and resulting offspring. PMID:29082207

[The Spectrum of Neuromyotonia: Clinics, Therapy and Outcome].

PubMed

Wenninger, S; Schoser, B

2015-08-01

Neuromyotonia (NM), Isaacs-Zschoke-Mertens syndrome or continuous muscle fiber activity (CMFA), is a rare condition associated with VGKC-antibodies. Clinically, fasciculations, myokymias, muscle stiffness and a myotonic appearance of movements after contraction are typical findings. In addition, CNS-symptoms vary from moderate fatigue, poor concentration and autonomic symptoms to severe encephalopathy in Morvan's syndrome. In electromyography, spontaneous irregular discharges can be found frequently with typical di-, tri- or multiplet single motor unit discharges. In up to 60 %, serum antibodies against VGKC-complexes can be detected. Patients with neuromyotonia were evaluated for clinical symptoms, response to treatment and outcome over a five-year period of follow-up. For evaluation, we used video recording of clinical symptoms, electroneurography, electromyography and myosonography as well as immunological tests (VGKC-complex antibody including CASPR2 and IGL1). Furthermore, cerebral fluid and screening for neoplasias were done. Patients with evidence for neuropathy, myopathy or motor neuron disease, even if diagnosed in the follow-up, were excluded. In 3 of 5 patients, neuromyotonia was diagnosed by electromyography and positive VGKC antibodies. In two patients, diagnosis was based on typical clinical symptoms and electromyographical changes. Anticonvulsants (carbamazepine) for symptomatic treatment were moderately effective in four patients; treatment with i. v. immunoglobulins was highly successful in one patient with high positive VGKC-complex antibody titers. In one patient with low-titer VGKC antibodies, neither anticonvulsants nor i. v. immunoglobulins nor prednisone was a successful treatment. Neuromyotonia is a rare, treatable condition. However, due to the high variability of symptoms, response to therapy and outcome, neuromyotonia treatment needs to be highly individualized. © Georg Thieme Verlag KG Stuttgart · New York.

Mixed copper-platinum complex formation could explain synergistic antiproliferative effect exhibited by binary mixtures of cisplatin and copper-1,10-phenanthroline compounds: An ESI-MS study.

PubMed

Pivetta, Tiziana; Lallai, Viola; Valletta, Elisa; Trudu, Federica; Isaia, Francesco; Perra, Daniela; Pinna, Elisabetta; Pani, Alessandra

2015-10-01

Cisplatin, cis-diammineplatinum(II) dichloride, is a metal complex used in clinical practice for the treatment of cancer. Despite its great efficacy, it causes adverse reactions and most patients develop a resistance to cisplatin. To overcome these issues, a multi-drug therapy was introduced as a modern approach to exploit the drug synergy. A synergistic effect had been previously found when testing binary combinations of cisplatin and three copper complexes in vitro, namely, Cu(phen)(OH2)2(OClO3)2, [Cu(phen)2(OH2)](ClO4)2 and [Cu(phen)2(H2dit)](ClO4)2,(phen=1,10-phenanthroline, H2dit=imidazolidine-2-thione), against the human acute T-lymphoblastic leukaemia cell line (CCRF-CEM). In this work [Cu(phen)2(OH2)](ClO4)2 was also tested in combination with cisplatin against cisplatin-resistant sublines of CCRF-CEM (CCRF-CEM-res) and ovarian (A2780-res) cancer cell lines. The tested combinations show a synergistic effect against both the types of resistant cells. The possibility that this effect was caused by the formation of new adducts was considered and mass spectra of solutions containing cisplatin and one of the three copper complexes at a time were measured using electrospray ionisation at atmospheric-pressure mass spectrometry (ESI-MS). A mixed complex was detected and its stoichiometry was assessed on the basis of the isotopic pattern and the results of tandem mass spectrometry experiments. The formed complex was found to be [Cu(phen)(OH)μ-(Cl)2Pt(NH3)(H2O)](+). Copyright © 2015 Elsevier Inc. All rights reserved.

Nested Machine Learning Facilitates Increased Sequence Content for Large-Scale Automated High Resolution Melt Genotyping

PubMed Central

Fraley, Stephanie I.; Athamanolap, Pornpat; Masek, Billie J.; Hardick, Justin; Carroll, Karen C.; Hsieh, Yu-Hsiang; Rothman, Richard E.; Gaydos, Charlotte A.; Wang, Tza-Huei; Yang, Samuel

2016-01-01

High Resolution Melt (HRM) is a versatile and rapid post-PCR DNA analysis technique primarily used to differentiate sequence variants among only a few short amplicons. We recently developed a one-vs-one support vector machine algorithm (OVO SVM) that enables the use of HRM for identifying numerous short amplicon sequences automatically and reliably. Herein, we set out to maximize the discriminating power of HRM + SVM for a single genetic locus by testing longer amplicons harboring significantly more sequence information. Using universal primers that amplify the hypervariable bacterial 16 S rRNA gene as a model system, we found that long amplicons yield more complex HRM curve shapes. We developed a novel nested OVO SVM approach to take advantage of this feature and achieved 100% accuracy in the identification of 37 clinically relevant bacteria in Leave-One-Out-Cross-Validation. A subset of organisms were independently tested. Those from pure culture were identified with high accuracy, while those tested directly from clinical blood bottles displayed more technical variability and reduced accuracy. Our findings demonstrate that long sequences can be accurately and automatically profiled by HRM with a novel nested SVM approach and suggest that clinical sample testing is feasible with further optimization. PMID:26778280

A novel approach to assess clinical competence of postgraduate year 1 surgery residents

PubMed Central

Qi, Xin; Ding, Lian; Zhai, Wei; Li, Qiang; Li, Yan; Li, Haichao; Wen, Bing

2017-01-01

ABSTRACT Background: An increased demand for accountability and transparency in medicine have initiated a shift toward a more objective and standardized approach for postgraduate medical training. Objective: To develop and evaluate an objective method to assess clinical competence of postgraduate year 1 surgery residents. Design: Thirty-one postgraduate year 1 surgery residents, who had been trained in the Surgical School of Peking University First Hospital for one year, participated in an objective structured clinical examination as a final assessment of their clinical competence. A test station of irregular wound repair (debridement and suture) was specially designed to test the residents’ surgical integrative competence in a complex-trauma treatment procedure. A modified global rating scale, in combination with wound area measurement, was applied to evaluate residents’ surgical performance. The validity of the subjective global rating scale was evaluated by the objective measurement results from the software. Results: The global rating scale score had no obvious correlation with the area of the removed tissue and the residual wound area after the suture. There was significant difference in the debridement time and the residual wound area between 0–3 and >3 total stitches. There were significant differences in the area of the removed tissue between 0 and 1–2 grey stitches and 0 and 3–4 grey stitches, and in the residual wound area after suture between 0 and 3–4 grey stitches and 1–2 and 3–4 grey stitches. Conclusions: An irregular wound repair procedure could be an effective method to assess the integrative competence of surgery residents. The training for surgical thinking in the early stage of junior residents needs to be strengthened. The entire measurement process was more complex and time-consuming than expected. The possibility of measurement by simply counting the numbers of the key spots might be explored in the future. Abbreviations: ACS/APDS American College of Surgeons/Association of Program Directors in Surgery; GRS Global rating scale; LSD-T Least significant difference-test; OSATS Objective structured assessment of technical skills; OSCE Objective structured clinical examination; PBT Proficiency based training; PGY1 Postgraduate Year 1 PMID:28670976

Warfarin Pharmacogenetics

PubMed Central

Johnson, Julie A.; Cavallari, Larisa H.

2014-01-01

The cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been strongly and consistently associated with warfarin dose requirements, and dosing algorithms incorporating genetic and clinical information have been shown to be predictive of stable warfarin dose. However, clinical trials evaluating genotype-guided warfarin dosing produced mixed results, calling into question the utility of this approach. Recent trials used surrogate markers as endpoints rather than clinical endpoints, further complicating translation of the data to clinical practice. The present data do not support genetic testing to guide warfarin dosing, but in the setting where genotype data are available, use of such data in those of European ancestry is reasonable. Outcomes data are expected from an on-going trial, observational studies continue, and more work is needed to define dosing algorithms that incorporate appropriate variants in minority populations; all these will further shape guidelines and recommendations on the clinical utility of genotype-guided warfarin dosing. PMID:25282448

American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.

PubMed

Robson, Mark E; Bradbury, Angela R; Arun, Banu; Domchek, Susan M; Ford, James M; Hampel, Heather L; Lipkin, Stephen M; Syngal, Sapna; Wollins, Dana S; Lindor, Noralane M

2015-11-01

The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. © 2015 by American Society of Clinical Oncology.

Clinical evaluation of the Abbott RealTime MTB Assay for direct detection of Mycobacterium tuberculosis-complex from respiratory and non-respiratory samples.

PubMed

Hinić, Vladimira; Feuz, Kinga; Turan, Selda; Berini, Andrea; Frei, Reno; Pfeifer, Karin; Goldenberger, Daniel

2017-05-01

Rapid and reliable diagnosis is crucial for correct management of tuberculosis. The Abbott RealTime MTB Assay represents a novel qualitative real-time PCR assay for direct detection of M. tuberculosis-complex (MTB) DNA from respiratory samples. The test targets two highly conserved sequences, the multi-copy insertion element IS6110 and the protein antigen B (PAB) gene of MTB, allowing even the detection of IS6610-deficient strains. We evaluated this commercial diagnostic test by analyzing 200 respiratory and, for the first time, 87 non-respiratory clinical specimens from our tertiary care institution and compared its results to our IS6110-based in-house real-time PCR for MTB as well as MTB culture. Overall sensitivity for Abbott RealTime MTB was 100% (19/19) in smear positive and 87.5% (7/8) in smear negative specimens, while the specificity of the assay was 100% (260/260). For both non-respiratory smear positive and smear negative specimens Abbott RealTime MTB tests showed 100% (8/8) sensitivity and 100% (8/8) specificity. Cycle threshold (Ct) value analysis of 16 MTB positive samples showed a slightly higher Ct value of the Abbott RealTime MTB test compared to our in-house MTB assay (mean delta Ct = 2.55). In conclusion, the performance of the new Abbott RealTime MTB Assay was highly similar to culture and in-house MTB PCR. We document successful analysis of 87 non-respiratory samples with the highly automated Abbott RealTime MTB test with no inhibition observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Standing of nucleic acid testing strategies in veterinary diagnosis laboratories to uncover Mycobacterium tuberculosis complex members

PubMed Central

Costa, Pedro; Botelho, Ana; Couto, Isabel; Viveiros, Miguel; Inácio, João

2014-01-01

Nucleic acid testing (NAT) designate any molecular approach used for the detection, identification, and characterization of pathogenic microorganisms, enabling the rapid, specific, and sensitive diagnostic of infectious diseases, such as tuberculosis. These assays have been widely used since the 90s of the last century in human clinical laboratories and, subsequently, also in veterinary diagnostics. Most NAT strategies are based in the polymerase chain reaction (PCR) and its several enhancements and variations. From the conventional PCR, real-time PCR and its combinations, isothermal DNA amplification, to the nanotechnologies, here we review how the NAT assays have been applied to decipher if and which member of the Mycobacterium tuberculosis complex is present in a clinical sample. Recent advances in DNA sequencing also brought new challenges and have made possible to generate rapidly and at a low cost, large amounts of sequence data. This revolution with the high-throughput sequencing (HTS) technologies makes whole genome sequencing (WGS) and metagenomics the trendiest NAT strategies, today. The ranking of NAT techniques in the field of clinical diagnostics is rising, and we provide a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis with our view of the use of molecular diagnostics for detecting tuberculosis in veterinary laboratories, notwithstanding the gold standard being still the classical culture of the agent. The complementary use of both classical and molecular diagnostics approaches is recommended to speed the diagnostic, enabling a fast decision by competent authorities and rapid tackling of the disease. PMID:25988157

Standing of nucleic acid testing strategies in veterinary diagnosis laboratories to uncover Mycobacterium tuberculosis complex members.

PubMed

Costa, Pedro; Botelho, Ana; Couto, Isabel; Viveiros, Miguel; Inácio, João

2014-01-01

Nucleic acid testing (NAT) designate any molecular approach used for the detection, identification, and characterization of pathogenic microorganisms, enabling the rapid, specific, and sensitive diagnostic of infectious diseases, such as tuberculosis. These assays have been widely used since the 90s of the last century in human clinical laboratories and, subsequently, also in veterinary diagnostics. Most NAT strategies are based in the polymerase chain reaction (PCR) and its several enhancements and variations. From the conventional PCR, real-time PCR and its combinations, isothermal DNA amplification, to the nanotechnologies, here we review how the NAT assays have been applied to decipher if and which member of the Mycobacterium tuberculosis complex is present in a clinical sample. Recent advances in DNA sequencing also brought new challenges and have made possible to generate rapidly and at a low cost, large amounts of sequence data. This revolution with the high-throughput sequencing (HTS) technologies makes whole genome sequencing (WGS) and metagenomics the trendiest NAT strategies, today. The ranking of NAT techniques in the field of clinical diagnostics is rising, and we provide a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis with our view of the use of molecular diagnostics for detecting tuberculosis in veterinary laboratories, notwithstanding the gold standard being still the classical culture of the agent. The complementary use of both classical and molecular diagnostics approaches is recommended to speed the diagnostic, enabling a fast decision by competent authorities and rapid tackling of the disease.

Design and Implementation of a Randomized Controlled Trial of Genomic Counseling for Patients with Chronic Disease

PubMed Central

Sweet, Kevin; Gordon, Erynn S.; Sturm, Amy C.; Schmidlen, Tara J.; Manickam, Kandamurugu; Toland, Amanda Ewart; Keller, Margaret A.; Stack, Catharine B.; García-España, J. Felipe; Bellafante, Mark; Tayal, Neeraj; Embi, Peter; Binkley, Philip; Hershberger, Ray E.; Sadee, Wolfgang; Christman, Michael; Marsh, Clay

2014-01-01

We describe the development and implementation of a randomized controlled trial to investigate the impact of genomic counseling on a cohort of patients with heart failure (HF) or hypertension (HTN), managed at a large academic medical center, the Ohio State University Wexner Medical Center (OSUWMC). Our study is built upon the existing Coriell Personalized Medicine Collaborative (CPMC®). OSUWMC patient participants with chronic disease (CD) receive eight actionable complex disease and one pharmacogenomic test report through the CPMC® web portal. Participants are randomized to either the in-person post-test genomic counseling—active arm, versus web-based only return of results—control arm. Study-specific surveys measure: (1) change in risk perception; (2) knowledge retention; (3) perceived personal control; (4) health behavior change; and, for the active arm (5), overall satisfaction with genomic counseling. This ongoing partnership has spurred creation of both infrastructure and procedures necessary for the implementation of genomics and genomic counseling in clinical care and clinical research. This included creation of a comprehensive informed consent document and processes for prospective return of actionable results for multiple complex diseases and pharmacogenomics (PGx) through a web portal, and integration of genomic data files and clinical decision support into an EPIC-based electronic medical record. We present this partnership, the infrastructure, genomic counseling approach, and the challenges that arose in the design and conduct of this ongoing trial to inform subsequent collaborative efforts and best genomic counseling practices. PMID:24926413

Detection of Botulinum Neurotoxin Serotype A, B, and F Proteolytic Activity in Complex Matrices with Picomolar to Femtomolar Sensitivity

PubMed Central

Dunning, F. Mark; Ruge, Daniel R.; Piazza, Timothy M.; Stanker, Larry H.; Zeytin, Füsûn N.

2012-01-01

Rapid, high-throughput assays that detect and quantify botulinum neurotoxin (BoNT) activity in diverse matrices are required for environmental, clinical, pharmaceutical, and food testing. The current standard, the mouse bioassay, is sensitive but is low in throughput and precision. In this study, we present three biochemical assays for the detection and quantification of BoNT serotype A, B, and F proteolytic activities in complex matrices that offer picomolar to femtomolar sensitivity with small assay volumes and total assay times of less than 24 h. These assays consist of magnetic beads conjugated with BoNT serotype-specific antibodies that are used to purify BoNT from complex matrices before the quantification of bound BoNT proteolytic activity using the previously described BoTest reporter substrates. The matrices tested include human serum, whole milk, carrot juice, and baby food, as well as buffers containing common pharmaceutical excipients. The limits of detection were below 1 pM for BoNT/A and BoNT/F and below 10 pM for BoNT/B in most tested matrices using 200-μl samples and as low as 10 fM for BoNT/A with an increased sample volume. Together, these data describe rapid, robust, and high-throughput assays for BoNT detection that are compatible with a wide range of matrices. PMID:22923410

Development of a test battery for evaluating speech perception in complex listening environments.

PubMed

Brungart, Douglas S; Sheffield, Benjamin M; Kubli, Lina R

2014-08-01

In the real world, spoken communication occurs in complex environments that involve audiovisual speech cues, spatially separated sound sources, reverberant listening spaces, and other complicating factors that influence speech understanding. However, most clinical tools for assessing speech perception are based on simplified listening environments that do not reflect the complexities of real-world listening. In this study, speech materials from the QuickSIN speech-in-noise test by Killion, Niquette, Gudmundsen, Revit, and Banerjee [J. Acoust. Soc. Am. 116, 2395-2405 (2004)] were modified to simulate eight listening conditions spanning the range of auditory environments listeners encounter in everyday life. The standard QuickSIN test method was used to estimate 50% speech reception thresholds (SRT50) in each condition. A method of adjustment procedure was also used to obtain subjective estimates of the lowest signal-to-noise ratio (SNR) where the listeners were able to understand 100% of the speech (SRT100) and the highest SNR where they could detect the speech but could not understand any of the words (SRT0). The results show that the modified materials maintained most of the efficiency of the QuickSIN test procedure while capturing performance differences across listening conditions comparable to those reported in previous studies that have examined the effects of audiovisual cues, binaural cues, room reverberation, and time compression on the intelligibility of speech.

Advancing Clinical Proteomics via Analysis Based on Biological Complexes: A Tale of Five Paradigms.

PubMed

Goh, Wilson Wen Bin; Wong, Limsoon

2016-09-02

Despite advances in proteomic technologies, idiosyncratic data issues, for example, incomplete coverage and inconsistency, resulting in large data holes, persist. Moreover, because of naïve reliance on statistical testing and its accompanying p values, differential protein signatures identified from such proteomics data have little diagnostic power. Thus, deploying conventional analytics on proteomics data is insufficient for identifying novel drug targets or precise yet sensitive biomarkers. Complex-based analysis is a new analytical approach that has potential to resolve these issues but requires formalization. We categorize complex-based analysis into five method classes or paradigms and propose an even-handed yet comprehensive evaluation rubric based on both simulated and real data. The first four paradigms are well represented in the literature. The fifth and newest paradigm, the network-paired (NP) paradigm, represented by a method called Extremely Small SubNET (ESSNET), dominates in precision-recall and reproducibility, maintains strong performance in small sample sizes, and sensitively detects low-abundance complexes. In contrast, the commonly used over-representation analysis (ORA) and direct-group (DG) test paradigms maintain good overall precision but have severe reproducibility issues. The other two paradigms considered here are the hit-rate and rank-based network analysis paradigms; both of these have good precision-recall and reproducibility, but they do not consider low-abundance complexes. Therefore, given its strong performance, NP/ESSNET may prove to be a useful approach for improving the analytical resolution of proteomics data. Additionally, given its stability, it may also be a powerful new approach toward functional enrichment tests, much like its ORA and DG counterparts.

Patients with triangular fibrocartilage complex injuries and distal radioulnar joint instability have reduced rotational torque in the forearm.

PubMed

Andersson, J K; Axelsson, P; Strömberg, J; Karlsson, J; Fridén, J

2016-09-01

A total of 20 patients scheduled for wrist arthroscopy, all with clinical signs of rupture to the triangular fibrocartilage complex and distal radioulnar joint instability, were tested pre-operatively by an independent observer for strength of forearm rotation. During surgery, the intra-articular pathology was documented by photography and also subsequently individually analysed by another independent hand surgeon. Arthroscopy revealed a type 1-B injury to the triangular fibrocartilage complex in 18 of 20 patients. Inter-rater reliability between the operating surgeon and the independent reviewer showed absolute agreement in all but one patient (95%) in terms of the injury to the triangular fibrocartilage complex and its classification. The average pre-operative torque strength was 71% of the strength of the non-injured contralateral side in pronation and supination. Distal radioulnar joint instability with an arthroscopically verified injury to the triangular fibrocartilage complex is associated with a significant loss of both pronation and supination torque. Case series, Level IV. © The Author(s) 2015.

Factors influencing polymerase chain reaction outcomes in patients with clinically suspected ocular tuberculosis.

PubMed

Balne, Praveen Kumar; Modi, Rohit Ramesh; Choudhury, Nuzhat; Mohan, Neha; Barik, Manas Ranjan; Padhi, Tapas Ranjan; Sharma, Savitri; Panigrahi, Satya Ranjan; Basu, Soumyava

2014-03-25

Polymerase chain reaction (PCR) assay can be a useful method for definitive diagnosis in paucibacillary infections such as ocular tuberculosis (TB). In this study, we have evaluated factors affecting PCR outcomes in patients with clinically suspected ocular TB. Patients with clinically suspected ocular TB were investigated by PCR of aqueous or vitreous samples. Three control groups were also tested: group 1 included culture-proven non-tuberculous endophthalmitis, group 2 culture-negative non-tuberculous endophthalmitis, and group 3 patients undergoing surgery for uncomplicated cataract. PCR targeted one or more of following targets: IS6110, MPB64, and protein b genes of Mycobacterium tuberculosis complex. Multiple regression analysis (5% level of significance) was done to evaluate the associations between positive PCR outcome and laterality of disease, tuberculin skin test (TST)/interferon-gamma release assay (IGRA), chest radiography, and type of sample (aqueous or vitreous). The main outcome measures were positive PCR by one or more gene targets, and factors influencing positive PCR outcomes. All 114 samples were tested for MPB64, 110 for protein b, and 88 for IS6110. MPB64 was positive in 70.2% (n = 80) of tested samples, protein b in 40.0% (n = 44), and IS6110 in only 9.1% (n = 8). DNA sequencing of amplicons from four randomly chosen PCR reactions showed homology for M. tuberculosis complex. Of the 80 PCR-positive patients, 71 completed a full course of antitubercular therapy, of which 65 patients (91.5%) had complete resolution of inflammation at final follow-up. Among controls, 12.5% (3 out of 24) in group 1 and 18.7% (6 out of 32) in group 2 also tested positive by PCR. No PCR-positive outcome was observed in control group 3 (n = 25). Multiple regression analysis revealed significant association of positive PCR outcome with bilateral presentation, but not with a positive TST/IGRA, chest radiography, or type of sample (aqueous/vitreous) used. Careful selection of gene targets can yield high PCR positivity in clinically suspected ocular TB. Bilateral disease presentation but not any evidence of latent systemic TB influences PCR outcomes. False-positive results may be seen in ocular inflammation unrelated to ocular TB.

A retrospective study of clinical and mutational findings in 45 Danish families with ectodermal dysplasia.

