clinical reference standard: Topics by Science.gov

Sample records for clinical reference standard

Development and Evaluation of Reference Standards for Image-based Telemedicine Diagnosis and Clinical Research Studies in Ophthalmology

PubMed Central

Ryan, Michael C.; Ostmo, Susan; Jonas, Karyn; Berrocal, Audina; Drenser, Kimberly; Horowitz, Jason; Lee, Thomas C.; Simmons, Charles; Martinez-Castellanos, Maria-Ana; Chan, R.V. Paul; Chiang, Michael F.

2014-01-01

Information systems managing image-based data for telemedicine or clinical research applications require a reference standard representing the correct diagnosis. Accurate reference standards are difficult to establish because of imperfect agreement among physicians, and discrepancies between clinical vs. image-based diagnosis. This study is designed to describe the development and evaluation of reference standards for image-based diagnosis, which combine diagnostic impressions of multiple image readers with the actual clinical diagnoses. We show that agreement between image reading and clinical examinations was imperfect (689 [32%] discrepancies in 2148 image readings), as was inter-reader agreement (kappa 0.490-0.652). This was improved by establishing an image-based reference standard defined as the majority diagnosis given by three readers (13% discrepancies with image readers). It was further improved by establishing an overall reference standard that incorporated the clinical diagnosis (10% discrepancies with image readers). These principles of establishing reference standards may be applied to improve robustness of real-world systems supporting image-based diagnosis. PMID:25954463
Agreement between diagnoses reached by clinical examination and available reference standards: a prospective study of 216 patients with lumbopelvic pain

PubMed Central

Laslett, Mark; McDonald, Barry; Tropp, Hans; Aprill, Charles N; Öberg, Birgitta

2005-01-01

Background The tissue origin of low back pain (LBP) or referred lower extremity symptoms (LES) may be identified in about 70% of cases using advanced imaging, discography and facet or sacroiliac joint blocks. These techniques are invasive and availability varies. A clinical examination is non-invasive and widely available but its validity is questioned. Diagnostic studies usually examine single tests in relation to single reference standards, yet in clinical practice, clinicians use multiple tests and select from a range of possible diagnoses. There is a need for studies that evaluate the diagnostic performance of clinical diagnoses against available reference standards. Methods We compared blinded clinical diagnoses with diagnoses based on available reference standards for known causes of LBP or LES such as discography, facet, sacroiliac or hip joint blocks, epidurals injections, advanced imaging studies or any combination of these tests. A prospective, blinded validity design was employed. Physiotherapists examined consecutive patients with chronic lumbopelvic pain and/or referred LES scheduled to receive the reference standard examinations. When diagnoses were in complete agreement regardless of complexity, "exact" agreement was recorded. When the clinical diagnosis was included within the reference standard diagnoses, "clinical agreement" was recorded. The proportional chance criterion (PCC) statistic was used to estimate agreement on multiple diagnostic possibilities because it accounts for the prevalence of individual categories in the sample. The kappa statistic was used to estimate agreement on six pathoanatomic diagnoses. Results In a sample of chronic LBP patients (n = 216) with high levels of disability and distress, 67% received a patho-anatomic diagnosis based on available reference standards, and 10% had more than one tissue origin of pain identified. For 27 diagnostic categories and combinations, chance clinical agreement (PCC) was estimated at 13%. "Exact" agreement between clinical and reference standard diagnoses was 32% and "clinical agreement" 51%. For six pathoanatomic categories (disc, facet joint, sacroiliac joint, hip joint, nerve root and spinal stenosis), PCC was 33% with actual agreement 56%. There was no overlap of 95% confidence intervals on any comparison. Diagnostic agreement on the six most common patho-anatomic categories produced a kappa of 0.31. Conclusion Clinical diagnoses agree with reference standards diagnoses more often than chance. Using available reference standards, most patients can have a tissue source of pain identified. PMID:15943873
Sensitivity and specificity of visual clinical assessment as compared to WHO 2006 standard and NCHS 1977 reference in measuring the growth status of Malaysian infants.

PubMed

Selamat, Rusidah; Zain, Fuziah; Raib, Junidah; Zakaria, Rosini; Marzuki, Mohd Shaffari; Ibrahim, Taziah Fatimah

2011-12-01

To study the validity of the visual clinical assessment of weight relative to length and length relative to age as compared to the World Health Organization (WHO) 2006 standard and National Center for Health Statistics (NCHS) 1977 reference in asssessing the physical growth of children younger than 1 year. A prospective cohort study was carried out among 684 infants attending goverment health clinics in 2 states in Malaysia. Body weight, length, and clinical assessment were measured on the same day for 9 visits, scheduled every month until 6 months of age and every 2 months until 12 months of age. All of the 3 z-scores for weight for age (WAZ), length for age (HAZ), and weight for length (WHZ) were calculated using WHO Anthro for Personal Computers software. The average sensitivity and specificity for the visual clinical assessment for the detection of thinness were higher using the WHO 2006 standard as compared with using NCHS 1977. However, the overall sensitivity of the visual clinical assessment for the detection of thin and lean children was lower from 1 month of age until a year as compared with the WHO 2006 standard and NCHS 1977 reference. The positive predictive value (PPV) for the visual clinical assessment versus the WHO 2006 standard was almost doubled as compared with the PPV of visual clinical assessment versus the NCHS 1977 reference. The overall average sensitivity, specificity, PPV, and negative predictive value for the detection of stunting was higher for visual clinical assessment versus the WHO 2006 standard as compared with visual clinical assessment versus the NCHS 1977 reference. The sensitivity and specificity of visual clinical assessment for the detection of wasting and stunting among infants are better for the WHO 2006 standard than the NCHS 1977 reference.
Clinical diagnostic model for sciatica developed in primary care patients with low back-related leg pain

PubMed Central

Konstantinou, Kika; Ogollah, Reuben; Hay, Elaine M.; Dunn, Kate M.

2018-01-01

Background Identification of sciatica may assist timely management but can be challenging in clinical practice. Diagnostic models to identify sciatica have mainly been developed in secondary care settings with conflicting reference standard selection. This study explores the challenges of reference standard selection and aims to ascertain which combination of clinical assessment items best identify sciatica in people seeking primary healthcare. Methods Data on 394 low back-related leg pain consulters were analysed. Potential sciatica indicators were seven clinical assessment items. Two reference standards were used: (i) high confidence sciatica clinical diagnosis; (ii) high confidence sciatica clinical diagnosis with confirmatory magnetic resonance imaging findings. Multivariable logistic regression models were produced for both reference standards. A tool predicting sciatica diagnosis in low back-related leg pain was derived. Latent class modelling explored the validity of the reference standard. Results Model (i) retained five items; model (ii) retained six items. Four items remained in both models: below knee pain, leg pain worse than back pain, positive neural tension tests and neurological deficit. Model (i) was well calibrated (p = 0.18), discrimination was area under the receiver operating characteristic curve (AUC) 0.95 (95% CI 0.93, 0.98). Model (ii) showed good discrimination (AUC 0.82; 0.78, 0.86) but poor calibration (p = 0.004). Bootstrapping revealed minimal overfitting in both models. Agreement between the two latent classes and clinical diagnosis groups defined by model (i) was substantial, and fair for model (ii). Conclusion Four clinical assessment items were common in both reference standard definitions of sciatica. A simple scoring tool for identifying sciatica was developed. These criteria could be used clinically and in research to improve accuracy of identification of this subgroup of back pain patients. PMID:29621243
[Research strategies in standard decoction of medicinal slices].

PubMed

Chen, Shi-Lin; Liu, An; Li, Qi; Toru, Sugita; Zhu, Guang-Wei; Sun, Yi; Dai, Yun-Tao; Zhang, Jun; Zhang, Tie-Jun; Takehisa, Tomoda; Liu, Chang-Xiao

2016-04-01

This paper discusses the research situation of the standard decoction of medicinal slices at home and abroad. Combined with the experimental data, the author proposes that the standard decoction of medicinal slices is made of single herb using standard process which should be guided by the theory of traditional Chinese medicine, based on clinical practice and referred to modern extraction method with a standard process. And the author also proposes the principles of establishing the specification of process parameters and quality standards and established the basis of drug efficacy material and biological reference. As a standard material and standard system, the standard decoction of medicinal slices can provide standards for clinical medication, standardize the use of the new type of medicinal slices especially for dispensing granules, which were widely used in clinical. It can ensure the accuracy of drugs and consistency of dose, and to solve current supervision difficulties. Moreover the study of standard decoction of medicinal slices will provide the research on dispensing granules, traditional Chinese medicine prescription standard decoction and couplet medicines standard decoction a useful reference. Copyright© by the Chinese Pharmaceutical Association.
The role of standards in the development and implementation of clinical laboratory tests: a domestic and global perspective.

PubMed

Michaud, Ginette Y

2005-01-01

In the field of clinical laboratory medicine, standardization is aimed at increasing the trueness and reliability of measured values. Standardization relies on the use of written standards, reference measurement procedures and reference materials. These are important tools for the design and validation of new tests, and for establishing the metrological traceability of diagnostic assays. Their use supports the translation of research technologies into new diagnostic assays and leads to more rapid advances in science and medicine, as well as improvements in the quality of patient care. The various standardization tools are described, as are the procedures by which written standards, reference procedures and reference materials are developed. Recent efforts to develop standards for use in the field of molecular diagnostics are discussed. The recognition of standardization tools by the FDA and other regulatory authorities is noted as evidence of their important role in ensuring the safety and performance of in vitro diagnostic devices.
Proposed Clinical Decision Rules to Diagnose Acute Rhinosinusitis Among Adults in Primary Care.

PubMed

Ebell, Mark H; Hansen, Jens Georg

2017-07-01

To reduce inappropriate antibiotic prescribing, we sought to develop a clinical decision rule for the diagnosis of acute rhinosinusitis and acute bacterial rhinosinusitis. Multivariate analysis and classification and regression tree (CART) analysis were used to develop clinical decision rules for the diagnosis of acute rhinosinusitis, defined using 3 different reference standards (purulent antral puncture fluid or abnormal finding on a computed tomographic (CT) scan; for acute bacterial rhinosinusitis, we used a positive bacterial culture of antral fluid). Signs, symptoms, C-reactive protein (CRP), and reference standard tests were prospectively recorded in 175 Danish patients aged 18 to 65 years seeking care for suspected acute rhinosinusitis. For each reference standard, we developed 2 clinical decision rules: a point score based on a logistic regression model and an algorithm based on a CART model. We identified low-, moderate-, and high-risk groups for acute rhinosinusitis or acute bacterial rhinosinusitis for each clinical decision rule. The point scores each had between 5 and 6 predictors, and an area under the receiver operating characteristic curve (AUROCC) between 0.721 and 0.767. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a 16%, 49%, and 73% likelihood of acute bacterial rhinosinusitis, respectively. CART models had an AUROCC ranging from 0.783 to 0.827. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a likelihood of acute bacterial rhinosinusitis of 6%, 31%, and 59% respectively. We have developed a series of clinical decision rules integrating signs, symptoms, and CRP to diagnose acute rhinosinusitis and acute bacterial rhinosinusitis with good accuracy. They now require prospective validation and an assessment of their effect on clinical and process outcomes. © 2017 Annals of Family Medicine, Inc.
Toward Clarity in Clinical Vitamin D Status Assessment: 25(OH)D Assay Standardization.

PubMed

Binkley, Neil; Carter, Graham D

2017-12-01

Widespread variation in 25-hydroxyvitamin D (25(OH)D) assays continues to compromise efforts to develop clinical and public health guidelines regarding vitamin D status. The Vitamin D Standardization Program helps alleviate this problem. Reference measurement procedures and standard reference materials have been developed to allow current, prospective, and retrospective standardization of 25(OH)D results. Despite advances in 25(OH)D measurement, substantial variability in clinical laboratory 25(OH)D measurement persists. Existing guidelines have not used standardized data and, as a result, it seems unlikely that consensus regarding definitions of vitamin D deficiency, inadequacy, sufficiency, and excess will soon be reached. Until evidence-based consensus is reached, a reasonable clinical approach is advocated. Copyright © 2017 Elsevier Inc. All rights reserved.
Designing image segmentation studies: Statistical power, sample size and reference standard quality.

PubMed

Gibson, Eli; Hu, Yipeng; Huisman, Henkjan J; Barratt, Dean C

2017-12-01

Segmentation algorithms are typically evaluated by comparison to an accepted reference standard. The cost of generating accurate reference standards for medical image segmentation can be substantial. Since the study cost and the likelihood of detecting a clinically meaningful difference in accuracy both depend on the size and on the quality of the study reference standard, balancing these trade-offs supports the efficient use of research resources. In this work, we derive a statistical power calculation that enables researchers to estimate the appropriate sample size to detect clinically meaningful differences in segmentation accuracy (i.e. the proportion of voxels matching the reference standard) between two algorithms. Furthermore, we derive a formula to relate reference standard errors to their effect on the sample sizes of studies using lower-quality (but potentially more affordable and practically available) reference standards. The accuracy of the derived sample size formula was estimated through Monte Carlo simulation, demonstrating, with 95% confidence, a predicted statistical power within 4% of simulated values across a range of model parameters. This corresponds to sample size errors of less than 4 subjects and errors in the detectable accuracy difference less than 0.6%. The applicability of the formula to real-world data was assessed using bootstrap resampling simulations for pairs of algorithms from the PROMISE12 prostate MR segmentation challenge data set. The model predicted the simulated power for the majority of algorithm pairs within 4% for simulated experiments using a high-quality reference standard and within 6% for simulated experiments using a low-quality reference standard. A case study, also based on the PROMISE12 data, illustrates using the formulae to evaluate whether to use a lower-quality reference standard in a prostate segmentation study. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Implementation of standardization in clinical practice: not always an easy task.

PubMed

Panteghini, Mauro

2012-02-29

As soon as a new reference measurement system is adopted, clinical validation of correctly calibrated commercial methods should take place. Tracing back the calibration of routine assays to a reference system can actually modify the relation of analyte results to existing reference intervals and decision limits and this may invalidate some of the clinical decision-making criteria currently used. To maintain the accumulated clinical experience, the quantitative relationship to the previous calibration system should be established and, if necessary, the clinical decision-making criteria should be adjusted accordingly. The implementation of standardization should take place in a concerted action of laboratorians, manufacturers, external quality assessment scheme organizers and clinicians. Dedicated meetings with manufacturers should be organized to discuss the process of assay recalibration and studies should be performed to obtain convincing evidence that the standardization works, improving result comparability. Another important issue relates to the surveillance of the performance of standardized assays through the organization of appropriate analytical internal and external quality controls. Last but not least, uncertainty of measurement that fits for this purpose must be defined across the entire traceability chain, starting with the available reference materials, extending through the manufacturers and their processes for assignment of calibrator values and ultimately to the final result reported to clinicians by laboratories.
Clinical pathology accreditation: standards for the medical laboratory

PubMed Central

Burnett, D; Blair, C; Haeney, M R; Jeffcoate, S L; Scott, K W M; Williams, D L

2002-01-01

This article describes a new set of revised standards for the medical laboratory, which have been produced by Clinical Pathology Accreditation (UK) Ltd (CPA). The original standards have been in use since 1992 and it was recognised that extensive revision was required. A standards revision group was established by CPA and this group used several international standards as source references, so that the resulting new standards are compatible with the most recent international reference sources. The aim is to make the assessment of medical laboratories as objective as possible in the future. CPA plans to introduce these standards in the UK in 2003 following extensive consultation with professional bodies, piloting in selected laboratories, and training of assessors. PMID:12354795
Employment references: defamation law in the clinical laboratory.

PubMed

Parks, D G

1993-01-01

The law of defamation and the risks involved in issuing employment references are discussed. A hypothetical scenario is used to illustrate the legal standards governing the tort of defamation and to apply those standards to employment references. Practical suggestions for a "controlled reference" policy are provided, with the objective of allowing for responsible exchange of employment information and avoiding a defamation lawsuit.
National Survey of Adult and Pediatric Reference Intervals in Clinical Laboratories across Canada: A Report of the CSCC Working Group on Reference Interval Harmonization.

PubMed

Adeli, Khosrow; Higgins, Victoria; Seccombe, David; Collier, Christine P; Balion, Cynthia M; Cembrowski, George; Venner, Allison A; Shaw, Julie

2017-11-01

Reference intervals are widely used decision-making tools in laboratory medicine, serving as health-associated standards to interpret laboratory test results. Numerous studies have shown wide variation in reference intervals, even between laboratories using assays from the same manufacturer. Lack of consistency in either sample measurement or reference intervals across laboratories challenges the expectation of standardized patient care regardless of testing location. Here, we present data from a national survey conducted by the Canadian Society of Clinical Chemists (CSCC) Reference Interval Harmonization (hRI) Working Group that examines variation in laboratory reference sample measurements, as well as pediatric and adult reference intervals currently used in clinical practice across Canada. Data on reference intervals currently used by 37 laboratories were collected through a national survey to examine the variation in reference intervals for seven common laboratory tests. Additionally, 40 clinical laboratories participated in a baseline assessment by measuring six analytes in a reference sample. Of the seven analytes examined, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatinine reference intervals were most variable. As expected, reference interval variation was more substantial in the pediatric population and varied between laboratories using the same instrumentation. Reference sample results differed between laboratories, particularly for ALT and free thyroxine (FT4). Reference interval variation was greater than test result variation for the majority of analytes. It is evident that there is a critical lack of harmonization in laboratory reference intervals, particularly for the pediatric population. Furthermore, the observed variation in reference intervals across instruments cannot be explained by the bias between the results obtained on instruments by different manufacturers. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
[Laboratory accreditation and proficiency testing].

PubMed

Kuwa, Katsuhiko

2003-05-01

ISO/TC 212 covering clinical laboratory testing and in vitro diagnostic test systems will issue the international standard for medical laboratory quality and competence requirements, ISO 15189. This standard is based on the ISO/IEC 17025, general requirements for competence of testing and calibration laboratories and ISO 9001, quality management systems-requirements. Clinical laboratory services are essential to patient care and therefore should be available to meet the needs of all patients and clinical personnel responsible for human health care. If a laboratory seeks accreditation, it should select an accreditation body that operates according to this international standard and in a manner which takes into account the particular requirements of clinical laboratories. Proficiency testing should be available to evaluate the calibration laboratories and reference measurement laboratories in clinical medicine. Reference measurement procedures should be of precise and the analytical principle of measurement applied should ensure reliability. We should be prepared to establish a quality management system and proficiency testing in clinical laboratories.
A pilot study of clinical agreement in cardiovascular preparticipation examinations: how good is the standard of care?

PubMed

O'Connor, Francis G; Johnson, Jeremy D; Chapin, Mark; Oriscello, Ralph G; Taylor, Dean C

2005-05-01

To evaluate the interobserver agreement between physicians regarding a abnormal cardiovascular assessment on athletic preparticipation examinations. Cross-sectional clinical survey. Outpatient Clinic, United States Military Academy, West Point, NY. We randomly selected 101 out of 539 cadet-athletes presenting for a preparticipation examination. Two primary care sports medicine fellows and a cardiologist examined the cadets. After obtaining informed consent from all participants, all 3 physicians separately evaluated all 101 cadets. The physicians recorded their clinical findings and whether they thought further cardiovascular evaluation (echocardiography) was indicated. Rate of referral for further cardiovascular evaluation, clinical agreement between sports medicine fellows, and clinical agreement between sports medicine fellows and the cardiologist. Each fellow referred 6 of the 101 evaluated cadets (5.9%). The cardiologist referred none. Although each fellow referred 6 cadets, only 1 cadet was referred by both. The kappa statistic for clinical agreement between fellows is 0.114 (95% CI, -0.182 to 0.411). There was no clinical agreement between the fellows and the cardiologist. This pilot study reveals a low level of agreement between physicians regarding which athletes with an abnormal examination deserved further testing. It challenges the standard of care and questions whether there is a need for improved technologies or improved training in cardiovascular clinical assessment.
Clinical accuracy of point-of-care urine culture in general practice.

PubMed

Holm, Anne; Cordoba, Gloria; Sørensen, Tina Møller; Jessen, Lisbeth Rem; Frimodt-Møller, Niels; Siersma, Volkert; Bjerrum, Lars

2017-06-01

To assess the clinical accuracy (sensitivity (SEN), specificity (SPE), positive predictive value and negative predictive value) of two point-of-care (POC) urine culture tests for the identification of urinary tract infection (UTI) in general practice. Prospective diagnostic accuracy study comparing two index tests (Flexicult™ SSI-Urinary Kit or ID Flexicult™) with a reference standard (urine culture performed in the microbiological department). General practice in the Copenhagen area patients. Adult female patients consulting their general practitioner with suspected uncomplicated, symptomatic UTI. (1) Overall accuracy of POC urine culture in general practice. (2) Individual accuracy of each of the two POC tests in this study. (3) Accuracy of POC urine culture in general practice with enterococci excluded, since enterococci are known to multiply in boric acid used for transportation for the reference standard. (4) Accuracy based on expert reading of photographs of POC urine cultures performed in general practice. Standard culture performed in the microbiological department was used as reference standard for all four measures. Twenty general practices recruited 341 patients with suspected uncomplicated UTI. The overall agreement between index test and reference was 0.76 (CI: 0.71-0.80), SEN 0.88 (CI: 0.83-0.92) and SPE 0.55 (CI: 0.46-0.64). The two POC tests produced similar results individually. Overall agreement with enterococci excluded was 0.82 (0.77-0.86) and agreement between expert readings of photographs and reference results was 0.81 (CI: 0.76-0.85). POC culture used in general practice has high SEN but low SPE. Low SPE could be due to both misinterpretation in general practice and an imperfect reference standard. Registration number: ClinicalTrials.gov NCT02323087.
Mould routine identification in the clinical laboratory by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

PubMed

Cassagne, Carole; Ranque, Stéphane; Normand, Anne-Cécile; Fourquet, Patrick; Thiebault, Sandrine; Planard, Chantal; Hendrickx, Marijke; Piarroux, Renaud

2011-01-01

MALDI-TOF MS recently emerged as a valuable identification tool for bacteria and yeasts and revolutionized the daily clinical laboratory routine. But it has not been established for routine mould identification. This study aimed to validate a standardized procedure for MALDI-TOF MS-based mould identification in clinical laboratory. First, pre-extraction and extraction procedures were optimized. With this standardized procedure, a 143 mould strains reference spectra library was built. Then, the mould isolates cultured from sequential clinical samples were prospectively subjected to this MALDI-TOF MS based-identification assay. MALDI-TOF MS-based identification was considered correct if it was concordant with the phenotypic identification; otherwise, the gold standard was DNA sequence comparison-based identification. The optimized procedure comprised a culture on sabouraud-gentamicin-chloramphenicol agar followed by a chemical extraction of the fungal colonies with formic acid and acetonitril. The identification was done using a reference database built with references from at least four culture replicates. For five months, 197 clinical isolates were analyzed; 20 were excluded because they were not identified at the species level. MALDI-TOF MS-based approach correctly identified 87% (154/177) of the isolates analyzed in a routine clinical laboratory activity. It failed in 12% (21/177), whose species were not represented in the reference library. MALDI-TOF MS-based identification was correct in 154 out of the remaining 156 isolates. One Beauveria bassiana was not identified and one Rhizopus oryzae was misidentified as Mucor circinelloides. This work's seminal finding is that a standardized procedure can also be used for MALDI-TOF MS-based identification of a wide array of clinically relevant mould species. It thus makes it possible to identify moulds in the routine clinical laboratory setting and opens new avenues for the development of an integrated MALDI-TOF MS-based solution for the identification of any clinically relevant microorganism.
National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges.

PubMed

Bauer, D; Krege, J; Lane, N; Leary, E; Libanati, C; Miller, P; Myers, G; Silverman, S; Vesper, H W; Lee, D; Payette, M; Randall, S

2012-10-01

This position paper reviews how the National Bone Health Alliance (NBHA) will execute a project to help assure health professionals of the clinical utility of bone turnover markers; the current clinical approaches concerning osteoporosis and the status and use of bone turnover markers in the USA; the rationale for focusing this effort around two specific bone turnover markers; the need to standardize bone marker sample collection procedures, reference ranges, and bone turnover marker assays in clinical laboratories; and the importance of harmonization for future research of bone turnover markers. Osteoporosis is a major global health problem, with the prevalence and incidence of osteoporosis for at-risk populations estimated to be 44 million Americans. The potential of bone markers as an additional tool for health care professionals to improve patient outcomes and impact morbidity and mortality is crucial in providing better health care and addressing rising health care costs. This need to advance the field of bone turnover markers has been recognized by a number of organizations, including the International Osteoporosis Foundation (IOF), National Osteoporosis Foundation, International Federation of Clinical Chemistry, and Laboratory Medicine (IFCC), and the NBHA. This position paper elucidates how this project will standardize bone turnover marker sample collection procedures in the USA, establish a USA reference range for one bone formation (serum procollagen type I N propeptide, s-PINP) and one bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) marker, and standardize bone turnover marker assays used in clinical laboratories. This effort will allow clinicians from the USA to have confidence in their use of bone turnover markers to help monitor osteoporosis treatment and assess future fracture risk. This project builds on the recommendations of the IOF/IFCC Bone Marker Standards Working Group by developing USA reference standards for s-PINP and s-CTX, the markers identified as most promising for use as reference markers. The goals of this project will be realized through the NBHA and will include its governmental, academic, for-profit, and non-profit sector stakeholders as well as major academic and commercial laboratories. Upon completion, a parallel effort will be pursued to make bone turnover marker measurements reliable and accepted by all health care professionals for facilitating treatment decisions and ultimately be reimbursed by all health insurance payers. Successful completion of this project will help assure health professionals from the USA of the clinical utility of bone turnover markers and ties in with the parallel effort of the IOF/IFCC to develop worldwide bone turnover reference ranges.
The gallium melting-point standard: its role in our temperature measurement system.

PubMed

Mangum, B W

1977-01-01

The latest internationally-adopted temperature scale, the International Practical Temperature Scale of 1968 (amended edition of 1975), is discussed in some detail and a brief description is given of its evolution. The melting point of high-purity gallium (stated to be at least 99.99999% pure) as a secondary temperature reference point is evaluated. I believe that this melting-point temperature of gallium should be adopted by the various medical professional societies and voluntary standards groups as the reaction temperature for enzyme reference methods in clinical enzymology. Gallium melting-point cells are available at the National Bureau of Standards as Standard Reference Material No. 1968.
Assessment of the Validity of the Research Diagnostic Criteria for Temporomandibular Disorders: Overview and Methodology

PubMed Central

Schiffman, Eric L.; Truelove, Edmond L.; Ohrbach, Richard; Anderson, Gary C.; John, Mike T.; List, Thomas; Look, John O.

2011-01-01

AIMS The purpose of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Validation Project was to assess the diagnostic validity of this examination protocol. An overview is presented, including Axis I and II methodology and descriptive statistics for the study participant sample. This paper details the development of reliable methods to establish the reference standards for assessing criterion validity of the Axis I RDC/TMD diagnoses. Validity testing for the Axis II biobehavioral instruments was based on previously validated reference standards. METHODS The Axis I reference standards were based on the consensus of 2 criterion examiners independently performing a comprehensive history, clinical examination, and evaluation of imaging. Intersite reliability was assessed annually for criterion examiners and radiologists. Criterion exam reliability was also assessed within study sites. RESULTS Study participant demographics were comparable to those of participants in previous studies using the RDC/TMD. Diagnostic agreement of the criterion examiners with each other and with the consensus-based reference standards was excellent with all kappas ≥ 0.81, except for osteoarthrosis (moderate agreement, k = 0.53). Intrasite criterion exam agreement with reference standards was excellent (k ≥ 0.95). Intersite reliability of the radiologists for detecting computed tomography-disclosed osteoarthrosis and magnetic resonance imaging-disclosed disc displacement was good to excellent (k = 0.71 and 0.84, respectively). CONCLUSION The Validation Project study population was appropriate for assessing the reliability and validity of the RDC/TMD Axis I and II. The reference standards used to assess the validity of Axis I TMD were based on reliable and clinically credible methods. PMID:20213028

Development and validation of electronic surveillance tool for acute kidney injury: A retrospective analysis.

PubMed

Ahmed, Adil; Vairavan, Srinivasan; Akhoundi, Abbasali; Wilson, Gregory; Chiofolo, Caitlyn; Chbat, Nicolas; Cartin-Ceba, Rodrigo; Li, Guangxi; Kashani, Kianoush

2015-10-01

Timely detection of acute kidney injury (AKI) facilitates prevention of its progress and potentially therapeutic interventions. The study objective is to develop and validate an electronic surveillance tool (AKI sniffer) to detect AKI in 2 independent retrospective cohorts of intensive care unit (ICU) patients. The primary aim is to compare the sensitivity, specificity, and positive and negative predictive values of AKI sniffer performance against a reference standard. This study is conducted in the ICUs of a tertiary care center. The derivation cohort study subjects were Olmsted County, MN, residents admitted to all Mayo Clinic ICUs from July 1, 2010, through December 31, 2010, and the validation cohort study subjects were all patients admitted to a Mayo Clinic, Rochester, campus medical/surgical ICU on January 12, 2010, through March 23, 2010. All included records were reviewed by 2 independent investigators who adjudicated AKI using the Acute Kidney Injury Network criteria; disagreements were resolved by a third reviewer. This constituted the reference standard. An electronic algorithm was developed; its precision and reliability were assessed in comparison with the reference standard in 2 separate cohorts, derivation and validation. Of 1466 screened patients, a total of 944 patients were included in the study: 482 for derivation and 462 for validation. Compared with the reference standard in the validation cohort, the sensitivity and specificity of the AKI sniffer were 88% and 96%, respectively. The Cohen κ (95% confidence interval) agreement between the electronic and the reference standard was 0.84 (0.78-0.89) and 0.85 (0.80-0.90) in the derivation and validation cohorts. Acute kidney injury can reliably and accurately be detected electronically in ICU patients. The presented method is applicable for both clinical (decision support) and research (enrollment for clinical trials) settings. Prospective validation is required. Copyright © 2015 Elsevier Inc. All rights reserved.
Nutrition screening and assessment of anthropometry and bioelectrical impedance in the frail elderly: a clinical appraisal of methodology in a clinical setting.

PubMed

Davidson, Jeanette; Getz, Majorie

2004-01-01

Nutrition screening is recommended to identify those at risk for malnutrition; nutrition assessment by anthropometry and impedance is widely used to indicate nutritional status but may be problematical in the frail elderly in nursing homes. Acceptability, availability, suitability and appropriate reference data influence clinical application of these measurements. In our study, nutrition screening and assessment methodology were evaluated in 46 nursing home residents, mean age 86.3 +/- 6.6 years, mean weight 66.1 +/- 12.9 kg, mean height 163.1 +/- 9.6 cm, and mean BMI 24.9 +/- 4.6 kg/m2. Significant correlations (P < 0.05) were found in all measures of body weight, BMI, body fatness and leanness. Interpretation of data by five different reference standards and cutoff points revealed wide variation in identification of malnutrition by anthropometry. Appropriate reference data for body lean and fatness are not yet available. Thus, population-specific methodology and reference standards are of crucial importance.
The role of ion mobility spectrometry-mass spectrometry in the analysis of protein reference standards.

PubMed

Pritchard, Caroline; O'Connor, Gavin; Ashcroft, Alison E

2013-08-06

To achieve comparability of measurement results of protein amount of substance content between clinical laboratories, suitable reference materials are required. The impact on measurement comparability of potential differences in the tertiary and quaternary structure of protein reference standards is as yet not well understood. With the use of human growth hormone as a model protein, the potential of ion mobility spectrometry-mass spectrometry as a tool to assess differences in the structure of protein reference materials and their interactions with antibodies has been investigated here.
[Quality standards for ultrasound assessment of the superficial venous system of the lower limbs. Report of the French Society for Vascular Medicine].

PubMed

Auvert, J-F; Chleir, F; Coppé, G; Hamel-Desnos, C; Moraglia, L; Pichot, O

2014-02-01

The quality standards of the French Society for Vascular Medicine for the ultrasound assessment of the superficial venous system of the lower limbs are based on the two following requirements: technical know-how (mastering the use of ultrasound devices and the method of examination); medical know-how (ability to adapt the methods and scope of the examination to its clinical indications and purpose and to rationally analyze and interpret its results). To describe an optimal method of examination in relation to the clinical question and hypothesis; to achieve consistent practice, methods, glossary terminologies and reporting; to provide good practice reference points and to promote a high quality process. The three levels of examination. Their clinical indications and goals. The reference standard examination (level 2) and its variants according to clinical needs. The minimal content of the examination report, the letter to the referring physician (synthesis, conclusion and management suggestions) and iconography. Commented glossary (anatomy, hemodynamics, semiology). Technical basis. Ultrasound devices settings. We discuss of use of Duplex ultrasound for the assessment of the superficial veins of the lower limbs in vascular medicine practice. Copyright © 2014. Published by Elsevier Masson SAS.
Recommendation for the review of biological reference intervals in medical laboratories.

PubMed

Henny, Joseph; Vassault, Anne; Boursier, Guilaine; Vukasovic, Ines; Mesko Brguljan, Pika; Lohmander, Maria; Ghita, Irina; Andreu, Francisco A Bernabeu; Kroupis, Christos; Sprongl, Ludek; Thelen, Marc H M; Vanstapel, Florent J L A; Vodnik, Tatjana; Huisman, Willem; Vaubourdolle, Michel

2016-12-01

This document is based on the original recommendation of the Expert Panel on the Theory of Reference Values of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), updated guidelines were recently published under the auspices of the IFCC and the Clinical and Laboratory Standards Institute (CLSI). This document summarizes proposals for recommendations on: (i) The terminology, which is often confusing, noticeably concerning the terms of reference limits and decision limits. (ii) The method for the determination of reference limits according to the original procedure and the conditions, which should be used. (iii) A simple procedure allowing the medical laboratories to fulfill the requirements of the regulation and standards. The updated document proposes to verify that published reference limits are applicable to the laboratory involved. Finally, the strengths and limits of the revised recommendations (especially the selection of the reference population, the maintenance of the analytical quality, the choice of the statistical method used…) will be briefly discussed.
Pitfalls in the measurement of muscle mass: a need for a reference standard

PubMed Central

Landi, Francesco; Cesari, Matteo; Fielding, Roger A.; Visser, Marjolein; Engelke, Klaus; Maggi, Stefania; Dennison, Elaine; Al‐Daghri, Nasser M.; Allepaerts, Sophie; Bauer, Jurgen; Bautmans, Ivan; Brandi, Maria Luisa; Bruyère, Olivier; Cederholm, Tommy; Cerreta, Francesca; Cherubini, Antonio; Cooper, Cyrus; Cruz‐Jentoft, Alphonso; McCloskey, Eugene; Dawson‐Hughes, Bess; Kaufman, Jean‐Marc; Laslop, Andrea; Petermans, Jean; Reginster, Jean‐Yves; Rizzoli, René; Robinson, Sian; Rolland, Yves; Rueda, Ricardo; Vellas, Bruno; Kanis, John A.

2018-01-01

Abstract Background All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. Methods Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face‐to‐face meetings were organized for the whole group to make amendments and discuss further recommendations. Results A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X‐ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. Conclusions Based on the feasibility, accuracy, safety, and low cost, dual energy X‐ray absorptiometry can be considered as the reference standard for measuring muscle mass. PMID:29349935
Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis.

PubMed

Pradhan, Richeek; Singh, Sonal

2018-04-11

Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency. The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews. We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard. We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for mortality rates. There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.
[Overweight and obesity prevalence estimates in a population from Zaragoza by using different growth references].

PubMed

Lasarte-Velillas, J J; Hernández-Aguilar, M T; Martínez-Boyero, T; Soria-Cabeza, G; Soria-Ruiz, D; Bastarós-García, J C; Gil-Hernández, I; Pastor-Arilla, C; Lasarte-Sanz, I

2015-03-01

To investigate the prevalence of overweight and obesity among our pediatric population and observe whether the use of different growth references for classification produce significant differences. A total of 35824 boys and girls aged between 2 and 14 years were included. Body mass index (BMI) was used to calculate the prevalence of overweight-obesity by age and sex. Prevalence was obtained by using a set of national references (Hernández's standards) and the references of World Health Organization (WHO standards). Prevalences were compared for each age and sex subset, as well as with the percentage of patients who had an overweight-obesity diagnosis in the clinical record. The overall prevalence of overweight-obesity among children aged 2 to 14 years was 17.0% (95% CI; 16.1%-18.0%) according to the Hernández standards vs 30.8% (95% CI; 29.9%-31.7%) according to WHO standards (10.1% vs 12.2% obese, and 6.9% vs 18.6% overweight). It was significantly higher in boys, by both standards, due to the higher prevalence of obesity. By using the Hernández standards the prevalence was significantly lower than by using WHO standards for all ages and for both sexes. A low percentage of patients were found to have an obesity-overweight diagnosis in the clinical record (from 3% to 22% at the ages of 2 and 14 years, respectively). The prevalence of overweight-obesity in our population is high, especially among boys. Using Hernández standards leads to an under-estimation of the problem, especially because it detects less overweight patients, thus we recommend using the WHO standards in our daily practice. The low number of overweight-obesity diagnoses in the clinical records might reflect that there is little awareness of the problem by the professionals. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.
Detecting inflammation in inflammatory bowel disease - how does ultrasound compare to magnetic resonance enterography using standardised scoring systems?

PubMed

Barber, Joy L; Zambrano-Perez, Alexsandra; Olsen, Øystein E; Kiparissi, Fevronia; Baycheva, Mila; Knaflez, Daniela; Shah, Neil; Watson, Tom A

2018-06-01

Magnetic resonance enterography (MRE) is the current gold standard for imaging in inflammatory bowel disease, but ultrasound (US) is a potential alternative. To determine whether US is as good as MRE for the detecting inflamed bowel, using a combined consensus score as the reference standard. We conducted a retrospective cohort study in children and adolescents <18 years with inflammatory bowel disease (IBD) at a tertiary and quaternary centre. We included children who underwent MRE and US within 4 weeks. We scored MRE using the London score and US using a score adapted from the METRIC (MR Enterography or Ultrasound in Crohn's Disease) trial. Four gastroenterologists assessed an independent clinical consensus score. A combined consensus score using the imaging and clinical scores was agreed upon and used as the reference standard to compare MRE with US. We included 53 children. At a whole-patient level, MRE scores were 2% higher than US scores. We used Lin coefficient to assess inter-observer variability. The repeatability of MRE scores was poor (Lin 0.6). Agreement for US scoring was substantial (Lin 0.95). There was a significant positive correlation between MRE and clinical consensus scores (Spearman's rho = 0.598, P=0.0053) and US and clinical consensus scores (Spearman's rho = 0.657, P=0.0016). US detects as much clinically significant bowel disease as MRE. It is possible that MRE overestimates the presence of disease when using a scoring system. This study demonstrates the feasibility of using a clinical consensus reference standard in paediatric IBD imaging studies.
Validation of diabetes mellitus and hypertension diagnosis in computerized medical records in primary health care

PubMed Central

2011-01-01

Background Computerized Clinical Records, which are incorporated in primary health care practice, have great potential for research. In order to use this information, data quality and reliability must be assessed to prevent compromising the validity of the results. The aim of this study is to validate the diagnosis of hypertension and diabetes mellitus in the computerized clinical records of primary health care, taking the diagnosis criteria established in the most prominently used clinical guidelines as the gold standard against which what measure the sensitivity, specificity, and determine the predictive values. The gold standard for diabetes mellitus was the diagnostic criteria established in 2003 American Diabetes Association Consensus Statement for diabetic subjects. The gold standard for hypertension was the diagnostic criteria established in the Joint National Committee published in 2003. Methods A cross-sectional multicentre validation study of diabetes mellitus and hypertension diagnoses in computerized clinical records of primary health care was carried out. Diagnostic criteria from the most prominently clinical practice guidelines were considered for standard reference. Sensitivity, specificity, positive and negative predictive values, and global agreement (with kappa index), were calculated. Results were shown overall and stratified by sex and age groups. Results The agreement for diabetes mellitus with the reference standard as determined by the guideline was almost perfect (κ = 0.990), with a sensitivity of 99.53%, a specificity of 99.49%, a positive predictive value of 91.23% and a negative predictive value of 99.98%. Hypertension diagnosis showed substantial agreement with the reference standard as determined by the guideline (κ = 0.778), the sensitivity was 85.22%, the specificity 96.95%, the positive predictive value 85.24%, and the negative predictive value was 96.95%. Sensitivity results were worse in patients who also had diabetes and in those aged 70 years or over. Conclusions Our results substantiate the validity of using diagnoses of diabetes and hypertension found within the computerized clinical records for epidemiologic studies. PMID:22035202
The Research Diagnostic Criteria for Temporomandibular Disorders. I: overview and methodology for assessment of validity.

PubMed

Schiffman, Eric L; Truelove, Edmond L; Ohrbach, Richard; Anderson, Gary C; John, Mike T; List, Thomas; Look, John O

2010-01-01

The purpose of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Validation Project was to assess the diagnostic validity of this examination protocol. The aim of this article is to provide an overview of the project's methodology, descriptive statistics, and data for the study participant sample. This article also details the development of reliable methods to establish the reference standards for assessing criterion validity of the Axis I RDC/TMD diagnoses. The Axis I reference standards were based on the consensus of two criterion examiners independently performing a comprehensive history, clinical examination, and evaluation of imaging. Intersite reliability was assessed annually for criterion examiners and radiologists. Criterion examination reliability was also assessed within study sites. Study participant demographics were comparable to those of participants in previous studies using the RDC/TMD. Diagnostic agreement of the criterion examiners with each other and with the consensus-based reference standards was excellent with all kappas > or = 0.81, except for osteoarthrosis (moderate agreement, k = 0.53). Intrasite criterion examiner agreement with reference standards was excellent (k > or = 0.95). Intersite reliability of the radiologists for detecting computed tomography-disclosed osteoarthrosis and magnetic resonance imaging-disclosed disc displacement was good to excellent (k = 0.71 and 0.84, respectively). The Validation Project study population was appropriate for assessing the reliability and validity of the RDC/TMD Axis I and II. The reference standards used to assess the validity of Axis I TMD were based on reliable and clinically credible methods.
Performance evaluation of the HepB Typer-Entecavir kit for detection of entecavir resistance mutations in chronic hepatitis B.

PubMed

Ahn, Sang Hoon; Chun, Ji-Yong; Shin, Soo-Kyung; Park, Jun Yong; Yoo, Wangdon; Hong, Sun Pyo; Kim, Soo-Ok; Han, Kwang-Hyub

2013-12-01

Molecular diagnostic methods have enabled the rapid diagnosis of drug-resistant mutations in hepatitis B virus (HBV) and have reduced both unnecessary therapeutic interventions and medical costs. In this study we evaluated the analytical and clinical performances of the HepB Typer-Entecavir kit (GeneMatrix, Korea) in detecting entecavir-resistance-associated mutations. The HepB Typer-Entecavir kit was evaluated for its limit of detection, interference, cross-reactivity, and precision using HBV reference standards made by diluting high-titer viral stocks in HBV-negative human serum. The performance of the HepB Typer-Entecavir kit for detecting mutations related to entecavir resistance was compared with direct sequencing for 396 clinical samples from 108 patients. Using the reference standards, the detection limit of the HepB Typer-Entecavir kit was found to be as low as 500 copies/mL. No cross-reactivity was observed, and elevated levels of various interfering substances did not adversely affect its analytical performance. The precision test conducted by repetitive analysis of 2,400 replicates with reference standards at various concentrations showed 99.9% agreement (2398/2400). The overall concordance rate between the HepB Typer-Entecavir kit and direct sequencing assays in 396 clinical samples was 99.5%. The HepB Typer-Entecavir kit showed high reliability and precision, and comparable sensitivity and specificity for detecting mutant virus populations in reference and clinical samples in comparison with direct sequencing. Therefore, this assay would be clinically useful in the diagnosis of entecavir-resistance-associated mutations in chronic hepatitis B.
Quantitative Assessment of Commutability for Clinical Viral Load Testing Using a Digital PCR-Based Reference Standard

PubMed Central

Tang, L.; Sun, Y.; Buelow, D.; Gu, Z.; Caliendo, A. M.; Pounds, S.

2016-01-01

Given recent advances in the development of quantitative standards, particularly WHO international standards, efforts to better understand the commutability of reference materials have been made. Existing approaches in evaluating commutability include prediction intervals and correspondence analysis; however, the results obtained from existing approaches may be ambiguous. We have developed a “deviation-from-ideal” (DFI) approach to evaluate commutability of standards and applied it to the assessment of Epstein-Bar virus (EBV) load testing in four quantitative PCR assays, treating digital PCR as a reference assay. We then discuss advantages and limitations of the DFI approach as well as experimental design to best evaluate the commutability of an assay in practice. PMID:27076654
Hematology and Serum Biochemistry Reference Intervals for Six-Week-Old, Farm-Reared Chinese Ring-Necked Pheasants ( Phasianus colchicus ) from Minnesota.

PubMed

Dzikamunhenga, R S; Griffith, R W; Hostetter, S; Fisher, P; Larson, W

2017-06-01

Chinese ring-necked pheasants ( Phasianus colchicus ) are commonly farmed in intensive operations for purposes such as meat production, hunting preserves, or research. Under these conditions, pheasants frequently suffer medical ailments such as bacterial, viral, and parasitic infections or nutritional or metabolic disorders. Relatively little scientific information exists regarding clinical pathology reference intervals (RIs) for farm-reared pheasants. The objective of this study was to determine RIs for hematologic and serum biochemical variables for Chinese ring-necked pheasants from Minnesota at 6 wk of age. Blood samples from 119 clinically healthy Chinese ring-necked pheasants were analyzed using standard techniques. Reference intervals were generated in Microsoft® Excel® 2013 (Microsoft, Redmond, WA) using Reference Value Advisor freeware version 2.1 (Microsoft). Ninety-five percent RIs were determined using nonparametric methods that followed Clinical and Laboratory Standards Institute guidelines. These RIs will be useful for the monitoring of health and diagnosis of disease in confined Chinese ring-necked pheasant populations that are approximately 6 wk old.
Automated Detection of Glaucoma From Topographic Features of the Optic Nerve Head in Color Fundus Photographs.