PubMed

Tiedemann Svendsen, Mathias; Henningsen, Emil; Hertz, Jens Michael; Vestergaard Grejsen, Dorthe; Bygum, Anette

2014-09-01

Ectodermal dysplasias form a complex, nosologic group of diseases with defects in at least 2 ectodermal structures. A retrospective study of patients with ectodermal dysplasia seen at our department over a period of 19 years (1994-2013) was performed. The study population consisted of 67 patients covering 17 different diagnoses. Forty-five families were identified of which 26 were sporadic cases with no affected family members. In 27 tested families a disease-causing mutation was identified in 23 families. Eleven mutations were novel mutations. To our knowledge, we present the first large ectodermal dysplasia cohort focusing on clinical manifestations in combination with mutational analysis. We recommend a nationwide study to estimate the prevalence of the ectodermal dysplasia and to ensure relevant molecular genetic testing which may form the basis of a national ectodermal dysplasia database.

Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style?

PubMed

Lang, Katie; Lloyd, Samantha; Khondoker, Mizanur; Simic, Mima; Treasure, Janet; Tchanturia, Kate

2015-01-01

This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored. The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures. There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs. Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed.

Real-time monitoring of clinical processes using complex event processing and transition systems.

PubMed

Meinecke, Sebastian

2014-01-01

Dependencies between tasks in clinical processes are often complex and error-prone. Our aim is to describe a new approach for the automatic derivation of clinical events identified via the behaviour of IT systems using Complex Event Processing. Furthermore we map these events on transition systems to monitor crucial clinical processes in real-time for preventing and detecting erroneous situations.

Clinical exome sequencing reports: current informatics practice and future opportunities.

PubMed

Swaminathan, Rajeswari; Huang, Yungui; Astbury, Caroline; Fitzgerald-Butt, Sara; Miller, Katherine; Cole, Justin; Bartlett, Christopher; Lin, Simon

2017-11-01

The increased adoption of clinical whole exome sequencing (WES) has improved the diagnostic yield for patients with complex genetic conditions. However, the informatics practice for handling information contained in whole exome reports is still in its infancy, as evidenced by the lack of a common vocabulary within clinical sequencing reports generated across genetic laboratories. Genetic testing results are mostly transmitted using portable document format, which can make secondary analysis and data extraction challenging. This paper reviews a sample of clinical exome reports generated by Clinical Laboratory Improvement Amendments-certified genetic testing laboratories at tertiary-care facilities to assess and identify common data elements. Like structured radiology reports, which enable faster information retrieval and reuse, structuring genetic information within clinical WES reports would help facilitate integration of genetic information into electronic health records and enable retrospective research on the clinical utility of WES. We identify elements listed as mandatory according to practice guidelines but are currently missing from some of the clinical reports, which might help to organize the data when stored within structured databases. We also highlight elements, such as patient consent, that, although they do not appear within any of the current reports, may help in interpreting some of the information within the reports. Integrating genetic and clinical information would assist the adoption of personalized medicine for improved patient care and outcomes. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improving the Efficiency and Quality of the Value Assessment Process for Companion Diagnostic Tests: The Companion test Assessment Tool (CAT).

PubMed

Canestaro, William J; Pritchard, Daryl E; Garrison, Louis P; Dubois, Robert; Veenstra, David L

2015-08-01

Companion diagnostic tests (CDTs) have emerged as a vital technology in the effective use of an increasing number of targeted drug therapies. Although CDTs can offer a multitude of potential benefits, assessing their value within a health technology appraisal process can be challenging because of a complex array of factors that influence clinical and economic outcomes. To develop a user-friendly tool to assist managed care and other health care decision makers in screening companion tests and determining whether an intensive technology review is necessary and, if so, where the review should be focused to improve efficiency. First, we conducted a systematic literature review of CDT cost-effectiveness studies to identify value drivers. Second, we conducted key informant interviews with a diverse group of stakeholders to elicit feedback and solicit any additional value drivers and identify desirable attributes for an evidence review tool. A draft tool was developed based on this information that captured value drivers, usability features, and had a particular focus on practical use by nonexperts. Finally, the tool was pilot tested with test developers and managed care evidence evaluators to assess face-validity and usability. The tool was also evaluated using several diverse examples of existing companion diagnostics and refined accordingly. We identified 65 cost-effectiveness studies of companion diagnostic technologies. The following factors were most commonly identified as value drivers from our literature review: clinical validity of testing; efficacy, safety, and cost of baseline and alternative treatments; cost and mortality of health states; and biomarker prevalence and testing cost. Stakeholders identified the following additional factors that they believed influenced the overall value of a companion test: regulatory status, actionability, utility, and market penetration. These factors were used to maximize the efficiency of the evidence review process. Stakeholders also stated that a tool should be easy to use and time efficient. Cognitive interviews with stakeholders led to minor changes in the draft tool to improve usability and relevance. The final tool consisted of 4 sections: (1) eligibility for review (2 questions), (2) prioritization of review (3 questions), (3) clinical review (3 questions), and (4) economic review (5 questions). Although the evaluation of CDTs can be challenging because of limited evidence and the added complexity of incorporating a diagnostic test into drug treatment decisions, using a pragmatic tool to identify tests that do not need extensive evaluation may improve the efficiency and effectiveness of CDT value assessments.

Hybridization-Induced Aggregation Technology for Practical Clinical Testing: KRAS Mutation Detection in Lung and Colorectal Tumors.

PubMed

Sloane, Hillary S; Landers, James P; Kelly, Kimberly A

2016-07-01

KRAS mutations have emerged as powerful predictors of response to targeted therapies in the treatment of lung and colorectal cancers; thus, prospective KRAS genotyping is essential for appropriate treatment stratification. Conventional mutation testing technologies are not ideal for routine clinical screening, as they often involve complex, time-consuming processes and/or costly instrumentation. In response, we recently introduced a unique analytical strategy for revealing KRAS mutations, based on the allele-specific hybridization-induced aggregation (HIA) of oligonucleotide probe-conjugated microbeads. Using simple, inexpensive instrumentation, this approach allows for the detection of any common KRAS mutation in <10 minutes after PCR. Here, we evaluate the clinical utility of the HIA method for mutation detection (HIAMD). In the analysis of 20 lung and colon tumor pathology specimens, we observed a 100% correlation between the KRAS mutation statuses determined by HIAMD and sequencing. In addition, we were able to detect KRAS mutations in a background of 75% wild-type DNA-a finding consistent with that reported for sequencing. With this, we show that HIAMD allows for the rapid and cost-effective detection of KRAS mutations, without compromising analytical performance. These results indicate the validity of HIAMD as a mutation-testing technology suitable for practical clinical testing. Further expansion of this platform may involve the detection of mutations in other key oncogenic pathways. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

End-to-end tests using alanine dosimetry in scanned proton beams

NASA Astrophysics Data System (ADS)

Carlino, A.; Gouldstone, C.; Kragl, G.; Traneus, E.; Marrale, M.; Vatnitsky, S.; Stock, M.; Palmans, H.

2018-03-01

This paper describes end-to-end test procedures as the last fundamental step of medical commissioning before starting clinical operation of the MedAustron synchrotron-based pencil beam scanning (PBS) therapy facility with protons. One in-house homogeneous phantom and two anthropomorphic heterogeneous (head and pelvis) phantoms were used for end-to-end tests at MedAustron. The phantoms were equipped with alanine detectors, radiochromic films and ionization chambers. The correction for the ‘quenching’ effect of alanine pellets was implemented in the Monte Carlo platform of the evaluation version of RayStation TPS. During the end-to-end tests, the phantoms were transferred through the workflow like real patients to simulate the entire clinical workflow: immobilization, imaging, treatment planning and dose delivery. Different clinical scenarios of increasing complexity were simulated: delivery of a single beam, two oblique beams without and with range shifter. In addition to the dose comparison in the plastic phantoms the dose obtained from alanine pellet readings was compared with the dose determined with the Farmer ionization chamber in water. A consistent systematic deviation of about 2% was found between alanine dosimetry and the ionization chamber dosimetry in water and plastic materials. Acceptable agreement of planned and delivered doses was observed together with consistent and reproducible results of the end-to-end testing performed with different dosimetric techniques (alanine detectors, ionization chambers and EBT3 radiochromic films). The results confirmed the adequate implementation and integration of the new PBS technology at MedAustron. This work demonstrates that alanine pellets are suitable detectors for end-to-end tests in proton beam therapy and the developed procedures with customized anthropomorphic phantoms can be used to support implementation of PBS technology in clinical practice.

Cornelia de Lange syndrome and molecular implications of the cohesin complex: Abstracts from the 7th biennial scientific and educational symposium 2016

PubMed Central

Kline, Antonie D.; Krantz, Ian D.; Deardorff, Matthew A.; Shirahige, Katsuhiko; Dorsett, Dale; Gerton, Jennifer L.; Wu, Meng; Mehta, Devanshi; Mills, Jason A.; Carrico, Cheri S.; Noon, Sarah; Herrera, Pamela S.; Horsfield, Julia A.; Bettale, Chiara; Morgan, Jeremy; Huisman, Sylvia A.; Moss, Jo; McCleery, Joseph; Grados, Marco; Hansen, Blake D.; Srivastava, Siddharth; Taylor-Snell, Emily; Kerr, Lynne M.; Katz, Olivia; Calof, Anne L.; Musio, Antonio; Egense, Alena; Haaland, Richard E.

2017-01-01

Cornelia de Lange Syndrome (CdLS) is due to mutations in the genes for the structural and regulatory proteins that make up the cohesin complex, and is considered a cohesinopathy disorder or, more recently, a transcriptomopathy. New phenotypes have been recognized in this expanding field. There are multiple clinical issues facing individuals with all forms of CdLS, particularly in the neurodevelopmental system, but also gastrointestinal, cardiac, and musculoskeletal. Aspects of developmental and cell biology have found common endpoints in the biology of the cohesin complex, with improved understanding of the mechanisms, easier diagnostic tests, and the possibility of potential therapeutics, all major clinical implications for the individual with CdLS. The following abstracts are the presentations from the 7th Cornelia de Lange Syndrome Scientific and Educational Symposium, June 22–23, 2016, in Orlando, FL, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting. In addition to the scientific and clinical discussions, there were talks related to practical aspects of behavior including autism, transitions, communication, access to medical care, and databases. At the end of the symposium, a panel was held, which included several parents, affected individuals and genetic counselors, and discussed the greatest challenges in life and how this information can assist in guiding future research. The Research Committee of the CdLS Foundation organizes this meeting, reviews, and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board and publications. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD. PMID:28190301

Chronic pain as a manifestation of potassium channel-complex autoimmunity

PubMed Central

Lennon, Vanda A.; Aston, Paula A.; McKeon, Andrew; Pittock, Sean J.

2012-01-01

Objective: Autoantibodies targeting voltage-gated potassium channel (VGKC) complexes cause a spectrum of neuronal hyperexcitability disorders. We investigated pain as a manifestation of VGKC-complex autoimmunity. Methods: We reviewed the prevalence and characteristics of pain in VGKC-complex-immunoglobulin G (IgG)–seropositive patients in 25 months of comprehensive service testing for neural autoantibodies, subtyped positive sera for LGI1-IgG and CASPR2-IgG specificities, and reviewed pain prevalence in autoimmune control patients. Results: VGKC-complex-IgG was identified in 1,992 patients of 54,853 tested (4%). Of 316 evaluated neurologically at Mayo Clinic, 159 (50%) had pain, in isolation (28%) or with accompanying neurologic manifestations (72%), and not attributable to alternative cause. Pain was subacute in onset, chronic in course, neuropathic, nociceptive, regional, or diffuse and sometimes attributed to fibromyalgia (6%) or psychogenic cause (13%). Most patients had normal peripheral nervous system function, measured by neuropathy impairment scores and nerve conduction. Evidence of neuronal hyperexcitability (hyperhidrosis, quantitative heat-pain hyperalgesia, or electromyographic excitability) was 25-fold more common in pain patients. Pain management required multiple medications in 70% (narcotics, 30%); 13 of 16 patients reported pain relief with immunotherapy. Pain was significantly associated with CASPR2-IgG-positivity (16% positive with pain, 7% without pain; p = 0.014) but not with LGI1-IgG. Less than 10% of 167 patients with neural autoantibodies other than VGKC-complex-IgG reported pain. Conclusions: Chronic idiopathic pain is a syndromic manifestation of VGKC-complex autoimmunity. Hyperexcitability of nociceptive pathways is implicated. CASPR2-IgG significantly associates with pain, but in most patients the antigenic VGKC-complex molecule remains to be determined. VGKC-complex autoimmunity represents an important new direction for pain research and therapy. PMID:22895588

Chronic pain as a manifestation of potassium channel-complex autoimmunity.

PubMed

Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; Pittock, Sean J

2012-09-11

Autoantibodies targeting voltage-gated potassium channel (VGKC) complexes cause a spectrum of neuronal hyperexcitability disorders. We investigated pain as a manifestation of VGKC-complex autoimmunity. We reviewed the prevalence and characteristics of pain in VGKC-complex-immunoglobulin G (IgG)-seropositive patients in 25 months of comprehensive service testing for neural autoantibodies, subtyped positive sera for LGI1-IgG and CASPR2-IgG specificities, and reviewed pain prevalence in autoimmune control patients. VGKC-complex-IgG was identified in 1,992 patients of 54,853 tested (4%). Of 316 evaluated neurologically at Mayo Clinic, 159 (50%) had pain, in isolation (28%) or with accompanying neurologic manifestations (72%), and not attributable to alternative cause. Pain was subacute in onset, chronic in course, neuropathic, nociceptive, regional, or diffuse and sometimes attributed to fibromyalgia (6%) or psychogenic cause (13%). Most patients had normal peripheral nervous system function, measured by neuropathy impairment scores and nerve conduction. Evidence of neuronal hyperexcitability (hyperhidrosis, quantitative heat-pain hyperalgesia, or electromyographic excitability) was 25-fold more common in pain patients. Pain management required multiple medications in 70% (narcotics, 30%); 13 of 16 patients reported pain relief with immunotherapy. Pain was significantly associated with CASPR2-IgG-positivity (16% positive with pain, 7% without pain; p = 0.014) but not with LGI1-IgG. Less than 10% of 167 patients with neural autoantibodies other than VGKC-complex-IgG reported pain. Chronic idiopathic pain is a syndromic manifestation of VGKC-complex autoimmunity. Hyperexcitability of nociceptive pathways is implicated. CASPR2-IgG significantly associates with pain, but in most patients the antigenic VGKC-complex molecule remains to be determined. VGKC-complex autoimmunity represents an important new direction for pain research and therapy.

Interventions to evaluate fitness to drive among people with chronic conditions: Systematic review of literature.

PubMed

Marino, Marta; de Belvis, Antonio; Basso, Danila; Avolio, Maria; Pelone, Ferruccio; Tanzariello, Maria; Ricciardi, Walter

2013-01-01

When an health condition has been identified, the question of whether to continue driving depends not on a medical diagnosis, but on the functional consequences of the illness. The complex nature of physical and mental impairments and their relationship with safe driving make the availability of evidence based tools necessary for health professionals. The review aims at identifying and summarizing scientific findings concerning the relationship between neuropsychological and clinical screening tests and fitness to drive among people with chronic conditions. Studies were searched for driving ability evaluation by road test or simulator, clinical/neuropsychological examinations of participants with chronic diseases or permanent disablement impairing driving performance, primary outcomes as fatal/non-fatal traffic injuries and secondary outcomes as fitness to drive assessment. Twenty-seven studies fulfilled the inclusion criteria. Some studies included more than one clinical condition. The illness investigated were Alzheimer Disease (n=6), Parkinson Disease (n=8), Cardiovascular Accident (n=4), Traumatic Brain Injuries (n=3), Sleep Apnea Syndrome (n=2), Narcolepsy (n=1), Multiple Sclerosis (n=1) and Hepatic Encephalopathy (n=1), comorbidities (n=3). No studies match inclusion criteria about Myasthenia Gravis, Diabetes Mellitus, Renal Diseases, Hearing Disorders and Sight Diseases. No studies referred to primary outcomes. The selected studies provided opposite evidences. It would be reasonable to argue that some clinical and neuropsychological tests are effective in predicting fitness to drive even if contrasting results support that driving performance decreases as a function of clinical and neuropsychological decline in some chronic diseases. Nevertheless we found no evidence that clinical and neuropsychological screening tests would lead to a reduction in motor vehicle crashes involving chronic disabled drivers. It seems necessary to develop tests with proven validity for identifying high-risk drivers so that physicians can provide guidance to their patients in chronic conditions, and also to medical advisory boards working with licensing offices. Copyright © 2012 Elsevier Ltd. All rights reserved.

Physiological and biochemical basis of clinical liver function tests: a review.

PubMed

Hoekstra, Lisette T; de Graaf, Wilmar; Nibourg, Geert A A; Heger, Michal; Bennink, Roelof J; Stieger, Bruno; van Gulik, Thomas M

2013-01-01

To review the literature on the most clinically relevant and novel liver function tests used for the assessment of hepatic function before liver surgery. Postoperative liver failure is the major cause of mortality and morbidity after partial liver resection and develops as a result of insufficient remnant liver function. Therefore, accurate preoperative assessment of the future remnant liver function is mandatory in the selection of candidates for safe partial liver resection. A MEDLINE search was performed using the key words "liver function tests," "functional studies in the liver," "compromised liver," "physiological basis," and "mechanistic background," with and without Boolean operators. Passive liver function tests, including biochemical parameters and clinical grading systems, are not accurate enough in predicting outcome after liver surgery. Dynamic quantitative liver function tests, such as the indocyanine green test and galactose elimination capacity, are more accurate as they measure the elimination process of a substance that is cleared and/or metabolized almost exclusively by the liver. However, these tests only measure global liver function. Nuclear imaging techniques ((99m)Tc-galactosyl serum albumin scintigraphy and (99m)Tc-mebrofenin hepatobiliary scintigraphy) can measure both total and future remnant liver function and potentially identify patients at risk for postresectional liver failure. Because of the complexity of liver function, one single test does not represent overall liver function. In addition to computed tomography volumetry, quantitative liver function tests should be used to determine whether a safe resection can be performed. Presently, (99m)Tc-mebrofenin hepatobiliary scintigraphy seems to be the most valuable quantitative liver function test, as it can measure multiple aspects of liver function in, specifically, the future remnant liver.

Autism biomarkers: challenges, pitfalls and possibilities.

PubMed

Anderson, George M

2015-04-01

Network perspectives, in their emphasis on components and their interactions, might afford the best approach to the complexities of the ASD realm. Categorical approaches are unlikely to be fruitful as one should not expect to find a single or even predominant underlying cause of autism behavior across individuals. It is possible that the complex, highly interactive, heterogeneous and individualistic nature of the autism realm is intractable in terms of identifying clinically useful biomarker tests. It is hopeful from an emergenic perspective that small corrective changes in a single component of a deleterious network/configuration might have large beneficial consequences on developmental trajectories and in later treatment. It is suggested that the relationship between ASD and intellectual disability might be fundamentally different in single-gene versus nonsyndromic ASD. It is strongly stated that available biomarker "tests" for autism/ASD will do more harm than good. Finally, the serotonin-melatonin-oxidative stress-placental intersection might be an especially fruitful area of biological investigation.

Improving performance of natural language processing part-of-speech tagging on clinical narratives through domain adaptation.

PubMed

Ferraro, Jeffrey P; Daumé, Hal; Duvall, Scott L; Chapman, Wendy W; Harkema, Henk; Haug, Peter J

2013-01-01

Natural language processing (NLP) tasks are commonly decomposed into subtasks, chained together to form processing pipelines. The residual error produced in these subtasks propagates, adversely affecting the end objectives. Limited availability of annotated clinical data remains a barrier to reaching state-of-the-art operating characteristics using statistically based NLP tools in the clinical domain. Here we explore the unique linguistic constructions of clinical texts and demonstrate the loss in operating characteristics when out-of-the-box part-of-speech (POS) tagging tools are applied to the clinical domain. We test a domain adaptation approach integrating a novel lexical-generation probability rule used in a transformation-based learner to boost POS performance on clinical narratives. Two target corpora from independent healthcare institutions were constructed from high frequency clinical narratives. Four leading POS taggers with their out-of-the-box models trained from general English and biomedical abstracts were evaluated against these clinical corpora. A high performing domain adaptation method, Easy Adapt, was compared to our newly proposed method ClinAdapt. The evaluated POS taggers drop in accuracy by 8.5-15% when tested on clinical narratives. The highest performing tagger reports an accuracy of 88.6%. Domain adaptation with Easy Adapt reports accuracies of 88.3-91.0% on clinical texts. ClinAdapt reports 93.2-93.9%. ClinAdapt successfully boosts POS tagging performance through domain adaptation requiring a modest amount of annotated clinical data. Improving the performance of critical NLP subtasks is expected to reduce pipeline error propagation leading to better overall results on complex processing tasks.

The ethics of disclosing genetic diagnosis for Alzheimer's disease: do we need a new paradigm?

PubMed

Arribas-Ayllon, Michael

2011-01-01

Genetic testing for rare Mendelian disorders represents the dominant ethical paradigm in clinical and professional practice. Predictive testing for Huntington's disease is the model against which other kinds of genetic testing are evaluated, including testing for Alzheimer's disease. This paper retraces the historical development of ethical reasoning in relation to predictive genetic testing and reviews a range of ethical, sociological and psychological literature from the 1970s to the present. In the past, ethical reasoning has embodied a distinct style whereby normative principles are developed from a dominant disease exemplar. This reductionist approach to formulating ethical frameworks breaks down in the case of disease susceptibility. Recent developments in the genetics of Alzheimer's disease present a significant case for reconsidering the ethics of disclosing risk for common complex diseases. Disclosing the results of susceptibility testing for Alzheimer's disease has different social, psychological and behavioural consequences. Furthermore, what genetic susceptibility means to individuals and their families is diffuse and often mitigated by other factors and concerns. The ethics of disclosing a genetic diagnosis of susceptibility is contingent on whether professionals accept that probabilistic risk information is in fact 'diagnostic' and it will rely substantially on empirical evidence of how people actually perceive, recall and communicate complex risk information.

A feasibility study of a theory-based intervention to improve appropriate polypharmacy for older people in primary care.

PubMed

Cadogan, Cathal A; Ryan, Cristín; Gormley, Gerard J; Francis, Jill J; Passmore, Peter; Kerse, Ngaire; Hughes, Carmel M

2018-01-01

A general practitioner (GP)-targeted intervention aimed at improving the prescribing of appropriate polypharmacy for older people was previously developed using a systematic, theory-based approach based on the UK Medical Research Council's complex intervention framework. The primary intervention component comprised a video demonstration of a GP prescribing appropriate polypharmacy during a consultation with an older patient. The video was delivered to GPs online and included feedback emphasising the positive outcomes of performing the behaviour. As a complementary intervention component, patients were invited to scheduled medication review consultations with GPs. This study aimed to test the feasibility of the intervention and study procedures (recruitment, data collection). GPs from two general practices were given access to the video, and reception staff scheduled consultations with older patients receiving polypharmacy (≥4 medicines). Primary feasibility study outcomes were the usability and acceptability of the intervention to GPs. Feedback was collected from GP and patient participants using structured questionnaires. Clinical data were also extracted from recruited patients' medical records (baseline and 1 month post-consultation). The feasibility of applying validated assessment of prescribing appropriateness (STOPP/START criteria, Medication Appropriateness Index) and medication regimen complexity (Medication Regimen Complexity Index) to these data was investigated. Data analysis was descriptive, providing an overview of participants' feedback and clinical assessment findings. Four GPs and ten patients were recruited across two practices. The intervention was considered usable and acceptable by GPs. Some reservations were expressed by GPs as to whether the video truly reflected resource and time pressures encountered in the general practice working environment. Patient feedback on the scheduled consultations was positive. Patients welcomed the opportunity to have their medications reviewed. Due to the short time to follow-up and a lack of detailed clinical information in patient records, it was not feasible to detect any prescribing changes or to apply the assessment tools to patients' clinical data. The findings will help to further refine the intervention and study procedures (including time to follow-up) which will be tested in a randomised pilot study that will inform the design of a definitive trial to evaluate the intervention's effectiveness. ISRCTN18176245.