PubMed

Chakrabarty, Lipi; Joshi, Gopal Datt; Chakravarty, Arunava; Raman, Ganesh V; Krishnadas, S R; Sivaswamy, Jayanthi

2016-07-01

To describe and evaluate the performance of an automated CAD system for detection of glaucoma from color fundus photographs. Color fundus photographs of 2252 eyes from 1126 subjects were collected from 2 centers: Aravind Eye Hospital, Madurai and Coimbatore, India. The images of 1926 eyes (963 subjects) were used to train an automated image analysis-based system, which was developed to provide a decision on a given fundus image. A total of 163 subjects were clinically examined by 2 ophthalmologists independently and their diagnostic decisions were recorded. The consensus decision was defined to be the clinical reference (gold standard). Fundus images of eyes with disagreement in diagnosis were excluded from the study. The fundus images of the remaining 314 eyes (157 subjects) were presented to 4 graders and their diagnostic decisions on the same were collected. The performance of the system was evaluated on the 314 images, using the reference standard. The sensitivity and specificity of the system and 4 independent graders were determined against the clinical reference standard. The system achieved an area under receiver operating characteristic curve of 0.792 with a sensitivity of 0.716 and specificity of 0.717 at a selected threshold for the detection of glaucoma. The agreement with the clinical reference standard as determined by Cohen κ is 0.45 for the proposed system. This is comparable to that of the image-based decisions of 4 ophthalmologists. An automated system was presented for glaucoma detection from color fundus photographs. The overall evaluation results indicated that the presented system was comparable in performance to glaucoma classification by a manual grader solely based on fundus image examination.
LC-MS/MS-based approach for obtaining exposure estimates of metabolites in early clinical trials using radioactive metabolites as reference standards.

PubMed

Zhang, Donglu; Raghavan, Nirmala; Chando, Theodore; Gambardella, Janice; Fu, Yunlin; Zhang, Duxi; Unger, Steve E; Humphreys, W Griffith

2007-12-01

An LC-MS/MS-based approach that employs authentic radioactive metabolites as reference standards was developed to estimate metabolite exposures in early drug development studies. This method is useful to estimate metabolite levels in studies done with non-radiolabeled compounds where metabolite standards are not available to allow standard LC-MS/MS assay development. A metabolite mixture obtained from an in vivo source treated with a radiolabeled compound was partially purified, quantified, and spiked into human plasma to provide metabolite standard curves. Metabolites were analyzed by LC-MS/MS using the specific mass transitions and an internal standard. The metabolite concentrations determined by this approach were found to be comparable to those determined by valid LC-MS/MS assays. This approach does not requires synthesis of authentic metabolites or the knowledge of exact structures of metabolites, and therefore should provide a useful method to obtain early estimates of circulating metabolites in early clinical or toxicological studies.
Pitfalls in the measurement of muscle mass: a need for a reference standard.

PubMed

Buckinx, Fanny; Landi, Francesco; Cesari, Matteo; Fielding, Roger A; Visser, Marjolein; Engelke, Klaus; Maggi, Stefania; Dennison, Elaine; Al-Daghri, Nasser M; Allepaerts, Sophie; Bauer, Jurgen; Bautmans, Ivan; Brandi, Maria Luisa; Bruyère, Olivier; Cederholm, Tommy; Cerreta, Francesca; Cherubini, Antonio; Cooper, Cyrus; Cruz-Jentoft, Alphonso; McCloskey, Eugene; Dawson-Hughes, Bess; Kaufman, Jean-Marc; Laslop, Andrea; Petermans, Jean; Reginster, Jean-Yves; Rizzoli, René; Robinson, Sian; Rolland, Yves; Rueda, Ricardo; Vellas, Bruno; Kanis, John A

2018-04-01

All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings were organized for the whole group to make amendments and discuss further recommendations. A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X-ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. Based on the feasibility, accuracy, safety, and low cost, dual energy X-ray absorptiometry can be considered as the reference standard for measuring muscle mass. © 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.
[The requirements of standard and conditions of interchangeability of medical articles].

PubMed

Men'shikov, V V; Lukicheva, T I

2013-11-01

The article deals with possibility to apply specific approaches under evaluation of interchangeability of medical articles for laboratory analysis. The development of standardized analytical technologies of laboratory medicine and formulation of requirements of standards addressed to manufacturers of medical articles the clinically validated requirements are to be followed. These requirements include sensitivity and specificity of techniques, accuracy and precision of research results, stability of reagents' quality in particular conditions of their transportation and storage. The validity of requirements formulated in standards and addressed to manufacturers of medical articles can be proved using reference system, which includes master forms and standard samples, reference techniques and reference laboratories. This approach is supported by data of evaluation of testing systems for measurement of level of thyrotrophic hormone, thyroid hormones and glycated hemoglobin HB A1c. The versions of testing systems can be considered as interchangeable only in case of results corresponding to the results of reference technique and comparable with them. In case of absence of functioning reference system the possibilities of the Joined committee of traceability in laboratory medicine make it possible for manufacturers of reagent sets to apply the certified reference materials under development of manufacturing of sets for large listing of analytes.
Glucose Measurement: Time for a Gold Standard

PubMed Central

Hagvik, Joakim

2007-01-01

There is no internationally recognized reference method for the measurement of blood glucose. The Centers for Disease Control and Prevention (CDC) highlighted the need for standardization some years ago when a project was started. The project objectives were to (1) investigate whether there are significant differences in calibration levels among currently used glucose monitors for home use and (2) develop a reference method for glucose determination. A first study confirmed the assumption that currently used home-use monitors differ significantly and that standardization is necessary in order to minimize variability and to improve patient care. As a reference method, CDC recommended a method based on isotope dilution gas chromatography–mass spectrometry, an assay that has received support from clinical chemists worldwide. CDC initiated a preliminary study to establish the suitability of this method, but then the project came to a halt. It is hoped that CDC, with support from the industry, as well as academic and professional organizations such as the American Association for Clinical Chemistry and International Federation of Clinical Chemistry and Laboratory Medicine, will be able to finalize the project and develop the long-awaited and much needed “gold standard” for glucose measurement. PMID:19888402
Performance evaluation of the HepB Typer-Entecavir kit for detection of entecavir resistance mutations in chronic hepatitis B

PubMed Central

Ahn, Sang Hoon; Chun, Ji-Yong; Shin, Soo-Kyung; Park, Jun Yong; Yoo, Wangdon; Hong, Sun Pyo; Han, Kwang-Hyub

2013-01-01

Background/Aims Molecular diagnostic methods have enabled the rapid diagnosis of drug-resistant mutations in hepatitis B virus (HBV) and have reduced both unnecessary therapeutic interventions and medical costs. In this study we evaluated the analytical and clinical performances of the HepB Typer-Entecavir kit (GeneMatrix, Korea) in detecting entecavir-resistance-associated mutations. Methods The HepB Typer-Entecavir kit was evaluated for its limit of detection, interference, cross-reactivity, and precision using HBV reference standards made by diluting high-titer viral stocks in HBV-negative human serum. The performance of the HepB Typer-Entecavir kit for detecting mutations related to entecavir resistance was compared with direct sequencing for 396 clinical samples from 108 patients. Results Using the reference standards, the detection limit of the HepB Typer-Entecavir kit was found to be as low as 500 copies/mL. No cross-reactivity was observed, and elevated levels of various interfering substances did not adversely affect its analytical performance. The precision test conducted by repetitive analysis of 2,400 replicates with reference standards at various concentrations showed 99.9% agreement (2398/2400). The overall concordance rate between the HepB Typer-Entecavir kit and direct sequencing assays in 396 clinical samples was 99.5%. Conclusions The HepB Typer-Entecavir kit showed high reliability and precision, and comparable sensitivity and specificity for detecting mutant virus populations in reference and clinical samples in comparison with direct sequencing. Therefore, this assay would be clinically useful in the diagnosis of entecavir-resistance-associated mutations in chronic hepatitis B. PMID:24459645

Global standardization measurement of cerebral spinal fluid for Alzheimer's disease: an update from the Alzheimer's Association Global Biomarkers Consortium.

PubMed

Carrillo, Maria C; Blennow, Kaj; Soares, Holly; Lewczuk, Piotr; Mattsson, Niklas; Oberoi, Pankaj; Umek, Robert; Vandijck, Manu; Salamone, Salvatore; Bittner, Tobias; Shaw, Leslie M; Stephenson, Diane; Bain, Lisa; Zetterberg, Henrik

2013-03-01

Recognizing that international collaboration is critical for the acceleration of biomarker standardization efforts and the efficient development of improved diagnosis and therapy, the Alzheimer's Association created the Global Biomarkers Standardization Consortium (GBSC) in 2010. The consortium brings together representatives of academic centers, industry, and the regulatory community with the common goal of developing internationally accepted common reference standards and reference methods for the assessment of cerebrospinal fluid (CSF) amyloid β42 (Aβ42) and tau biomarkers. Such standards are essential to ensure that analytical measurements are reproducible and consistent across multiple laboratories and across multiple kit manufacturers. Analytical harmonization for CSF Aβ42 and tau will help reduce confusion in the AD community regarding the absolute values associated with the clinical interpretation of CSF biomarker results and enable worldwide comparison of CSF biomarker results across AD clinical studies. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Standardization in laboratory medicine: Adoption of common reference intervals to the Croatian population.

PubMed

Flegar-Meštrić, Zlata; Perkov, Sonja; Radeljak, Andrea

2016-03-26

Considering the fact that the results of laboratory tests provide useful information about the state of health of patients, determination of reference value is considered an intrinsic part in the development of laboratory medicine. There are still huge differences in the analytical methods used as well as in the associated reference intervals which could consequently significantly affect the proper assessment of patient health. In a constant effort to increase the quality of patients' care, there are numerous international initiatives for standardization and/or harmonization of laboratory diagnostics in order to achieve maximum comparability of laboratory test results and improve patient safety. Through the standardization and harmonization processes of analytical methods the ability to create unique reference intervals is achieved. Such reference intervals could be applied globally in all laboratories using methods traceable to the same reference measuring system and analysing the biological samples from the populations with similar socio-demographic and ethnic characteristics. In this review we outlined the results of the harmonization processes in Croatia in the field of population based reference intervals for clinically relevant blood and serum constituents which are in accordance with ongoing activity for worldwide standardization and harmonization based on traceability in laboratory medicine.
Standardization in laboratory medicine: Adoption of common reference intervals to the Croatian population

PubMed Central

Flegar-Meštrić, Zlata; Perkov, Sonja; Radeljak, Andrea

2016-01-01

Considering the fact that the results of laboratory tests provide useful information about the state of health of patients, determination of reference value is considered an intrinsic part in the development of laboratory medicine. There are still huge differences in the analytical methods used as well as in the associated reference intervals which could consequently significantly affect the proper assessment of patient health. In a constant effort to increase the quality of patients’ care, there are numerous international initiatives for standardization and/or harmonization of laboratory diagnostics in order to achieve maximum comparability of laboratory test results and improve patient safety. Through the standardization and harmonization processes of analytical methods the ability to create unique reference intervals is achieved. Such reference intervals could be applied globally in all laboratories using methods traceable to the same reference measuring system and analysing the biological samples from the populations with similar socio-demographic and ethnic characteristics. In this review we outlined the results of the harmonization processes in Croatia in the field of population based reference intervals for clinically relevant blood and serum constituents which are in accordance with ongoing activity for worldwide standardization and harmonization based on traceability in laboratory medicine. PMID:27019800
Determination of reference ranges for elements in human scalp hair.

PubMed

Druyan, M E; Bass, D; Puchyr, R; Urek, K; Quig, D; Harmon, E; Marquardt, W

1998-06-01

Expected values, reference ranges, or reference limits are necessary to enable clinicians to apply analytical chemical data in the delivery of health care. Determination of references ranges is not straightforward in terms of either selecting a reference population or performing statistical analysis. In light of logistical, scientific, and economic obstacles, it is understandable that clinical laboratories often combine approaches in developing health associated reference values. A laboratory may choose to: 1. Validate either reference ranges of other laboratories or published data from clinical research or both, through comparison of patients test data. 2. Base the laboratory's reference values on statistical analysis of results from specimens assayed by the clinical reference laboratory itself. 3. Adopt standards or recommendations of regulatory agencies and governmental bodies. 4. Initiate population studies to validate transferred reference ranges or to determine them anew. Effects of external contamination and anecdotal information from clinicians may be considered. The clinical utility of hair analysis is well accepted for some elements. For others, it remains in the realm of clinical investigation. This article elucidates an approach for establishment of reference ranges for elements in human scalp hair. Observed levels of analytes from hair specimens from both our laboratory's total patient population and from a physician-defined healthy American population have been evaluated. Examination of levels of elements often associated with toxicity serves to exemplify the process of determining reference ranges in hair. In addition the approach serves as a model for setting reference ranges for analytes in a variety of matrices.
Hematology and plasma chemistry reference intervals for mature laboratory pine voles (Microtus pinetorum) as determined by using the nonparametric rank percentile method.

PubMed

Harvey, Stephen B; Krimer, Paula M; Correa, Maria T; Hanes, Martha A

2008-07-01

Plasma biochemical and hematologic values are important parameters for assessing animal health and experimental results. Although normal reference values for many rodent species have been published, there is a dearth of similar information for the genus Microtus. In addition, most studies use a mean and standard deviation to establish reference intervals, but doing so is not the recommendation of the Clinical and Laboratory Standards Institute (formerly the National Committee on Clinical Laboratory Standards) or the International Federation of Clinical Chemistry and Laboratory Medicine. The purpose of this study was to establish normal reference parameters for plasma biochemistry and hematology in mature pine voles (Microtus pinetorum) by using the nonparametric rank percentile method as recommended by the 2 laboratory medicine organizations mentioned. Samples of cardiac blood from a closed colony of pine voles were collected at euthanasia and evaluated under rodent settings on 2 automated hematology analyzers from 2 different manufacturers and on the same type of automated biochemistry analyzer. There were no sex-associated clinically significant differences between the sexes; younger animals had a lower hematocrit, higher mean corpuscular volume, and lower mean corpuscular hemoglobin concentration than did older animals. Only platelet counts differed when comparing hematologic values from different analyzers. Relative to rats and mice, pine voles have a lower mean corpuscular volume and higher red blood cell count, higher blood urea nitrogen, much higher alanine aminotransferase, and lower glucose and phosphorous concentrations. Hematology and plasma biochemical results obtained in this study are considered representative for healthy adult laboratory pine voles under similar environmental conditions.
[On the way to national reference system of laboratory medicine].

PubMed

Muravskaia, N P; Men'shikov, V V

2014-10-01

The application of standard samples and reference techniques of implementation of measurements is needed for a valid support of reliability of analyses applied in clinical diagnostic laboratories. They play role of landmarks under metrologic monitoring, calibration of devices and control of quality of results. The article presents analysis of shortcomings interfering with formation of national reference system in Russia harmonized with possibilities provided by international organizations. Among them are the joint Committee on metrologic monitoring in laboratory medicine under the auspices of the International Bureau of Weights and Measures, the International Federation of clinical chemistry and laboratory medicine, etc. The results of the recent development of national normative documents, standard samples and techniques assisted by the authors of article are considered. They are the first steps to organization of national reference system which would comprise all range of modern analytical technologies of laboratory medicine. The national and international measures are proposed to enhance the promptest resolving of task of organization of national reference system for laboratory medicine in the interests of increasing of effectiveness of medical care to citizen of Russia.
Clinical Validation of Targeted Next Generation Sequencing for Colon and Lung Cancers

PubMed Central

D’Haene, Nicky; Le Mercier, Marie; De Nève, Nancy; Blanchard, Oriane; Delaunoy, Mélanie; El Housni, Hakim; Dessars, Barbara; Heimann, Pierre; Remmelink, Myriam; Demetter, Pieter; Tejpar, Sabine; Salmon, Isabelle

2015-01-01

Objective Recently, Next Generation Sequencing (NGS) has begun to supplant other technologies for gene mutation testing that is now required for targeted therapies. However, transfer of NGS technology to clinical daily practice requires validation. Methods We validated the Ion Torrent AmpliSeq Colon and Lung cancer panel interrogating 1850 hotspots in 22 genes using the Ion Torrent Personal Genome Machine. First, we used commercial reference standards that carry mutations at defined allelic frequency (AF). Then, 51 colorectal adenocarcinomas (CRC) and 39 non small cell lung carcinomas (NSCLC) were retrospectively analyzed. Results Sensitivity and accuracy for detecting variants at an AF >4% was 100% for commercial reference standards. Among the 90 cases, 89 (98.9%) were successfully sequenced. Among the 86 samples for which NGS and the reference test were both informative, 83 showed concordant results between NGS and the reference test; i.e. KRAS and BRAF for CRC and EGFR for NSCLC, with the 3 discordant cases each characterized by an AF <10%. Conclusions Overall, the AmpliSeq colon/lung cancer panel was specific and sensitive for mutation analysis of gene panels and can be incorporated into clinical daily practice. PMID:26366557
Multicenter Evaluation of a Commercial Cytomegalovirus Quantitative Standard: Effects of Commutability on Interlaboratory Concordance

PubMed Central

Shahbazian, M. D.; Valsamakis, A.; Boonyaratanakornkit, J.; Cook, L.; Pang, X. L.; Preiksaitis, J. K.; Schönbrunner, E. R.; Caliendo, A. M.

2013-01-01

Commutability of quantitative reference materials has proven important for reliable and accurate results in clinical chemistry. As international reference standards and commercially produced calibration material have become available to address the variability of viral load assays, the degree to which such materials are commutable and the effect of commutability on assay concordance have been questioned. To investigate this, 60 archived clinical plasma samples, which previously tested positive for cytomegalovirus (CMV), were retested by five different laboratories, each using a different quantitative CMV PCR assay. Results from each laboratory were calibrated both with lab-specific quantitative CMV standards (“lab standards”) and with common, commercially available standards (“CMV panel”). Pairwise analyses among laboratories were performed using mean results from each clinical sample, calibrated first with lab standards and then with the CMV panel. Commutability of the CMV panel was determined based on difference plots for each laboratory pair showing plotted values of standards that were within the 95% prediction intervals for the clinical specimens. Commutability was demonstrated for 6 of 10 laboratory pairs using the CMV panel. In half of these pairs, use of the CMV panel improved quantitative agreement compared to use of lab standards. Two of four laboratory pairs for which the CMV panel was noncommutable showed reduced quantitative agreement when that panel was used as a common calibrator. Commutability of calibration material varies across different quantitative PCR methods. Use of a common, commutable quantitative standard can improve agreement across different assays; use of a noncommutable calibrator can reduce agreement among laboratories. PMID:24025907
Baseline Assessment of 25-Hydroxyvitamin D Reference Material and Proficiency Testing/External Quality Assurance Material Commutability: A Vitamin D Standardization Program Study.

PubMed

Phinney, Karen W; Sempos, Christopher T; Tai, Susan S-C; Camara, Johanna E; Wise, Stephen A; Eckfeldt, John H; Hoofnagle, Andrew N; Carter, Graham D; Jones, Julia; Myers, Gary L; Durazo-Arvizu, Ramon; Miller, W Greg; Bachmann, Lorin M; Young, Ian S; Pettit, Juanita; Caldwell, Grahame; Liu, Andrew; Brooks, Stephen P J; Sarafin, Kurtis; Thamm, Michael; Mensink, Gert B M; Busch, Markus; Rabenberg, Martina; Cashman, Kevin D; Kiely, Mairead; Galvin, Karen; Zhang, Joy Y; Kinsella, Michael; Oh, Kyungwon; Lee, Sun-Wha; Jung, Chae L; Cox, Lorna; Goldberg, Gail; Guberg, Kate; Meadows, Sarah; Prentice, Ann; Tian, Lu; Brannon, Patsy M; Lucas, Robyn M; Crump, Peter M; Cavalier, Etienne; Merkel, Joyce; Betz, Joseph M

2017-09-01

The Vitamin D Standardization Program (VDSP) coordinated a study in 2012 to assess the commutability of reference materials and proficiency testing/external quality assurance materials for total 25-hydroxyvitamin D [25(OH)D] in human serum, the primary indicator of vitamin D status. A set of 50 single-donor serum samples as well as 17 reference and proficiency testing/external quality assessment materials were analyzed by participating laboratories that used either immunoassay or LC-MS methods for total 25(OH)D. The commutability test materials included National Institute of Standards and Technology Standard Reference Material 972a Vitamin D Metabolites in Human Serum as well as materials from the College of American Pathologists and the Vitamin D External Quality Assessment Scheme. Study protocols and data analysis procedures were in accordance with Clinical and Laboratory Standards Institute guidelines. The majority of the test materials were found to be commutable with the methods used in this commutability study. These results provide guidance for laboratories needing to choose appropriate reference materials and select proficiency or external quality assessment programs and will serve as a foundation for additional VDSP studies.
Validity of the WISC-IV Spanish for a clinically referred sample of Hispanic children.

PubMed

San Miguel Montes, Liza E; Allen, Daniel N; Puente, Antonio E; Neblina, Cris

2010-06-01

The Wechsler Intelligence Scale for Children (WISC) is the most commonly used intelligence test for children. Five years ago, a Spanish version of the WISC-IV was published (WISC-IV Spanish; Wechsler, 2005), but a limited amount of published information is available regarding its utility when assessing clinical samples. The current study included 107 children who were Spanish speaking and of Puerto Rican descent that had been administered the WISC-IV Spanish. They were subdivided into a clinical sample of 35 children with diagnoses of various forms of brain dysfunction (primarily learning disability, attention-deficit/hyperactivity disorder, and epilepsy) and a comparison group made up of 72 normal children who were part of the WISC-IV Spanish version standardization sample. Comparisons between these groups and the standardization sample were performed for the WISC-IV Spanish index and subtest scores. Results indicated that the clinical sample performed worse than the comparison samples on the Working Memory and Processing Speed Indexes, although findings varied to some extent depending on whether the clinical group was compared with the normal comparison group or the standardization sample. These findings provide support for the criterion validity of the WISC-IV Spanish when it is used to assess a clinically referred sample with brain dysfunction.
Comparison of the gold standard of hemoglobin measurement with the clinical standard (BGA) and noninvasive hemoglobin measurement (SpHb) in small children: a prospective diagnostic observational study.