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.

Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma?

PubMed

Giourou, Evangelia; Skokou, Maria; Andrew, Stuart P; Alexopoulou, Konstantina; Gourzis, Philippos; Jelastopulu, Eleni

2018-03-22

Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11 th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities' biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.

[The Amsterdam Dementia Screening Test in cognitively healthy and clinical samples. An update of normative data].

PubMed

van Toutert, Meta; Diesfeldt, Han; Hoek, Dirk

2016-10-01

The six tests in the Amsterdam Dementia Screening Test (ADST) examine the cognitive domains of episodic memory (delayed picture recognition, word learning), orientation, category fluency (animals and occupations), constructional ability (figure copying) and executive function (alternating sequences). New normative data were collected in a sample of 102 elderly volunteers (aged 65-94), including subjects with medical or other health conditions, except dementia or frank cognitive impairment (MMSE > 24). Included subjects were independent in complex instrumental activities of daily living.Fluency, not the other tests, needed adjustment for age and education. A deficit score (0-1) was computed for each test. Summation (range 0-6) proved useful in differentiating patients with dementia (N = 741) from normal elderly (N = 102).Positive and negative predictive power across a range of summed deficit scores and base rates are displayed in Bayesian probability tables.In the normal elderly, delayed recall for eight words was tested and adjusted for initial recall. A recognition test mixed the target words with eight distractors. Delayed recognition was adjusted for immediate and delayed recall.The ADST and the normative data in this paper help the clinical neuropsychologist to make decisions concerning the presence or absence of neurocognitive disorder in individual elderly examinees.

Design and implementation of software for automated quality control and data analysis for a complex LC/MS/MS assay for urine opiates and metabolites.

PubMed

Dickerson, Jane A; Schmeling, Michael; Hoofnagle, Andrew N; Hoffman, Noah G

2013-01-16

Mass spectrometry provides a powerful platform for performing quantitative, multiplexed assays in the clinical laboratory, but at the cost of increased complexity of analysis and quality assurance calculations compared to other methodologies. Here we describe the design and implementation of a software application that performs quality control calculations for a complex, multiplexed, mass spectrometric analysis of opioids and opioid metabolites. The development and implementation of this application improved our data analysis and quality assurance processes in several ways. First, use of the software significantly improved the procedural consistency for performing quality control calculations. Second, it reduced the amount of time technologists spent preparing and reviewing the data, saving on average over four hours per run, and in some cases improving turnaround time by a day. Third, it provides a mechanism for coupling procedural and software changes with the results of each analysis. We describe several key details of the implementation including the use of version control software and automated unit tests. These generally useful software engineering principles should be considered for any software development project in the clinical lab. Copyright © 2012 Elsevier B.V. All rights reserved.

Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus.

PubMed

Nathan, Neera; Wang, Ji-an; Li, Shaowei; Cowen, Edward W; Haughey, Mary; Moss, Joel; Darling, Thomas N

2015-11-01

Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC). We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects. A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment. Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment). This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis. Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated. Published by Elsevier Inc.

Evaluation of the Efficiency of the Sample Inactivation Reagent in the Abbott RealTime MTB Assay for Inactivation of Mycobacterium tuberculosis

PubMed Central

Wallis, Carole; Pahalawatta, Vihanga; Frank, Andrea; Ramdin, Neeshan; Viana, Raquel; Abravaya, Klara; Leckie, Gregor; Tang, Ning

2015-01-01

The Abbott RealTime MTB assay is a nucleic acid amplification test (NAAT) for the detection of Mycobacterium tuberculosis complex DNA. The sample inactivation procedure used in the assay, consisting of one part sample treated with 3 parts inactivation reagent for 60 min, effectively reduced viscosity and inactivated M. tuberculosis in clinical specimens. PMID:26085611

Jaundice and bilirubinemia as manifestations of canine distemper in raccoons and ferrets

USGS Publications Warehouse

Kilham, L.; Habermann, R.T.; Herman, C.M.

1956-01-01

1) Two strains of distemper virus have been isolated from wild raccoons and one strain from ferrets. 2) All strains isolated have induced bilirubinemia in raccoons and ferrets. Many raccoons with bilirubinemia also had jaundice. 3) Identification of these strains as members of the canine distemper virus complex has been by clinical and pathological findings consistent with this diagnosis as well as by cross-immunity tests.

Biosimilars in Inflammatory Bowel Disease: Facts and Fears of Extrapolation.

PubMed

Ben-Horin, Shomron; Vande Casteele, Niels; Schreiber, Stefan; Lakatos, Peter Laszlo

2016-12-01

Biologic drugs such as infliximab and other anti-tumor necrosis factor monoclonal antibodies have transformed the treatment of immune-mediated inflammatory conditions such as Crohn's disease and ulcerative colitis (collectively known as inflammatory bowel disease [IBD]). However, the complex manufacturing processes involved in producing these drugs mean their use in clinical practice is expensive. Recent or impending expiration of patents for several biologics has led to development of biosimilar versions of these drugs, with the aim of providing substantial cost savings and increased accessibility to treatment. Biosimilars undergo an expedited regulatory process. This involves proving structural, functional, and biological biosimilarity to the reference product (RP). It is also expected that clinical equivalency/comparability will be demonstrated in a clinical trial in one (or more) sensitive population. Once these requirements are fulfilled, extrapolation of biosimilar approval to other indications for which the RP is approved is permitted without the need for further clinical trials, as long as this is scientifically justifiable. However, such justification requires that the mechanism(s) of action of the RP in question should be similar across indications and also comparable between the RP and the biosimilar in the clinically tested population(s). Likewise, the pharmacokinetics, immunogenicity, and safety of the RP should be similar across indications and comparable between the RP and biosimilar in the clinically tested population(s). To date, most anti-tumor necrosis factor biosimilars have been tested in trials recruiting patients with rheumatoid arthritis. Concerns have been raised regarding extrapolation of clinical data obtained in rheumatologic populations to IBD indications. In this review, we discuss the issues surrounding indication extrapolation, with a focus on extrapolation to IBD. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Proviral Latency, Persistent Human Immunodeficiency Virus Infection, and the Development of Latency Reversing Agents

PubMed Central

Archin, Nancie M.

2017-01-01

Abstract Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound viremia after ART interruption and is a central obstacle to the cure of HIV infection. The induction of quiescent provirus is the goal of a new class of potential therapeutics, latency reversing agents (LRAs). The discovery, development, and testing of HIV LRAs is a key part of current efforts to develop latency reversal and viral clearance strategies to eradicate established HIV infection. The development of LRAs is burdened by many uncertainties that make drug discovery difficult. The biology of HIV latency is complex and incompletely understood. Potential targets for LRAs are host factors, and the potential toxicities of host-directed therapies in individuals that are otherwise clinically stable may be unacceptable. Assays to measure latency reversal and assess the effectiveness of potential therapeutics are complex and incompletely validated. Despite these obstacles, novel LRAs are under development and beginning to enter combination testing with viral clearance strategies. It is hoped that the steady advances in the development of LRAs now being paired with emerging immunotherapeutics to clear persistently infected cells will soon allow measurable clinical advances toward an HIV cure. PMID:28520964

Rapid and visual detection of Mycobacterium tuberculosis complex using recombinase polymerase amplification combined with lateral flow strips.

PubMed

Ma, Qinglin; Liu, Houming; Ye, Feidi; Xiang, Guangxin; Shan, Wanshui; Xing, Wanli

2017-12-01

To definitively diagnose active pulmonary Tuberculosis (TB), Mycobacterium tuberculosis complex (MTBC) bacilli must be identified within clinical specimens from patients. In this study, we introduced a rapid and visual detection method of MTBC using recombinase polymerase amplification (RPA) combined with lateral flow (LF) strips. The LF-RPA assay, read results with naked eyes, could detect as few as 5 genome copies of M. tuberculosis H37Rv (ATCC 27294) per reaction and had no cross-reactions with other control bacteria even using excessive amount of template DNA. The system could work well at a broad range of temperature 25-45 °C and reach detectable level even within 5 min. When testing a total of 137 clinical specimens, the sensitivity and specificity of the LF-RPA assay were 100% (95% CI: 95.94%-100%) and 97.92% (95% CI: 88.93%-99.95%), respectively, compared to culture identification method. Therefore, the LF-RPA system we have demonstrated is a rapid, simple, robust method for MTBC detection which, subject to the availability of a suitable sample extraction method, has the potentiality to diagnose TB at the point-of-care testing. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

PubMed

Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

2017-01-04

We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

PubMed

Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

Impact of Patient Reminders on Papanicolaou Test Completion for High-Risk Patients Identified by a Clinical Decision Support System.

PubMed

MacLaughlin, Kathy L; Kessler, Maya E; Komandur Elayavilli, Ravikumar; Hickey, Branden C; Scheitel, Marianne R; Wagholikar, Kavishwar B; Liu, Hongfang; Kremers, Walter K; Chaudhry, Rajeev

2018-05-01

A clinical decision support system (CDSS) for cervical cancer screening identifies patients due for routine cervical cancer screening. Yet, high-risk patients who require more frequent screening or earlier follow-up to address past abnormal results are not identified. We aimed to assess the effect of a complex CDSS, incorporating national guidelines for high-risk patient screening and abnormal result management, its implementation to identify patients overdue for testing, and the outcome of sending a targeted recommendation for follow-up. At three primary care clinics affiliated with an academic medical center, a reminder recommending an appointment for Papanicolaou (Pap) testing or Pap and human papillomavirus cotesting was sent to high-risk women aged 18 through 65 years (intervention group) identified by CDSS as overdue for testing. Historical control patients, who did not receive a reminder, were identified by CDSS 1 year before the date when reminders were sent to the intervention group. Test completion rates were compared between the intervention and control groups through a generalized estimating equation extension. Across the three sites, the average completion rate of recommended follow-up testing was significantly higher in the intervention group at 23.7% (61/257) than the completion rate at 3.3% (17/516) in the control group (p < 0.001). A CDSS with enhanced capabilities to identify high-risk women due for cervical cancer testing beyond routine screening intervals, with subsequent patient notification, has the potential to decrease cervical precancer and cancer by improving adherence to guideline-compliant follow-up and needed treatment.

Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura – Therapeutic plasma exchange is the answer

PubMed Central

Nasa, Prashant; Dua, J. M.; Kansal, Sudha; Chadha, Geeta; Chawla, Rajesh; Manchanda, Manav

2011-01-01

The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia–eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management. PMID:21814380

Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura - Therapeutic plasma exchange is the answer.

PubMed

Nasa, Prashant; Dua, J M; Kansal, Sudha; Chadha, Geeta; Chawla, Rajesh; Manchanda, Manav

2011-04-01

The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia-eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management.

In vitro antifungal activity of silver nanoparticles against ocular pathogenic filamentous fungi.

PubMed

Xu, Yan; Gao, Chuanwen; Li, Xiaohua; He, Yi; Zhou, Lutan; Pang, Guangren; Sun, Shengtao

2013-03-01

Fungal keratitis is emerging as a major cause of vision loss in a developing country such as China because of higher incidence and the unavailability of effective antifungals. It is urgent to explore broad-spectrum antifungals to effectively suppress ocular fungal pathogens, and to develop new antifungal eye drops to combat this vision-threatening infection. The aim of this study is to investigate the antifungal activity of silver nanoparticles (nano-Ag) in comparison with that of natamycin against ocular pathogenic filamentous fungi in vitro. Susceptibility tests were performed against 216 strains of fungi isolated from patients with fungal keratitis from the Henan Eye Institute in China by broth dilution antifungal susceptibility test of filamentous fungi approved by the Clinical and Laboratory Standards Institute M38-A document. The isolates included 112 Fusarium isolates (82 Fusarium solani species complex, 20 Fusarium verticillioides species complex, and 10 Fusarium oxysporum species complex), 94 Aspergillus isolates (61 Aspergillus flavus species complex, 11 Aspergillus fumigatus species complex, 12 Aspergillus versicolor species complex, and 10 Aspergillus niger species complex), and 10 Alternaria alternata isolates. The minimum inhibitory concentration (MIC) range and mode, the MIC for 50% of the strains tested (MIC50 value), and the MIC90 value were provided for the isolates with the SPSS statistical package. MIC50 value of nano-Ag were 1, 0.5, and 0.5 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of nano-Ag were 1, 1, and 1 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC50 values of natamycin were 4, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. MIC90 values of natamycin were 8, 32, and 4 μg/mL for Fusarium spp., Aspergillus spp., and Al. alternata, respectively. Nano-Ag, relative to natamycin, exhibits potent in vitro activity against ocular pathogenic filamentous fungi.

Promoting the Self-Regulation of Clinical Reasoning Skills in Nursing Students

PubMed Central

Kuiper, R; Pesut, D; Kautz, D

2009-01-01

Aim: The purpose of this paper is to describe the research surrounding the theories and models the authors united to describe the essential components of clinical reasoning in nursing practice education. The research was conducted with nursing students in health care settings through the application of teaching and learning strategies with the Self-Regulated Learning Model (SRL) and the Outcome-Present-State-Test (OPT) Model of Reflective Clinical Reasoning. Standardized nursing languages provided the content and clinical vocabulary for the clinical reasoning task. Materials and Methods: This descriptive study described the application of the OPT model of clinical reasoning, use of nursing language content, and reflective journals based on the SRL model with 66 undergraduate nursing students over an 8 month period of time. The study tested the idea that self-regulation of clinical reasoning skills can be developed using self-regulation theory and the OPT model. Results: This research supports a framework for effective teaching and learning methods to promote and document learner progress in mastering clinical reasoning skills. Self-regulated Learning strategies coupled with the OPT model suggest benefits of self-observation and self-monitoring during clinical reasoning activities, and pinpoints where guidance is needed for the development of cognitive and metacognitive awareness. Recommendations and Conclusions: Thinking and reasoning about the complexities of patient care needs requires attention to the content, processes and outcomes that make a nursing care difference. These principles and concepts are valuable to clinical decision making for nurses globally as they deal with local, regional, national and international health care issues. PMID:19888432

Clinical and Taxonomic Status of Pathogenic Nonpigmented or Late-Pigmenting Rapidly Growing Mycobacteria

PubMed Central

Brown-Elliott, Barbara A.; Wallace, Richard J.

2002-01-01

The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on the Mycobacterium fortuitum group, including M. fortuitum, M. peregrinum, and the unnamed third biovariant complex with its recent taxonomic changes and newly recognized species (including M. septicum, M. mageritense, and proposed species M. houstonense and M. bonickei). The clinical and taxonomic status of M. chelonae, M. abscessus, and M. mucogenicum is also detailed, along with that of the closely related new species, M. immunogenum. Additionally, newly recognized species, M. wolinskyi and M. goodii, as well as M. smegmatis sensu stricto, are included in a discussion of the M. smegmatis group. Laboratory diagnosis of RGM using phenotypic methods such as biochemical testing and high-performance liquid chromatography and molecular methods of diagnosis are also discussed. The latter includes PCR-restriction fragment length polymorphism analysis, hybridization, ribotyping, and sequence analysis. Susceptibility testing and antibiotic susceptibility patterns of the RGM are also annotated, along with the current recommendations from the National Committee for Clinical Laboratory Standards (NCCLS) for mycobacterial susceptibility testing. PMID:12364376

Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria.

PubMed

Brown-Elliott, Barbara A; Wallace, Richard J

2002-10-01

The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on the Mycobacterium fortuitum group, including M. fortuitum, M. peregrinum, and the unnamed third biovariant complex with its recent taxonomic changes and newly recognized species (including M. septicum, M. mageritense, and proposed species M. houstonense and M. bonickei). The clinical and taxonomic status of M. chelonae, M. abscessus, and M. mucogenicum is also detailed, along with that of the closely related new species, M. immunogenum. Additionally, newly recognized species, M. wolinskyi and M. goodii, as well as M. smegmatis sensu stricto, are included in a discussion of the M. smegmatis group. Laboratory diagnosis of RGM using phenotypic methods such as biochemical testing and high-performance liquid chromatography and molecular methods of diagnosis are also discussed. The latter includes PCR-restriction fragment length polymorphism analysis, hybridization, ribotyping, and sequence analysis. Susceptibility testing and antibiotic susceptibility patterns of the RGM are also annotated, along with the current recommendations from the National Committee for Clinical Laboratory Standards (NCCLS) for mycobacterial susceptibility testing.

Recent advances in biochemical and molecular diagnostics for the rapid detection of antibiotic-resistant Enterobacteriaceae: a focus on ß-lactam resistance.

PubMed

Decousser, Jean-Winoc; Poirel, Laurent; Nordmann, Patrice

2017-04-01

The rapid detection of resistance is a challenge for clinical microbiologists who wish to prevent deleterious individual and collective consequences such as (i) delaying efficient antibiotic therapy, which worsens the survival rate of the most severely ill patients, or (ii) delaying the isolation of the carriers of multidrug-resistant bacteria and promoting outbreaks; this last consequence is of special concern, and there are an increasing number of approaches and market-based solutions in response. Areas covered: From simple, cheap biochemical tests to whole-genome sequencing, clinical microbiologists must select the most adequate phenotypic and genotypic tools to promptly detect and confirm β-lactam resistance from cultivated bacteria or from clinical specimens. Here, the authors review the published literature from the last 5 years about the primary technical approaches and commercial laboratory reagents for these purposes, including molecular, biochemical and immune assays. Furthermore, the authors discuss their intrinsic and relative performance, and we challenge their putative clinical impact. Expert commentary: Until the availability of fully automated wet and dry whole genome sequencing solutions, microbiologists should focus on inexpensive biochemical tests for cultured isolates or monomicrobial clinical specimen and on using the expensive molecular PCR-based strategies for the targeted screening of complex biological environments.

Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study.

PubMed

van Halsema, Clare L; Chihota, Violet N; Gey van Pittius, Nicolaas C; Fielding, Katherine L; Lewis, James J; van Helden, Paul D; Churchyard, Gavin J; Grant, Alison D

2015-01-01

The clinical relevance of nontuberculous mycobacteria (NTM), detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively. Of 232 individuals included (228 (98%) male, median age 44 years), M. gordonae (60 individuals), M. kansasii (50), and M. avium complex (MAC: 38) were the commonest species. Of 38 MAC isolates, only 2 (5.3%) were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77%) among those tested. No differences were found in probability of death or medical separation by NTM species. M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment.

Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study

PubMed Central

van Halsema, Clare L.; Chihota, Violet N.; Gey van Pittius, Nicolaas C.; Fielding, Katherine L.; Lewis, James J.; van Helden, Paul D.; Churchyard, Gavin J.; Grant, Alison D.

2015-01-01

Background. The clinical relevance of nontuberculous mycobacteria (NTM), detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. Methods. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and clinical records and chest radiographs reviewed retrospectively. Results. Of 232 individuals included (228 (98%) male, median age 44 years), M. gordonae (60 individuals), M. kansasii (50), and M. avium complex (MAC: 38) were the commonest species. Of 38 MAC isolates, only 2 (5.3%) were from smear-positive sputum specimens and 30/38 grew in liquid but not solid culture. MAC was especially prevalent among symptomatic, HIV-positive individuals. HIV prevalence was high: 57/74 (77%) among those tested. No differences were found in probability of death or medical separation by NTM species. Conclusions. M. gordonae, M. kansasii, and MAC were the commonest NTM among miners with suspected tuberculosis, with most MAC from smear-negative specimens in liquid culture only. HIV testing and identification of key pathogenic NTM in this setting are essential to ensure optimal treatment. PMID:26180817

Big data, miniregistries: a rapid-turnaround solution to get quality improvement data into the hands of medical specialists.

PubMed

Herrinton, Lisa J; Liu, Liyan; Altschuler, Andrea; Dell, Richard; Rabrenovich, Violeta; Compton-Phillips, Amy L

2015-01-01

The cost to build and to maintain traditional registries for many dire, complex, low-frequency conditions is prohibitive. The authors used accessible technology to develop a platform that would generate miniregistries (small, routinely updated datasets) for surveillance, to identify patients who were missing elected utilization and to influence clinicians to change practices to improve care. The platform, tested in 5 medical specialty departments, enabled the specialists to rapidly and effectively communicate clinical questions, knowledge of disease, clinical workflows, and improve opportunities. Each miniregistry required 1 to 2 hours of collaboration by a specialist. Turnaround was 1 to 14 days.

Implementing resilience engineering for healthcare quality improvement using the CARE model: a feasibility study protocol.

PubMed

Anderson, J E; Ross, A J; Back, J; Duncan, M; Snell, P; Walsh, K; Jaye, P

2016-01-01

Resilience engineering (RE) is an emerging perspective on safety in complex adaptive systems that emphasises how outcomes emerge from the complexity of the clinical environment. Complexity creates the need for flexible adaptation to achieve outcomes. RE focuses on understanding the nature of adaptations, learning from success and increasing adaptive capacity. Although the philosophy is clear, progress in applying the ideas to quality improvement has been slow. The aim of this study is to test the feasibility of translating RE concepts into practical methods to improve quality by designing, implementing and evaluating interventions based on RE theory. The CARE model operationalises the key concepts and their relationships to guide the empirical investigation. The settings are the Emergency Department and the Older Person's Unit in a large London teaching hospital. Phases 1 and 2 of our work, leading to the development of interventions to improve the quality of care, are described in this paper. Ethical approval has been granted for these phases. Phase 1 will use ethnographic methods, including observation of work practices and interviews with staff, to understand adaptations and outcomes. The findings will be used to collaboratively design, with clinical staff in interactive design workshops, interventions to improve the quality of care. The evaluation phase will be designed and submitted for ethical approval when the outcomes of phases 1 and 2 are known. Study outcomes will be knowledge about the feasibility of applying RE to improve quality, the development of RE theory and a validated model of resilience in clinical work which can be used to guide other applications. Tools, methods and practical guidance for practitioners will also be produced, as well as specific knowledge of the potential effectiveness of the implemented interventions in emergency and older people's care. Further studies to test the application of RE at a larger scale will be required, including studies of other healthcare settings, organisational contexts and different interventions.

The importance of relational coordination and reciprocal learning for chronic illness care within primary care teams.

PubMed

Noël, Polly Hitchcock; Lanham, Holly J; Palmer, Ray F; Leykum, Luci K; Parchman, Michael L

2013-01-01

Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with Type 2 diabetes in small primary care practices. Practice members (i.e., physicians, nonphysician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics and tested for mediation effects. A total of 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p < .01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual- and practice-level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members.

The Importance of Relational Coordination and Reciprocal Learning for Chronic Illness Care within Primary Care Teams

PubMed Central

Noël, Polly Hitchcock; Lanham, Holly J.; Palmer, Ray F.; Leykum, Luci K.; Parchman, Michael L.