PubMed

Wittenmeier, Eva; Bellosevich, Sophia; Mauff, Susanne; Schmidtmann, Irene; Eli, Michael; Pestel, Gunther; Noppens, Ruediger R

2015-10-01

Collecting a blood sample is usually necessary to measure hemoglobin levels in children. Especially in small children, noninvasively measuring the hemoglobin level could be extraordinarily helpful, but its precision and accuracy in the clinical environment remain unclear. In this study, noninvasive hemoglobin measurement and blood gas analysis were compared to hemoglobin measurement in a clinical laboratory. In 60 healthy preoperative children (0.2-7.6 years old), hemoglobin was measured using a noninvasive method (SpHb; Radical-7 Pulse Co-Oximeter), a blood gas analyzer (clinical standard, BGAHb; ABL 800 Flex), and a laboratory hematology analyzer (reference method, labHb; Siemens Advia). Agreement between the results was assessed by Bland-Altman analysis and by determining the percentage of outliers. Sixty SpHb measurements, 60 labHb measurements, and 59 BGAHb measurements were evaluated. In 38% of the children, the location of the SpHb sensor had to be changed more than twice for the signal quality to be sufficient. The bias/limits of agreement between SpHb and labHb were -0.65/-3.4 to 2.1 g·dl(-1) . Forty-four percent of the SpHb values differed from the reference value by more than 1 g·dl(-1) . Age, difficulty of measurement, and the perfusion index (PI) had no influence on the accuracy of SpHb. The bias/limits of agreement between BGAHb and labHb were 1.14/-1.6 to 3.9 g·dl(-1) . Furthermore, 66% of the BGAHb values differed from the reference values by more than 1 g·dl(-1) . The absolute mean difference between SpHb and labHb (1.1 g·dl(-1) ) was smaller than the absolute mean difference between BGAHb and labHb (1.5 g·dl(-1) /P = 0.024). Noninvasive measurement of hemoglobin agrees more with the reference method than the measurement of hemoglobin using a blood gas analyzer. However, both methods can show clinically relevant differences from the reference method (ClinicalTrials.gov: NCT01693016). © 2015 John Wiley & Sons Ltd.
Harmonization in laboratory medicine: Requests, samples, measurements and reports.

PubMed

Plebani, Mario

2016-01-01

In laboratory medicine, the terms "standardization" and "harmonization" are frequently used interchangeably as the final goal is the same: the equivalence of measurement results among different routine measurement procedures over time and space according to defined analytical and clinical quality specifications. However, the terms define two distinct, albeit closely linked, concepts based on traceability principles. The word "standardization" is used when results for a measurement are equivalent and traceable to the International System of Units (SI) through a high-order primary reference material and/or a reference measurement procedure (RMP). "Harmonization" is generally used when results are equivalent, but neither a high-order primary reference material nor a reference measurement procedure is available. Harmonization is a fundamental aspect of quality in laboratory medicine as its ultimate goal is to improve patient outcomes through the provision of accurate and actionable laboratory information. Patients, clinicians and other healthcare professionals assume that clinical laboratory tests performed by different laboratories at different times on the same sample and specimen can be compared, and that results can be reliably and consistently interpreted. Unfortunately, this is not necessarily the case, because many laboratory test results are still highly variable and poorly standardized and harmonized. Although the initial focus was mainly on harmonizing and standardizing analytical processes and methods, the scope of harmonization now also includes all other aspects of the total testing process (TTP), such as terminology and units, report formats, reference intervals and decision limits as well as tests and test profiles, requests and criteria for interpretation. Several projects and initiatives aiming to improve standardization and harmonization in the testing process are now underway. Laboratory professionals should therefore step up their efforts to provide interchangeable and comparable laboratory information in order to ultimately assure better diagnosis and treatment in patient care.
Systematic review of emergency medicine clinical practice guidelines: Implications for research and policy.

PubMed

Venkatesh, Arjun K; Savage, Dan; Sandefur, Benjamin; Bernard, Kenneth R; Rothenberg, Craig; Schuur, Jeremiah D

2017-01-01

Over 25 years, emergency medicine in the United States has amassed a large evidence base that has been systematically assessed and interpreted through ACEP Clinical Policies. While not previously studied in emergency medicine, prior work has shown that nearly half of all recommendations in medical specialty practice guidelines may be based on limited or inconclusive evidence. We sought to describe the proportion of clinical practice guideline recommendations in Emergency Medicine that are based upon expert opinion and low level evidence. Systematic review of clinical practice guidelines (Clinical Policies) published by the American College of Emergency Physicians from January 1990 to January 2016. Standardized data were abstracted from each Clinical Policy including the number and level of recommendations as well as the reported class of evidence. Primary outcomes were the proportion of Level C equivalent recommendations and Class III equivalent evidence. The primary analysis was limited to current Clinical Policies, while secondary analysis included all Clinical Policies. A total of 54 Clinical Policies including 421 recommendations and 2801 cited references, with an average of 7.8 recommendations and 52 references per guideline were included. Of 19 current Clinical Policies, 13 of 141 (9.2%) recommendations were Level A, 57 (40.4%) Level B, and 71 (50.4%) Level C. Of 845 references in current Clinical Policies, 67 (7.9%) were Class I, 272 (32.3%) Class II, and 506 (59.9%) Class III equivalent. Among all Clinical Policies, 200 (47.5%) recommendations were Level C equivalent, and 1371 (48.9%) of references were Class III equivalent. Emergency medicine clinical practice guidelines are largely based on lower classes of evidence and a majority of recommendations are expert opinion based. Emergency medicine appears to suffer from an evidence gap that should be prioritized in the national research agenda and considered by policymakers prior to developing future quality standards.
Standard reference material for Her2 testing: report of a National Institute of Standards and Technology-sponsored Consensus Workshop.

PubMed

Hammond, M Elizabeth H; Barker, Peter; Taube, Sheila; Gutman, Steven

2003-06-01

A workshop was sponsored by the National Institute of Standards and Technology, the Cancer Diagnosis Program of the National Cancer Institute, the Food and Drug Administration, and the College of American Pathologists to address the need for a reference material for Her2 gene protein testing. It was agreed that such a standard was desirable and necessary to ensure the reliability of Her2 testing to qualify patients for trastuzumab therapy. Two standards consisting of well characterized cell lines will be produced, 1 that will be a National Institute of Standards and Technology-certifiable standard, and 1 that will be a commercially developed standard for use in all Her2 testing. It was also agreed that all Her2 testing must be performed on samples fixed only in 10% buffered formalin, as specified in the Food and Drug Administration-approved testing methods. Participants agreed to plan strategies to educate pathologists, clinicians, and laboratories about the need and use of such a standard. A National Committee for Clinical Laboratory Standards guideline for the use of the standard reference material will be created to facilitate this process.
The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy.

PubMed

Hartlage, Gregory R; Kim, Jonathan H; Strickland, Patrick T; Cheng, Alan C; Ghasemzadeh, Nima; Pernetz, Maria A; Clements, Stephen D; Williams, B Robinson

2015-03-01

Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may provide substantial prognostic information for hypertrophic cardiomyopathy (HCM) patients. Reference values for GLS have been recently published. We aimed to evaluate the prognostic value of standardized reference values for GLS in HCM patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS was defined as normal (more negative or equal to -16%) and abnormal (less negative than -16%) based on recently published reference values. Patients were followed for a composite of events including heart failure hospitalization, sustained ventricular arrhythmia, and all-cause death. The power of GLS to predict outcomes was assessed relative to traditional clinical and echocardiographic variables present in HCM. 79 HCM patients were followed for a median of 22 months (interquartile range 9-30 months) after imaging. During follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only echocardiographic variable independently predictive of the primary outcome [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)]. When combined with traditional clinical variables, abnormal GLS remained independently predictive of the primary outcome [multivariate Hazard ratio 5.31 (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the strongest clinical and echocardiographic predictors of the primary outcome, abnormal GLS demonstrated significant incremental benefit for risk stratification [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p < 0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM patients. Standardized use of GLS may provide significant incremental value over traditional variables for risk stratification.
Hematology and Plasma Chemistry Reference Intervals for Mature Laboratory Pine Voles (Microtus pinetorum) as Determined by Using the Nonparametric Rank Percentile Method

PubMed Central

Harvey, Stephen B; Krimer, Paula M; Correa, Maria T; Hanes, Martha A

2008-01-01

Plasma biochemical and hematologic values are important parameters for assessing animal health and experimental results. Although normal reference values for many rodent species have been published, there is a dearth of similar information for the genus Microtus. In addition, most studies use a mean and standard deviation to establish reference intervals, but doing so is not the recommendation of the Clinical and Laboratory Standards Institute (formerly the National Committee on Clinical Laboratory Standards) or the International Federation of Clinical Chemistry and Laboratory Medicine. The purpose of this study was to establish normal reference parameters for plasma biochemistry and hematology in mature pine voles (Microtus pinetorum) by using the nonparametric rank percentile method as recommended by the 2 laboratory medicine organizations mentioned. Samples of cardiac blood from a closed colony of pine voles were collected at euthanasia and evaluated under rodent settings on 2 automated hematology analyzers from 2 different manufacturers and on the same type of automated biochemistry analyzer. There were no sex-associated clinically significant differences between the sexes; younger animals had a lower hematocrit, higher mean corpuscular volume, and lower mean corpuscular hemoglobin concentration than did older animals. Only platelet counts differed when comparing hematologic values from different analyzers. Relative to rats and mice, pine voles have a lower mean corpuscular volume and higher red blood cell count, higher blood urea nitrogen, much higher alanine aminotransferase, and lower glucose and phosphorous concentrations. Hematology and plasma biochemical results obtained in this study are considered representative for healthy adult laboratory pine voles under similar environmental conditions. PMID:18702449
[The analytical reliability of clinical laboratory information and role of the standards in its support].

PubMed

Men'shikov, V V

2012-12-01

The article deals with the factors impacting the reliability of clinical laboratory information. The differences of qualities of laboratory analysis tools produced by various manufacturers are discussed. These characteristics are the causes of discrepancy of the results of laboratory analyses of the same analite. The role of the reference system in supporting the comparability of laboratory analysis results is demonstrated. The project of national standard is presented to regulate the requirements to standards and calibrators for analysis of qualitative and non-metrical characteristics of components of biomaterials.
The Joint Clinic: Managing Excess Demand for Hip and Knee Osteoarthritis Referrals Using a New Physiotherapy-Led Outpatient Service.

PubMed

Gwynne-Jones, David P; Hutton, Liam R; Stout, Kirsten M; Abbott, J Haxby

2018-04-01

There are increasing problems with access to both outpatient assessment and joint replacement surgery for patients with hip or knee osteoarthritis. Data were collected on all patients seen at the Joint Clinic over a 2-year period with minimum 12-month follow-up. Patients were assessed by a nurse and a physiotherapist, baseline scores and demographic details collected, and an individualized personal care plan developed. Patients could be referred for a first specialist assessment (FSA) if their severity justified surgical assessment. Three hundred fifty-eight patients were seen at Joint Clinic, of whom 150 (44%) had hip and 189 (56%) had knee OA. The mean age was 67.4 years and there were 152 men (45%) and 187 women (55%). The mean baseline Oxford score was 19.8 (standard deviation 8.2). Fifty-four patients were referred directly to FSA (mean Oxford score 13.0, standard deviation 6.7) and 89 after a subsequent review. The scores of patients referred for FSA were significantly worse than those managed in the Joint Clinic (P < .001). Of the 143 referred for FSA, 115 underwent or were awaiting surgery, 18 were recommended surgery but scored below prioritization threshold, and 10 were not recommended surgery. The Oxford scores of the 194 patients managed non-operatively improved from 22.0 to 25.0 (P = .0013). This study shows that the Joint Clinic was effective as a triage tool with 93% of those referred for FSA being recommended surgery. This has freed up surgeon time to see only those patients most in need of surgical assessment. Copyright © 2017 Elsevier Inc. All rights reserved.
Effect of Harm Anchors in Visual Displays of Test Results on Patient Perceptions of Urgency About Near-Normal Values: Experimental Study.

PubMed

Zikmund-Fisher, Brian J; Scherer, Aaron M; Witteman, Holly O; Solomon, Jacob B; Exe, Nicole L; Fagerlin, Angela

2018-03-26

Patient-facing displays of laboratory test results typically provide patients with one reference point (the "standard range"). To test the effect of including an additional harm anchor reference point in visual displays of laboratory test results, which indicates how far outside of the standard range values would need to be in order to suggest substantial patient risk. Using a demographically diverse, online sample, we compared the reactions of 1618 adults in the United States who viewed visual line displays that included both standard range and harm anchor reference points ("Many doctors are not concerned until here") to displays that included either (1) only a standard range, (2) standard range plus evaluative categories (eg, "borderline high"), or (3) a color gradient showing degree of deviation from the standard range. Providing the harm anchor reference point significantly reduced perceived urgency of close-to-normal alanine aminotransferase and creatinine results (P values <.001) but not generally for platelet count results. Notably, display type did not significantly alter perceptions of more extreme results in potentially harmful ranges. Harm anchors also substantially reduced the number of participants who wanted to contact their doctor urgently or go to the hospital about these test results. Presenting patients with evaluative cues regarding when test results become clinically concerning can reduce the perceived urgency of out-of-range results that do not require immediate clinical action. ©Brian J Zikmund-Fisher, Aaron M Scherer, Holly O Witteman, Jacob B Solomon, Nicole L Exe, Angela Fagerlin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.03.2018.
Sealant retention is better assessed through colour photographs than through the replica and the visual examination methods.

PubMed

Hu, Xuan; Fan, Mingwan; Rong, Wensheng; Lo, Edward C M; Bronkhorst, Ewald; Frencken, Jo E

2014-08-01

The aim of this study was to test the hypothesis that the colour photograph method has a higher level of validity for assessing sealant retention than the visual clinical examination and replica methods. Sealed molars were assessed by two evaluators. The scores for the three methods were compared against consensus scores derived through assessing retention from scanning electron microscopy images (reference standard). The presence/absence (survival) of retained sealants on occlusal surfaces was determined according to the traditional and modified categorizations of retention. Sensitivity, specificity, and Youden-index scores were calculated. Sealant retention assessment scores for visual clinical examinations and for colour photographs were compared with those of the reference standard on 95 surfaces, and sealant retention assessment scores for replicas were compared with those of the reference standard on 33 surfaces. The highest mean Youden-index score for the presence/absence of sealant material was observed for the colour photograph method, followed by that for the replica method; the visual clinical examination method scored lowest. The mean Youden-index score for the survival of retained sealants was highest for the colour photograph method for both the traditional (0.882) and the modified (0.768) categories of sealant retention, whilst the visual clinical examination method had the lowest Youden-index score for these categories (0.745 and 0.063, respectively). The colour photograph method had a higher validity than the replica and the visual examination methods for assessing sealant retention. © 2014 Eur J Oral Sci.

Validity of clinical outcome measures to evaluate ankle range of motion during the weight-bearing lunge test.

PubMed

Hall, Emily A; Docherty, Carrie L

2017-07-01

To determine the concurrent validity of standard clinical outcome measures compared to laboratory outcome measure while performing the weight-bearing lunge test (WBLT). Cross-sectional study. Fifty participants performed the WBLT to determine dorsiflexion ROM using four different measurement techniques: dorsiflexion angle with digital inclinometer at 15cm distal to the tibial tuberosity (°), dorsiflexion angle with inclinometer at tibial tuberosity (°), maximum lunge distance (cm), and dorsiflexion angle using a 2D motion capture system (°). Outcome measures were recorded concurrently during each trial. To establish concurrent validity, Pearson product-moment correlation coefficients (r) were conducted, comparing each dependent variable to the 2D motion capture analysis (identified as the reference standard). A higher correlation indicates strong concurrent validity. There was a high correlation between each measurement technique and the reference standard. Specifically the correlation between the inclinometer placement at 15cm below the tibial tuberosity (44.9°±5.5°) and the motion capture angle (27.0°±6.0°) was r=0.76 (p=0.001), between the inclinometer placement at the tibial tuberosity angle (39.0°±4.6°) and the motion capture angle was r=0.71 (p=0.001), and between the distance from the wall clinical measure (10.3±3.0cm) to the motion capture angle was r=0.74 (p=0.001). This study determined that the clinical measures used during the WBLT have a high correlation with the reference standard for assessing dorsiflexion range of motion. Therefore, obtaining maximum lunge distance and inclinometer angles are both valid assessments during the weight-bearing lunge test. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
Detailed clinical models: representing knowledge, data and semantics in healthcare information technology.

PubMed

Goossen, William T F

2014-07-01

This paper will present an overview of the developmental effort in harmonizing clinical knowledge modeling using the Detailed Clinical Models (DCMs), and will explain how it can contribute to the preservation of Electronic Health Records (EHR) data. Clinical knowledge modeling is vital for the management and preservation of EHR and data. Such modeling provides common data elements and terminology binding with the intention of capturing and managing clinical information over time and location independent from technology. Any EHR data exchange without an agreed clinical knowledge modeling will potentially result in loss of information. Many attempts exist from the past to model clinical knowledge for the benefits of semantic interoperability using standardized data representation and common terminologies. The objective of each project is similar with respect to consistent representation of clinical data, using standardized terminologies, and an overall logical approach. However, the conceptual, logical, and the technical expressions are quite different in one clinical knowledge modeling approach versus another. There currently are synergies under the Clinical Information Modeling Initiative (CIMI) in order to create a harmonized reference model for clinical knowledge models. The goal for the CIMI is to create a reference model and formalisms based on for instance the DCM (ISO/TS 13972), among other work. A global repository of DCMs may potentially be established in the future.
Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus type 1 isolates. The RV-43 Study Group, the AIDS Clinical Trials Group Virology Committee Resistance Working Group.

PubMed Central

Japour, A J; Mayers, D L; Johnson, V A; Kuritzkes, D R; Beckett, L A; Arduino, J M; Lane, J; Black, R J; Reichelderfer, P S; D'Aquila, R T

1993-01-01

A standardized antiviral drug susceptibility assay for clinical human immunodeficiency virus type 1 (HIV-1) isolates has been developed for use in clinical trials. The protocol is a two-step procedure that first involves cocultivation of patient infected peripheral blood mononuclear cells (PBMC) with seronegative phytohemagglutinin-stimulated donor PBMC to obtain an HIV-1 stock. The virus stock is titrated for viral infectivity (50% tissue culture infective dose) by use of serial fourfold virus dilutions in donor PBMC. A standardized inoculum of 1,000 50% tissue culture infective doses per 10(6) cells is used in the second step of the procedure to acutely infect seronegative donor PBMC in a 7-day microtiter plate assay with triplicate wells containing zidovudine (ZDV) concentrations ranging from 0 to 5.0 microM. The ZDV 50% inhibitory concentrations (IC50) for reference ZDV-susceptible and ZDV-resistant HIV-1 isolates ranged from 0.002 to 0.113 microM and from 0.15 to > 5.0 microM, respectively. Use of this consensus protocol reduced interlaboratory variability for ZDV IC50 determinations with reference HIV-1 isolates. Among eight laboratories, the coefficient of variation ranged from 0.85 to 1.25 with different PBMC protocols and was reduced to 0.39 to 0.98 with the standardized assay. Among the clinical HIV-1 isolates assayed by the standardized drug susceptibility assay, the median ZDV IC50 increased gradually with more ZDV therapy. This protocol provides an efficient and reproducible means to assess the in vitro susceptibility to antiretroviral agents of virtually all clinical HIV-1 isolates. PMID:8517697
Building a semantic web-based metadata repository for facilitating detailed clinical modeling in cancer genome studies.

PubMed

Sharma, Deepak K; Solbrig, Harold R; Tao, Cui; Weng, Chunhua; Chute, Christopher G; Jiang, Guoqian

2017-06-05

Detailed Clinical Models (DCMs) have been regarded as the basis for retaining computable meaning when data are exchanged between heterogeneous computer systems. To better support clinical cancer data capturing and reporting, there is an emerging need to develop informatics solutions for standards-based clinical models in cancer study domains. The objective of the study is to develop and evaluate a cancer genome study metadata management system that serves as a key infrastructure in supporting clinical information modeling in cancer genome study domains. We leveraged a Semantic Web-based metadata repository enhanced with both ISO11179 metadata standard and Clinical Information Modeling Initiative (CIMI) Reference Model. We used the common data elements (CDEs) defined in The Cancer Genome Atlas (TCGA) data dictionary, and extracted the metadata of the CDEs using the NCI Cancer Data Standards Repository (caDSR) CDE dataset rendered in the Resource Description Framework (RDF). The ITEM/ITEM_GROUP pattern defined in the latest CIMI Reference Model is used to represent reusable model elements (mini-Archetypes). We produced a metadata repository with 38 clinical cancer genome study domains, comprising a rich collection of mini-Archetype pattern instances. We performed a case study of the domain "clinical pharmaceutical" in the TCGA data dictionary and demonstrated enriched data elements in the metadata repository are very useful in support of building detailed clinical models. Our informatics approach leveraging Semantic Web technologies provides an effective way to build a CIMI-compliant metadata repository that would facilitate the detailed clinical modeling to support use cases beyond TCGA in clinical cancer study domains.
Certified reference materials (GBW09170 and 09171) of creatinine in human serum.

PubMed

Dai, Xinhua; Fang, Xiang; Shao, Mingwu; Li, Ming; Huang, Zejian; Li, Hongmei; Jiang, You; Song, Dewei; He, Yajuan

2011-02-15

Creatinine is the most widely used clinical marker for assessing renal function. Concentrations of creatinine in human serum need to be carefully checked in order to ensure accurate diagnosis of renal function. Therefore, development of certified reference materials (CRMs) of creatinine in serum is of increasing importance. In this study, two new CRMs (Nos. GBW09170 and 09171) for creatinine in human serum have been developed. They were prepared with mixtures of several dozens of healthy people's and kidney disease patient's serum, respectively. The certified values of 8.10, 34.1 mg/kg for these two CRMs have been assigned by liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) method which was validated by using standard reference material (SRM) of SRM909b (a reference material obtained from National Institute of Standards and Technology, NIST). The expanded uncertainties of certified values for low and high concentrations were estimated to be 1.2 and 1.1%, respectively. The certified values were further confirmed by an international intercomparison for the determination of creatinine in human serum (Consultative Committee for Amount of Substance, CCQM) of K80 (CCQM-K80). These new CRMs of creatinine in human serum pool are totally native without additional creatinine spiked for enrichment. These new CRMs are capable of validating routine clinical methods for ensuring accuracy, reliability and comparability of analytical results from different clinical laboratories. They can also be used for instrument validation, development of secondary reference materials, and evaluating the accuracy of high order clinical methods for the determination of creatinine in human serum. Copyright © 2011 Elsevier B.V. All rights reserved.
Improving stressful working lives: complementary therapies, counselling and clinical supervision for staff.