2012-01-01

Background Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. Purposes Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. Methodology/Approach We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with type 2 diabetes in small primary care practices. Practice members (i.e., physicians, non-physician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics, and tested for mediation effects. Findings 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p<.01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual and practice level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. Practice Implications Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members. PMID:22310483

New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine

PubMed Central

Masuda, Koichi

2010-01-01

The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on preclinical models for safety and efficacy testing. Although the issues associated with model selection for studying orthopedic diseases or treatments have been discussed often, the multifaceted challenges associated with developing intervertebral disc tissue engineering therapies require special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: (1) the unmet clinical need, (2) appropriate models for safety and efficacy testing, (3) the need for standardized model systems, and (4) the translational pathways leading to a clinical trial. For preclinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), and then large animals (goat and minipig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early postoperative period. PMID:19903086

Pre- and post-test genetic counseling for chromosomal and Mendelian disorders.

PubMed

Fonda Allen, Jill; Stoll, Katie; Bernhardt, Barbara A

2016-02-01

Genetic carrier screening, prenatal screening for aneuploidy, and prenatal diagnostic testing have expanded dramatically over the past 2 decades. Driven in part by powerful market forces, new complex testing modalities have become available after limited clinical research. The responsibility for offering these tests lies primarily on the obstetrical care provider and has become more burdensome as the number of testing options expands. Genetic testing in pregnancy is optional, and decisions about undergoing tests, as well as follow-up testing, should be informed and based on individual patients' values and needs. Careful pre- and post-test counseling is central to supporting informed decision-making. This article explores three areas of technical expansion in genetic testing: expanded carrier screening, non-invasive prenatal screening for fetal aneuploidies using cell-free DNA, and diagnostic testing using fetal chromosomal microarray testing, and provides insights aimed at enabling the obstetrical practitioner to better support patients considering these tests. Copyright © 2016 Elsevier Inc. All rights reserved.

The clinical educator and complexity: a review.

PubMed

Schoo, Adrian; Kumar, Koshila

2018-02-08

Complexity science perspectives have helped in examining fundamental assumptions about learning and teaching in the health professions. The implications of complexity thinking for how we understand the role and development of the clinical educator is less well articulated. This review article outlines: the key principles of complexity science; a conceptual model that situates the clinical educator in a complex system; and the implications for the individual, organisation and the system. Our conceptual model situates the clinical educator at the centre of a complex and dynamic system spanning four domains and multiple levels. The four domains are: personal (encompassing personal/professional needs and expectations); health services (health agencies and their consumers); educational (educational institutions and their health students); and societal (local community/region and government). The system also comprises: micro or individual, meso or organisational, and macro or socio-political levels. Our model highlights that clinical educators are situated within a complex system comprising different agents and connections. It emphasises that individuals, teams and organisations need to recognise and be responsive to the unpredictability, interconnectedness and evolving nature of this system. Importantly, our article also calls for an epistemological shift from faculty development to capacity building in health professions education, aimed at developing individual, team, organisational and system capabilities to work with(in) complexity. Clinical educators are situated within a complex system comprising different agents and connections. © 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Candida glabrata species complex prevalence and antifungal susceptibility testing in a culture collection: First description of Candida nivariensis in Argentina.

PubMed

Morales-López, Soraya Eugenia; Taverna, Constanza G; Bosco-Borgeat, María Eugenia; Maldonado, Ivana; Vivot, Walter; Szusz, Wanda; Garcia-Effron, Guillermo; Córdoba, Susana B

2016-12-01

The presence of the cryptic species belonging to the Candida glabrata complex has not been studied in Argentina. We analyzed a collection of 117 clinical isolates of C. glabrata complex belonging to a National Culture Collection of Instituto Nacional de Microbiología "Dr. Carlos G. Malbrán" from Argentina (40 isolates from blood samples, 18 from other normally sterile sites, 20 from vagina, 14 from urine, 7 from oral cavity, 3 from catheter, 1 from a stool sample and 14 isolates whose clinical origin was not recorded). The aims of this work were to determine the prevalence of the cryptic species Candida nivariensis and Candida bracarensis and to evaluate the susceptibility profile of isolates against nine antifungal drugs. Identification was carried out by using classical phenotypic tests, CHROMagar™ Candida, PCR and MALDI-TOF. The minimal inhibitory concentrations of amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, voriconazole, ketoconazole, posaconazole, caspofungin and anidulafungin were determined according to the EDef 7.3 (EUCAST) reference document. Of the 117 isolates, 114 were identified as C. glabrata and three as C. nivariensis by using PCR and MALDI-TOF. There were no major differences between C. nivariensis and C. glabrata susceptibility profiles. No resistant strains were found to echinocandins. We have found that the percentage of C. nivariensis in our culture collection was 2.56. This is the first description of C. nivariensis in Argentina, and data obtained could contribute to the knowledge of the epidemiology of this cryptic species.

Detection of LGI1 and CASPR2 antibodies with a commercial cell-based assay in patients with very high VGKC-complex antibody levels.

PubMed

Yeo, T; Chen, Z; Chai, J Y H; Tan, K

2017-07-15

The presence of VGKC-complex antibodies, without LGI1/CASPR2 antibodies, as a standalone marker for neurological autoimmunity remains controversial. Additionally, the lack of an unequivocal VGKC-complex antibody cut-off level defining neurological autoimmunity makes it important to test for monospecific antibodies. We aim to determine the performance characteristics of a commercial assay (Euroimmun, Lübeck, Germany) for LGI1/CASPR2 antibody detection in patients with very high VGKC-complex antibody levels and report their clinico-serological associations. We identified 8 patients in our cohort with the highest VGKC-complex antibody levels (median 2663.5pM, range 933-6730pM) with VGKC-complex antibody related syndromes (Group A). Two other groups were identified; 1 group with suspected neuronal surface antibody syndromes and negative for VGKC-complex antibodies (Group B, n=8), and another group with cerebellar ataxia and negative for onconeuronal antibodies (Group C, n=8). Seven out of 8 patients (87.5%) in Group A had LGI1 and/or CASPR2 antibodies. One Group B patient had LGI1 antibodies but was negative on re-testing with a live cell assay. No Group C patients had monospecific antibodies. Inter-rater reliability was high; combining Groups A and B patients, the kappa statistic was 0.87 and 1.0 for LGI1 and CASPR2 antibodies respectively. We demonstrated that a high proportion of patients with very high VGKC-complex antibody levels and relevant clinical syndromes have LGI1 and/or CASPR2 antibodies detected by the commercial assay. Our findings lend support to the use of the assay for rapid and reliable detection of LGI1 and CASPR2 antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct-to-consumer genetic testing in Slovenia: availability, ethical dilemmas and legislation.

PubMed

Vrecar, Irena; Peterlin, Borut; Teran, Natasa; Lovrecic, Luca

2015-01-01

Over the last few years, many private companies are advertising direct-to-consumer genetic testing (DTC GT), mostly with no or only minor clinical utility and validity of tests and without genetic counselling. International professional community does not approve provision of DTC GT and situation in some EU countries has been analysed already. The aim of our study was to analyse current situation in the field of DTC GT in Slovenia and related legal and ethical issues. Information was retrieved through internet search, performed independently by two authors, structured according to individual private company and the types of offered genetic testing. Five private companies and three Health Insurance Companies offer DTC GT and it is provided without genetic counselling. Available tests include testing for breast cancer, tests with other health-related information (complex diseases, drug responses) and other tests (nutrigenetic, ancestry, paternity). National legislation is currently being developed and Council of Experts in Medical Genetics has issued an opinion about Genetic Testing and Commercialization of Genetic Tests in Slovenia. Despite the fact that Slovenia has signed the Additional protocol to the convention on human rights and biomedicine, concerning genetic testing for health purposes, DTC GT in Slovenia is present and against all international recommendations. There is lack of or no medical supervision, clinical validity and utility of tests and inappropriate genetic testing of minors is available. There is urgent need for regulation of ethical, legal, and social aspects. National legislation on DTC GT is being prepared.

National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities.

PubMed

Ricordi, Camillo; Goldstein, Julia S; Balamurugan, A N; Szot, Gregory L; Kin, Tatsuya; Liu, Chengyang; Czarniecki, Christine W; Barbaro, Barbara; Bridges, Nancy D; Cano, Jose; Clarke, William R; Eggerman, Thomas L; Hunsicker, Lawrence G; Kaufman, Dixon B; Khan, Aisha; Lafontant, David-Erick; Linetsky, Elina; Luo, Xunrong; Markmann, James F; Naji, Ali; Korsgren, Olle; Oberholzer, Jose; Turgeon, Nicole A; Brandhorst, Daniel; Chen, Xiaojuan; Friberg, Andrew S; Lei, Ji; Wang, Ling-Jia; Wilhelm, Joshua J; Willits, Jamie; Zhang, Xiaomin; Hering, Bernhard J; Posselt, Andrew M; Stock, Peter G; Shapiro, A M James; Chen, Xiaojuan

2016-11-01

Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed. © 2016 by the American Diabetes Association.

National Institutes of Health–Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities

PubMed Central

Balamurugan, A.N.; Szot, Gregory L.; Kin, Tatsuya; Liu, Chengyang; Czarniecki, Christine W.; Barbaro, Barbara; Bridges, Nancy D.; Cano, Jose; Clarke, William R.; Eggerman, Thomas L.; Hunsicker, Lawrence G.; Kaufman, Dixon B.; Khan, Aisha; Lafontant, David-Erick; Linetsky, Elina; Luo, Xunrong; Markmann, James F.; Naji, Ali; Korsgren, Olle; Oberholzer, Jose; Turgeon, Nicole A.; Brandhorst, Daniel; Chen, Xiaojuan; Friberg, Andrew S.; Lei, Ji; Wang, Ling-jia; Wilhelm, Joshua J.; Willits, Jamie; Zhang, Xiaomin; Hering, Bernhard J.; Posselt, Andrew M.; Stock, Peter G.; Shapiro, A.M. James

2016-01-01

Eight manufacturing facilities participating in the National Institutes of Health–sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed. PMID:27465220

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines.

PubMed

Braverman, Nancy E; Raymond, Gerald V; Rizzo, William B; Moser, Ann B; Wilkinson, Mark E; Stone, Edwin M; Steinberg, Steven J; Wangler, Michael F; Rush, Eric T; Hacia, Joseph G; Bose, Mousumi

2016-03-01

Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care. Copyright © 2015 Elsevier Inc. All rights reserved.

The Impact of Telehealth and Care Coordination on the Number and Type of Clinical Visits for Children With Medical Complexity.

PubMed

McKissick, Holly D; Cady, Rhonda G; Looman, Wendy S; Finkelstein, Stanley M

The purpose of this analysis was to evaluate the effects of an advanced practice nurse-delivered telehealth intervention on health care use by children with medical complexity (CMC). Because CMC account for a large share of health care use costs, finding effective ways to care for them is an important challenge requiring exploration. This was a secondary analysis of data from a randomized clinical trial with a control group and two intervention groups. The focus of the analysis was planned and unplanned clinical and therapy visits by CMC over a 30-month data collection period. Nonparametric tests were used to compare visit counts among and within the three groups. The number of unplanned visits decreased over time across all groups, with the greatest decrease in the video telehealth intervention group. Planned visits were higher in the video telehealth group across all time periods. Advanced practice registered nurse-delivered telehealth care coordination may support a shift from unplanned to planned health care service use among CMC. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

Thiourea derivatives as chelating agents for bioconjugation of rhenium and technetium.

PubMed

Gomez, J D Castillo; Hagenbach, A; Gerling-Driessen, U I M; Koksch, B; Beindorff, N; Brenner, W; Abram, U

2017-10-31

Potential tetradentate thiocarbamoylbenzamidine derivatives H 4 L have been synthesized from the corresponding benzimidoyl chlorides and triglycine. They are suitable chelating agents for the oxidotechnetium(v) and oxidorhenium(v) cores and form stable, neutral [MO(HL)] complexes with an equatorial SN 3 coordination sphere and an additional, uncoordinated carboxylic group, which can be used for bioconjugation. Representatives of the rhenium and 99 Tc products have been isolated and analyzed with spectroscopic methods and X-ray diffraction. Bioconjugates of these complexes with angiotensin-II have been synthesized and structurally characterized. Analogous 99m Tc complexes have been produced and tested in vitro and in vivo. The experiments confirm a considerable stability for the [ 99m Tc(HL)] product as well as for its bioconjugate and recommend this class of compounds for further bioconjugation studies towards clinical applications.

Information retrieval pathways for health information exchange in multiple care settings.

PubMed

Kierkegaard, Patrick; Kaushal, Rainu; Vest, Joshua R

2014-11-01

To determine which health information exchange (HIE) technologies and information retrieval pathways healthcare professionals relied on to meet their information needs in the context of laboratory test results, radiological images and reports, and medication histories. Primary data was collected over a 2-month period across 3 emergency departments, 7 primary care practices, and 2 public health clinics in New York state. Qualitative research methods were used to collect and analyze data from semi-structured interviews and participant observation. The study reveals that healthcare professionals used a complex combination of information retrieval pathways for HIE to obtain clinical information from external organizations. The choice for each approach was setting- and information-specific, but was also highly dynamic across users and their information needs. Our findings about the complex nature of information sharing in healthcare provide insights for informatics professionals about the usage of information; indicate the need for managerial support within each organization; and suggest approaches to improve systems for organizations and agencies working to expand HIE adoption.

Myopathology of Adult and Paediatric Mitochondrial Diseases

PubMed Central

Phadke, Rahul

2017-01-01

Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA (nDNA) and mitochondrial DNA (mtDNA)) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various omics platforms in unravelling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype–phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field. PMID:28677615

Molecular identification and in vitro antifungal susceptibility of Scedosporium complex isolates from high-human-activity sites in Mexico.

PubMed

Elizondo-Zertuche, Mariana; de J Treviño-Rangel, Rogelio; Robledo-Leal, Efrén; Luna-Rodríguez, Carolina E; Martínez-Fierro, Margarita L; Rodríguez-Sánchez, Iram P; González, Gloria M

2017-01-01

The genus Scedosporium is a complex of ubiquitous moulds associated with a wide spectrum of clinical entities, with high mortality principally in immunocompromised hosts. Ecology of these microorganisms has been studied performing isolations from environmental sources, showing a preference for human-impacted environments. This study aimed to evaluate the presence and antifungal susceptibility of Scedosporium complex species in soil samples collected in high-human-activity sites of Mexico. A total of 97 soil samples from 25 Mexican states were collected. Identifications were performed by microscopic morphology and confirmed by sequencing of the rDNA (internal transcribed spacer [ITS], D1/D2) and β-tubulin partial loci. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) protocols. Soil samples of urban gardens and industrial parks constituted the best sources for isolation of Scedosporium complex species. S. apiospermum sensu stricto was the most prevalent species (69%), followed by S. boydii (16%). Voriconazole (minimal inhibitory concentration [MIC] geometric mean ≤2.08 µg/mL), followed by posaconazole (MIC geometric mean ≤2.64 µg/mL), exhibited excellent in vitro activity for most species. Amphotericin B and fluconazole demonstrated limited antifungal activity, and all of the strains were resistant to echinocandins. This is the first report in Mexico of environmental distribution and antifungal in vitro susceptibility of these emergent pathogens.

The 'species complex' issue in clinically relevant fungi: A case study in Scedosporium apiospermum.

PubMed

Chen, Min; Zeng, Jingsi; De Hoog, G Sybren; Stielow, Benjamin; Gerrits Van Den Ende, A H G; Liao, Wanqing; Lackner, Michaela

2016-02-01

The genus Scedosporium currently comprises six species, Scedosporium apiospermum, Scedosporium boydii, Pseudallescheria angusta, Scedosporium minutisporum, Scedosporium dehoogii, and Scedosporium aurantiacum, most of which can be distinguished with the primary fungal DNA barcode, the ITS1/2 region of the rDNA gene cluster. In the present study, four additional genetic loci were explored from a phylogenetic point of view enabling a barcoding approach based on K2P pairwise distances to resolve the taxa Scedosporium. We included partial γ-actin (ACT), β-tubulin (BT2), elongation factor 1α (TEF1), and the small ribosomal protein 60S L10 (L1) (RP60S). Phylogenetic inference of each marker individually showed that four out of six species within Scedosporium can be distinguished unambiguously, while strains of S. apiospermum, S. boydii, and P. angusta showed occasional recombination, and accordingly, no genealogical concordance between markers was obtainable. We defined S. apiospermum, S. boydii, and P. angusta as the 'S. apiospermum species complex' since observed differences were not consistent between lineages, and no clinical differences are known between entities within the complex. While BT2 revealed the best performance among the genetic loci tested at the lineage level, barcoding of the ITS region is sufficient for distinction of all entities in Scedosporium at the species or 'complex' level. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Education research: a case-based bioethics curriculum for neurology residents.

PubMed

Tolchin, Benjamin; Willey, Joshua Z; Prager, Kenneth

2015-03-31

In 2012, the American Academy of Neurology (AAN) updated and expanded its ethics curriculum into Practical Ethics in Clinical Neurology, a case-based ethics curriculum for neurologists. We piloted a case-based bioethics curriculum for neurology residents using the framework and topics recommended by the AAN, matched to clinical cases drawn from Columbia's neurologic services. Our primary outcome was residents' ability to analyze and manage ethically complex cases as measured on precurriculum and postcurriculum multiple-choice quizzes. Secondary outcomes included precurriculum and postcurriculum self-assessed comfort in discussing and managing ethically complex cases, as well as attendance at ethics discussion sessions as compared to attendance at other didactic sessions. Resident performance on quizzes improved from 75.8% to 86.7% (p = 0.02). Comfort in discussing ethically complex cases improved from 6.4 to 7.4 on a 10-point scale (p = 0.03). Comfort in managing such cases trended toward improvement but did not reach statistical significance. Attendance was significantly better at ethics discussions (73.5%) than at other didactic sessions (61.7%, p = 0.04). Our formal case-based ethics curriculum for neurology residents, based on core topics drawn from the AAN's published curricula, was successfully piloted. Our study showed a statistically significant improvement in residents' ability to analyze and manage ethically complex cases as measured by multiple-choice tests and self-assessments. © 2015 American Academy of Neurology.

Patients' perception of risk: informed choice in prenatal testing for foetal aneuploidy.

PubMed

Choolani, Mahesh; Biswas, Arijit

2012-10-01

Each of us perceives risk differently, and so do our patients. This perception of risk gets even more complex when multiple individuals and interactions are involved: the doctor, the patient-pregnant mother, the spouse-father and the foetus-unborn child. In this review, we address the relationship between different levels of information gathering, from clinical data to experiential knowledge - data, information, knowledge, perception, attitude, wisdom - and how these would impact the perception of risk and informed consent. We discuss how patients might interpret the risks of the same event differently based upon past experiences, and suggest how risk data could be presented more meaningfully for patients and family to assimilate for informed decision making. Finally, we demonstrate how patients' expectations and risk management can impact scientific research and clinical progress by way of the most topical subject of risk screening in pregnancy - non-invasive prenatal testing using cell-free DNA in maternal plasma.

[Molecular farming has come of age].

PubMed

Chiao, J S

2001-07-01

Important development in plant biotechnology has been ushered in the 1990s, the most astounding field is the establishment of various transgenic crops, including cotton, corn, rice, tomato etc. In addition, utilization of transgenic plants for the generation of antibodies, gene epitopes and complex proteins has drawn much attention recently. Among these results, the use of plant parts with inducted antigens such as cholera toxin B subunit, toxigenic E. coli LT-B subunit as oral vaccines is attractive as a new route of medication. Considering their effectiveness as vaccines in animal and clinical tests, and simple agricultural practice for large scale production it is anticipated that these antibodies are bound to offer impact to health care for people of the Third World. In this short review, the laboratory and successful clinical test, merits and demerits in comparison with the currently used bioreactors, methods of extraction, and cost estimation of transgenic plant products for medical purposes are briefly reviewed.

The Systems SOAP Note: A Systems Learning Tool.

PubMed

Mitsuishi, Fumi; Young, John Q; Leary, Mark; Dilley, James; Mangurian, Christina

2016-02-01

Systems-based practice (SBP) is the only Accreditation Council for Graduate Medical Education (ACGME) competency concerned with public health and is relatively neglected in residency curricula. A tool was developed and pilot-tested to improve SBP learning on inpatient psychiatry rotations. A four-step approach was used: (1) literature review, (2) expert consultation, (3) tool development, and (4) pilot testing on four cases and evaluation for completion time and preliminary efficacy. Out of 51 SBP articles, six (12%) focused on psychiatric residency programs, and none had a practical SBP learning tool. The "systems SOAP (subjective, objective, assessment, plan) note" (S-SOAP) was structured after a clinical SOAP note and was easy to use (mean completion time = 60 min), and residents self-reported more insight into systems issues. The S-SOAP tool was effectively integrated into clinical experience and provided insight into systemic complexities. Future research should assess SBP knowledge acquisition after the use of such tools.

Hand stereotypies distinguish Rett syndrome from autism disorder.

PubMed

Goldman, Sylvie; Temudo, Teresa

2012-07-01

Rett syndrome (RTT) and autism disorder (AD) are 2 neurodevelopmental disorders of early life that share phenotypic features, one being hand stereotypies. Distinguishing RTT from AD often represents a challenge, and given their distinct long-term prognoses, this issue may have far-reaching implications. With the advances in genetic testing, the contribution of clinical manifestations in distinguishing RTT from AD has been overlooked. A comparison of hand stereotypies in 20 children with RTT and 20 with AD was performed using detailed analyses of videotaped standardized observations. Striking differences are observed between RTT and AD children. In RTT, hand stereotypies are predominantly complex, continuous, localized to the body midline, and involving mouthing. Conversely, in AD children, hand stereotypies are simple, bilateral, intermittent, and often involving objects. These results provide important clinical signs useful to the differential diagnosis of RTT versus AD, especially when genetic testing for RTT is not an option. Copyright © 2012 Movement Disorder Society.

Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style?

PubMed Central

Lang, Katie; Lloyd, Samantha; Khondoker, Mizanur; Simic, Mima; Treasure, Janet; Tchanturia, Kate

2015-01-01

Objective This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored. Method The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures. Results There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs. Conclusion Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed. PMID:26133552

Cardiac examination and the effect of dual-processing instruction in a cardiopulmonary simulator.

PubMed

Sibbald, Matt; McKinney, James; Cavalcanti, Rodrigo B; Yu, Eric; Wood, David A; Nair, Parvathy; Eva, Kevin W; Hatala, Rose

2013-08-01

Use of dual-processing has been widely touted as a strategy to reduce diagnostic error in clinical medicine. However, this strategy has not been tested among medical trainees with complex diagnostic problems. We sought to determine whether dual-processing instruction could reduce diagnostic error across a spectrum of experience with trainees undertaking cardiac physical exam. Three experiments were conducted using a similar design to teach cardiac physical exam using a cardiopulmonary simulator. One experiment was conducted in each of three groups: experienced, intermediate and novice trainees. In all three experiments, participants were randomized to receive undirected or dual-processing verbal instruction during teaching, practice and testing phases. When tested, dual-processing instruction did not change the probability assigned to the correct diagnosis in any of the three experiments. Among intermediates, there was an apparent interaction between the diagnosis tested and the effect of dual-processing instruction. Among relative novices, dual processing instruction may have dampened the harmful effect of a bias away from the correct diagnosis. Further work is needed to define the role of dual-processing instruction to reduce cognitive error. This study suggests that it cannot be blindly applied to complex diagnostic problems such as cardiac physical exam.