PubMed

Mackereth, Peter A; White, Keven; Cawthorn, Anne; Lynch, Barbara

2005-06-01

The aim of this paper is to briefly examine the contemporary phenomenon of "burnout" within oncology and palliative care. In discussing the suitable interventions to manage stress and avoid burnout, reference will be made to counselling and clinical supervision, but more substantially the paper will report on an innovative subsidised complementary therapy service for staff. The Government's Improving Working Lives Standard will be referred as an initiative that supports the development of supportive services for NHS staff.
Assessing FDG-PET diagnostic accuracy studies to develop recommendations for clinical use in dementia.

PubMed

Boccardi, Marina; Festari, Cristina; Altomare, Daniele; Gandolfo, Federica; Orini, Stefania; Nobili, Flavio; Frisoni, Giovanni B

2018-04-30

FDG-PET is frequently used as a marker of synaptic damage to diagnose dementing neurodegenerative disorders. We aimed to adapt the items of evidence quality to FDG-PET diagnostic studies, and assess the evidence available in current literature to assist Delphi decisions for European recommendations for clinical use. Based on acknowledged methodological guidance, we defined the domains, specific to FDG-PET, required to assess the quality of evidence in 21 literature searches addressing as many Population Intervention Comparison Outcome (PICO) questions. We ranked findings for each PICO and fed experts making Delphi decisions for recommending clinical use. Among the 1435 retrieved studies, most lacked validated measures of test performance, an adequate gold standard, and head-to-head comparison of FDG-PET and clinical diagnosis, and only 58 entered detailed assessment. Only two studies assessed the accuracy of the comparator (clinical diagnosis) versus any kind of gold-/reference-standard. As to the index-test (FDG-PET-based diagnosis), an independent gold-standard was available in 24% of the examined papers; 38% used an acceptable reference-standard (clinical follow-up); and 38% compared FDG-PET-based diagnosis only to baseline clinical diagnosis. These methodological limitations did not allow for deriving recommendations from evidence. An incremental diagnostic value of FDG-PET versus clinical diagnosis or lack thereof cannot be derived from the current literature. Many of the observed limitations may easily be overcome, and we outlined them as research priorities to improve the quality of current evidence. Such improvement is necessary to outline evidence-based guidelines. The available data were anyway provided to expert clinicians who defined interim recommendations.
The STARD statement for reporting diagnostic accuracy studies: application to the history and physical examination.

PubMed

Simel, David L; Rennie, Drummond; Bossuyt, Patrick M M

2008-06-01

The Standards for Reporting of Diagnostic Accuracy (STARD) statement provided guidelines for investigators conducting diagnostic accuracy studies. We reviewed each item in the statement for its applicability to clinical examination diagnostic accuracy research, viewing each discrete aspect of the history and physical examination as a diagnostic test. Nonsystematic review of the STARD statement. Two former STARD Group participants and 1 editor of a journal series on clinical examination research reviewed each STARD item. Suggested interpretations and comments were shared to develop consensus. The STARD Statement applies generally well to clinical examination diagnostic accuracy studies. Three items are the most important for clinical examination diagnostic accuracy studies, and investigators should pay particular attention to their requirements: describe carefully the patient recruitment process, describe participant sampling and address if patients were from a consecutive series, and describe whether the clinicians were masked to the reference standard tests and whether the interpretation of the reference standard test was masked to the clinical examination components or overall clinical impression. The consideration of these and the other STARD items in clinical examination diagnostic research studies would improve the quality of investigations and strengthen conclusions reached by practicing clinicians. The STARD statement provides a very useful framework for diagnostic accuracy studies. The group correctly anticipated that there would be nuances applicable to studies of the clinical examination. We offer guidance that should enhance their usefulness to investigators embarking on original studies of a patient's history and physical examination.
The Swedish strategy and method for development of a national healthcare information architecture.

PubMed

Rosenälv, Jessica; Lundell, Karl-Henrik

2012-01-01

"We need a precise framework of regulations in order to maintain appropriate and structured health care documentation that ensures that the information maintains a sufficient level of quality to be used in treatment, in research and by the actual patient. The users shall be aided by clearly and uniformly defined terms and concepts, and there should be an information structure that clarifies what to document and how to make the information more useful. Most of all, we need to standardize the information, not just the technical systems." (eHälsa - nytta och näring, Riksdag report 2011/12:RFR5, p. 37). In 2010, the Swedish Government adopted the National e-Health - the national strategy for accessible and secure information in healthcare. The strategy is a revision and extension of the previous strategy from 2006, which was used as input for the most recent efforts to develop a national information structure utilizing business-oriented generic models. A national decision on healthcare informatics standards was made by the Swedish County Councils, which decided to follow and use EN/ISO 13606 as a standard for the development of a universally applicable information structure, including archetypes and templates. The overall aim of the Swedish strategy for development of National Healthcare Information Architecture is to achieve high level semantic interoperability for clinical content and clinical contexts. High level semantic interoperability requires consistently structured clinical data and other types of data with coherent traceability to be mapped to reference clinical models. Archetypes that are formal definitions of the clinical and demographic concepts and some administrative data were developed. Each archetype describes the information structure and content of overarching core clinical concepts. Information that is defined in archetypes should be used for different purposes. Generic clinical process model was made concrete and analyzed. For each decision-making step in the process where information is processed, the amount and type of information and its structure were defined in terms of reference templates. Reference templates manage clinical, administrative and demographic types of information in a specific clinical context. Based on a survey of clinical processes at the reference level, the identification of specific clinical processes such as diabetes and congestive heart failure in adults were made. Process-specific templates were defined by using reference templates and populated with information that was relevant to each health problem in a specific clinical context. Throughout this process, medical data for knowledge management were collected for each health problem. Parallel with the efforts to define archetypes and templates, terminology binding work is on-going. Different strategies are used depending on the terminology binding level.
International Standards and Reference Materials for Quantitative Molecular Infectious Disease Testing

PubMed Central

Madej, Roberta M.; Davis, Jack; Holden, Marcia J.; Kwang, Stan; Labourier, Emmanuel; Schneider, George J.

2010-01-01

The utility of quantitative molecular diagnostics for patient management depends on the ability to relate patient results to prior results or to absolute values in clinical practice guidelines. To do this, those results need to be comparable across time and methods, either by producing the same value across methods and test versions or by using reliable and stable conversions. Universally available standards and reference materials specific to quantitative molecular technologies are critical to this process but are few in number. This review describes recent history in the establishment of international standards for nucleic acid test development, organizations involved in current efforts, and future issues and initiatives. PMID:20075208
Understanding health care provider barriers to hospital affiliated medical fitness center facility referral: a questionnaire survey and semi structured interviews.

PubMed

Smock, Carissa; Alemagno, Sonia

2017-08-03

The purpose of this study is to understand health care provider barriers to referring patients to Medical Fitness Center Facilities within an affiliated teaching hospital system using referral of diabetic services as an example. The aims of this study include: (1) to assess health care providers' awareness and use of facilities, (2) to determine barriers to referring patients to facilities, (3) identify current and needed resources and/or changes to increase referral to facilities. A 20-item electronic survey and requests for semi-structured interviews were administered to hospital system directors and managers (n = 51). Directors and managers instructed physicians and staff to complete the survey and interviews as applicable. Perceived barriers, knowledge, utilization, and referral of patients to Medical Fitness Center Facilities were collected and examined. Descriptive statistics were generated regarding practice characteristics, provider characteristics, and referral. Of the health care providers surveyed and interviewed (n = 25) 40% indicated verbally suggesting use of facilities, 24% provided a flyer about the facilities. No respondents indicated that they directly referred patients to the facilities. However, 16% referred patients to other locations for physical activity - including their own department's management and prevention services. 20% do not refer to Medical Fitness Center Facilities or any other lifestyle programs/locations. Lack of time (92%) and lack of standard guidelines and operating procedures (88%) are barriers to referral. All respondents indicated a strong ability to refer patients to Medical Fitness Center Facilities if given education about referral programs available as well as standard clinical guidelines and protocol for delivery. The results of this study indicate that, although few healthcare providers are currently referring patients to Medical Fitness Center Facilities, health care providers with an affiliated Medical Fitness Center Facility not only want clinical standard guidelines, protocol, and training to refer patients to Medical Fitness Center Facilities, but believe they have the ability to increase referral if given these tools. The Medical Fitness Association has a unique opportunity to bridge health care providers to Medical Fitness Center Facilities by developing clinical practice guidelines in cooperation with the American Diabetes Association.
12. Children and Adolescents: Standards of Medical Care in Diabetes-2018.

PubMed

2018-01-01

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. © 2017 by the American Diabetes Association.
A preliminary study of the impact of a handover cognitive aid on clinical reasoning and information transfer.

PubMed

Weiss, Matthew J; Bhanji, Farhan; Fontela, Patricia S; Razack, Saleem I

2013-08-01

To assess the impact of a written cognitive aid on expressed clinical reasoning and quantity and the accuracy of information transfer during resident doctor handover. This study was a randomised controlled trial in an academic paediatric intensive care unit (PICU) of 20 handover events (10 events per group) from residents in their first PICU rotation using a written handover cognitive aid (intervention) or standard practice (control). Before rounds, an investigator generated a reference standard of the handover event by completing a handover aid. Resident handovers were then audio-recorded and transcribed by a blinded research assistant. The content of this transcript was inserted into a blank handover aid. A blinded content expert scored the quantity and accuracy of the information in this aid according to predetermined criteria and these information scores (ISs) were compared with the reference standard. The same expert also blindly scored the transcripts in five domains of clinical reasoning and effectiveness: (i) effective summary of events; (ii) expressed understanding of the care plan; (iii) presentation clarity; (iv) organisation; (v) overall handover effectiveness. Differences between intervention and control groups were assessed using the Mann-Whitney test and multivariate linear regression. The intervention group had total ISs that more closely approximated the reference standard (81% versus 61%; p < 0.01). The intervention group had significantly higher clinical reasoning scores when compared by total score (21.1 versus 15.9 points; p = 0.01) and in each of the five domains. No difference was observed in the duration of handover between groups (7.4 versus 7.7 minutes; p = 0.97). Using a novel scoring system, our simple handover cognitive aid was shown to improve information transfer and resident expression of clinical reasoning without prolonging the handover duration. © 2013 John Wiley & Sons Ltd.
Quadruple Inversion-Recovery b-SSFP MRA of the Abdomen: Initial Clinical Validation

PubMed Central

Atanasova, Iliyana P.; Lim, Ruth P.; Chandarana, Hersh; Storey, Pippa; Bruno, Mary T; Kim, Daniel; Lee, Vivian S.

2014-01-01

The purpose of this study is to assess the image quality and diagnostic accuracy of non-contrast quadruple inversion-recovery balanced-SSFP MRA (QIR MRA) for detection of aortoiliac disease in a clinical population. QIR MRA was performed in 26 patients referred for routine clinical gadolinium-enhanced MRA (Gd-MRA) for known or suspected aortoiliac disease. Non-contrast images were independently evaluated for image qualityand degree of stenosisby two radiologists, usingconsensus Gd-MRA as the reference standard. Hemodynamically significant stenosis (≥ 50%) was found in 10% (22/226) of all evaluable segments on Gd-MRA. The sensitivity and specificity for stenosis evaluation by QIR MRA for the two readers were 86%/86% and 95%/93% respectively. Negative predictive value and positive predictive value were 98%/98% and 63%/53% respectively. For stenosis evaluation of the aortoiliac region QIR MRA showed good agreement with the reference standard with high negative predictive value and a tendency to overestimate mild disease presumably due to the flow-dependence of the technique. QIR MRA could be a reasonable alternative to Gd-MRA for ruling out stenosis when contrast is contraindicated due to impaired kidney function or in patients who undergo abdominal MRA for screening purposes. Further work is necessary to improve performance and justify routine clinical use. PMID:24998363
Impact of Image Noise on Gamma Index Calculation

NASA Astrophysics Data System (ADS)

Chen, M.; Mo, X.; Parnell, D.; Olivera, G.; Galmarini, D.; Lu, W.

2014-03-01

Purpose: The Gamma Index defines an asymmetric metric between the evaluated image and the reference image. It provides a quantitative comparison that can be used to indicate sample-wised pass/fail on the agreement of the two images. The Gamma passing/failing rate has become an important clinical evaluation tool. However, the presence of noise in the evaluated and/or reference images may change the Gamma Index, hence the passing/failing rate, and further, clinical decisions. In this work, we systematically studied the impact of the image noise on the Gamma Index calculation. Methods: We used both analytic formulation and numerical calculations in our study. The numerical calculations included simulations and clinical images. Three different noise scenarios were studied in simulations: noise in reference images only, in evaluated images only, and in both. Both white and spatially correlated noises of various magnitudes were simulated. For clinical images of various noise levels, the Gamma Index of measurement against calculation, calculation against measurement, and measurement against measurement, were evaluated. Results: Numerical calculations for both the simulation and clinical data agreed with the analytic formulations, and the clinical data agreed with the simulations. For the Gamma Index of measurement against calculation, its distribution has an increased mean and an increased standard deviation as the noise increases. On the contrary, for the Gamma index of calculation against measurement, its distribution has a decreased mean and stabilized standard deviation as the noise increases. White noise has greater impact on the Gamma Index than spatially correlated noise. Conclusions: The noise has significant impact on the Gamma Index calculation and the impact is asymmetric. The Gamma Index should be reported along with the noise levels in both reference and evaluated images. Reporting of the Gamma Index with switched roles of the images as reference and evaluated images or some composite metrics would be a good practice.
Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

PubMed Central

Ni, Yizhao; Kennebeck, Stephanie; Dexheimer, Judith W; McAneney, Constance M; Tang, Huaxiu; Lingren, Todd; Li, Qi; Zhai, Haijun; Solti, Imre

2015-01-01

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials. Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed. Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches. Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials. PMID:25030032
Query Health: standards-based, cross-platform population health surveillance

PubMed Central

Klann, Jeffrey G; Buck, Michael D; Brown, Jeffrey; Hadley, Marc; Elmore, Richard; Weber, Griffin M; Murphy, Shawn N

2014-01-01

Objective Understanding population-level health trends is essential to effectively monitor and improve public health. The Office of the National Coordinator for Health Information Technology (ONC) Query Health initiative is a collaboration to develop a national architecture for distributed, population-level health queries across diverse clinical systems with disparate data models. Here we review Query Health activities, including a standards-based methodology, an open-source reference implementation, and three pilot projects. Materials and methods Query Health defined a standards-based approach for distributed population health queries, using an ontology based on the Quality Data Model and Consolidated Clinical Document Architecture, Health Quality Measures Format (HQMF) as the query language, the Query Envelope as the secure transport layer, and the Quality Reporting Document Architecture as the result language. Results We implemented this approach using Informatics for Integrating Biology and the Bedside (i2b2) and hQuery for data analytics and PopMedNet for access control, secure query distribution, and response. We deployed the reference implementation at three pilot sites: two public health departments (New York City and Massachusetts) and one pilot designed to support Food and Drug Administration post-market safety surveillance activities. The pilots were successful, although improved cross-platform data normalization is needed. Discussions This initiative resulted in a standards-based methodology for population health queries, a reference implementation, and revision of the HQMF standard. It also informed future directions regarding interoperability and data access for ONC's Data Access Framework initiative. Conclusions Query Health was a test of the learning health system that supplied a functional methodology and reference implementation for distributed population health queries that has been validated at three sites. PMID:24699371
Query Health: standards-based, cross-platform population health surveillance.

PubMed

Klann, Jeffrey G; Buck, Michael D; Brown, Jeffrey; Hadley, Marc; Elmore, Richard; Weber, Griffin M; Murphy, Shawn N

2014-01-01

Understanding population-level health trends is essential to effectively monitor and improve public health. The Office of the National Coordinator for Health Information Technology (ONC) Query Health initiative is a collaboration to develop a national architecture for distributed, population-level health queries across diverse clinical systems with disparate data models. Here we review Query Health activities, including a standards-based methodology, an open-source reference implementation, and three pilot projects. Query Health defined a standards-based approach for distributed population health queries, using an ontology based on the Quality Data Model and Consolidated Clinical Document Architecture, Health Quality Measures Format (HQMF) as the query language, the Query Envelope as the secure transport layer, and the Quality Reporting Document Architecture as the result language. We implemented this approach using Informatics for Integrating Biology and the Bedside (i2b2) and hQuery for data analytics and PopMedNet for access control, secure query distribution, and response. We deployed the reference implementation at three pilot sites: two public health departments (New York City and Massachusetts) and one pilot designed to support Food and Drug Administration post-market safety surveillance activities. The pilots were successful, although improved cross-platform data normalization is needed. This initiative resulted in a standards-based methodology for population health queries, a reference implementation, and revision of the HQMF standard. It also informed future directions regarding interoperability and data access for ONC's Data Access Framework initiative. Query Health was a test of the learning health system that supplied a functional methodology and reference implementation for distributed population health queries that has been validated at three sites. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research.

PubMed

Manolio, Teri A; Fowler, Douglas M; Starita, Lea M; Haendel, Melissa A; MacArthur, Daniel G; Biesecker, Leslie G; Worthey, Elizabeth; Chisholm, Rex L; Green, Eric D; Jacob, Howard J; McLeod, Howard L; Roden, Dan; Rodriguez, Laura Lyman; Williams, Marc S; Cooper, Gregory M; Cox, Nancy J; Herman, Gail E; Kingsmore, Stephen; Lo, Cecilia; Lutz, Cathleen; MacRae, Calum A; Nussbaum, Robert L; Ordovas, Jose M; Ramos, Erin M; Robinson, Peter N; Rubinstein, Wendy S; Seidman, Christine; Stranger, Barbara E; Wang, Haoyi; Westerfield, Monte; Bult, Carol

2017-03-23

Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations, we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, and promoting data sharing. Published by Elsevier Inc.
Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research

PubMed Central

Manolio, Teri A.; Fowler, Douglas M.; Starita, Lea M.; Haendel, Melissa A.; MacArthur, Daniel G.; Biesecker, Leslie G.; Worthey, Elizabeth; Chisholm, Rex L.; Green, Eric D.; Jacob, Howard J.; McLeod, Howard L.; Roden, Dan; Rodriguez, Laura Lyman; Williams, Marc S.; Cooper, Gregory M.; Cox, Nancy J.; Herman, Gail E.; Kingsmore, Stephen; Lo, Cecilia; Lutz, Cathleen; MacRae, Calum A.; Nussbaum, Robert L.; Ordovas, Jose M.; Ramos, Erin M.; Robinson, Peter N.; Rubinstein, Wendy S.; Seidman, Christine; Stranger, Barbara E.; Wang, Haoyi; Westerfield, Monte; Bult, Carol

2017-01-01

Summary Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, and promoting data sharing. PMID:28340351

[Marketing orientation in rehabilitation--exemplified by image analysis of a rehabilitation clinic for addictions].

PubMed

Altenhöner, T; Schönhoff, T; Wehmeier, D

2001-06-01

This article presents the findings of an image analysis carried out for a rehabilitation clinic for addictive diseases. The cross-sectional study was designed as an anonymous survey sent to relevant (regional) referral agencies (n = 90), e.g. counselling services for addictive diseases. The study covers the clinic's actual and ideal image, discriminating frequency of referrals, diagnostic categories, region, and type of institution. Results concerning the real profile indicate that on average the dimensions cooperation, communication with regard to personal contact, and reputation of the clinic were more critically judged than the issues information, communication with regard to discharge reports, standards of quality, and consideration of patients' needs. Cooperation, communication with regard to personal contact, and quality standards turned out to be the most important criteria from the referring agencies' perspective (ideal profile). A statistical comparison between those with high and low assignment rates suggested that customers rated the clinic more favourably than non-customers. Thus, it seems that the clinic's image has considerable influence on referral decisions. Particularly interesting is the additional finding that the referring institutions perceive pension insurers' directives to be of secondary relevance.
Quantitative Imaging Biomarkers: A Review of Statistical Methods for Computer Algorithm Comparisons

PubMed Central

2014-01-01

Quantitative biomarkers from medical images are becoming important tools for clinical diagnosis, staging, monitoring, treatment planning, and development of new therapies. While there is a rich history of the development of quantitative imaging biomarker (QIB) techniques, little attention has been paid to the validation and comparison of the computer algorithms that implement the QIB measurements. In this paper we provide a framework for QIB algorithm comparisons. We first review and compare various study designs, including designs with the true value (e.g. phantoms, digital reference images, and zero-change studies), designs with a reference standard (e.g. studies testing equivalence with a reference standard), and designs without a reference standard (e.g. agreement studies and studies of algorithm precision). The statistical methods for comparing QIB algorithms are then presented for various study types using both aggregate and disaggregate approaches. We propose a series of steps for establishing the performance of a QIB algorithm, identify limitations in the current statistical literature, and suggest future directions for research. PMID:24919829
The Kjeldahl method as a primary reference procedure for total protein in certified reference materials used in clinical chemistry. I. A review of Kjeldahl methods adopted by laboratory medicine.

PubMed

Chromý, Vratislav; Vinklárková, Bára; Šprongl, Luděk; Bittová, Miroslava

2015-01-01

We found previously that albumin-calibrated total protein in certified reference materials causes unacceptable positive bias in analysis of human sera. The simplest way to cure this defect is the use of human-based serum/plasma standards calibrated by the Kjeldahl method. Such standards, commutative with serum samples, will compensate for bias caused by lipids and bilirubin in most human sera. To find a suitable primary reference procedure for total protein in reference materials, we reviewed Kjeldahl methods adopted by laboratory medicine. We found two methods recommended for total protein in human samples: an indirect analysis based on total Kjeldahl nitrogen corrected for its nonprotein nitrogen and a direct analysis made on isolated protein precipitates. The methods found will be assessed in a subsequent article.
[Differences and international standardization between acupuncture as therapy and as specialty].

PubMed

Ng, Szetuen

2017-01-12

The purpose of this study is to explore the differences of definition and clinical roles as well as international standardization between acupuncture as therapy and as specialty, which can provide reference evidence for specialization and internationalization of acupuncture. Owing to the clinical efficacy and safety, the credibility and controversy both exist in acupuncture; moreover, there is a lack of fair definition and international precedent regarding acupuncture specialty. Therefore, it is particularly essential to objectively compare the differences of definitions and clinical roles as well as criteria of international standardization for acupuncture as therapy and as specialty. It is believed acupuncture standardization can draw lessons from the international medical standards, evidence-based medicine and acupuncture theory from the following three major projects:acupuncture safety and contraindications; acupuncture indications and treatment guidelines; acupuncture indication classified into 3 levels of evidence-based acupuncture disease spectrum, as objective evidence of indication of acupuncture specialty.
Standardized protocols for quality control of MRM-based plasma proteomic workflows.