Conflicts of interest in translational research

PubMed Central

Parks, Malcolm R; Disis, Mary L

2004-01-01

Translational research requires a team approach to scientific inquiry and product development. Translational research teams consist of basic and clinical scientists who can be members of both academic and industrial communities. The conception, pre-clinical testing, and clinical evaluation of a diagnostic or therapeutic approach demands an intense interaction between investigators with diverse backgrounds. As the barriers between industry and academia are removed, issues of potential conflict of interest become more complex. Translational researchers must become aware of the situations which constitute conflict of interest and understand how such conflicts can impact their research programs. Finally, the translational research community must participate in the dialogue ongoing in the public and private sectors and help shape the rules that will govern conflicts that arise during the evolution of their research programs. PMID:15301694

Interpretative commenting.

PubMed

Vasikaran, Samuel

2008-08-01

* Clinical laboratories should be able to offer interpretation of the results they produce. * At a minimum, contact details for interpretative advice should be available on laboratory reports.Interpretative comments may be verbal or written and printed. * Printed comments on reports should be offered judiciously, only where they would add value; no comment preferred to inappropriate or dangerous comment. * Interpretation should be based on locally agreed or nationally recognised clinical guidelines where available. * Standard tied comments ("canned" comments) can have some limited use.Individualised narrative comments may be particularly useful in the case of tests that are new, complex or unfamiliar to the requesting clinicians and where clinical details are available. * Interpretative commenting should only be provided by appropriately trained and credentialed personnel. * Audit of comments and continued professional development of personnel providing them are important for quality assurance.

Practical considerations to guide development of access controls and decision support for genetic information in electronic medical records.

PubMed

Darcy, Diana C; Lewis, Eleanor T; Ormond, Kelly E; Clark, David J; Trafton, Jodie A

2011-11-02

Genetic testing is increasingly used as a tool throughout the health care system. In 2011 the number of clinically available genetic tests is approaching 2,000, and wide variation exists between these tests in their sensitivity, specificity, and clinical implications, as well as the potential for discrimination based on the results. As health care systems increasingly implement electronic medical record systems (EMRs) they must carefully consider how to use information from this wide spectrum of genetic tests, with whom to share information, and how to provide decision support for clinicians to properly interpret the information. Although some characteristics of genetic tests overlap with other medical test results, there are reasons to make genetic test results widely available to health care providers and counterbalancing reasons to restrict access to these test results to honor patient preferences, and avoid distracting or confusing clinicians with irrelevant but complex information. Electronic medical records can facilitate and provide reasonable restrictions on access to genetic test results and deliver education and decision support tools to guide appropriate interpretation and use. This paper will serve to review some of the key characteristics of genetic tests as they relate to design of access control and decision support of genetic test information in the EMR, emphasizing the clear need for health information technology (HIT) to be part of optimal implementation of genetic medicine, and the importance of understanding key characteristics of genetic tests when designing HIT applications.

Bradykinesia and bradyphrenia revisited: patterns of subclinical deficit in motor speed and cognitive functioning in head-injured patients with good recovery.

PubMed

Gray, C; Cantagallo, A; Della Sala, S; Basaglia, N

1998-05-01

Twenty-four patients, showing a good clinical recovery from coma-inducing injury and coping well with the activities of everyday living, were tested, at least 1 year after trauma, on motor speed and reaction time, and given a neuropsychological examination. While the patients generally performed within the normal range on the neuropsychological tests, their motor speeds and reaction times--both simple (SRT) and complex (CRT)--were significantly slower than those of matched controls. This points to a subclinical bradykinesia. The patients' motor speed scores did not correlate significantly with any of the neuropsychological tests; nor did SRT or CRT. While the difference between simple and complex reaction time was significantly greater in the patient group, the percentage difference was not significantly different between the two groups. Collectively, these results suggest that bradykinesia and bradyphrenia do not necessarily overlap. Finally, there was no significant correlation between motor performance and severity of original injury, whether the latter was measured by number and size of lesions or by duration of post-traumatic amnesia.

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.

The script concordance test in radiation oncology: validation study of a new tool to assess clinical reasoning

PubMed Central

Lambert, Carole; Gagnon, Robert; Nguyen, David; Charlin, Bernard

2009-01-01

Background The Script Concordance test (SCT) is a reliable and valid tool to evaluate clinical reasoning in complex situations where experts' opinions may be divided. Scores reflect the degree of concordance between the performance of examinees and that of a reference panel of experienced physicians. The purpose of this study is to demonstrate SCT's usefulness in radiation oncology. Methods A 90 items radiation oncology SCT was administered to 155 participants. Three levels of experience were tested: medical students (n = 70), radiation oncology residents (n = 38) and radiation oncologists (n = 47). Statistical tests were performed to assess reliability and to document validity. Results After item optimization, the test comprised 30 cases and 70 questions. Cronbach alpha was 0.90. Mean scores were 51.62 (± 8.19) for students, 71.20 (± 9.45) for residents and 76.67 (± 6.14) for radiation oncologists. The difference between the three groups was statistically significant when compared by the Kruskall-Wallis test (p < 0.001). Conclusion The SCT is reliable and useful to discriminate among participants according to their level of experience in radiation oncology. It appears as a useful tool to document the progression of reasoning during residency training. PMID:19203358

Logistic regression function for detection of suspicious performance during baseline evaluations using concussion vital signs.

PubMed

Hill, Benjamin David; Womble, Melissa N; Rohling, Martin L

2015-01-01

This study utilized logistic regression to determine whether performance patterns on Concussion Vital Signs (CVS) could differentiate known groups with either genuine or feigned performance. For the embedded measure development group (n = 174), clinical patients and undergraduate students categorized as feigning obtained significantly lower scores on the overall test battery mean for the CVS, Shipley-2 composite score, and California Verbal Learning Test-Second Edition subtests than did genuinely performing individuals. The final full model of 3 predictor variables (Verbal Memory immediate hits, Verbal Memory immediate correct passes, and Stroop Test complex reaction time correct) was significant and correctly classified individuals in their known group 83% of the time (sensitivity = .65; specificity = .97) in a mixed sample of young-adult clinical cases and simulators. The CVS logistic regression function was applied to a separate undergraduate college group (n = 378) that was asked to perform genuinely and identified 5% as having possibly feigned performance indicating a low false-positive rate. The failure rate was 11% and 16% at baseline cognitive testing in samples of high school and college athletes, respectively. These findings have particular relevance given the increasing use of computerized test batteries for baseline cognitive testing and return-to-play decisions after concussion.

Identification of small molecules that improve ATP synthesis defects conferred by Leber’s hereditary optic neuropathy mutations

PubMed Central

Datta, Sandipan; Tomilov, Alexey; Cortopassi, Gino

2016-01-01

Inherited mitochondrial complex I mutations cause blinding Leber's hereditary Optic Neuropathy (LHON), for which no curative therapy exists. A specific biochemical consequence of LHON mutations in the presence of trace rotenone was observed: deficient complex I-dependent ATP synthesis (CIDAS) and mitochondrial O2 consumption, proportional to the clinical severity of the three primary LHON mutations. We optimized a high-throughput assay of CIDAS to screen 1600 drugs to 2, papaverine and zolpidem, which protected CIDAS in LHON cells concentration-dependently. TSPO and cAMP were investigated as protective mechanisms, but a conclusive mechanism remains to be elucidated; next steps include testing in animal models. PMID:27497748

Systematic review of autosomal recessive ataxias and proposal for a classification.

PubMed

Beaudin, Marie; Klein, Christopher J; Rouleau, Guy A; Dupré, Nicolas

2017-01-01

The classification of autosomal recessive ataxias represents a significant challenge because of high genetic heterogeneity and complex phenotypes. We conducted a comprehensive systematic review of the literature to examine all recessive ataxias in order to propose a new classification and properly circumscribe this field as new technologies are emerging for comprehensive targeted gene testing. We searched Pubmed and Embase to identify original articles on recessive forms of ataxia in humans for which a causative gene had been identified. Reference lists and public databases, including OMIM and GeneReviews, were also reviewed. We evaluated the clinical descriptions to determine if ataxia was a core feature of the phenotype and assessed the available evidence on the genotype-phenotype association. Included disorders were classified as primary recessive ataxias, as other complex movement or multisystem disorders with prominent ataxia, or as disorders that may occasionally present with ataxia. After removal of duplicates, 2354 references were reviewed and assessed for inclusion. A total of 130 articles were completely reviewed and included in this qualitative analysis. The proposed new list of autosomal recessive ataxias includes 45 gene-defined disorders for which ataxia is a core presenting feature. We propose a clinical algorithm based on the associated symptoms. We present a new classification for autosomal recessive ataxias that brings awareness to their complex phenotypes while providing a unified categorization of this group of disorders. This review should assist in the development of a consensus nomenclature useful in both clinical and research applications.

Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: comparison of primer sets for Cryptococcus neoformans and Cryptococcus gattii species complex.

PubMed

Martins, Marilena dos Anjos; Brighente, Kate Bastos Santos; Matos, Terezinha Aparecida de; Vidal, Jose Ernesto; Hipólito, Daise Damaris Carnietto de; Pereira-Chioccola, Vera Lucia

2015-01-01

This study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples. The sensitivity and specificity of the methodology were evaluated using eight Cryptococcus neoformans/C. gattii species complex reference strains and 165 cerebrospinal fluid samples from patients with neurological diseases divided into two groups: 96 patients with cryptococcal meningitis and AIDS; and 69 patients with other neurological opportunistic diseases (CRL/AIDS). Two primer sets were tested (CN4-CN5 and the multiplex CNa70S-CNa70A/CNb49S-CNb-49A that amplify a specific product for C. neoformans and another for C. gattii). CN4-CN5 primer set was positive in all Cryptococcus standard strains and in 94.8% in DNA samples from cryptococcal meningitis and AIDS group. With the multiplex, no 448-bp product of C. gattii was observed in the clinical samples of either group. The 695bp products of C. neoformans were observed only in 64.6% of the cryptococcal meningitis and AIDS group. This primer set was negative for two standard strains. The specificity based on the negative samples from the CTL/AIDS group was 98.5% in both primer sets. These data suggest that the CN4/CN5 primer set was highly sensitive for the identification of C. neoformans/C. gattii species complex in cerebrospinal fluid samples from patients with clinical suspicion of cryptococcal meningitis. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Prolaris Cell Cycle Progression Test for Localized Prostate Cancer: A Health Technology Assessment

PubMed Central

Schaink, Alexis; Li, Chunmei; Wells, David; Holubowich, Corinne

2017-01-01

Background Prostate cancer is very common and many localized tumours are non-aggressive. Determining which cancers are aggressive is important for choosing the most appropriate treatment (e.g., surgery, radiation, active surveillance). Current clinical risk stratification is reliable in forecasting the prognosis of groups of men with similar clinical and pathologic characteristics, but there is residual uncertainty at the individual level. The Prolaris cell cycle progression (CCP) test, a genomic test that estimates how fast tumour cells are proliferating, could potentially be used to improve the accuracy of individual risk assessment. This health technology assessment sought to determine the clinical utility, economic impact, and patients' perceptions of the value of the CCP test in low- and intermediate-risk localized prostate cancer. Methods We conducted a systematic review of the clinical and economic evidence of the CCP test in low-and intermediate-risk, localized prostate cancer. Medical and health economic databases were searched from 2010 to June or July 2016. The critical appraisal of the clinical evidence included risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also analyzed the potential budget impact of adding the CCP test into current practice, from the perspective the Ontario Ministry of Health and Long-Term Care. Finally, we conducted qualitative interviews with men with prostate cancer, on the factors that influenced their treatment decision-making. Results For the review of clinical effectiveness, we screened 3,021 citations, and two before–after studies met our inclusion criteria. In one study, the results of the CCP test appeared to change the treatment plan (from initial to final plan) in 64.9% of cases overall (GRADE rating of the quality of evidence: Very low). In the other study, the CCP test changed the treatment received in nearly half of cases overall, compared with the initial plan (GRADE: Very low). No evidence was available on clinical outcomes of patients whose treatment was informed by CCP results. For the review of cost-effectiveness, 100 citations were identified and screened. No studies met the inclusion criteria. In our economic evaluation, we estimated that publicly funding the CCP test would result in a total net budget impact of $41.3 million in the first 5 years, mostly due to the cost of the CCP test. In our model, the relatively small cost savings ($7.3 million) due to treatment change (increased use of active surveillance and decreased use of interventional treatment) was not large enough to offset the high cost of the test. Patients viewed the test as potentially helpful but, due to the complexity of treatment decision-making, were unsure the test would ultimately change their treatment choices. Conclusions We found no evidence to demonstrate the impact of the Prolaris CCP test on patient-important clinical outcomes. The limited evidence available shows that the test appears to provide information that, when considered in addition to clinical risk stratification, may change the treatment plan or actual treatment for some low- and intermediate-risk prostate cancer patients. As a result, there is insufficient data to inform the cost-effectiveness of the CCP test. Publicly funding the CCP test would result in a large incremental cost to the provincial budget. PMID:28572867

Computerized provider order entry in the clinical laboratory

PubMed Central

Baron, Jason M.; Dighe, Anand S.

2011-01-01

Clinicians have traditionally ordered laboratory tests using paper-based orders and requisitions. However, paper orders are becoming increasingly incompatible with the complexities, challenges, and resource constraints of our modern healthcare systems and are being replaced by electronic order entry systems. Electronic systems that allow direct provider input of diagnostic testing or medication orders into a computer system are known as Computerized Provider Order Entry (CPOE) systems. Adoption of laboratory CPOE systems may offer institutions many benefits, including reduced test turnaround time, improved test utilization, and better adherence to practice guidelines. In this review, we outline the functionality of various CPOE implementations, review the reported benefits, and discuss strategies for using CPOE to improve the test ordering process. Further, we discuss barriers to the implementation of CPOE systems that have prevented their more widespread adoption. PMID:21886891

[Research applications in digital radiology. Big data and co].

PubMed

Müller, H; Hanbury, A

2016-02-01

Medical imaging produces increasingly complex images (e.g. thinner slices and higher resolution) with more protocols, so that image reading has also become much more complex. More information needs to be processed and usually the number of radiologists available for these tasks has not increased to the same extent. The objective of this article is to present current research results from projects on the use of image data for clinical decision support. An infrastructure that can allow large volumes of data to be accessed is presented. In this way the best performing tools can be identified without the medical data having to leave secure servers. The text presents the results of the VISCERAL and Khresmoi EU-funded projects, which allow the analysis of previous cases from institutional archives to support decision-making and for process automation. The results also represent a secure evaluation environment for medical image analysis. This allows the use of data extracted from past cases to solve information needs occurring when diagnosing new cases. The presented research prototypes allow direct extraction of knowledge from the visual data of the images and to use this for decision support or process automation. Real clinical use has not been tested but several subjective user tests showed the effectiveness and efficiency of the process. The future in radiology will clearly depend on better use of the important knowledge in clinical image archives to automate processes and aid decision-making via big data analysis. This can help concentrate the work of radiologists towards the most important parts of diagnostics.

Goats challenged with different members of the Mycobacterium tuberculosis complex display different clinical pictures.

PubMed

Bezos, J; Casal, C; Díez-Delgado, I; Romero, B; Liandris, E; Álvarez, J; Sevilla, I A; Juan, L de; Domínguez, L; Gortázar, C

2015-10-15

Tuberculosis (TB) in goats (Capra hircus) is due to infection with members of the Mycobacterium tuberculosis complex (MTC), mainly Mycobacterium bovis and Mycobacterium caprae. We report a comparative experimental infection of goats with M. bovis, M. caprae and M. tuberculosis strains. We hypothesized that goats experimentally infected with different members of the MTC would display different clinical pictures. Three groups of goats were challenged with either M. bovis SB0134 (group 1, n=5), M. caprae SB0157 (group 2, n=5) and M. tuberculosis SIT58 (group 3, n=4). The highest mean total lesion score was observed in M. bovis challenged goats (mean 15.2, range 9-19), followed by those challenged with M. caprae (10.8, 2-23). The lowest score was recorded in goats challenged with M. tuberculosis (3, 1-6). Culture results coincided with the lesion scores in yielding more positive pools (7/15) in M. bovis challenged goats. By contrast, only three pools were positive from goats challenged M. tuberculosis (3/12) and with M. caprae (3/15), respectively. Differences in the performance of the intradermal and gamma-interferon (IFN-γ) tests depending of the group were observed since all goats from group 1 were diagnosed using intradermal test and these goats reacted earlier to the IFN-γ assay in comparison to the other groups. This study confirmed that goats experimentally infected with different members of the MTC display different clinical pictures and this fact may have implications for MTC maintenance and bacterial shedding. Copyright © 2015 Elsevier B.V. All rights reserved.

The investigation of vertebral injury sustained during aircrew ejection

NASA Technical Reports Server (NTRS)

Benedict, J. V.

1972-01-01

A series of tests were performed on excised human vertebral segments to determine the static and dynamic response of the thoraco-lumbar spine when loaded in flexion. A total of fifteen tests were performed on eleven specimens. Specimens were obtained from male donors ranging in age from 34 to 60 years. Demographic data pertinent to each specimen and the elapsed time between death of the donor and testing of each corresponding specimen are presented. Only spinal segments comprised of lower thoracic and upper lumbar vertebrae were tested because in aircraft ejection injuries clinical complications in this anatomical region predominate. A complex continuum mathematical model describing the dynamic response of the human spine was formulated, solved, and verified experimentally. Detailed results are presented in figures, tables, and equations.

Exploring for the optimal structural design for the 3D-printing technology for cranial reconstruction: a biomechanical and histological study comparison of solid vs. porous structure.

PubMed

Lim, Jun Young; Kim, Namhyun; Park, Jong-Chul; Yoo, Sun K; Shin, Dong Ah; Shim, Kyu-Won

2017-09-01

Cranioplasty for recovering skull defects carries the risk for a number of complications. Various materials are used, including autologous bone graft, metallic materials, and non-metallic materials, each of which has advantages and disadvantages. If the use of autologous bone is not feasible, those artificial materials also have constraints in the case of complex anatomy and/or irregular defects. This study used metal 3D-printing technology to overcome these existing drawbacks and analyze the clinical and mechanical performance requirements. To find an optimal structure that satisfied the structural and mechanical stability requirements, we evaluated biomechanical stability using finite element analysis (FEA) and mechanical testing. To ensure clinical applicability, the model was subjected to histological evaluation. Each specimen was implanted in the femur of a rabbit and was evaluated using histological measurements and push-out test. We believe that our data will provide the basis for future applications of a variety of unit structures and further clinical trials and research, as well as the direction for the study of other patient-specific implants.

Diagnostic imaging learning resources evaluated by students and recent graduates.

PubMed

Alexander, Kate; Bélisle, Marilou; Dallaire, Sébastien; Fernandez, Nicolas; Doucet, Michèle

2013-01-01

Many learning resources can help students develop the problem-solving abilities and clinical skills required for diagnostic imaging. This study explored veterinary students' perceptions of the usefulness of a variety of learning resources. Perceived resource usefulness was measured for different levels of students and for academic versus clinical preparation. Third-year (n=139) and final (fifth) year (n=105) students and recent graduates (n=56) completed questionnaires on perceived usefulness of each resource. Resources were grouped for comparison: abstract/low complexity (e.g., notes, multimedia presentations), abstract/high complexity (e.g., Web-based and film case repositories), concrete/low complexity (e.g., large-group "clicker" workshops), and concrete/high complexity (e.g., small-group interpretation workshops). Lower-level students considered abstract/low-complexity resources more useful for academic preparation and concrete resources more useful for clinical preparation. Higher-level students/recent graduates also considered abstract/low-complexity resources more useful for academic preparation. For all levels, lecture notes were considered highly useful. Multimedia slideshows were an interactive complement to notes. The usefulness of a Web-based case repository was limited by accessibility problems and difficulty. Traditional abstract/low-complexity resources were considered useful for more levels and contexts than expected. Concrete/high-complexity resources need to better represent clinical practice to be considered more useful for clinical preparation.

Academic Health Center Management of Chronic Diseases through Knowledge Networks: Project ECHO

PubMed Central

Arora, Sanjeev; Geppert, Cynthia M. A.; Kalishman, Summers; Dion, Denise; Pullara, Frank; Bjeletich, Barbara; Simpson, Gary; Alverson, Dale C.; Moore, Lori B.; Kuhl, Dave; Scaletti, Joseph V.

2013-01-01

The authors describe an innovative academic health center (AHC)-led program of health care delivery and clinical education for the management of complex, common, and chronic diseases in underserved areas, using hepatitis C virus (HCV) as a model. The program, based at the University of New Mexico School of Medicine, represents a paradigm shift in thinking and funding for the threefold mission of AHCs, moving from traditional fee-for-service models to public health funding of knowledge networks. This program, Project Extension for Community Healthcare Outcomes (ECHO), involves a partnership of academic medicine, public health offices, corrections departments, and rural community clinics dedicated to providing best practices and protocol-driven health care in rural areas. Telemedicine and Internet connections enable specialists in the program to comanage patients with complex diseases, using case-based knowledge networks and learning loops. Project ECHO partners (nurse practitioners, primary care physicians, physician assistants, and pharmacists) present HCV-positive patients during weekly two-hour telemedicine clinics using a standardized, case-based format that includes discussion of history, physical examination, test results, treatment complications, and psychiatric, medical, and substance abuse issues. In these case-based learning clinics, partners rapidly gain deep domain expertise in HCV as they collaborate with university specialists in hepatology, infectious disease, psychiatry, and substance abuse in comanaging their patients. Systematic monitoring of treatment outcomes is an integral aspect of the project. The authors believe this methodology will be generalizable to other complex and chronic conditions in a wide variety of underserved areas to improve disease outcomes, and it offers an opportunity for AHCs to enhance and expand their traditional mission of teaching, patient care, and research. PMID:17264693

Cornelia de Lange syndrome and molecular implications of the cohesin complex: Abstracts from the 7th biennial scientific and educational symposium 2016.

PubMed

Kline, Antonie D; Krantz, Ian D; Deardorff, Matthew A; Shirahige, Katsuhiko; Dorsett, Dale; Gerton, Jennifer L; Wu, Meng; Mehta, Devanshi; Mills, Jason A; Carrico, Cheri S; Noon, Sarah; Herrera, Pamela S; Horsfield, Julia A; Bettale, Chiara; Morgan, Jeremy; Huisman, Sylvia A; Moss, Jo; McCleery, Joseph; Grados, Marco; Hansen, Blake D; Srivastava, Siddharth; Taylor-Snell, Emily; Kerr, Lynne M; Katz, Olivia; Calof, Anne L; Musio, Antonio; Egense, Alena; Haaland, Richard E

2017-05-01

Cornelia de Lange Syndrome (CdLS) is due to mutations in the genes for the structural and regulatory proteins that make up the cohesin complex, and is considered a cohesinopathy disorder or, more recently, a transcriptomopathy. New phenotypes have been recognized in this expanding field. There are multiple clinical issues facing individuals with all forms of CdLS, particularly in the neurodevelopmental system, but also gastrointestinal, cardiac, and musculoskeletal. Aspects of developmental and cell biology have found common endpoints in the biology of the cohesin complex, with improved understanding of the mechanisms, easier diagnostic tests, and the possibility of potential therapeutics, all major clinical implications for the individual with CdLS. The following abstracts are the presentations from the 7th Cornelia de Lange Syndrome Scientific and Educational Symposium, June 22-23, 2016, in Orlando, FL, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting. In addition to the scientific and clinical discussions, there were talks related to practical aspects of behavior including autism, transitions, communication, access to medical care, and databases. At the end of the symposium, a panel was held, which included several parents, affected individuals and genetic counselors, and discussed the greatest challenges in life and how this information can assist in guiding future research. The Research Committee of the CdLS Foundation organizes this meeting, reviews, and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board and publications. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD. © 2017 Wiley Periodicals, Inc.