PubMed

Percy, Andrew J; Chambers, Andrew G; Smith, Derek S; Borchers, Christoph H

2013-01-04

Mass spectrometry (MS)-based proteomics is rapidly emerging as a viable technology for the identification and quantitation of biological samples, such as human plasma--the most complex yet commonly employed biofluid in clinical analyses. The transition from a qualitative to quantitative science is required if proteomics is going to successfully make the transition to a clinically useful technique. MS, however, has been criticized for a lack of reproducibility and interlaboratory transferability. Currently, the MS and plasma proteomics communities lack standardized protocols and reagents to ensure that high-quality quantitative data can be accurately and precisely reproduced by laboratories across the world using different MS technologies. Toward addressing this issue, we have developed standard protocols for multiple reaction monitoring (MRM)-based assays with customized isotopically labeled internal standards for quality control of the sample preparation workflow and the MS platform in quantitative plasma proteomic analyses. The development of reference standards and their application to a single MS platform is discussed herein, along with the results from intralaboratory tests. The tests highlighted the importance of the reference standards in assessing the efficiency and reproducibility of the entire bottom-up proteomic workflow and revealed errors related to the sample preparation and performance quality and deficits of the MS and LC systems. Such evaluations are necessary if MRM-based quantitative plasma proteomics is to be used in verifying and validating putative disease biomarkers across different research laboratories and eventually in clinical laboratories.
A clinical investigation of motivation to change standards and cognitions about failure in perfectionism.

PubMed

Egan, Sarah J; Piek, Jan P; Dyck, Murray J; Rees, Clare S; Hagger, Martin S

2013-10-01

Clinical perfectionism is a transdiagnostic process that has been found to maintain eating disorders, anxiety disorders and depression. Cognitive behavioural models explaining the maintenance of clinical perfectionism emphasize the contribution of dichotomous thinking and resetting standards higher following both success and failure in meeting their goals. There has been a paucity of research examining the predictions of the models and motivation to change perfectionism. Motivation to change is important as individuals with clinical perfectionism often report many perceived benefits of their perfectionism; they are, therefore, likely to be ambivalent regarding changing perfectionism. The aim was to compare qualitative responses regarding questions about motivation to change standards and cognitions regarding failure to meet a personal standard in two contrasting groups with high and low negative perfectionism. Negative perfectionism refers to concern over not meeting personal standards. A clinical group with a range of axis 1 diagnoses who were elevated on negative perfectionism were compared to a group of athletes who were low on negative perfectionism. Results indicated that the clinical group perceived many negative consequences of their perfectionism. They also, however, reported numerous benefits and the majority stated that they would prefer not to change their perfectionism. The clinical group also reported dichotomous thinking and preferring to either keep standards the same or reset standards higher following failure, whilst the athlete group reported they would keep standards the same or set them lower. The findings support predictions of the cognitive behavioural model of clinical perfectionism.
Establishment and validation of analytical reference panels for the standardization of quantitative BCR-ABL1 measurements on the international scale.

PubMed

White, Helen E; Hedges, John; Bendit, Israel; Branford, Susan; Colomer, Dolors; Hochhaus, Andreas; Hughes, Timothy; Kamel-Reid, Suzanne; Kim, Dong-Wook; Modur, Vijay; Müller, Martin C; Pagnano, Katia B; Pane, Fabrizio; Radich, Jerry; Cross, Nicholas C P; Labourier, Emmanuel

2013-06-01

Current guidelines for managing Philadelphia-positive chronic myeloid leukemia include monitoring the expression of the BCR-ABL1 (breakpoint cluster region/c-abl oncogene 1, non-receptor tyrosine kinase) fusion gene by quantitative reverse-transcription PCR (RT-qPCR). Our goal was to establish and validate reference panels to mitigate the interlaboratory imprecision of quantitative BCR-ABL1 measurements and to facilitate global standardization on the international scale (IS). Four-level secondary reference panels were manufactured under controlled and validated processes with synthetic Armored RNA Quant molecules (Asuragen) calibrated to reference standards from the WHO and the NIST. Performance was evaluated in IS reference laboratories and with non-IS-standardized RT-qPCR methods. For most methods, percent ratios for BCR-ABL1 e13a2 and e14a2 relative to ABL1 or BCR were robust at 4 different levels and linear over 3 logarithms, from 10% to 0.01% on the IS. The intraassay and interassay imprecision was <2-fold overall. Performance was stable across 3 consecutive lots, in multiple laboratories, and over a period of 18 months to date. International field trials demonstrated the commutability of the reagents and their accurate alignment to the IS within the intra- and interlaboratory imprecision of IS-standardized methods. The synthetic calibrator panels are robust, reproducibly manufactured, analytically calibrated to the WHO primary standards, and compatible with most BCR-ABL1 RT-qPCR assay designs. The broad availability of secondary reference reagents will further facilitate interlaboratory comparative studies and independent quality assessment programs, which are of paramount importance for worldwide standardization of BCR-ABL1 monitoring results and the optimization of current and new therapeutic approaches for chronic myeloid leukemia. © 2013 American Association for Clinical Chemistry.
The STARD Statement for Reporting Diagnostic Accuracy Studies: Application to the History and Physical Examination

PubMed Central

Rennie, Drummond; Bossuyt, Patrick M. M.

2008-01-01

Summary Objective The Standards for Reporting of Diagnostic Accuracy (STARD) statement provided guidelines for investigators conducting diagnostic accuracy studies. We reviewed each item in the statement for its applicability to clinical examination diagnostic accuracy research, viewing each discrete aspect of the history and physical examination as a diagnostic test. Setting Nonsystematic review of the STARD statement. Interventions Two former STARD Group participants and 1 editor of a journal series on clinical examination research reviewed each STARD item. Suggested interpretations and comments were shared to develop consensus. Measurements and Main Results The STARD Statement applies generally well to clinical examination diagnostic accuracy studies. Three items are the most important for clinical examination diagnostic accuracy studies, and investigators should pay particular attention to their requirements: describe carefully the patient recruitment process, describe participant sampling and address if patients were from a consecutive series, and describe whether the clinicians were masked to the reference standard tests and whether the interpretation of the reference standard test was masked to the clinical examination components or overall clinical impression. The consideration of these and the other STARD items in clinical examination diagnostic research studies would improve the quality of investigations and strengthen conclusions reached by practicing clinicians. Conclusions The STARD statement provides a very useful framework for diagnostic accuracy studies. The group correctly anticipated that there would be nuances applicable to studies of the clinical examination. We offer guidance that should enhance their usefulness to investigators embarking on original studies of a patient’s history and physical examination. PMID:18347878
Integration of nursing assessment concepts into the medical entities dictionary using the LOINC semantic structure as a terminology model.

PubMed

Cieslowski, B J; Wajngurt, D; Cimino, J J; Bakken, S

2001-01-01

Recent investigations have tested the applicability of various terminology models for the representing nursing concepts including those related to nursing diagnoses, nursing interventions, and standardized nursing assessments as a prerequisite for building a reference terminology that supports the nursing domain. We used the semantic structure of Clinical LOINC (Logical Observations, Identifiers, Names, and Codes) as a reference terminology model to support the integration of standardized assessment terms from two nursing terminologies into the Medical Entities Dictionary (MED), the concept-oriented, metadata dictionary at New York Presbyterian Hospital. Although the LOINC semantic structure was used previously to represent laboratory terms in the MED, selected hierarchies and semantic slots required revisions in order to incorporate the nursing assessment concepts. This project was an initial step in integrating nursing assessment concepts into the MED in a manner consistent with evolving standards for reference terminology models. Moreover, the revisions provide the foundation for adding other types of standardized assessments to the MED.
Integration of nursing assessment concepts into the medical entities dictionary using the LOINC semantic structure as a terminology model.

PubMed Central

Cieslowski, B. J.; Wajngurt, D.; Cimino, J. J.; Bakken, S.

2001-01-01

Recent investigations have tested the applicability of various terminology models for the representing nursing concepts including those related to nursing diagnoses, nursing interventions, and standardized nursing assessments as a prerequisite for building a reference terminology that supports the nursing domain. We used the semantic structure of Clinical LOINC (Logical Observations, Identifiers, Names, and Codes) as a reference terminology model to support the integration of standardized assessment terms from two nursing terminologies into the Medical Entities Dictionary (MED), the concept-oriented, metadata dictionary at New York Presbyterian Hospital. Although the LOINC semantic structure was used previously to represent laboratory terms in the MED, selected hierarchies and semantic slots required revisions in order to incorporate the nursing assessment concepts. This project was an initial step in integrating nursing assessment concepts into the MED in a manner consistent with evolving standards for reference terminology models. Moreover, the revisions provide the foundation for adding other types of standardized assessments to the MED. PMID:11825165
Plasma creatinine in dogs: intra- and inter-laboratory variation in 10 European veterinary laboratories

PubMed Central

2011-01-01

Background There is substantial variation in reported reference intervals for canine plasma creatinine among veterinary laboratories, thereby influencing the clinical assessment of analytical results. The aims of the study was to determine the inter- and intra-laboratory variation in plasma creatinine among 10 veterinary laboratories, and to compare results from each laboratory with the upper limit of its reference interval. Methods Samples were collected from 10 healthy dogs, 10 dogs with expected intermediate plasma creatinine concentrations, and 10 dogs with azotemia. Overlap was observed for the first two groups. The 30 samples were divided into 3 batches and shipped in random order by postal delivery for plasma creatinine determination. Statistical testing was performed in accordance with ISO standard methodology. Results Inter- and intra-laboratory variation was clinically acceptable as plasma creatinine values for most samples were usually of the same magnitude. A few extreme outliers caused three laboratories to fail statistical testing for consistency. Laboratory sample means above or below the overall sample mean, did not unequivocally reflect high or low reference intervals in that laboratory. Conclusions In spite of close analytical results, further standardization among laboratories is warranted. The discrepant reference intervals seem to largely reflect different populations used in establishing the reference intervals, rather than analytical variation due to different laboratory methods. PMID:21477356
TREAT Asia Quality Assessment Scheme (TAQAS) to standardize the outcome of HIV genotypic resistance testing in a group of Asian laboratories

PubMed Central

Land, Sally; Cunningham, Philip; Zhou, Jialun; Frost, Kevin; Katzenstein, David; Kantor, Rami; Chen, Yi-Ming Arthur; Oka, Shinichi; DeLong, Allison; Sayer, David; Smith, Jeffery; Dax, Elizabeth M.; Law, Matthew

2010-01-01

The TREAT Asia (Therapeutics, Research, Education, and AIDS Training in Asia) Network is building capacity for Human Immunodeficiency Virus Type-1 (HIV-1) drug resistance testing in the region. The objective of the TREAT Asia Quality Assessment Scheme – designated TAQAS – is to standardize HIV-1 genotypic resistance testing (HIV genotyping) among laboratories to permit rigorous comparison of results from different clinics and testing centres. TAQAS has evaluated three panels of HIV-1-positive plasma from clinical material or low-passage, culture supernatant for up to 10 Asian laboratories. Laboratory participants used their standard protocols to perform HIV genotyping. Assessment was in comparison to a target genotype derived from all participants and the reference laboratory’s result. Agreement between most participants at the edited nucleotide sequence level was high (>98%). Most participants performed to the reference laboratory standard in detection of drug resistance mutations (DRMs). However, there was variation in the detection of nucleotide mixtures (0–83%) and a significant correlation with the detection of DRMs (p < 0.01). Interpretation of antiretroviral resistance showed ~70% agreement among participants when different interpretation systems were used but >90% agreement with a common interpretation system, within the Stanford University Drug Resistance Database. Using the principles of external quality assessment and a reference laboratory, TAQAS has demonstrated high quality HIV genotyping results from Asian laboratories. PMID:19490972
Assessing voids in SNOMED CT for pediatric concepts.

PubMed

Wade, Geraldine; Gotlieb, Edward M; Weigle, Carl; Warren, Robert

2008-11-06

Reference terminologies such as SNOMED CT may have voids in their representation of concepts important to the practice of pediatrics. In this project, relevant pediatric concepts were extracted from an American Academy of Pediatrics guideline and were mapped to SNOMED CT. Concepts were identified that should be included in the standard reference terminology. A process for formally evaluating voids in reference terminologies for concepts needed in pediatric clinical decision-making is planned as a next step.
3D-CAM: Derivation and Validation of a 3-Minute Diagnostic Interview for CAM-defined Delirium

PubMed Central

Marcantonio, Edward R.; Ngo, Long H.; O’Connor, Margaret; Jones, Richard N.; Crane, Paul K.; Metzger, Eran D.; Inouye, Sharon K.

2015-01-01

Background Delirium is common, morbid, and costly, yet remains often unrecognized in most clinical settings. The Confusion Assessment Method (CAM) is the most widely used diagnostic algorithm, and operationalizing its features would represent a substantial advance for clinical care. Objective To derive the 3D-CAM, a new 3-minute diagnostic assessment for CAM-defined delirium, and to validate it against a clinical reference standard. Design Diagnostic test study Setting 4 general medicine units in an academic medical center Participants 201 inpatients aged ≥ 75 years old Measurements We identified 20 items that best operationalized the 4 CAM diagnostic features to create the 3D-CAM. For prospective validation, 3D-CAM assessments were administered by trained research assistants. Independently, clinicians performed an extensive assessment that included patient interviews, family interviews, and review of the medical record. These data were considered by an expert panel to determine the presence or absence of delirium and dementia (reference standard). We compared the 3D-CAM delirium determination to the reference standard in all patients and in subgroups with and without dementia. Results The 201 participants in the prospective validation study had mean age (SD) of 84 (5.5) years, and 27% had dementia. The expert panel identified delirium in 21%. Median administration time for 3D-CAM was 3 minutes (inter-quartile range: 2–5 minutes). The sensitivity [95% CI] of 3D-CAM was 95% [84%, 99%] and the specificity was 94% [90%, 97%]. The 3D-CAM performed well in patients both with dementia (sensitivity=96% [82%, 100%], specificity=86% [67%, 96%]) and without dementia (sensitivity=93% [66%, 100%], specificity=96% [91%,99%]). Limitations Limited to single center, cross-sectional, and medicine patients only Conclusion The 3D-CAM operationalizes the CAM algorithm using a 3-minute structured assessment with high sensitivity and specificity relative to a reference standard and could be an important tool for improving recognition of delirium. PMID:25329203
A review of standardized patients in clinical education: Implications for speech-language pathology programs.

PubMed

Hill, Anne E; Davidson, Bronwyn J; Theodoros, Deborah G

2010-06-01

The use of standardized patients has been reported as a viable addition to traditional models of professional practice education in medicine, nursing and allied health programs. Educational programs rely on the inclusion of work-integrated learning components in order to graduate competent practitioners. Allied health programs world-wide have reported increasing difficulty in attaining sufficient traditional placements for students within the workplace. In response to this, allied health professionals are challenged to be innovative and problem-solving in the development and maintenance of clinical education placements and to consider potential alternative learning opportunities for students. Whilst there is a bank of literature describing the use of standardized patients in medicine and nursing, reports of its use in speech-language pathology clinical education are limited. Therefore, this paper aims to (1) provide a review of literature reporting on the use of standardized patients within medical and allied health professions with particular reference to use in speech-language pathology, (2) discuss methodological and practical issues involved in establishing and maintaining a standardized patient program and (3) identify future directions for research and clinical programs using standardized patients to build foundation clinical skills such as communication, interpersonal interaction and interviewing.
Validating automated kidney stone volumetry in computed tomography and mathematical correlation with estimated stone volume based on diameter.

PubMed

Wilhelm, Konrad; Miernik, Arkadiusz; Hein, Simon; Schlager, Daniel; Adams, Fabian; Benndorf, Matthias; Fritz, Benjamin; Langer, Mathias; Hesse, Albrecht; Schoenthaler, Martin; Neubauer, Jakob

2018-06-02

To validate AutoMated UroLithiasis Evaluation Tool (AMULET) software for kidney stone volumetry and compare its performance to standard clinical practice. Maximum diameter and volume of 96 urinary stones were measured as reference standard by three independent urologists. The same stones were positioned in an anthropomorphic phantom and CT scans acquired in standard settings. Three independent radiologists blinded to the reference values took manual measurements of the maximum diameter and automatic measurements of maximum diameter and volume. An "expected volume" was calculated based on manual diameter measurements using the formula: V=4/3 πr³. 96 stones were analyzed in the study. We had initially aimed to assess 100. Nine were replaced during data acquisition due of crumbling and 4 had to be excluded because the automated measurement did not work. Mean reference maximum diameter was 13.3 mm (5.2-32.1 mm). Correlation coefficients among all measured outcomes were compared. The correlation between the manual and automatic diameter measurements to the reference was 0.98 and 0.91, respectively (p<0.001). Mean reference volume was 1200 mm³ (10-9000 mm³). The correlation between the "expected volume" and automatically measured volume to the reference was 0.95 and 0.99, respectively (p<0.001). Patients' kidney stone burden is usually assessed according to maximum diameter. However, as most stones are not spherical, this entails a potential bias. Automated stone volumetry is possible and significantly more accurate than diameter-based volumetric calculations. To avoid bias in clinical trials, size should be measured as volume. However, automated diameter measurements are not as accurate as manual measurements.
Example of monitoring measurements in a virtual eye clinic using 'big data'.

PubMed

Jones, Lee; Bryan, Susan R; Miranda, Marco A; Crabb, David P; Kotecha, Aachal

2017-10-26

To assess the equivalence of measurement outcomes between patients attending a standard glaucoma care service, where patients see an ophthalmologist in a face-to-face setting, and a glaucoma monitoring service (GMS). The average mean deviation (MD) measurement on the visual field (VF) test for 250 patients attending a GMS were compared with a 'big data' repository of patients attending a standard glaucoma care service (reference database). In addition, the speed of VF progression between GMS patients and reference database patients was compared. Reference database patients were used to create expected outcomes that GMS patients could be compared with. For GMS patients falling outside of the expected limits, further analysis was carried out on the clinical management decisions for these patients. The average MD of patients in the GMS ranged from +1.6 dB to -18.9 dB between two consecutive appointments at the clinic. In the first analysis, 12 (4.8%; 95% CI 2.5% to 8.2%) GMS patients scored outside the 90% expected values based on the reference database. In the second analysis, 1.9% (95% CI 0.4% to 5.4%) GMS patients had VF changes outside of the expected 90% limits. Using 'big data' collected in the standard glaucoma care service, we found that patients attending a GMS have equivalent outcomes on the VF test. Our findings provide support for the implementation of virtual healthcare delivery in the hospital eye service. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Reference Standards, Judges, and Comparison Subjects

PubMed Central

Hripcsak, George; Wilcox, Adam

2002-01-01

Medical informatics systems are often designed to perform at the level of human experts. Evaluation of the performance of these systems is often constrained by lack of reference standards, either because the appropriate response is not known or because no simple appropriate response exists. Even when performance can be assessed, it is not always clear whether the performance is sufficient or reasonable. These challenges can be addressed if an evaluator enlists the help of clinical domain experts. 1) The experts can carry out the same tasks as the system, and then their responses can be combined to generate a reference standard. 2)The experts can judge the appropriateness of system output directly. 3) The experts can serve as comparison subjects with which the system can be compared. These are separate roles that have different implications for study design, metrics, and issues of reliability and validity. Diagrams help delineate the roles of experts in complex study designs. PMID:11751799
Challenges imposed by minor reference alleles on the identification and reporting of clinical variants from exome data.

PubMed

Koko, Mahmoud; Abdallah, Mohammed O E; Amin, Mutaz; Ibrahim, Muntaser

2018-01-15

The conventional variant calling of pathogenic alleles in exome and genome sequencing requires the presence of the non-pathogenic alleles as genome references. This hinders the correct identification of variants with minor and/or pathogenic reference alleles warranting additional approaches for variant calling. More than 26,000 Exome Aggregation Consortium (ExAC) variants have a minor reference allele including variants with known ClinVar disease alleles. For instance, in a number of variants related to clotting disorders, the phenotype-associated allele is a human genome reference allele (rs6025, rs6003, rs1799983, and rs2227564 using the assembly hg19). We highlighted how the current variant calling standards miss homozygous reference disease variants in these sites and provided a bioinformatic panel that can be used to screen these variants using commonly available variant callers. We present exome sequencing results from an individual with venous thrombosis to emphasize how pathogenic alleles in clinically relevant variants escape variant calling while non-pathogenic alleles are detected. This article highlights the importance of specialized variant calling strategies in clinical variants with minor reference alleles especially in the context of personal genomes and exomes. We provide here a simple strategy to screen potential disease-causing variants when present in homozygous reference state.
Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criteria for Alzheimer’s disease

PubMed Central

Jack, Clifford R; Barkhof, Frederik; Bernstein, Matt A; Cantillon, Marc; Cole, Patricia E; DeCarli, Charles; Dubois, Bruno; Duchesne, Simon; Fox, Nick C; Frisoni, Giovanni B; Hampel, Harald; Hill, Derek LG; Johnson, Keith; Mangin, Jean-François; Scheltens, Philip; Schwarz, Adam J; Sperling, Reisa; Suhy, Joyce; Thompson, Paul M; Weiner, Michael; Foster, Norman L

2012-01-01

Background The promise of Alzheimer’s disease (AD) biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging (MRI) measure in AD and thus represents the most rational target for an initial effort at standardization. Methods and Results The authors of this position paper propose a path toward this goal. The steps include: 1) Establish and empower an oversight board to manage and assess the effort, 2) Adopt the standardized definition of anatomic hippocampal boundaries on MRI arising from the EADC-ADNI hippocampal harmonization effort as a Reference Standard, 3) Establish a scientifically appropriate, publicly available Reference Standard Dataset based on manual delineation of the hippocampus in an appropriate sample of subjects (ADNI), and 4) Define minimum technical and prognostic performance metrics for validation of new measurement techniques using the Reference Standard Dataset as a benchmark. Conclusions Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent is to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry is envisioned as a template that could be applied to other imaging biomarkers. PMID:21784356

45 CFR 170.205 - Content exchange standards and implementation specifications for exchanging electronic health...

Code of Federal Regulations, 2014 CFR

2014-10-01

...) (incorporated by reference in § 170.299). Implementation specifications. The Healthcare Information Technology... Guide for Ambulatory Healthcare Provider Reporting to Central Cancer Registries, HL7 Clinical Document...
Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections.

PubMed

Self, Wesley H; Rosen, Jeffrey; Sharp, Stephan C; Filbin, Michael R; Hou, Peter C; Parekh, Amisha D; Kurz, Michael C; Shapiro, Nathan I

2017-10-07

C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59-93%), specificity of 93% (89-97%), positive predictive value (PPV) of 63% (45-79%), and a negative predictive value (NPV) of 97% (94-99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75-95%), specificity of 83% (76-89%), PPV of 64% (63-75%), and NPV of 95% (90-98%). FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship.
Standards for Clinical Grade Genomic Databases.

PubMed

Yohe, Sophia L; Carter, Alexis B; Pfeifer, John D; Crawford, James M; Cushman-Vokoun, Allison; Caughron, Samuel; Leonard, Debra G B

2015-11-01

Next-generation sequencing performed in a clinical environment must meet clinical standards, which requires reproducibility of all aspects of the testing. Clinical-grade genomic databases (CGGDs) are required to classify a variant and to assist in the professional interpretation of clinical next-generation sequencing. Applying quality laboratory standards to the reference databases used for sequence-variant interpretation presents a new challenge for validation and curation. To define CGGD and the categories of information contained in CGGDs and to frame recommendations for the structure and use of these databases in clinical patient care. Members of the College of American Pathologists Personalized Health Care Committee reviewed the literature and existing state of genomic databases and developed a framework for guiding CGGD development in the future. Clinical-grade genomic databases may provide different types of information. This work group defined 3 layers of information in CGGDs: clinical genomic variant repositories, genomic medical data repositories, and genomic medicine evidence databases. The layers are differentiated by the types of genomic and medical information contained and the utility in assisting with clinical interpretation of genomic variants. Clinical-grade genomic databases must meet specific standards regarding submission, curation, and retrieval of data, as well as the maintenance of privacy and security. These organizing principles for CGGDs should serve as a foundation for future development of specific standards that support the use of such databases for patient care.
Quadruple inversion-recovery b-SSFP MRA of the abdomen: initial clinical validation.

PubMed

Atanasova, Iliyana P; Lim, Ruth P; Chandarana, Hersh; Storey, Pippa; Bruno, Mary T; Kim, Daniel; Lee, Vivian S

2014-09-01

The purpose of this study is to assess the image quality and diagnostic accuracy of non-contrast quadruple inversion-recovery balanced-SSFP MRA (QIR MRA) for detection of aortoiliac disease in a clinical population. QIR MRA was performed in 26 patients referred for routine clinical gadolinium-enhanced MRA (Gd-MRA) for known or suspected aortoiliac disease. Non-contrast images were independently evaluated for image quality and degree of stenosis by two radiologists, using consensus Gd-MRA as the reference standard. Hemodynamically significant stenosis (≥50%) was found in 10% (22/226) of all evaluable segments on Gd-MRA. The sensitivity and specificity for stenosis evaluation by QIR MRA for the two readers were 86%/86% and 95%/93% respectively. Negative predictive value and positive predictive value were 98%/98% and 63%/53% respectively. For stenosis evaluation of the aortoiliac region QIR MRA showed good agreement with the reference standard with high negative predictive value and a tendency to overestimate mild disease presumably due to the flow-dependence of the technique. QIR MRA could be a reasonable alternative to Gd-MRA for ruling out stenosis when contrast is contraindicated due to impaired kidney function or in patients who undergo abdominal MRA for screening purposes. Further work is necessary to improve performance and justify routine clinical use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Creation of a cerebellar diameter reference standard and its clinical application to the detection of cerebellar hypoplasia unique to trisomy 18.

PubMed

Hayata, Kei; Hiramatsu, Yuji; Masuyama, Hisashi; Etou, Eriko; Nobumoto, Etsuko; Mitsui, Takashi

2015-12-01

We created a new reference standard focusing on the hemispheric anteroposterior cerebellar diameter (APCD) in addition to the transverse cerebellar diameter (TCD) and discussed whether or not the cerebellar measurement was useful for the detection of trisomy 18 (T18). In 150 normal fetuses between 14 and 36 weeks of gestational age (GA), the TCD and APCD were prospectively measured. In 26 cases with T18, the value was compared with the control. At <22 weeks of gestation, the TCD reference standard was calculated as follows: TCD = (1.027 × GA) - 0.674 (R(2) = 0.97, P < 0.001). The reference standard of the APCD was calculated as follows: APCD = (0.682 × GA) - 3.925 (R(2) = 0.73, P < 0.001). In eight cases with T18, the TCD was below the 5th percentile value in 7/8 (88%) cases and the APCD was below the 5th percentile value in 8/8 (100%) cases. At >22 weeks of gestation, the reference standard of the TCD was calculated as follows: TCD = (1.603 × GA) - 13.216 (R(2) = 0.92, P < 0.001). The reference standard of the APCD was calculated as follows: APCD = (0.859 × GA) - 7.30 (R(2) = 0.84, P < 0.001). In 18 cases with T18, the TCD was below the 5th percentile value in 14/18 (78%) cases and the APCD was below the 5th percentile value in 18/18 (100%) cases. APCD reference standard, divided by the gestational age of more or less than 22 weeks, might be useful to diagnose T18. © 2015 Japan Society of Obstetrics and Gynecology.
Quantification of drugs in plasma without primary reference standards by liquid chromatography-chemiluminescence nitrogen detection: application to tramadol metabolite ratios.

PubMed

Ojanperä, Suvi; Rasanen, Ilpo; Sistonen, Johanna; Pelander, Anna; Vuori, Erkki; Ojanperä, Ilkka

2007-08-01

Lack of availability of reference standards for drug metabolites, newly released drugs, and illicit drugs hinders the analysis of these substances in biologic samples. To counter this problem, an approach is presented here for quantitative drug analysis in plasma without primary reference standards by liquid chromatography-chemiluminescence nitrogen detection (LC-CLND). To demonstrate the feasibility of the method, metabolic ratios of the opioid drug tramadol were determined in the setting of a pharmacogenetic study. Four volunteers were given a single 100-mg oral dose of tramadol, and a blood sample was collected from each subject 1 hour later. Tramadol, O-desmethyltramadol, and nortramadol were determined in plasma by LC-CLND without reference standards and by a gas chromatography-mass spectrometry reference method. In contrast to previous CLND studies lacking an extraction step, a liquid-liquid extraction system was created for 5-mL plasma samples using n-butyl chloride-isopropyl alcohol (98 + 2) at pH 10. Extraction recovery estimation was based on model compounds chosen according to their similar physicochemical characteristics (retention time, pKa, logD). Instrument calibration was performed with a single secondary standard (caffeine) using the equimolar response of the detector to nitrogen. The mean differences between the results of the LC-CLND and gas chromatography-mass spectrometry methods for tramadol, O-desmethyltramadol, and nortramadol were 8%, 32%, and 19%, respectively. The sensitivity of LC-CLND was sufficient for therapeutic concentrations of tramadol and metabolites. A good correlation was obtained between genotype, expressed by the number of functional genes, and the plasma metabolite ratios. This experiment suggests that a recovery-corrected LC-CLND analysis produces sufficiently accurate results to be useful in a clinical context, particularly in instances in which reference standards are not readily accessible.
A Meta-Analysis of Typhoid Diagnostic Accuracy Studies: A Recommendation to Adopt a Standardized Composite Reference

PubMed Central

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

2015-01-01

Novel typhoid diagnostics currently under development have the potential to improve clinical care, surveillance, and the disease burden estimates that support vaccine introduction. Blood culture is most often used as the reference method to evaluate the accuracy of new typhoid tests; however, it is recognized to be an imperfect gold standard. If no single gold standard test exists, use of a composite reference standard (CRS) can improve estimation of diagnostic accuracy. Numerous studies have used a CRS to evaluate new typhoid diagnostics; however, there is no consensus on an appropriate CRS. In order to evaluate existing tests for use as a reference test or inclusion in a CRS, we performed a systematic review of the typhoid literature to include all index/reference test combinations observed. We described the landscape of comparisons performed, showed results of a meta-analysis on the accuracy of the more common combinations, and evaluated sources of variability based on study quality. This wide-ranging meta-analysis suggests that no single test has sufficiently good performance but some existing diagnostics may be useful as part of a CRS. Additionally, based on findings from the meta-analysis and a constructed numerical example demonstrating the use of CRS, we proposed necessary criteria and potential components of a typhoid CRS to guide future recommendations. Agreement and adoption by all investigators of a standardized CRS is requisite, and would improve comparison of new diagnostics across independent studies, leading to the identification of a better reference test and improved confidence in prevalence estimates. PMID:26566275
Collaborative studies on the development of national reference standards for potency determination of H7N9 influenza vaccine

PubMed Central

Li, Changgui; Xu, Kangwei; Hashem, Anwar; Shao, Ming; Liu, Shuzhen; Zou, Yong; Gao, Qiang; Zhang, Yongchao; Yuan, Liyong; Xu, Miao; Li, Xuguang; Wang, Junzhi

2015-01-01

The outbreak of human infections of a novel avian influenza virus A (H7N9) prompted the development of the vaccines against this virus. Like all types of influenza vaccines, H7N9 vaccine must be tested for its potency prior to being used in humans. However, the unavailability of international reference reagents for the potency determination of H7N9 vaccines substantially hinders the progress in vaccine development. To facilitate clinical development, we enlisted 5 participants in a collaborative study to develop critical reagents used in Single Radial Immunodiffusion (SRID), the currently acceptable assay for potency determination of influenza vaccine. Specifically, the hemagglutinin (HA) content of one vaccine bulk for influenza A (H7N9), herein designated as Primary Liquid Standard (PLS), was determined by SDS-PAGE. In addition, the freeze-dried antigen references derived from PLS were prepared to enhance the stability for long term storage. The final HA content of lyophilized antigen references were calibrated against PLS by SRID assay in a collaborative study. Importantly, application of these national reference standards to potency analyses greatly facilitated the development of H7N9 vaccines in China. PMID:25970793
A Comparative Study of Different EEG Reference Choices for Diagnosing Unipolar Depression.

PubMed

Mumtaz, Wajid; Malik, Aamir Saeed

2018-06-02

The choice of an electroencephalogram (EEG) reference has fundamental importance and could be critical during clinical decision-making because an impure EEG reference could falsify the clinical measurements and subsequent inferences. In this research, the suitability of three EEG references was compared while classifying depressed and healthy brains using a machine-learning (ML)-based validation method. In this research, the EEG data of 30 unipolar depressed subjects and 30 age-matched healthy controls were recorded. The EEG data were analyzed in three different EEG references, the link-ear reference (LE), average reference (AR), and reference electrode standardization technique (REST). The EEG-based functional connectivity (FC) was computed. Also, the graph-based measures, such as the distances between nodes, minimum spanning tree, and maximum flow between the nodes for each channel pair, were calculated. An ML scheme provided a mechanism to compare the performances of the extracted features that involved a general framework such as the feature extraction (graph-based theoretic measures), feature selection, classification, and validation. For comparison purposes, the performance metrics such as the classification accuracies, sensitivities, specificities, and F scores were computed. When comparing the three references, the diagnostic accuracy showed better performances during the REST, while the LE and AR showed less discrimination between the two groups. Based on the results, it can be concluded that the choice of appropriate reference is critical during the clinical scenario. The REST reference is recommended for future applications of EEG-based diagnosis of mental illnesses.
Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry-recommended reference measurement procedure and reference materials for glycated albumin determination.

PubMed

Takei, Izumi; Hoshino, Tadao; Tominaga, Makoto; Ishibashi, Midori; Kuwa, Katsuhiko; Umemoto, Masao; Tani, Wataru; Okahashi, Mikiko; Yasukawa, Keiko; Kohzuma, Takuji; Sato, Asako

2016-01-01

Glycated albumin is an intermediate glycaemic control marker for which there are several measurement procedures with entirely different reference intervals. We have developed a reference measurement procedure for the purpose of standardizing glycated albumin measurements. The isotope dilution liquid chromatography/tandem mass spectrometry method was developed as a reference measurement procedure for glycated albumin. The stable isotopes of lysine and fructosyl-lysine, which serve as an internal standard, were added to albumin isolated from serum, followed by hydrogenation. After hydrolysis of albumin with hot hydrochloric acid, the liberated lysine and fructosyl-lysine were measured by liquid chromatography/tandem mass spectrometry, and their concentrations were determined from each isotope ratio. The reference materials (JCCRM611) for determining of glycated albumin were prepared from pooled patient blood samples. The isotope dilution-tandem mass spectrometry calibration curve of fructosyl-lysine and lysine showed good linearity (r = 0.999). The inter-assay and intra-assay coefficient of variation values of glycated albumin measurement were 1.2 and 1.4%, respectively. The glycated albumin values of serum in patients with diabetes assessed through the use of this method showed a good relationship with routine measurement procedures (r = 0.997). The relationship of glycated albumin values of the reference material (JCCRM611) between these two methods was the same as the relationship with the patient serum samples. The Committee on Diabetes Mellitus Indices of the Japan Society of Clinical Chemistry recommends the isotope dilution liquid chromatography/tandem mass spectrometry method as a reference measurement procedure, and JCCRM611 as a certified reference material for glycated albumin measurement. In addition, we recommend the traceability system for glycated albumin measurement. © The Author(s) 2015.
Audit of dental practice record-keeping: a PCT-coordinated clinical audit by Worcestershire dentists.

PubMed

Cole, Andrew; McMichael, Alan

2009-07-01

A collaborative audit of clinical record-keeping standards was performed among Worcestershire dentists. Its aims were to improve the quality of National Health Service (NHS) patient care and to assist dentists to perform well during Dental Reference Service practice visits. Worcestershire dentists with NHS contracts were invited to take part in this audit. Each dentist audited a random selection of 30 of their dental clinical records against a common framework comprising eight domains. Record-keeping, and the presence or absence of key diagnostic and treatment planning details were recorded. Grading was applied in four categories, in which grades 1 and 2 were good (1) and adequate (2), captured on data-collection sheets and centrally analysed for frequency of each grade. Out of a total of 184 Worcestershire general dental practitioners, 161 (87.5%) submitted usable responses. The audit revealed wide variation between dentists in clinical record-keeping. The recording of soft tissues (36% below grade 2), periodontal status (30%), radiographic review (27%), and note-taking (25%) all fell below the standard that had been set (brackets show proportion not meeting the standard). The results provided baseline information about the standard of record-keeping in NHS dental practices in Worcestershire. The collaborative nature of the audit enabled dissemination of individual results to participants, to facilitate comparison (anonymously) against their peers. The audit provided impetus for the Primary Care Trust (PCT) to arrange postgraduate education on record-keeping and to raise awareness among local dentists about record-keeping. The subsequent report to dentists explored the record-keeping standards expected during practice inspections undertaken by the Dental Reference Service. Worcestershire PCT's method of collaborative dental audit could potentially replace the previous national programme of dental audit, formerly coordinated locally.
Impact of a dedicated cancer-associated thrombosis service on clinical outcomes: a mixed-methods evaluation of a clinical improvement exercise

PubMed Central

Noble, Simon; Pease, Nikki; Sui, Jessica; Davies, James; Lewis, Sarah; Malik, Usman; Alikhan, Raza; Prout, Hayley; Nelson, Annmarie

2016-01-01

Objectives Cancer-associated thrombosis (CAT) complex condition, which may present to any healthcare professional and at any point during the cancer journey. As such, patients may be managed by a number of specialties, resulting in inconsistent practice and suboptimal care. We describe the development of a dedicated CAT service and its evaluation. Setting Specialist cancer centre, district general hospital and primary care. Participants Patients with CAT and their referring clinicians. Intervention A cross specialty team developed a dedicated CAT service , including clear referral pathways, consistent access to medicines, patient's information and a specialist clinic. Primary and secondary outcome measures The service was evaluated using a mixed-methods evaluation , including audits of clinical practice, clinical outcomes, staff surveys and qualitative interviewing of patients and healthcare professionals. Results Data from 457 consecutive referrals over an 18-month period were evaluated. The CAT service has led to an 88% increase in safe and consistent community prescribing of low-molecular-weight heparin, with improved access to specialist advice and information. Patients reported improved understanding of their condition, enabling better self-management as well as better access to support and information. Referring clinicians reported better care standards for their patients with improved access to expertise and appropriate management. Conclusions A dedicated CAT service improves overall standards of care and is viewed positively by patients and clinicians alike. Further health economic evaluation would enhance the case for establishing this as the standard model of care. PMID:27895068
Quantitative imaging biomarkers: a review of statistical methods for computer algorithm comparisons.

PubMed

Obuchowski, Nancy A; Reeves, Anthony P; Huang, Erich P; Wang, Xiao-Feng; Buckler, Andrew J; Kim, Hyun J Grace; Barnhart, Huiman X; Jackson, Edward F; Giger, Maryellen L; Pennello, Gene; Toledano, Alicia Y; Kalpathy-Cramer, Jayashree; Apanasovich, Tatiyana V; Kinahan, Paul E; Myers, Kyle J; Goldgof, Dmitry B; Barboriak, Daniel P; Gillies, Robert J; Schwartz, Lawrence H; Sullivan, Daniel C

2015-02-01

Quantitative biomarkers from medical images are becoming important tools for clinical diagnosis, staging, monitoring, treatment planning, and development of new therapies. While there is a rich history of the development of quantitative imaging biomarker (QIB) techniques, little attention has been paid to the validation and comparison of the computer algorithms that implement the QIB measurements. In this paper we provide a framework for QIB algorithm comparisons. We first review and compare various study designs, including designs with the true value (e.g. phantoms, digital reference images, and zero-change studies), designs with a reference standard (e.g. studies testing equivalence with a reference standard), and designs without a reference standard (e.g. agreement studies and studies of algorithm precision). The statistical methods for comparing QIB algorithms are then presented for various study types using both aggregate and disaggregate approaches. We propose a series of steps for establishing the performance of a QIB algorithm, identify limitations in the current statistical literature, and suggest future directions for research. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
18O-labeled proteome reference as global internal standards for targeted quantification by selected reaction monitoring-mass spectrometry.

PubMed

Kim, Jong-Seo; Fillmore, Thomas L; Liu, Tao; Robinson, Errol; Hossain, Mahmud; Champion, Boyd L; Moore, Ronald J; Camp, David G; Smith, Richard D; Qian, Wei-Jun

2011-12-01

Selected reaction monitoring (SRM)-MS is an emerging technology for high throughput targeted protein quantification and verification in biomarker discovery studies; however, the cost associated with the application of stable isotope-labeled synthetic peptides as internal standards can be prohibitive for screening a large number of candidate proteins as often required in the preverification phase of discovery studies. Herein we present a proof of concept study using an (18)O-labeled proteome reference as global internal standards (GIS) for SRM-based relative quantification. The (18)O-labeled proteome reference (or GIS) can be readily prepared and contains a heavy isotope ((18)O)-labeled internal standard for every possible tryptic peptide. Our results showed that the percentage of heavy isotope ((18)O) incorporation applying an improved protocol was >99.5% for most peptides investigated. The accuracy, reproducibility, and linear dynamic range of quantification were further assessed based on known ratios of standard proteins spiked into the labeled mouse plasma reference. Reliable quantification was observed with high reproducibility (i.e. coefficient of variance <10%) for analyte concentrations that were set at 100-fold higher or lower than those of the GIS based on the light ((16)O)/heavy ((18)O) peak area ratios. The utility of (18)O-labeled GIS was further illustrated by accurate relative quantification of 45 major human plasma proteins. Moreover, quantification of the concentrations of C-reactive protein and prostate-specific antigen was illustrated by coupling the GIS with standard additions of purified protein standards. Collectively, our results demonstrated that the use of (18)O-labeled proteome reference as GIS provides a convenient, low cost, and effective strategy for relative quantification of a large number of candidate proteins in biological or clinical samples using SRM.
Effect of 25(OH) vitamin D reference method procedure (RMP) alignment on clinical measurements obtained with the IDS-iSYS chemiluminescent-based automated analyzer.

PubMed

Simpson, Christine A; Cusano, Anna Maria; Bihuniak, Jessica; Walker, Joanne; Insogna, Karl L

2015-04-01

The Vitamin D Standardization Program (VDSP) has identified ID-LC/MS/MS as the reference method procedure (RMP) for 25(OH) vitamin D and NIST Standard SRM2972 as the standard reference material (SRM). As manufacturers align their products to the RMP and NIST standard, a concern is that results obtained in aligned assays will be divergent from those obtained with pre-alignment assays. The Immunodiagnostic Systems Ltd., chemiluminescent, 25(OH) vitamin D iSYS platform assay, was recently harmonized to the RMP. To determine the impact of standardization on results obtained with iSYS reagents, 119 single donor serum samples from eight different disease categories were analyzed in four non-standardized and two standardized iSYS assays. There were strong correlations between the four non-standardized and two standardized assays with Spearman's rank r values between 0.975 and 0.961 and four of the eight r values were >0.97. R(2) values for the eight best-fit linear regression equations ranging between 0.947 and 0.916. None of the slopes were found to be significantly different from one another. Bland-Altman plots showed that the bias was comparable when each of the four non-standardized assays was compared to either of the standardized assays. When the data were segregated in values between 6 and 49ng/mL (15-122nmol/L) or between 50 and 100ng/mL (125-250nmol/L) significant associations remained between results obtained with non-standardized and standardized calibrators regardless of the absolute value. When five recent DEQAS unknowns were analyzed in one non-standardized and one standardized assay the mean percent difference from the NIST target in values obtained using standardized vs. non-standardized calibrators were not significantly different. Finally, strong and statistically significant associations between the results were obtained using non-standardized and standardized assays for six of eight clinical conditions. The only exceptions were hypocalcemia and breast cancer, which likely reflect the small sample sizes for each of these diseases. These initial data provide confidence that the move to a NIST standardized assay will have little impact on results obtained with the iSYS platform. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.
How do reference montage and electrodes setup affect the measured scalp EEG potentials?

NASA Astrophysics Data System (ADS)

Hu, Shiang; Lai, Yongxiu; Valdes-Sosa, Pedro A.; Bringas-Vega, Maria L.; Yao, Dezhong

2018-04-01

Objective. Human scalp electroencephalogram (EEG) is widely applied in cognitive neuroscience and clinical studies due to its non-invasiveness and ultra-high time resolution. However, the representativeness of the measured EEG potentials for the underneath neural activities is still a problem under debate. This study aims to investigate systematically how both reference montage and electrodes setup affect the accuracy of EEG potentials. Approach. First, the standard EEG potentials are generated by the forward calculation with a single dipole in the neural source space, for eleven channel numbers (10, 16, 21, 32, 64, 85, 96, 128, 129, 257, 335). Here, the reference is the ideal infinity implicitly determined by forward theory. Then, the standard EEG potentials are transformed to recordings with different references including five mono-polar references (Left earlobe, Fz, Pz, Oz, Cz), and three re-references (linked mastoids (LM), average reference (AR) and reference electrode standardization technique (REST)). Finally, the relative errors between the standard EEG potentials and the transformed ones are evaluated in terms of channel number, scalp regions, electrodes layout, dipole source position and orientation, as well as sensor noise and head model. Main results. Mono-polar reference recordings are usually of large distortions; thus, a re-reference after online mono-polar recording should be adopted in general to mitigate this effect. Among the three re-references, REST is generally superior to AR for all factors compared, and LM performs worst. REST is insensitive to head model perturbation. AR is subject to electrodes coverage and dipole orientation but no close relation with channel number. Significance. These results indicate that REST would be the first choice of re-reference and AR may be an alternative option for high level sensor noise case. Our findings may provide the helpful suggestions on how to obtain the EEG potentials as accurately as possible for cognitive neuroscientists and clinicians.
Results of the National CT Colonography Trial: Questions and Answers

Cancer.gov

Learn the results of the National Computerized Tomographic Colonography (CTC) clinical trial, which evaluated how well CTC identifies participants with at least one significantly large polyp using colonoscopy as the gold (or reference) standard.
Standard Specimen Reference Set: Colon — EDRN Public Portal

Cancer.gov

The Early Detection Research Network, Great Lakes-New England Clinical, Epidemiological and Validation Center (GLNE CVC) announces the availability of serum, plasma and urine samples for the early detection for colon cancer and validation studies.
Audit of memory clinic practice against CCG guidelines: West Suffolk Hospital.