The clinical impact of using complex molecular profiling strategies in routine oncology practice.

PubMed

Laes, Jean-François; Aftimos, Philippe; Barthelemy, Philippe; Bellmunt, Joaquim; Berchem, Guy; Camps, Carlos; Peñas, Ramón de Las; Finzel, Ana; García-Foncillas, Jesús; Hervonen, Petteri; Wahid, Ibrahim; Joensuu, Timo; Kathan, Louis; Kong, Anthony; Mackay, James; Mikropoulos, Christos; Mokbel, Kefah; Mouysset, Jean-Loup; Odarchenko, Sergey; Perren, Timothy J; Pienaar, Rika; Regonesi, Carlos; Alkhayyat, Shadi Salem; El Kinge, Abdul Rahman; Abulkhair, Omalkhair; Galal, Khaled Morsi; Ghanem, Hady; El Karak, Fadi; Garcia, Angel; Ghitti, Gregori; Sadik, Helen

2018-04-17

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.

Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

PubMed

2012-04-06

Biochemical genetic testing and newborn screening are essential laboratory services for the screening, detection, diagnosis, and monitoring of inborn errors of metabolism or inherited metabolic disorders. Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations, laboratory testing is categorized on the basis of the level of testing complexity as either waived (i.e., from routine regulatory oversight) or nonwaived testing (which includes tests of moderate and high complexity). Laboratories that perform biochemical genetic testing are required by CLIA regulations to meet the general quality systems requirements for nonwaived testing and the personnel requirements for high-complexity testing. Laboratories that perform public health newborn screening are subject to the same CLIA regulations and applicable state requirements. As the number of inherited metabolic diseases that are included in state-based newborn screening programs continues to increase, ensuring the quality of performance and delivery of testing services remains a continuous challenge not only for public health laboratories and other newborn screening facilities but also for biochemical genetic testing laboratories. To help ensure the quality of laboratory testing, CDC collaborated with the Centers for Medicare & Medicaid Services, the Food and Drug Administration, the Health Resources and Services Administration, and the National Institutes of Health to develop guidelines for laboratories to meet CLIA requirements and apply additional quality assurance measures for these areas of genetic testing. This report provides recommendations for good laboratory practices that were developed based on recommendations from the Clinical Laboratory Improvement Advisory Committee, with additional input from the Secretary's Advisory Committee on Genetics, Health, and Society; the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; and representatives of newborn screening laboratories. The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. These recommendations are intended for laboratories that perform biochemical genetic testing to improve the quality of laboratory services and for newborn screening laboratories to ensure the quality of laboratory practices for inherited metabolic disorders. These recommendations also are intended as a resource for medical and public health professionals who evaluate laboratory practices, for users of laboratory services to facilitate their collaboration with newborn screening systems and use of biochemical genetic tests, and for standard-setting organizations and professional societies in developing future laboratory quality standards and practice recommendations. This report complements Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6]) to provide guidance for ensuring and improving the quality of genetic laboratory services and public health outcomes. Future recommendations for additional areas of genetic testing will be considered on the basis of continued monitoring and evaluation of laboratory practices, technology advancements, and the development of laboratory standards and guidelines.

Usability Testing of a Complex Clinical Decision Support Tool in the Emergency Department: Lessons Learned.

PubMed

Press, Anne; McCullagh, Lauren; Khan, Sundas; Schachter, Andy; Pardo, Salvatore; McGinn, Thomas

2015-09-10

As the electronic health record (EHR) becomes the preferred documentation tool across medical practices, health care organizations are pushing for clinical decision support systems (CDSS) to help bring clinical decision support (CDS) tools to the forefront of patient-physician interactions. A CDSS is integrated into the EHR and allows physicians to easily utilize CDS tools. However, often CDSS are integrated into the EHR without an initial phase of usability testing, resulting in poor adoption rates. Usability testing is important because it evaluates a CDSS by testing it on actual users. This paper outlines the usability phase of a study, which will test the impact of integration of the Wells CDSS for pulmonary embolism (PE) diagnosis into a large urban emergency department, where workflow is often chaotic and high stakes decisions are frequently made. We hypothesize that conducting usability testing prior to integration of the Wells score into an emergency room EHR will result in increased adoption rates by physicians. The objective of the study was to conduct usability testing for the integration of the Wells clinical prediction rule into a tertiary care center's emergency department EHR. We conducted usability testing of a CDS tool in the emergency department EHR. The CDS tool consisted of the Wells rule for PE in the form of a calculator and was triggered off computed tomography (CT) orders or patients' chief complaint. The study was conducted at a tertiary hospital in Queens, New York. There were seven residents that were recruited and participated in two phases of usability testing. The usability testing employed a "think aloud" method and "near-live" clinical simulation, where care providers interacted with standardized patients enacting a clinical scenario. Both phases were audiotaped, video-taped, and had screen-capture software activated for onscreen recordings. Phase I: Data from the "think-aloud" phase of the study showed an overall positive outlook on the Wells tool in assessing a patient for a PE diagnosis. Subjects described the tool as "well-organized" and "better than clinical judgment". Changes were made to improve tool placement into the EHR to make it optimal for decision-making, auto-populating boxes, and minimizing click fatigue. Phase II: After incorporating the changes noted in Phase 1, the participants noted tool improvements. There was less toggling between screens, they had all the clinical information required to complete the tool, and were able to complete the patient visit efficiently. However, an optimal location for triggering the tool remained controversial. This study successfully combined "think-aloud" protocol analysis with "near-live" clinical simulations in a usability evaluation of a CDS tool that will be implemented into the emergency room environment. Both methods proved useful in the assessment of the CDS tool and allowed us to refine tool usability and workflow.

Safety study and characterization of E1A-liposome complex gene-delivery protocol in an ovarian cancer model.

PubMed

Xing, X; Zhang, S; Chang, J Y; Tucker, S D; Chen, H; Huang, L; Hung, M C

1998-11-01

A phase I clinical trial of E1A-liposome complex is currently ongoing in patients with HER-2/neu-overexpressing breast or ovarian cancers. To optimize the E1A-liposome complex for a further stage of clinical trial, several aspects of the current protocol have been examined in an animal model. In the orthotopic ovarian cancer model, different doses of lipid in the the E1A-liposome complex, which is currently used in clinical trials, were tested for the in vivo gene-transfer efficacy and tumor-suppression function. A lowered lipid dose--1/13 of the previous amount--produced gene expression level and E1A tumor-suppression efficacy similar to that of the original protocol. Mini-E1A, an E1A construct without its immortalization domain and yet capable of repressing HER-2/neu, was proved to be as potent as E1A in suppressing tumor development in vivo. These changes in the E1A-liposome complex will significantly reduce any potential adverse effects caused by lipid vector and E1A DNA. To examine further whether residual E1A DNA may still exist in normal organs after the E1A-liposome treatment, PCR was used to detect E1A DNA in mice that survived for 1 1/2 years after the last treatment. E1A DNA was detected only in the lungs and kidneys, but not in livers, hearts, spleens, brains, uterus or the ovaries. Furthermore, resistance of the E1A DNA extracted from tissues to the digestion of Dpnl restriction enzyme, which can cleave the methylated E1A plasmid DNA generated by methylation-competent bacteria, suggested integration of E1A DNA into the chromosome of the lungs and kidneys. Experimental results presented here provide important information for safety concerns and for the design of future phase II and phase III trials.

Surgical correction of urethral dilatation in an intersex goat.

PubMed

Karras, S; Modransky, P; Welker, B

1992-11-15

Multiple congenital urethral abnormalities were successfully corrected in a polled goat kid. Anatomic genito-urinary abnormalities identified were paired testes with associated epididymis, ductus deferens, and active endometrial tissue. Blood karyotyping revealed the female state--XX sex chromosomes. This case exemplifies the complex interactions in addition to Y dominant Mendelian genetics that determine reproductive tract development in goats. The resultant intersex state is clinically recognized with greater frequency in polled progeny.

SARCOPENIA: DESIGNING PHASE IIB TRIALS

PubMed Central

CHUMLEA, WM.C.; CESARI, M.; EVANS, W.J.; FERRUCCI, L.; FIELDING, R.A.; PAHOR, M.; STUDENSKI, S.; VELLAS, B.

2012-01-01

Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength. PMID:21623466

Ethical principles and pitfalls of genetic testing for dementia.

PubMed

Hedera, P

2001-01-01

Progress in the genetics of dementing disorders and the availability of clinical tests for practicing physicians increase the need for a better understanding of multifaceted issues associated with genetic testing. The genetics of dementia is complex, and genetic testing is fraught with many ethical concerns. Genetic testing can be considered for patients with a family history suggestive of a single gene disorder as a cause of dementia. Testing of affected patients should be accompanied by competent genetic counseling that focuses on probabilistic implications for at-risk first-degree relatives. Predictive testing of at-risk asymptomatic patients should be modeled after presymptomatic testing for Huntington's disease. Testing using susceptibility genes has only a limited diagnostic value at present because potential improvement in diagnostic accuracy does not justify potentially negative consequences for first-degree relatives. Predictive testing of unaffected subjects using susceptibility genes is currently not recommended because individual risk cannot be quantified and there are no therapeutic interventions for dementia in presymptomatic patients.

Young people's perceptions of smartphone-enabled self-testing and online care for sexually transmitted infections: qualitative interview study.

PubMed

Aicken, Catherine R H; Fuller, Sebastian S; Sutcliffe, Lorna J; Estcourt, Claudia S; Gkatzidou, Voula; Oakeshott, Pippa; Hone, Kate; Sadiq, S Tariq; Sonnenberg, Pam; Shahmanesh, Maryam

2016-09-13

Control of sexually transmitted infections (STI) is a global public health priority. Despite the UK's free, confidential sexual health clinical services, those at greatest risk of STIs, including young people, report barriers to use. These include: embarrassment regarding face-to-face consultations; the time-commitment needed to attend clinic; privacy concerns (e.g. being seen attending clinic); and issues related to confidentiality. A smartphone-enabled STI self-testing device, linked with online clinical care pathways for treatment, partner notification, and disease surveillance, is being developed by the eSTI(2) consortium. It is intended to benefit public health, and could do so by increasing testing among populations which underutilise existing services and/or by enabling rapid provision of effective treatment. We explored its acceptability among potential users. In-depth interviews were conducted in 2012 with 25 sexually-experienced 16-24 year olds, recruited from Further Education colleges in an urban, high STI prevalence area. Thematic analysis was undertaken. Nine females and 16 males participated. 21 self-defined as Black; three, mixed ethnicity; and one, Muslim/Asian. 22 reported experience of STI testing, two reported previous STI diagnoses, and all had owned smartphones. Participants expressed enthusiasm about the proposed service, and suggested that they and their peers would use it and test more often if it were available. Utilizing sexual healthcare was perceived to be easier and faster with STI self-testing and online clinical care, which facilitated concealment of STI testing from peers/family, and avoided embarrassing face-to-face consultations. Despite these perceived advantages to privacy, new privacy concerns arose regarding communications technology: principally the risk inherent in having evidence of STI testing or diagnosis visible or retrievable on their phone. Some concerns arose regarding the proposed self-test's accuracy, related to self-operation and the technology's novelty. Several expressed anxiety around the possibility of being diagnosed and treated without any contact with healthcare professionals. Remote STI self-testing and online care appealed to these young people. It addressed barriers they associated with conventional STI services, thus may benefit public health through earlier detection and treatment. Our findings underpin development of online care pathways, as part of ongoing research to create this complex e-health intervention.

Synthesis, characterization, antimicrobial and antitumor reactivity of new palladium(II) complexes with methionine and tryptophane coumarine derivatives

NASA Astrophysics Data System (ADS)

Stojković, Danijela Lj; Jevtić, Verica V.; Vuković, Nenad; Vukić, Milena; Čanović, Petar; Zarić, Milan M.; Mišić, Milena M.; Radovanović, Dragče M.; Baskić, Dejan; Trifunović, Srećko R.

2018-04-01

In reaction of 3-acetyl-4-hydroxy coumarine with methionine methyl ester hydrochloride and tryptophane methyl ester hydrochloride the corresponding enamine ligands were obtained. Palladium (II) complexes were prepared in reaction of potassium-tetrachloridopalladate (II) and corresponding enamine. All compounds were characterized by microanalysis, infrared, 1H and 13C NMR spectroscopy. In vitro antitumor activity of the mentioned ligands and corresponding palladium (II) complexes, as well as me-Gly and me-Val ligands and [Pd (me-Gly)]Cl and [Pd (me-Val)2] complexes was determined by MTT assay against two leukemia cell lines (JVM-13 and MOLT-4) and against primary leukemic cells isolated from chronic lymphocytic leukemia (CLL) patients. Antimicrobial activity of the tested compound was evaluated by determining the minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) against three reference bacterial strains: E. faecalis, P. aeruginosa, S. aureus and one clinical isolate of yeast: Candida spp.

A case study of quality improvement methods for complex adaptive systems applied to an academic hepatology program.

PubMed

Fontanesi, John; Martinez, Anthony; Boyo, Toritsesan O; Gish, Robert

2015-01-01

Although demands for greater access to hepatology services that are less costly and achieve better outcomes have led to numerous quality improvement initiatives, traditional quality management methods may be inappropriate for hepatology. We empirically tested a model for conducting quality improvement in an academic hepatology program using methods developed to analyze and improve complex adaptive systems. We achieved a 25% increase in volume using 15% more clinical sessions with no change in staff or faculty FTEs, generating a positive margin of 50%. Wait times for next available appointments were reduced from five months to two weeks; unscheduled appointment slots dropped from 7% to less than 1%; "no-show" rates dropped to less than 10%; Press-Ganey scores increased to the 100th percentile. We conclude that framing hepatology as a complex adaptive system may improve our understanding of the complex, interdependent actions required to improve quality of care, patient satisfaction, and cost-effectiveness.

Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Del-Aguila, Jorge L.; Fernandez, Maria Victoria; Carrell, David; Black, Kathleen; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Bailey, Matthew; Ridge, Perry G.; Hefti, Franz; Fillit, Howard; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Carrillo, Maria; Fleisher, Adam; Reeder, Stephanie; Trncic, Nadira; Burke, Anna; Tariot, Pierre; Reiman, Eric M.; Chen, Kewei; Sabbagh, Marwan N.; Beiden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Green, Robert C.; Marshall, Gad; Johnson, Keith A.; Sperling, Reisa A.; Snyder, Peter; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Bernick, Charles; Munic, Donna; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Relkin, Norman; Chaing, Gloria; Ravdin, Lisa; Paul, Steven; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Friedl, Karl; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Borges-Neto, Salvador; James, Olga; Wong, Terence; Coleman, Edward; Schwartz, Adam; Cellar, Janet S.; Levey, Allan L.; Lah, James J.; Behan, Kelly; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Farlow, Martin R.; Saykin, Andrew J.; Foroud, Tatiana M.; Shen, Li; Faber, Kelly; Kim, Sungeun; Nho, Kwangsik; Marie Hake, Ann; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Petersen, Ronald; Jack, Clifford R.; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Chertkow, Howard; Hosein, Chris; Mintzer, Jacob; Spicer, Kenneth; Bachman, David; Grossman, Hillel; Mitsis, Effie; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Potter, William; Buckholtz, Neil; Hsiao, John; Kittur, Smita; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Johnson, Nancy; Chuang-Kuo; Kerwin, Diana; Bonakdarpour, Borna; Weintraub, Sandra; Grafman, Jordan; Lipowski, Kristine; Mesulam, Marek-Marsel; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Borrie, Michael; Lee, T-Y; Bartha, Rob; Martinez, Walter; Villena, Teresa; Sadowsky, Carl; Khachaturian, Zaven; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Frank, Richard; Fleischman, Debra; Arfanakis, Konstantinos; Shah, Raj C.; deToledo-Morrell, Leyla; Sorensen, Greg; Finger, Elizabeth; Pasternack, Stephen; Rachinsky, Irina; Drost, Dick; Rogers, John; Kertesz, Andrew; Furst, Ansgar J.; Chad, Stevan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Mudge, Benita; Assaly, Michele; Fox, Nick; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Ekstam Smith, Karen; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Natelson Love, Marissa; DeCarli, Charles; Carmichael, Owen; Olichney, John; Maillard, Pauline; Fletcher, Evan; Nguyen, Dana; Preda, Andrian; Potkin, Steven; Mulnard, Ruth A.; Thai, Gaby; McAdams-Ortiz, Catherine; Landau, Susan; Jagust, William; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Thompson, Paul; Donohue, Michael; Thomas, Ronald G.; Walter, Sarah; Gessert, Devon; Brewer, James; Vanderswag, Helen; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Aisen, Paul; Davis, Melissa; Morrison, Rosemary; Harvey, Danielle; Thal, Lean; Beckett, Laurel; Neylan, Thomas; Finley, Shannon; Weiner, Michael W.; Hayes, Jacqueline; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Massoglia, Dino; Brawman-Mentzer, Olga; Schuff, Norbert; Smith, Charles D.; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Koeppe, Robert A.; Lord, Joanne L.; Heidebrink, Judith L.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Trojanowki, John Q.; Shaw, Leslie M.; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Foster, Norm; Montine, Tom; Fruehling, J. Jay; Harding, Sandra; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Petrie, Eric C.; Peskind, Elaine; Li, Gail; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Kuller, Lew; Mathis, Chet; Ann Oakley, Mary; Lopez, Oscar L.; Simpson, Donna M.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Cairns, Nigel J.; Raichle, Marc; Morris, John C.; Householder, Erin; Taylor-Reinwald, Lisa; Holtzman, David; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Varma, Pradeep; MacAvoy, Martha G.; Carson, Richard E.; van Dyck, Christopher H.; Davies, Peter; Holtzman, David; Morris, John C.; Bales, Kelly; Pickering, Eve H.; Lee, Jin-Moo; Heitsch, Laura; Kauwe, John; Goate, Alison; Piccio, Laura; Cruchaga, Carlos

2016-01-01

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes, and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels, and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r, and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects, and complex disease associations in the same locus.

Microchip Immunoaffinity Electrophoresis of Antibody-Thymidine Kinase 1 Complex

PubMed Central

Pagaduan, Jayson V.; Ramsden, Madison; O’Neill, Kim; Woolley, Adam T.

2015-01-01

Thymidine kinase-1 (TK1) is an important cancer biomarker whose serum levels are elevated in early cancer development. We developed a microchip electrophoresis immunoaffinity assay to measure recombinant purified TK1 (pTK1) using an antibody that binds to human TK1. We fabricated poly(methyl methacrylate) microfluidic devices to test the feasibility of detecting antibody (Ab)-pTK1 immune complexes as a step towards TK1 analysis in clinical serum samples. We were able to separate immune complexes from unbound antibodies using 0.5X phosphate buffer saline (pH 7.4) containing 0.01% Tween-20, with 1% w/v methylcellulose that acts as a dynamic surface coating and sieving matrix. Separation of the antibody and Ab-pTK1 complex was observed within a 5 mm effective separation length. This method of detecting pTK1 is easy to perform, requires only a 10 μL sample volume, and takes just 1 minute for separation. PMID:25486911

The value and cost of complexity in predictive modelling: role of tissue anisotropic conductivity and fibre tracts in neuromodulation

NASA Astrophysics Data System (ADS)

Salman Shahid, Syed; Bikson, Marom; Salman, Humaira; Wen, Peng; Ahfock, Tony

2014-06-01

Objectives. Computational methods are increasingly used to optimize transcranial direct current stimulation (tDCS) dose strategies and yet complexities of existing approaches limit their clinical access. Since predictive modelling indicates the relevance of subject/pathology based data and hence the need for subject specific modelling, the incremental clinical value of increasingly complex modelling methods must be balanced against the computational and clinical time and costs. For example, the incorporation of multiple tissue layers and measured diffusion tensor (DTI) based conductivity estimates increase model precision but at the cost of clinical and computational resources. Costs related to such complexities aggregate when considering individual optimization and the myriad of potential montages. Here, rather than considering if additional details change current-flow prediction, we consider when added complexities influence clinical decisions. Approach. Towards developing quantitative and qualitative metrics of value/cost associated with computational model complexity, we considered field distributions generated by two 4 × 1 high-definition montages (m1 = 4 × 1 HD montage with anode at C3 and m2 = 4 × 1 HD montage with anode at C1) and a single conventional (m3 = C3-Fp2) tDCS electrode montage. We evaluated statistical methods, including residual error (RE) and relative difference measure (RDM), to consider the clinical impact and utility of increased complexities, namely the influence of skull, muscle and brain anisotropic conductivities in a volume conductor model. Main results. Anisotropy modulated current-flow in a montage and region dependent manner. However, significant statistical changes, produced within montage by anisotropy, did not change qualitative peak and topographic comparisons across montages. Thus for the examples analysed, clinical decision on which dose to select would not be altered by the omission of anisotropic brain conductivity. Significance. Results illustrate the need to rationally balance the role of model complexity, such as anisotropy in detailed current flow analysis versus value in clinical dose design. However, when extending our analysis to include axonal polarization, the results provide presumably clinically meaningful information. Hence the importance of model complexity may be more relevant with cellular level predictions of neuromodulation.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: DIAGNOSIS OF RECURRENCE IN CUSHING DISEASE.

PubMed

Fleseriu, Maria; Hamrahian, Amir H; Hoffman, Andrew R; Kelly, Daniel F; Katznelson, Laurence

2016-12-01

Recurrence of hypercortisolemia after initial treatment of Cushing disease (CD) is more common than previously thought, with a third of patients suffering a recurrence over their lifetime. Awareness of this high rate and delayed timeline (sometimes decades) of potential recurrence is critical and patients with CD should be monitored at regular intervals throughout their lives. In this manuscript, we review the complex evaluation needed for defining CD remission versus persistent disease after surgery, and focus on challenges in diagnosing early recurrent hypercortisolemia. Late night salivary cortisol appears to be an earlier predictor of recurrence when compared with urinary free cortisol (UFC) excretion. We also review the criteria suggested to define recurrence of hypercortisolemia in patients treated with medical therapy. Further research is needed to determine the optimal way to evaluate a patient with CD recurrence as well as the riskbenefit ratio of treatment in early, mild recurrent disease. ACTH = adrenocorticotropic hormone AI = adrenal insufficiency CD = Cushing disease CDDT = coupled dexamethasone desmopressin test CR = circadian rhythm CRH = corticotropin-releasing hormone GC = glucocorticoid GCR = global clinical response HPA = hypothalamic-pituitary-adrenal LDDST = low-dose dexamethasone suppression test LNSC = late-night salivary cortisol ODST = overnight dexamethasone suppression test TSS = trans-sphenoidal surgery.

Need for gender-specific pre-analytical testing: the dark side of the moon in laboratory testing.

PubMed

Franconi, Flavia; Rosano, Giuseppe; Campesi, Ilaria

2015-01-20

Many international organisations encourage studies in a sex-gender perspective. However, research with a gender perspective presents a high degree of complexity, and the inclusion of sex-gender variable in experiments presents many methodological questions, the majority of which are still neglected. Overcoming these issues is fundamental to avoid erroneous results. Here, pre-analytical aspects of the research, such as study design, choice of utilised specimens, sample collection and processing, animal models of diseases, and the observer's role, are discussed. Artefacts in this stage of research could affect the predictive value of all analyses. Furthermore, the standardisation of research subjects according to their lifestyles and, if female, to their life phase and menses or oestrous cycle, is urgent to harmonise research worldwide. A sex-gender-specific attention to pre-analytical aspects could produce a decrease in the time for translation from the bench to bedside. Furthermore, sex-gender-specific pre-clinical pharmacological testing will enable adequate assessment of pharmacokinetic and pharmacodynamic actions of drugs and will enable, where appropriate, an adequate gender-specific clinical development plan. Therefore, sex-gender-specific pre-clinical research will increase the gender equity of care and will produce more evidence-based medicine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

On the design and analysis of clinical trials with correlated outcomes

PubMed Central

Follmann, Dean; Proschan, Michael

2014-01-01

SUMMARY The convention in clinical trials is to regard outcomes as independently distributed, but in some situations they may be correlated. For example, in infectious diseases, correlation may be induced if participants have contact with a common infectious source, or share hygienic tips that prevent infection. This paper discusses the design and analysis of randomized clinical trials that allow arbitrary correlation among all randomized volunteers. This perspective generalizes the traditional perspective of strata, where patients are exchangeable within strata, and independent across strata. For theoretical work, we focus on the test of no treatment effect μ1 − μ0 = 0 when the n dimensional vector of outcomes follows a Gaussian distribution with known n × n covariance matrix Σ, where the half randomized to treatment (placebo) have mean response μ1 (μ0). We show how the new test corresponds to familiar tests in simple situations for independent, exchangeable, paired, and clustered data. We also discuss the design of trials where Σ is known before or during randomization of patients and evaluate randomization schemes based on such knowledge. We provide two complex examples to illustrate the method, one for a study of 23 family clusters with cardiomyopathy, the other where the malaria attack rates vary within households and clusters of households in a Malian village. PMID:25111420

The Development of Delta: Using Agile to Develop a Decision Aid for Pediatric Oncology Clinical Trial Enrollment.

PubMed

Robertson, Eden G; Wakefield, Claire E; Cohn, Richard J; O'Brien, Tracey; Ziegler, David S; Fardell, Joanna E

2018-05-04

The internet is increasingly being used to disseminate health information. Given the complexity of pediatric oncology clinical trials, we developed Delta, a Web-based decision aid to support families deciding whether or not to enroll their child with cancer in a clinical trial. This paper details the Agile development process of Delta and user testing results of Delta. Development was iterative and involved 5 main stages: a requirements analysis, planning, design, development, and user testing. For user testing, we conducted 13 eye-tracking analyses and think-aloud interviews with health care professionals (n=6) and parents (n=7). Results suggested that there was minimal rereading of content and a high level of engagement in content. However, there were some navigational problems. Participants reported high acceptability (12/13) and high usability of the website (8/13). Delta demonstrates the utility for the use of Agile in the development of a Web-based decision aid for health purposes. Our study provides a clear step-by-step guide to develop a Web-based psychosocial tool within the health setting. ©Eden G Robertson, Claire E Wakefield, Richard J Cohn, Tracey O'Brien, David S Ziegler, Joanna E Fardell. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 04.05.2018.

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

PubMed

Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

2017-12-01

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

Synthesis, characterization, and antimicrobial activity of silver(I) and copper(II) complexes of phosphate derivatives of pyridine and benzimidazole.

PubMed

Kalinowska-Lis, Urszula; Szewczyk, Eligia M; Chęcińska, Lilianna; Wojciechowski, Jakub M; Wolf, Wojciech M; Ochocki, Justyn

2014-01-01

Two silver(I) complexes--[Ag(4-pmOpe)]NO₃}(n) and [Ag(2-bimOpe)₂]NO₃--and three copper(II) complexes--[Cu₄Cl₆O(2-bimOpe)₄], [CuCl₂(4-pmOpe)₂], and [CuCl₂(2-bis(pm)Ope]--were synthesized by reaction of silver(I) nitrate or copper(II) chloride with phosphate derivatives of pyridine and benzimidazole, namely diethyl (pyridin-4-ylmethyl)phosphate (4-pmOpe), 1H-benzimidazol-2-ylmethyl diethyl phosphate (2-bimOpe), and ethyl bis(pyridin-2-ylmethyl)phosphate (2-bis(pm)Ope). These compounds were characterized by ¹H, ¹³C, and ³¹P NMR as well as IR spectroscopy, elemental analysis, and ESIMS spectrometry. Additionally, molecular and crystal structures of {[Ag(4-pmOpe)]NO₃}n and [Cu₄Cl₆O(2-bimOpe)₄] were determined by single-crystal X-ray diffraction analysis. The antimicrobial profiles of synthesized complexes and free ligands against test organisms from the ATCC and clinical sources were determined. Silver(I) complexes showed good antimicrobial activities against Candida albicans strains (MIC values of ∼19 μM). [Ag(2-bimOpe)₂]NO₃ was particularly active against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus epidermidis, with MIC values of ∼5 and ∼10 μM, respectively. Neither copper(II) complexes nor the free ligands inhibited the growth of test organisms at concentrations below 500 μg mL⁻¹. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.

PubMed

Canu, Letizia; Rapizzi, Elena; Zampetti, Benedetta; Fucci, Rossella; Nesi, Gabriella; Richter, Susan; Qin, Nan; Giachè, Valentino; Bergamini, Carlo; Parenti, Gabriele; Valeri, Andrea; Ercolino, Tonino; Eisenhofer, Graeme; Mannelli, Massimo

2014-07-01

About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.

Predictive value of the complex magnetocardiographic index in patients with intermediate pretest probability of chronic coronary artery disease: results of a two-center study.

PubMed

Chaikovsky, Illya; Hailer, Birgit; Sosnytskyy, Volodymyr; Lutay, Mykhaylo; Mjasnikov, Georgiy; Kazmirchuk, Anatoly; Bydnyk, Mykola; Lomakovskyy, Alexander; Sosnytskaja, Taisia

2014-09-01

The aim of this paper is to investigate the predictive value of the new integrated magnetocardiographic (MCG) index (CI) in the diagnosis of coronary artery disease (CAD) in patients with suspected CAD with intermediate pretest probability of the disease and uninformative results of routine tests. The study was carried out in the Clinic of Cardiology of the Main Military Clinical Hospital of Ukraine, Kiev (clinic 1), and in the Second Medical Clinic of the 'Katholisches Klinikum Essen', Germany (clinic 2).The main group (group 1) included 89 patients without a history of myocardial infarction. Coronary angiography was performed because of chest pain. Depending on the results of coronary angiography, this group was divided into two subgroups: (i) those with at least 70% stenosis in at least one of the main coronary arteries (subgroup 1a) and (ii) those without hemodynamically significant stenosis (subgroup 1b). The control group included 43 healthy volunteers.In all participants, the MCG examination was performed using a seven-channel MCG system located in an unshielded room. An integrated MCG index (CI), consisting of six parameters, was calculated. It can be shown that CI was significantly higher in patients with stenosis 70% or more compared with the patients without stenosis and healthy volunteers. Sensitivity was 93%, specificity was 84%, positive predictive value was 85%, and negative predictive value was 93%. The MCG test at rest has the potential to be useful in the noninvasive diagnosis of CAD in patients with intermediate pretest probability of disease and uninformative results of routine tests.

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

Ranganathan, V; Kumar, P; Bzdusek, K

Purpose: We propose a novel data-driven method to predict the achievability of clinical objectives upfront before invoking the IMRT optimization. Methods: A new metric called “Geometric Complexity (GC)” is used to estimate the achievability of clinical objectives. Here, GC is the measure of the number of “unmodulated” beamlets or rays that intersect the Region-of-interest (ROI) and the target volume. We first compute the geometric complexity ratio (GCratio) between the GC of a ROI (say, parotid) in a reference plan and the GC of the same ROI in a given plan. The GCratio of a ROI indicates the relative geometric complexitymore » of the ROI as compared to the same ROI in the reference plan. Hence GCratio can be used to predict if a defined clinical objective associated with the ROI can be met by the optimizer for a given case. Basically a higher GCratio indicates a lesser likelihood for the optimizer to achieve the clinical objective defined for a given ROI. Similarly, a lower GCratio indicates a higher likelihood for the optimizer to achieve the clinical objective defined for the given ROI. We have evaluated the proposed method on four Head and Neck cases using Pinnacle3 (version 9.10.0) Treatment Planning System (TPS). Results: Out of the total of 28 clinical objectives from four head and neck cases included in the study, 25 were in agreement with the prediction, which implies an agreement of about 85% between predicted and obtained results. The Pearson correlation test shows a positive correlation between predicted and obtained results (Correlation = 0.82, r2 = 0.64, p < 0.005). Conclusion: The study demonstrates the feasibility of the proposed method in head and neck cases for predicting the achievability of clinical objectives with reasonable accuracy.« less

Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.

PubMed

Pillai, Sekhar C; Hacohen, Yael; Tantsis, Esther; Prelog, Kristina; Merheb, Vera; Kesson, Alison; Barnes, Elizabeth; Gill, Deepak; Webster, Richard; Menezes, Manoj; Ardern-Holmes, Simone; Gupta, Sachin; Procopis, Peter; Troedson, Christopher; Antony, Jayne; Ouvrier, Robert A; Polfrit, Yann; Davies, Nicholas W S; Waters, Patrick; Lang, Bethan; Lim, Ming J; Brilot, Fabienne; Vincent, Angela; Dale, Russell C

2015-04-01

Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome. By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis). An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. We have defined clinical and radiologic phenotypes of infectious and immune-mediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority. Copyright © 2015 by the American Academy of Pediatrics.

An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre.

PubMed

Huda, S; Wong, S H; Pettingill, P; O'Connell, D; Vincent, A; Steiger, M

2015-02-01

Acquired diseases classically associated with VGKC-complex antibodies include peripheral nerve hyperexcitability (PNH), Morvan's syndrome, limbic encephalitis (LE), and epilepsy. However, not all such patients have VGKC-complex antibodies and antibodies have been reported in patients without a defined immune-mediated syndrome. To analyse the clinical relevance of positive VGKC-complex antibodies requested on the basis of initial clinical suspicion. We retrospectively analysed patients with positive VGKC-complex antibodies (>100 pM) referred to our institution between 2001 and 2011. 1,614 VGKC-complex assays were performed in 1,298 patients. Titres >100 pM were detected in 57/1,298 (4 %) patients. A classic VGKC-complex channelopathy (60 %) was associated with VGKC-complex antibody titres >400 pM (p = 0.0004). LGI1 or CASPR2 antibodies were only detected in classic VGKC-complex channelopathies (LE; n = 3/4 and PNH; n = 1/5). VGKC-complex antibody titres <400 pM were seen with PNH (n = 15/22; 68 %) but also a heterogeneous range of central and/or peripheral nervous system disorders. Electromyography was supportive of PNH in 65 % of cases and symptomatic treatment was beneficial in 46 % of patients. Irrespective of titre, the rate of malignancy in patients with VGKC-complex antibodies was higher than the age-matched national incidence of malignancy (OR 19.9, 95 % CI 8.97-44.0 p<0.0001). Clinical phenotyping and antibody titres >400 pM can help determine VGKC-complex antibody relevance. Antibody titres <400 pM are associated with PNH but also a more heterogeneous clinical spectrum. The antibody association in the latter is of doubtful clinical relevance. The rate of malignancy was significantly higher than the national incidence irrespective of titre.

Waiting for the evidence: VEMP testing and the ability to differentiate utricular versus saccular function.

PubMed

Welgampola, Miriam S; Carey, John P

2010-08-01

The advent of cervical vestibular evoked myogenic potentials (CVEMPs) marked a milestone in clinical vestibular testing because they provided a simple means of assessing human otolith function. The availability of air-conducted (AC) sound and bone-conducted vibration (BCV) to evoke CVEMPs and development of a new technique of recording ocular vestibular-evoked myogenic potentials (OVEMPs) have increased the complexity of this simple test, yet extended its diagnostic capabilities. Here we highlight the evidence-based assumptions that guide interpretation of AC sound- and BCV-evoked VEMPs and the gaps in VEMP research thus far. Copyright (c) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

[Patient-related complexity in nursing care - Collective case studies in the acute care hospital].

PubMed

Gurtner, Caroline; Spirig, Rebecca; Staudacher, Diana; Huber, Evelyn

2018-06-04

Patient-related complexity in nursing care - Collective case studies in the acute care hospital Abstract. Patient-related complexity of nursing is defined by the three characteristics "instability", "uncertainty", and "variability". Complexity increased in the past years, due to reduced hospital length of stay and a growing number of patients with chronic and multiple diseases. We investigated the phenomenon of patient-related complexity from the point of view of nurses and clinical nurse specialists in an acute care hospital. In the context of a collective case study design, nurses and clinical nurse specialists assessed the complexity of nursing situations with a questionnaire. Subsequently, we interviewed nurses and clinical nurse specialists about their evaluation of patient-related complexity. In a within-case-analysis we summarized data inductively to create case narratives. By means of a cross-case-analysis we compared the cases with regard to deductively derived characteristics. The four cases exemplarily showed that the degree of complexity depends on the controllability and predictability of clinical problems. Additionally, complexity increases or decreases, according to patients' individual resources. Complex patient situations demand professional expertise, experience, communicative competencies and the ability for reflection. Beginner nurses would benefit from support and advice by experienced nurses to develop these skills.

Use of amplified Mycobacterium tuberculosis direct test in respiratory samples from HIV-infected patients in Brazil.

PubMed

Barreto, Leonardo Bruno Paz Ferreira; Lourenço, Maria Cristina da Silva; Rolla, Valéria Cavalcanti; Veloso, Valdiléia Gonçalves; Huf, Gisele

2014-01-01

To compare the accuracy of the amplified Mycobacterium tuberculosis direct (AMTD) test with reference methods for the laboratory diagnosis of tuberculosis in HIV-infected patients. This was a study of diagnostic accuracy comparing AMTD test results with those obtained by culture on Löwenstein-Jensen (LJ) medium and by the BACTEC Mycobacteria Growth Indicator Tube 960 (BACTEC MGIT 960) system in respiratory samples analyzed at the Bioassay and Bacteriology Laboratory of the Oswaldo Cruz Foundation Evandro Chagas Clinical Research Institute in the city of Rio de Janeiro, Brazil. We analyzed respiratory samples collected from 118 patients, of whom 88 (74.4%) were male. The mean age was 36.6 ± 10.6 years. Using the AMTD test, the BACTEC MGIT 960 system, and LJ culture, we identified M. tuberculosis complex in 31.0%, 29.7%, and 27.1% of the samples, respectively. In comparison with LJ culture, the AMTD test had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 89.4%, 75.7%, and 95.0%, respectively, for LJ culture, whereas, in comparison with the BACTEC MGIT 960 system, it showed values of 88.6%, 92.4%, 83.8%, and 94.8%, respectively. The AMTD test showed good sensitivity and specificity in the population studied, enabling the laboratory detection of M. tuberculosis complex in paucibacillary respiratory specimens.

Mass spectrometry in clinical chemistry: the case of newborn screening.

PubMed

la Marca, Giancarlo

2014-12-01

Newborn screening (NBS) program is a complex and organized system consisting of family and personnel education, biochemical tests, confirmatory biochemical and genetic tests, diagnosis, therapy, and patient follow up. The program identifies treatable metabolic disorders possibly when asymptomatic by using dried blood spot (DBS). During the last 20 years tandem mass spectrometry (TMS) has become the leading technology in NBS programs demonstrating to be versatile, sensitive and specific. There is consistent evidence of benefits from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fibrosis, congenital adrenal hyperplasia by immune-enzymatic methods. Real time PCR tests have more recently been proposed for the detection of some severe combined immunodeficiences (SCID) along with the use of TMS for ADA and PNP SCID; a first evaluation of their cost-benefit ratio is still ongoing. Avoiding false negative results by using specific biomarkers and reducing the false positive rate by using second tier tests, is fundamental for a successful NBS program. The fully integration of NBS and diagnostic laboratories with clinical service is crucial to have the best effectiveness in a comprehensive NBS system. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and Implementation of a Coagulation Factor Testing Method Utilizing Autoverification in a High-volume Clinical Reference Laboratory Environment

PubMed Central

Riley, Paul W.; Gallea, Benoit; Valcour, Andre

2017-01-01

Background: Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. Methods: The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Results: Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. Conclusions: To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process. PMID:28706751

Development and Implementation of a Coagulation Factor Testing Method Utilizing Autoverification in a High-volume Clinical Reference Laboratory Environment.

PubMed

Riley, Paul W; Gallea, Benoit; Valcour, Andre

2017-01-01

Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process.

Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy.

PubMed

Sleeper, Meg M; Rosato, Bradley P; Bansal, Seema; Avadhani, Narayan G

2012-11-01

To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy. Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy). Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs. Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy. Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

Anticancer polysaccharides from natural resources: a review of recent research.

PubMed

Zong, Aizhen; Cao, Hongzhi; Wang, Fengshan

2012-11-06

Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. However, almost all of the chemotherapy drugs currently on the market cause serious side effects. Fortunately, several previous studies have shown that some non-toxic biological macromolecules, including polysaccharides and polysaccharide-protein complexes, possess anti-cancer activities or can increase the efficacy of conventional chemotherapy drugs. Based on these encouraging observations, a great deal of effort has been focused on discovering anti-cancer polysaccharides and complexes for the development of effective therapeutics for various human cancers. This review focuses on the advancements in the anti-cancer efficacy of various natural polysaccharides and polysaccharide complexes in the past 5 years. Most polysaccharides were tested using model systems, while several involved clinical trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Computerization of Mental Health Integration Complexity Scores at Intermountain Healthcare

PubMed Central

Oniki, Thomas A.; Rodrigues, Drayton; Rahman, Noman; Patur, Saritha; Briot, Pascal; Taylor, David P.; Wilcox, Adam B.; Reiss-Brennan, Brenda; Cannon, Wayne H.

2014-01-01

Intermountain Healthcare’s Mental Health Integration (MHI) Care Process Model (CPM) contains formal scoring criteria for assessing a patient’s mental health complexity as “mild,” “medium,” or “high” based on patient data. The complexity score attempts to assist Primary Care Physicians in assessing the mental health needs of their patients and what resources will need to be brought to bear. We describe an effort to computerize the scoring. Informatics and MHI personnel collaboratively and iteratively refined the criteria to make them adequately explicit and reflective of MHI objectives. When tested on retrospective data of 540 patients, the clinician agreed with the computer’s conclusion in 52.8% of the cases (285/540). We considered the analysis sufficiently successful to begin piloting the computerized score in prospective clinical care. So far in the pilot, clinicians have agreed with the computer in 70.6% of the cases (24/34). PMID:25954401

Carbonic Anhydrase Inhibitors. Part 91. Metal Complexes of Heterocyclic Sulfonamides as Potential Pharmacological Agents in the Treatment of Gastric Acid Secretion Imbalances

PubMed Central

Ilies, Marc A.; Scozzafava, Andrea

2000-01-01

Zinc, magnesium, aluminum and copper complexes of several potent, clinically used carbonic anhydrase (CA) sulfonamide inhibitors, such as acetazolamide, methazolamide, ethoxzolamide and benzolamide were tested for their possible applications as antacids, in experimental animals. Gastric acid secretion parameters 3 days after treatment with these CA inhibitors (2 × 500 mg, twice a day), in dogs with chronic gastric fistulas, led to the observation that the gastric acid parameters BAO (the basal acid output), and MAO (the maximal acid output after stimulation with histamine) were drastically reduced, as compared to the same parameters in animals that did not receive these enzyme inhibitors. These are promising results for the possible use of metal complexes of heterocyclic sulfonamides as treatment alternatives (alone or in combination with other drugs) for gastric acid secretion imbalances. PMID:18475926

Utilization of individualized prostate cancer and genomic biomarkers for the practicing urologist

PubMed Central

McMahon, Gregory C.; Brown, Gordon A.; Mueller, Thomas J.

2017-01-01

Prostate cancer encompasses a complex heterogeneous disease spectrum. Physicians and patients are faced with the ambiguity of who should be screened, biopsied, rebiopsied, treated, or provided with adjuvant therapy. Personalized outcomes and treatments are especially important given the varied nature of the disease, plethora of treatment options, risks of morbidity, and quality of life. Today’s practicing urologist has a multitude of tests from which to choose, creating the difficult task of appropriate use. This review focuses on two blood-, one urine-, and five genomic-based tests, which, when used in the appropriate clinical setting, can facilitate the patient-physician decision-making process. PMID:28959146

What can be learned from the effects of benzodiazepines on exploratory behavior?

PubMed

File, S E

1985-01-01

The purpose of this review is to assess the value of using tests of exploratory behavior to study the actions of benzodiazepines. The methods of measuring exploration and the factors influencing it are briefly described. The effects of benzodiazepines on exploratory behavior of rats and mice are reviewed; and the dangers of interpreting the results of such tests in terms of any of the clinical effects of the benzodiazepines is stressed. Finally, the interactions between benzodiazepines and other drugs acting at the GABA-benzodiazepine receptor complex are described. The results of these experiments caution against global classification of compounds as benzodiazepine "antagonists."

Understanding complex clinical reasoning in infectious diseases for improving clinical decision support design.

PubMed

Islam, Roosan; Weir, Charlene R; Jones, Makoto; Del Fiol, Guilherme; Samore, Matthew H

2015-11-30

Clinical experts' cognitive mechanisms for managing complexity have implications for the design of future innovative healthcare systems. The purpose of the study is to examine the constituents of decision complexity and explore the cognitive strategies clinicians use to control and adapt to their information environment. We used Cognitive Task Analysis (CTA) methods to interview 10 Infectious Disease (ID) experts at the University of Utah and Salt Lake City Veterans Administration Medical Center. Participants were asked to recall a complex, critical and vivid antibiotic-prescribing incident using the Critical Decision Method (CDM), a type of Cognitive Task Analysis (CTA). Using the four iterations of the Critical Decision Method, questions were posed to fully explore the incident, focusing in depth on the clinical components underlying the complexity. Probes were included to assess cognitive and decision strategies used by participants. The following three themes emerged as the constituents of decision complexity experienced by the Infectious Diseases experts: 1) the overall clinical picture does not match the pattern, 2) a lack of comprehension of the situation and 3) dealing with social and emotional pressures such as fear and anxiety. All these factors contribute to decision complexity. These factors almost always occurred together, creating unexpected events and uncertainty in clinical reasoning. Five themes emerged in the analyses of how experts deal with the complexity. Expert clinicians frequently used 1) watchful waiting instead of over- prescribing antibiotics, engaged in 2) theory of mind to project and simulate other practitioners' perspectives, reduced very complex cases into simple 3) heuristics, employed 4) anticipatory thinking to plan and re-plan events and consulted with peers to share knowledge, solicit opinions and 5) seek help on patient cases. The cognitive strategies to deal with decision complexity found in this study have important implications for design future decision support systems for the management of complex patients.

Newborn screening of metabolic disorders: recent progress and future developments.

PubMed

Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

2008-01-01

Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation.

Evaluation of the Illumigene Malaria LAMP: A Robust Molecular Diagnostic Tool for Malaria Parasites

PubMed Central

Lucchi, Naomi W.; Gaye, Marie; Diallo, Mammadou Alpha; Goldman, Ira F.; Ljolje, Dragan; Deme, Awa Bineta; Badiane, Aida; Ndiaye, Yaye Die; Barnwell, John W.; Udhayakumar, Venkatachalam; Ndiaye, Daouda

2016-01-01

Isothermal nucleic acid amplification assays such as the loop mediated isothermal amplification (LAMP), are well suited for field use as they do not require thermal cyclers to amplify the DNA. To further facilitate the use of LAMP assays in remote settings, simpler sample preparation methods and lyophilized reagents are required. The performance of a commercial malaria LAMP assay (Illumigene Malaria LAMP) was evaluated using two sample preparation workflows (simple filtration prep (SFP)) and gravity-driven filtration prep (GFP)) and pre-dispensed lyophilized reagents. Laboratory and clinical samples were tested in a field laboratory in Senegal and the results independently confirmed in a reference laboratory in the U.S.A. The Illumigene Malaria LAMP assay was easily implemented in the clinical laboratory and gave similar results to a real-time PCR reference test with limits of detection of ≤2.0 parasites/μl depending on the sample preparation method used. This assay reliably detected Plasmodium sp. parasites in a simple low-tech format, providing a much needed alternative to the more complex molecular tests for malaria diagnosis. PMID:27827432

Point-of-care testing: applications of 3D printing.

PubMed

Chan, Ho Nam; Tan, Ming Jun Andrew; Wu, Hongkai

2017-08-08

Point-of-care testing (POCT) devices fulfil a critical need in the modern healthcare ecosystem, enabling the decentralized delivery of imperative clinical strategies in both developed and developing worlds. To achieve diagnostic utility and clinical impact, POCT technologies are immensely dependent on effective translation from academic laboratories out to real-world deployment. However, the current research and development pipeline is highly bottlenecked owing to multiple restraints in material, cost, and complexity of conventionally available fabrication techniques. Recently, 3D printing technology has emerged as a revolutionary, industry-compatible method enabling cost-effective, facile, and rapid manufacturing of objects. This has allowed iterative design-build-test cycles of various things, from microfluidic chips to smartphone interfaces, that are geared towards point-of-care applications. In this review, we focus on highlighting recent works that exploit 3D printing in developing POCT devices, underscoring its utility in all analytical steps. Moreover, we also discuss key advantages of adopting 3D printing in the device development pipeline and identify promising opportunities in 3D printing technology that can benefit global health applications.

Application of Proteomic Approaches to Accelerate Drug Development for Psychiatric Disorders.

PubMed

Rahmoune, Hassan; Martins-de-Souza, Daniel; Guest, Paul C

2017-01-01

Proteomic-based biomarkers are now an integral part of the drug development process. This chapter covers the role of proteomic biomarker tests as useful tools for improving preclinical research and clinical development. One medical area that has been lagging behind this process is the study of psychiatric disorders, and this is most likely due to the complexity of these diseases. The potential of incorporating biomarkers in the clinical pipeline to improve decision-making, accelerate drug development, improve translation and reduce development costs is also discussed, with a focus on psychiatric diseases like schizophrenia. This chapter will also discuss the next steps that must be taken to keep moving this process forwards.

[Care continuity for patients with Prader-Willi syndrome during transition from childhood to adulthood].

PubMed

Saitoh, Shinji

2010-01-01

Prader-Willi syndrome(PWS) is a complex multisystem genetic disorder, of which characteristic phenotypes include neonatal hypotonia, hyperphagia resulting in obesity, mental retardation, hypogonadism, and behavioral and psychiatric problems. The diagnosis can be obtained as early as during neonatal period thanks to development of genetic testing. Clinical features of PWS will change depending on age, although core phenotypes of hyperphagia, obesity and psychiatric issues stay for lifetime. Therefore, integrated multidisciplinary approach starting from neonatal period is mandatory to ensure optimal management to improve lifelong quality of life. For successful transition from childhood to adulthood, multidisciplinary team need to share clinical information, and should keep the same policy about food, environment and psychiatric issues.

[Automated RNA amplification for the rapid identification of Mycobacterium tuberculosis complex in respiratory specimens].

PubMed

Drouillon, V; Houriez, F; Buze, M; Lagrange, P; Herrmann, J-L

2006-01-01

Rapid and sensitive detection of Mycobacterium tuberculosis complex (MTB) directly on clinical respiratory specimens is essential for a correct management of patients suspected of tuberculosis. For this purpose PCR-based kits are available to detect MTB in respiratory specimen but most of them need at least 4 hours to be completed. New methods, based on TRC method (TRC: Transcription Reverse transcription Concerted--TRCRapid M. Tuberculosis--Tosoh Bioscience, Tokyo, Japon) and dedicated monitor have been developed. A new kit (TRC Rapid M. tuberculosis and Real-time monitor TRCRapid-160, Tosoh Corporation, Japan) enabling one step amplification and real-time detection of MTB 16S rRNA by a combination of intercalative dye oxazole yellow-linked DNA probe and isothermal RNA amplification directly on respiratory specimens has been tested in our laboratory. 319 respiratory specimens were tested in this preliminary study and results were compared to smear and culture. Fourteen had a positive culture for MTB. Among theses samples, smear was positive in 11 cases (78.6%) and TRC process was positive in 8 cases (57.1%). Overall sensitivity of TRC compared to smear positive samples is 73%. Theses first results demonstrated that a rapid identification of MTB was possible (less than 2 processing hours for 14 specimens and about 1 hour for 1 specimen) in most cases of smear positive samples using ready to use reagents for real time detection of MTB rRNA in clinical samples. New pretreatment and extraction reagents kits to increase the stability of the sputum RNA and the extraction efficiency are now tested in our laboratory.

Clinical evidence of parietal cortex dysfunction and correlation with extent of allodynia in CRPS type 1.

PubMed

Cohen, H; McCabe, C; Harris, N; Hall, J; Lewis, J; Blake, D R

2013-04-01

Unusual symptoms such as digit misidentification and neglect-like phenomena have been reported in complex regional pain syndrome (CRPS), which we hypothesized could be explained by parietal lobe dysfunction. Twenty-two patients with chronic CRPS attending an in-patient rehabilitation programme underwent standard neurological examination followed by clinical assessment of parietal lobe function and detailed sensory testing. Fifteen (68%) patients had evidence of parietal lobe dysfunction. Six (27%) subjects failed six or more test categories and demonstrated new clinical signs consistent with their parietal testing impairments, which were impacting significantly on activities of daily living. A higher incidence was noted in subjects with >1 limb involvement, CRPS affecting the dominant side and in left-handed subjects. Eighteen patients (82%) had mechanical allodynia covering 3-57.5% of the body surface area. Allochiria (unilateral tactile stimulation perceived only in the analogous location on the opposite limb), sensory extinction (concurrent bilateral tactile stimulation perceived only in one limb), referred sensations (unilateral tactile stimulation perceived concurrently in another discrete body area) and dysynchiria (unilateral non-noxious tactile stimulation perceived bilaterally as noxious) were present in some patients. Greater extent of body surface allodynia was correlated with worse parietal function (Spearman's rho = -0.674, p = 0.001). In patients with chronic CRPS, detailed clinical examination may reveal parietal dysfunction, with severity relating to the extent of allodynia. © 2012 European Federation of International Association for the Study of Pain Chapters.

Increasing chlamydia screening tests in general practice: a modified Zelen prospective Cluster Randomised Controlled Trial evaluating a complex intervention based on the Theory of Planned Behaviour.

PubMed

McNulty, Cliodna A M; Hogan, Angela H; Ricketts, Ellie J; Wallace, Louise; Oliver, Isabel; Campbell, Rona; Kalwij, Sebastian; O'Connell, Elaine; Charlett, Andre

2014-05-01

To determine if a structured complex intervention increases opportunistic chlamydia screening testing of patients aged 15-24 years attending English general practitioner (GP) practices. A prospective, Cluster Randomised Controlled Trial with a modified Zelen design involving 160 practices in South West England in 2010. The intervention was based on the Theory of Planned Behaviour (TPB). It comprised of practice-based education with up to two additional contacts to increase the importance of screening to GP staff and their confidence to offer tests through skill development (including videos). Practical resources (targets, posters, invitation cards, computer reminders, newsletters including feedback) aimed to actively influence social cognitions of staff, increasing their testing intention. Data from 76 intervention and 81 control practices were analysed. In intervention practices, chlamydia screening test rates were 2.43/100 15-24-year-olds registered preintervention, 4.34 during intervention and 3.46 postintervention; controls testing rates were 2.61/100 registered patients prior intervention, 3.0 during intervention and 2.82 postintervention. During the intervention period, testing in intervention practices was 1.76 times as great (CI 1.24 to 2.48) as controls; this persisted for 9 months postintervention (1.57 times as great, CI 1.27 to 2.30). Chlamydia infections detected increased in intervention practices from 2.1/1000 registered 15-24-year-olds prior intervention to 2.5 during the intervention compared with 2.0 and 2.3/1000 in controls (Estimated Rate Ratio intervention versus controls 1.4 (CI 1.01 to 1.93). This complex intervention doubled chlamydia screening tests in fully engaged practices. The modified Zelen design gave realistic measures of practice full engagement (63%) and efficacy of this educational intervention in general practice; it should be used more often. The trial was registered on the UK Clinical Research Network Study Portfolio database. UKCRN number 9722.

Characterisation of pks15/1 in clinical isolates of Mycobacterium tuberculosis from Mexico

PubMed Central

Zenteno-Cuevas, Roberto; Silva-Hernández, Francisco X; Mendoza-Damián, Fabiola; Ramírez-Hernández, Maria Dolores; Vázquez-Medina, Karen; Widrobo-García, Lorena; Cuellar-Sanchez, Aremy; Muñíz-Salazar, Raquel; Enciso-Moreno, Leonor; Pérez-Navarro, Lucia Monserrat; Enciso-Moreno, José Antonio

2013-01-01

Tuberculosis (TB) is an infectocontagious respiratory disease caused by members of the Mycobacterium tuberculosis complex. A 7 base pair (bp) deletion in the locus polyketide synthase (pks)15/1 is described as polymorphic among members of the M. tuberculosis complex, enabling the identification of Euro-American, Indo-Oceanic and Asian lineages. The aim of this study was to characterise this locus in TB isolates from Mexico. One hundred twenty clinical isolates were recovered from the states of Veracruz and Estado de Mexico. We determined the nucleotide sequence of a ± 400 bp fragment of the locus pks15/1, while genotypic characterisation was performed by spoligotyping. One hundred and fifty isolates contained the 7 bp deletion, while five had the wild type locus. Lineages X (22%), LAM (18%) and T (17%) were the most frequent; only three (2%) of the isolates were identified as Beijing and two (1%) EAI-Manila. The wild type pks15/1 locus was observed in all Asian lineage isolates tested. Our results confirm the utility of locus pks15/1 as a molecular marker for identifying Asian lineages of the M. tuberculosis complex. This marker could be of great value in the epidemiological surveillance of TB, especially in countries like Mexico, where the prevalence of such lineages is unknown. PMID:24037193

Determining access to assisted reproductive technology: reactions of clinic directors to ethically complex case scenarios.

PubMed

Stern, J E; Cramer, C P; Green, R M; Garrod, A; DeVries, K O

2003-06-01

Our aim was to increase understanding of how patient selection is handled by assisted reproductive technology (ART) clinicians. Ethically complex case scenarios were evaluated by the directors of USA ART clinics. Scenarios included using a son as sperm donor for his father, sex selection without associated disease, treatment of morally irresponsible couples, and a dispute over embryo disposition. Respondents reviewed eight scenarios and gave their opinions on whether to offer treatment. Reasons given for these decisions were placed into one of 13 categories. Survey response rate was 57%. Between 3 and 50% of respondents would treat in each case. Of reasons given, 'conditional' responses (requiring counselling, blood tests or agreement to other 'conditions') were common (31.4%). Non-maleficence (risk) accounted for 29.4% of responses, philosophy of medicine 18.9%, respect for patient autonomy 5.9% and legal concerns 4.6%. Discrimination and threats were each significant in one case. Reasons evoking absolutist beliefs, personal discomfort, commitment to justice, religion and ethical relativism were rare. Clinicians felt conflict between a desire to respect patient autonomy and their discomfort over the risk associated with the procedure. They raised concerns about misuse of medical technology. Attempts to resolve complex issues through negotiation and compromise were common.

Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

PubMed

García-Carbonero, R; Vilardell, F; Jiménez-Fonseca, P; González-Campora, R; González, E; Cuatrecasas, M; Capdevila, J; Aranda, I; Barriuso, J; Matías-Guiu, X

2014-03-01

The annual incidence of neuroendocrine tumours in the Caucasian population ranges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours is a family of neoplasms widely variable in terms of anatomical location, hormone composition, clinical syndromes they cause and in their biological behaviour. This high complexity and clinical heterogeneity, together with the known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been developed over the years in this field. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical practice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).

Informing family members of individuals with Lynch syndrome: a guideline for clinical geneticists.

PubMed

Menko, Fred H; Aalfs, Cora M; Henneman, Lidewij; Stol, Yrrah; Wijdenes, Miranda; Otten, Ellen; Ploegmakers, Marleen M J; Legemaate, Johan; Smets, Ellen M A; de Wert, Guido M W R; Tibben, Aad

2013-06-01

The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer through periodic colonoscopies and removal of premalignant lesions in susceptible individuals. Therefore, predisposed individuals identified by mutation analysis are advised to inform their at-risk relatives about the options of predictive DNA testing and preventive measures. However, it has now been established that more than half of these relatives do not receive the necessary information. Barriers in conveying information include family communication problems and variable attitudes and practice among clinical geneticists. In this complex field, both medical, psychological, ethical and juridical aspects deserve consideration. Here we summarize the development of a revised guideline for clinical geneticists that allows a more active role of the geneticist, aimed at improving procedures to inform family members in Lynch syndrome and other hereditary and familial cancer syndromes.

Interpretative Commenting

PubMed Central

Vasikaran, Samuel

2008-01-01

Summary Clinical laboratories should be able to offer interpretation of the results they produce.At a minimum, contact details for interpretative advice should be available on laboratory reports.Interpretative comments may be verbal or written and printed.Printed comments on reports should be offered judiciously, only where they would add value; no comment preferred to inappropriate or dangerous comment.Interpretation should be based on locally agreed or nationally recognised clinical guidelines where available.Standard tied comments (“canned” comments) can have some limited use.Individualised narrative comments may be particularly useful in the case of tests that are new, complex or unfamiliar to the requesting clinicians and where clinical details are available.Interpretative commenting should only be provided by appropriately trained and credentialed personnel.Audit of comments and continued professional development of personnel providing them are important for quality assurance. PMID:18852867

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

PubMed

Al-Wakeel, Nadya; O h-Ici, Darach; Schmitt, Katharina R; Messroghli, Daniel R; Riesenkampff, Eugénie; Berger, Felix; Kuehne, Titus; Peters, Bjoern

2016-02-01

In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

A unified framework for weighted parametric multiple test procedures.

PubMed

Xi, Dong; Glimm, Ekkehard; Maurer, Willi; Bretz, Frank

2017-09-01

We describe a general framework for weighted parametric multiple test procedures based on the closure principle. We utilize general weighting strategies that can reflect complex study objectives and include many procedures in the literature as special cases. The proposed weighted parametric tests bridge the gap between rejection rules using either adjusted significance levels or adjusted p-values. This connection is made by allowing intersection hypotheses of the underlying closed test procedure to be tested at level smaller than α. This may be also necessary to take certain study situations into account. For such cases we introduce a subclass of exact α-level parametric tests that satisfy the consonance property. When the correlation is known only for certain subsets of the test statistics, a new procedure is proposed to fully utilize this knowledge within each subset. We illustrate the proposed weighted parametric tests using a clinical trial example and conduct a simulation study to investigate its operating characteristics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aminoglycoside Resistance and Susceptibility Testing Errors in Acinetobacter baumannii-calcoaceticus Complex

DTIC Science & Technology

2010-04-01

the most active aminoglycoside (27.1% of isolates were susceptible ). Disk diffusion and Etest tended to be more accurate than the Vitek 2 , Phoenix...and MicroScan automated systems; but errors were noted with all methods. The Vitek 2 instrument incorrectly reported that more than one-third of the...Acinetobacter, we have observed in clinical practice at the San Antonio Mil- itary Medical Center results of susceptibility to amikacin from the Vitek 2

Physical Properties Of Acupuncture Needles: Do Disposable Acupuncture Needles Break With Normal Use

DTIC Science & Technology

2016-06-01

Lamb shank, which has complexity of tendon, fascia, and bone, was used to mimic human tissue. The needles (n=10) were stressed in the tissue substitute...needles were re-imaged after stressing and visually assessed. RESULTS: Only one manufacturing scuff mark was noted out of 90 needles before stress ...testing. Needles buckled but did not break when they were stressed beyond normal clinical use. No cracks or fractures were noted after stress

Evaluation of the Efficiency of the Sample Inactivation Reagent in the Abbott RealTime MTB Assay for Inactivation of Mycobacterium tuberculosis.

PubMed

Qi, Chao; Wallis, Carole; Pahalawatta, Vihanga; Frank, Andrea; Ramdin, Neeshan; Viana, Raquel; Abravaya, Klara; Leckie, Gregor; Tang, Ning

2015-09-01

The Abbott RealTime MTB assay is a nucleic acid amplification test (NAAT) for the detection of Mycobacterium tuberculosis complex DNA. The sample inactivation procedure used in the assay, consisting of one part sample treated with 3 parts inactivation reagent for 60 min, effectively reduced viscosity and inactivated M. tuberculosis in clinical specimens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Differential diagnosis of hyperkalemia: an update to a complex problem.

PubMed

Eleftheriadis, T; Leivaditis, K; Antoniadi, G; Liakopoulos, V

2012-10-01

Hyperkalemia is a relative common and sometimes life threatening electorlyte disorder. Although its symptomatic treatment is relatively easy, since precise therapeutic algorithms are available, its differential diagnosis is more complicated. The present review aims to unfold the differential diagnosis of hypekalemia using a pathophysiological, albeit clinically useful, approach. The basic elements of potassium homeostasis are provided, the causes of hyperkalemia are categorized and analysed and finally the required for the diferrential diagnosis laboratory tests are mentioned.

Modeling complex treatment strategies: construction and validation of a discrete event simulation model for glaucoma.

PubMed

van Gestel, Aukje; Severens, Johan L; Webers, Carroll A B; Beckers, Henny J M; Jansonius, Nomdo M; Schouten, Jan S A G

2010-01-01

Discrete event simulation (DES) modeling has several advantages over simpler modeling techniques in health economics, such as increased flexibility and the ability to model complex systems. Nevertheless, these benefits may come at the cost of reduced transparency, which may compromise the model's face validity and credibility. We aimed to produce a transparent report on the construction and validation of a DES model using a recently developed model of ocular hypertension and glaucoma. Current evidence of associations between prognostic factors and disease progression in ocular hypertension and glaucoma was translated into DES model elements. The model was extended to simulate treatment decisions and effects. Utility and costs were linked to disease status and treatment, and clinical and health economic outcomes were defined. The model was validated at several levels. The soundness of design and the plausibility of input estimates were evaluated in interdisciplinary meetings (face validity). Individual patients were traced throughout the simulation under a multitude of model settings to debug the model, and the model was run with a variety of extreme scenarios to compare the outcomes with prior expectations (internal validity). Finally, several intermediate (clinical) outcomes of the model were compared with those observed in experimental or observational studies (external validity) and the feasibility of evaluating hypothetical treatment strategies was tested. The model performed well in all validity tests. Analyses of hypothetical treatment strategies took about 30 minutes per cohort and lead to plausible health-economic outcomes. There is added value of DES models in complex treatment strategies such as glaucoma. Achieving transparency in model structure and outcomes may require some effort in reporting and validating the model, but it is feasible.

Rhinencephalon changes in tuberous sclerosis complex.

PubMed

Manara, Renzo; Brotto, Davide; Bugin, Samuela; Pelizza, Maria Federica; Sartori, Stefano; Nosadini, Margherita; Azzolini, Sara; Iaconetta, Giorgio; Parazzini, Cecilia; Murgia, Alessandra; Peron, Angela; Canevini, Paola; Labriola, Francesca; Vignoli, Aglaia; Toldo, Irene

2018-06-17

Despite complex olfactory bulb embryogenesis, its development abnormalities in tuberous sclerosis complex (TSC) have been poorly investigated. Brain MRIs of 110 TSC patients (mean age 11.5 years; age range 0.5-38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests. Eight of110 (7.2%) TSC patients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSC patient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSC patients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample. Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects.

Neuropsychological Profiles Correlated with Clinical and Behavioral Impairments in a Sample of Brazilian Children with Attention-Deficit Hyperactivity Disorder

PubMed Central

Rizzutti, Sueli; Schuch, Viviane; Augusto, Bruno Muszkat; Coimbra, Caio Colturato; Pereira, João Pedro Cabrera; Bueno, Orlando Francisco Amodeo

2015-01-01

Attention-deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder that implies several-step process, and there is no single test to diagnose both ADHD and associated comorbidities, such as oppositional-defiant disorder (ODD), anxiety disorder, depression, and certain types of learning disabilities. The purpose of the present study was to examine correlations between behavioral and clinical symptoms by administering an extensive neuropsychological battery to a sample of children and adolescents from a developing country. The sample was divided into three groups: non-ADHD, ADHD-non-comorbid, and ADHD + comorbidity. A full neuropsychological battery and clinical assessment found that 105 children met DSM-5 criteria, of whom 46.6% had the predominantly inattentive presentation, 37.3% had combined presentation, and 16% were predominantly hyperactive/impulsive presentation. The internal correlation between neuropsychological tests did not reach statistical significance in the comparison between ADHD and non-ADHD cases (p < 0.17). Clinical ADHD cases, including both + comorbidity and non-comorbid groups, performed substantially worse on continuous performance test (CPT), working memory. Comparing ADHD-non-comorbid and ADHD + comorbidity groups, the latter did significantly worse on inhibitory control, time processing, and the level of perseveration response on CPT indexes, as well as on working memory performance and child behavior checklist (CBCL) tests particularly the CBCL-deficient emotional self-regulation test in the ADHD + comorbidity group. Children diagnosed as ODD or with conduct disorder showed close correlations between clinical CBCL profiles and externalized symptoms. Our findings suggest that ADHD + comorbidity and ADHD non-comorbid cases may be differentiated by a number of neuropsychological measures, such as processing speed, inhibitory control, and working memory, that may reflect different levels of involvement of the hot and cool executive domains, which are more impaired in cases of severe symptomatic-externalized behavior and emotional regulation problems. Therefore, profiles based on clinical and behavioral findings can help clinicians select better strategies for detecting neuropsychological impairment in Brazilian children with ADHD. PMID:26635638