PubMed

Mahmoud, Afef; Vandana, Balakrishna Menon; Chipperfield, Ruth; Ferrera, Silvia; Rubinsztein, Judy

2015-09-01

The memory service based in the West Suffolk has received increased funding to deliver a high quality service against standards set by the Clinical Commissioning Group (CCG). This audit aims to examine if we are achieving the standards set by the local CCG and to identify areas to improve the quality of the service.We also aimed to assess information as to how many patients referred had dementia. If they had a dementia suitable for possible anti-dementia medication (such as dementia of Alzheimer's type, Alzheimer's mixed type or atypical or Lewy body/ Parkinson's dementia) to ascertain if they were being offered anti-dementia medication. Retrospective analysis of 60 patients from the memory service were analysed. The first 10 patients referred in alternative months were selected for inclusion. Standards were based on targets set by the CCG in terms of time needed to assess, diagnose, communicate diagnosis to the GP and give post diagnostic advice. Patients in this memory service were being seen 37 days (on average) after referral. Most patients received a diagnosis at their initial assessment but some needed further investigation to establish the diagnosis or the specific type of diagnosis. The time for letters to be typed did not meet standards and letters were sent out on average 23 days after patients were being seen. Post diagnostic advice was delivered to most who received a diagnosis. Our service is offering timely diagnosis to those referred to the memory service in line with national guidelines.
Diagnostic value of different adherence measures using electronic monitoring and virologic failure as reference standards.

PubMed

Deschamps, Ann E; De Geest, Sabina; Vandamme, Anne-Mieke; Bobbaers, Herman; Peetermans, Willy E; Van Wijngaerden, Eric

2008-09-01

Nonadherence to antiretroviral therapy is a substantial problem in HIV and jeopardizes the success of treatment. Accurate measurement of nonadherence is therefore imperative for good clinical management but no gold standard has been agreed on yet. In a single-center prospective study nonadherence was assessed by electronic monitoring: percentage of doses missed and drug holidays and by three self reports: (1) a visual analogue scale (VAS): percentage of overall doses taken; (2) the Swiss HIV Cohort Study Adherence Questionnaire (SHCS-AQ): percentage of overall doses missed and drug holidays and (3) the European HIV Treatment Questionnaire (EHTQ): percentage of doses missed and drug holidays for each antiretroviral drug separately. Virologic failure prospectively assessed during 1 year, and electronic monitoring were used as reference standards. Using virologic failure as reference standard, the best results were for (1) the SHCS-AQ after electronic monitoring (sensitivity, 87.5%; specificity, 78.6%); (2) electronic monitoring (sensitivity, 75%; specificity, 85.6%), and (3) the VAS combined with the SHCS-AQ before electronic monitoring (sensitivity, 87.5%; specificity, 58.6%). The sensitivity of the complex EHTQ was less than 50%. Asking simple questions about doses taken or missed is more sensitive than complex questioning about each drug separately. Combining the VAS with the SHCS-AQ seems a feasible nonadherence measure for daily clinical practice. Self-reports perform better after electronic monitoring: their diagnostic value could be lower when given independently.

A reference case for economic evaluations in osteoarthritis: an expert consensus article from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

PubMed

Hiligsmann, Mickaël; Cooper, Cyrus; Guillemin, Francis; Hochberg, Marc C; Tugwell, Peter; Arden, Nigel; Berenbaum, Francis; Boers, Maarten; Boonen, Annelies; Branco, Jaime C; Maria-Luisa, Brandi; Bruyère, Olivier; Gasparik, Andrea; Kanis, John A; Kvien, Tore K; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Pinedo-Villanueva, Rafael; Pinto, Daniel; Reiter-Niesert, Susanne; Rizzoli, René; Rovati, Lucio C; Severens, Johan L; Silverman, Stuart; Reginster, Jean-Yves

2014-12-01

General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach. To develop a reference case specific for economic studies in OA, including the standard optimal care, with which to judge new pharmacologic and non-pharmacologic interventions. Four subgroups of an ESCEO expert working group on economic assessments (13 experts representing diverse aspects of clinical research and/or economic evaluations) were charged with producing lists of recommendations that would potentially improve the comparability of economic analyses in OA: outcome measures, comparators, costs and methodology. These proposals were discussed and refined during a face-to-face meeting in 2013. They are presented here in the format of the recommendations of the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, so that an initiative on economic analysis methodology might be consolidated with an initiative on reporting standards. Overall, three distinct reference cases are proposed, one for each hand, knee and hip OA; with diagnostic variations in the first two, giving rise to different treatment options: interphalangeal or thumb-based disease for hand OA and the presence or absence of joint malalignment for knee OA. A set of management strategies is proposed, which should be further evaluated to help establish a consensus on the "standard optimal care" in each proposed reference case. The recommendations on outcome measures, cost itemisation and methodological approaches are also provided. The ESCEO group proposes a set of disease-specific recommendations on the conduct and reporting of economic evaluations in OA that could help the standardisation and comparability of studies that evaluate therapeutic strategies of OA in terms of costs and effectiveness. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Toward Worldwide Hepcidin Assay Harmonization: Identification of a Commutable Secondary Reference Material.

PubMed

van der Vorm, Lisa N; Hendriks, Jan C M; Laarakkers, Coby M; Klaver, Siem; Armitage, Andrew E; Bamberg, Alison; Geurts-Moespot, Anneke J; Girelli, Domenico; Herkert, Matthias; Itkonen, Outi; Konrad, Robert J; Tomosugi, Naohisa; Westerman, Mark; Bansal, Sukhvinder S; Campostrini, Natascia; Drakesmith, Hal; Fillet, Marianne; Olbina, Gordana; Pasricha, Sant-Rayn; Pitts, Kelly R; Sloan, John H; Tagliaro, Franco; Weykamp, Cas W; Swinkels, Dorine W

2016-07-01

Absolute plasma hepcidin concentrations measured by various procedures differ substantially, complicating interpretation of results and rendering reference intervals method dependent. We investigated the degree of equivalence achievable by harmonization and the identification of a commutable secondary reference material to accomplish this goal. We applied technical procedures to achieve harmonization developed by the Consortium for Harmonization of Clinical Laboratory Results. Eleven plasma hepcidin measurement procedures (5 mass spectrometry based and 6 immunochemical based) quantified native individual plasma samples (n = 32) and native plasma pools (n = 8) to assess analytical performance and current and achievable equivalence. In addition, 8 types of candidate reference materials (3 concentrations each, n = 24) were assessed for their suitability, most notably in terms of commutability, to serve as secondary reference material. Absolute hepcidin values and reproducibility (intrameasurement procedure CVs 2.9%-8.7%) differed substantially between measurement procedures, but all were linear and correlated well. The current equivalence (intermeasurement procedure CV 28.6%) between the methods was mainly attributable to differences in calibration and could thus be improved by harmonization with a common calibrator. Linear regression analysis and standardized residuals showed that a candidate reference material consisting of native lyophilized plasma with cryolyoprotectant was commutable for all measurement procedures. Mathematically simulated harmonization with this calibrator resulted in a maximum achievable equivalence of 7.7%. The secondary reference material identified in this study has the potential to substantially improve equivalence between hepcidin measurement procedures and contributes to the establishment of a traceability chain that will ultimately allow standardization of hepcidin measurement results. © 2016 American Association for Clinical Chemistry.
[Standardization of the terms for Chinese herbal functions based on functional targeting].

PubMed

Xiao, Bin; Tao, Ou; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

2011-03-01

Functional analysis concisely summarizes and concentrates on the therapeutic characteristics and features of Chinese herbal medicine. Standardization of the terms for Chinese herbal functions not only plays a key role in modern research and development of Chinese herbal medicine, but also has far-reaching clinical applications. In this paper, a new method for standardizing the terms for Chinese herbal function was proposed. Firstly, functional targets were collected. Secondly, the pathological conditions and the mode of action of every functional target were determined by analyzing the references. Thirdly, the relationships between the pathological condition and the mode of action were determined based on Chinese medicine theory and data. This three-step approach allows for standardization of the terms for Chinese herbal functions. Promoting the standardization of Chinese medicine terms will benefit the overall clinical application of Chinese herbal medicine.
Archetype-based semantic integration and standardization of clinical data.

PubMed

Moner, David; Maldonado, Jose A; Bosca, Diego; Fernandez, Jesualdo T; Angulo, Carlos; Crespo, Pere; Vivancos, Pedro J; Robles, Montserrat

2006-01-01

One of the basic needs for any healthcare professional is to be able to access to clinical information of patients in an understandable and normalized way. The lifelong clinical information of any person supported by electronic means configures his/her Electronic Health Record (EHR). This information is usually distributed among several independent and heterogeneous systems that may be syntactically or semantically incompatible. The Dual Model architecture has appeared as a new proposal for maintaining a homogeneous representation of the EHR with a clear separation between information and knowledge. Information is represented by a Reference Model which describes common data structures with minimal semantics. Knowledge is specified by archetypes, which are formal representations of clinical concepts built upon a particular Reference Model. This kind of architecture is originally thought for implantation of new clinical information systems, but archetypes can be also used for integrating data of existing and not normalized systems, adding at the same time a semantic meaning to the integrated data. In this paper we explain the possible use of a Dual Model approach for semantic integration and standardization of heterogeneous clinical data sources and present LinkEHR-Ed, a tool for developing archetypes as elements for integration purposes. LinkEHR-Ed has been designed to be easily used by the two main participants of the creation process of archetypes for clinical data integration: the Health domain expert and the Information Technologies domain expert.
Quality standards for rheumatology outpatient clinic. The EXTRELLA project.

PubMed

Nolla, Joan M; Martínez, Carmen; García-Vicuña, Rosario; Seoane-Mato, Daniel; Rosario Lozano, M Piedad; Alonso, Alberto; Alperi, Mercedes; Barbazán, Ceferino; Calvo, Jaime; Delgado, Concepción; Fernández-Nebro, Antonio; Mateo, Lourdes; Pérez Sandoval, Trinidad; Pérez Venegas, José; Rodríguez Lozano, Carlos; Rosas, José

2016-01-01

In recent years, outpatient clinics have undergone extensive development. At present, patients with rheumatic diseases are mainly assisted in this area. However, the quality standards of care are poorly documented. To develop specific quality criteria and standards for an outpatient rheumatology clinic. The project was based on the two-round Delphi method. The following groups of participants took part: scientific committee (13 rheumatologists), five nominal groups (45 rheumatologists and 12 nurses) and a group of discussion formed by 9 patients. Different drafts were consecutively generated until a final document was obtained that included the standards that received a punctuation equal or over 7 in at least 70% of the participants. 148 standards were developed, grouped into the following 9 dimensions: a) structure (22), b) clinical activity and relationship with the patients (34), c) planning (7), d) levels of priority (5), e) relations with primary care physicians, with Emergency Department and with other clinical departments, f) process (26), g) nursing (13), h) teaching and research (13) and i) activity measures (8). This study established specific quality standards for rheumatology outpatient clinic. It can be a useful tool for organising this area in the Rheumatology Department and as a reference when proposing improvement measures to health administrators. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
HTML5 microdata as a semantic container for medical information exchange.

PubMed

Kimura, Eizen; Kobayashi, Shinji; Ishihara, Ken

2014-01-01

Achieving interoperability between clinical electronic medical records (EMR) systems and cloud computing systems is challenging because of the lack of a universal reference method as a standard for information exchange with a secure connection. Here we describe an information exchange scheme using HTML5 microdata, where the standard semantic container is an HTML document. We embed HL7 messages describing laboratory test results in the microdata. We also annotate items in the clinical research report with the microdata. We mapped the laboratory test result data into the clinical research report using an HL7 selector specified in the microdata. This scheme can provide secure cooperation between the cloud-based service and the EMR system.
Reference standards, judges, and comparison subjects: roles for experts in evaluating system performance.

PubMed

Hripcsak, George; Wilcox, Adam

2002-01-01

Medical informatics systems are often designed to perform at the level of human experts. Evaluation of the performance of these systems is often constrained by lack of reference standards, either because the appropriate response is not known or because no simple appropriate response exists. Even when performance can be assessed, it is not always clear whether the performance is sufficient or reasonable. These challenges can be addressed if an evaluator enlists the help of clinical domain experts. 1) The experts can carry out the same tasks as the system, and then their responses can be combined to generate a reference standard. 2)The experts can judge the appropriateness of system output directly. 3) The experts can serve as comparison subjects with which the system can be compared. These are separate roles that have different implications for study design, metrics, and issues of reliability and validity. Diagrams help delineate the roles of experts in complex study designs.
TH-A-204-00: Key Dosimetry Data - Impact of New ICRU Recommendations

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

NONE

The ICRU is currently finalizing a report on key data for radiation dosimetry. This multi-year review has resulted in a number of recommendations regarding “fundamental” data that are used in dosimetry related to radiation therapy. This educational session will explain the background for the ICRU committee’s work, the content and conclusions of the report and the impact on outputs, including NIST primary standards, ADCL calibration coefficients and clinical reference dosimetry. Parameters and beam modalities potentially affected by this report include: The mean excitation energy, I, for graphite, air, and water, The average energy required to create an ion pair inmore » dry air (commonly referred to as W/e), The uncertainty in the determination of air kerma in kV xrays The absolute value of Co-60 and Cs-137 primary standards and the dissemination of calibration coefficients, The determination of air kerma strength for Ir-192 HDR brachytherapy sources Ion chamber kQ factors for linac MV beams Ion chamber kQ factors for proton beams. The changes in reference dosimetry that would result from adoption of the ICRU recommendations are of the order of 0.5% to 1%, an effect that will not impact clinical dose delivery but will be detectable in the clinical setting. This session will also outline how worldwide metrology is coordinated through the Convention of the Meter and therefore how the international dosimetry community will proceed with adopting these recommendations so that uniformity from country to country in reference dosimetry is maintained. Timelines and communications methods will also be discussed to ensure that users, such as clinical medical physicists, are not surprised when their chamber’s calibration coefficient apparently changes. Learning Objectives: Understand the background for the ICRU committee’s work on key dosimetry data. Understand the proposed changes to key data and the impacts on reference dosimetry. Understand the methodology and timeline for adoption of the ICRU recommendations.« less
TH-A-204-01: Part I - Key Data for Ionizing-Radiation Dosimetry

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

Seltzer, S.

The ICRU is currently finalizing a report on key data for radiation dosimetry. This multi-year review has resulted in a number of recommendations regarding “fundamental” data that are used in dosimetry related to radiation therapy. This educational session will explain the background for the ICRU committee’s work, the content and conclusions of the report and the impact on outputs, including NIST primary standards, ADCL calibration coefficients and clinical reference dosimetry. Parameters and beam modalities potentially affected by this report include: The mean excitation energy, I, for graphite, air, and water, The average energy required to create an ion pair inmore » dry air (commonly referred to as W/e), The uncertainty in the determination of air kerma in kV x-rays The absolute value of Co-60 and Cs-137 primary standards and the dissemination of calibration coefficients, The determination of air kerma strength for Ir-192 HDR brachytherapy sources Ion chamber kQ factors for linac MV beams Ion chamber kQ factors for proton beams. The changes in reference dosimetry that would result from adoption of the ICRU recommendations are of the order of 0.5% to 1%, an effect that will not impact clinical dose delivery but will be detectable in the clinical setting. This session will also outline how worldwide metrology is coordinated through the Convention of the Meter and therefore how the international dosimetry community will proceed with adopting these recommendations so that uniformity from country to country in reference dosimetry is maintained. Timelines and communications methods will also be discussed to ensure that users, such as clinical medical physicists, are not surprised when their chamber’s calibration coefficient apparently changes. Learning Objectives: Understand the background for the ICRU committee’s work on key dosimetry data. Understand the proposed changes to key data and the impacts on reference dosimetry. Understand the methodology and timeline for adoption of the ICRU recommendations.« less
TH-A-204-02: Part II - Worldwide Radiation Metrology

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

McEwen, M.

The ICRU is currently finalizing a report on key data for radiation dosimetry. This multi-year review has resulted in a number of recommendations regarding “fundamental” data that are used in dosimetry related to radiation therapy. This educational session will explain the background for the ICRU committee’s work, the content and conclusions of the report and the impact on outputs, including NIST primary standards, ADCL calibration coefficients and clinical reference dosimetry. Parameters and beam modalities potentially affected by this report include: The mean excitation energy, I, for graphite, air, and water, The average energy required to create an ion pair inmore » dry air (commonly referred to as W/e), The uncertainty in the determination of air kerma in kV x-rays The absolute value of Co-60 and Cs-137 primary standards and the dissemination of calibration coefficients, The determination of air kerma strength for Ir-192 HDR brachytherapy sources Ion chamber kQ factors for linac MV beams Ion chamber kQ factors for proton beams. The changes in reference dosimetry that would result from adoption of the ICRU recommendations are of the order of 0.5% to 1%, an effect that will not impact clinical dose delivery but will be detectable in the clinical setting. This session will also outline how worldwide metrology is coordinated through the Convention of the Meter and therefore how the international dosimetry community will proceed with adopting these recommendations so that uniformity from country to country in reference dosimetry is maintained. Timelines and communications methods will also be discussed to ensure that users, such as clinical medical physicists, are not surprised when their chamber’s calibration coefficient apparently changes. Learning Objectives: Understand the background for the ICRU committee’s work on key dosimetry data. Understand the proposed changes to key data and the impacts on reference dosimetry. Understand the methodology and timeline for adoption of the ICRU recommendations.« less
The uncertainty of reference standards--a guide to understanding factors impacting uncertainty, uncertainty calculations, and vendor certifications.

PubMed

Gates, Kevin; Chang, Ning; Dilek, Isil; Jian, Huahua; Pogue, Sherri; Sreenivasan, Uma

2009-10-01

Certified solution standards are widely used in forensic toxicological, clinical/diagnostic, and environmental testing. Typically, these standards are purchased as ampouled solutions with a certified concentration. Vendors present concentration and uncertainty differently on their Certificates of Analysis. Understanding the factors that impact uncertainty and which factors have been considered in the vendor's assignment of uncertainty are critical to understanding the accuracy of the standard and the impact on testing results. Understanding these variables is also important for laboratories seeking to comply with ISO/IEC 17025 requirements and for those preparing reference solutions from neat materials at the bench. The impact of uncertainty associated with the neat material purity (including residual water, residual solvent, and inorganic content), mass measurement (weighing techniques), and solvent addition (solution density) on the overall uncertainty of the certified concentration is described along with uncertainty calculations.
CLSI-based transference of CALIPER pediatric reference intervals to Beckman Coulter AU biochemical assays.

PubMed

Abou El Hassan, Mohamed; Stoianov, Alexandra; Araújo, Petra A T; Sadeghieh, Tara; Chan, Man Khun; Chen, Yunqi; Randell, Edward; Nieuwesteeg, Michelle; Adeli, Khosrow

2015-11-01

The CALIPER program has established a comprehensive database of pediatric reference intervals using largely the Abbott ARCHITECT biochemical assays. To expand clinical application of CALIPER reference standards, the present study is aimed at transferring CALIPER reference intervals from the Abbott ARCHITECT to Beckman Coulter AU assays. Transference of CALIPER reference intervals was performed based on the CLSI guidelines C28-A3 and EP9-A2. The new reference intervals were directly verified using up to 100 reference samples from the healthy CALIPER cohort. We found a strong correlation between Abbott ARCHITECT and Beckman Coulter AU biochemical assays, allowing the transference of the vast majority (94%; 30 out of 32 assays) of CALIPER reference intervals previously established using Abbott assays. Transferred reference intervals were, in general, similar to previously published CALIPER reference intervals, with some exceptions. Most of the transferred reference intervals were sex-specific and were verified using healthy reference samples from the CALIPER biobank based on CLSI criteria. It is important to note that the comparisons performed between the Abbott and Beckman Coulter assays make no assumptions as to assay accuracy or which system is more correct/accurate. The majority of CALIPER reference intervals were transferrable to Beckman Coulter AU assays, allowing the establishment of a new database of pediatric reference intervals. This further expands the utility of the CALIPER database to clinical laboratories using the AU assays; however, each laboratory should validate these intervals for their analytical platform and local population as recommended by the CLSI. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Performance of serological tests for syphilis in sexually transmitted diseases clinics in Guangxi Autonomous Region, China: implications for syphilis surveillance and control.

PubMed

Yin, Yue-Ping; Wei, Wan-Hui; Wang, Hong-Chun; Zhu, Bang-Yong; Yu, Yan-Hua; Chen, Xiang-Sheng; Peeling, Rosanna W; Cohen, Myron S

2009-03-01

China is experiencing a growing syphilis epidemic. Individuals are currently screened and cases are confirmed using traditional serological testing methods. A total of 11 558 serum specimens from patients at 14 sexually transmitted diseases (STD) clinics at provincial, prefecture and county levels in Guangxi Autonomous Region were tested at local clinics using the toluidine red unheated serum test (TRUST) and the SD Bioline Syphilis 3.0 Treponema Pallidum (SD-TP) test and then transported to the National STD Reference Laboratory for TRUST and confirmatory Treponema pallidum particle assay (TPPA) testing. In local clinics, 13.2% of specimens were TRUST positive and 12.8% were TRUST and SD-TP positive. At the Reference Laboratory, 15.4% of specimens were TRUST positive and 11.8% were TRUST and TPPA positive. Local clinics showed a significantly higher prevalence of active syphilis compared with results from the Reference Laboratory (12.8 v. 11.8%, chi(2) = 4.59, P = 0.03). The local TRUST tests had consistent results with Reference Laboratory tests qualitatively among 96.2% of the specimens and quantitatively among 95.5% of the specimens. The algorithm of TRUST screening and then SD-TP confirmation among positive TRUST specimens at local STD clinics had 96.6% sensitivity and 99.3% specificity in diagnosing active syphilis compared with the 'gold standard' based on TRUST and TPPA positivity at the Reference Laboratory (positive predictive value 95.1% and negative predictive value 99.5%). The TRUST screening and SD-TP confirmation in combination can be used at local STD clinics for the efficient diagnosis of serologically active syphilis. However, continuing capacity building and quality assurance remain critical in ensuring the quality of syphilis diagnosis at local clinics.
Reading Comprehension Assessment through Retelling: Performance Profiles of Children with Dyslexia and Language-Based Learning Disability

PubMed Central

Kida, Adriana de S. B.; de Ávila, Clara R. B.; Capellini, Simone A.

2016-01-01

Purpose: To study reading comprehension performance profiles of children with dyslexia as well as language-based learning disability (LBLD) by means of retelling tasks. Method: One hundred and five children from 2nd to 5th grades of elementary school were gathered into six groups: Dyslexia group (D; n = 19), language-based learning disability group (LBLD; n = 16); their respective control groups paired according to different variables – age, gender, grade and school system (public or private; D-control and LBLD-control); and other control groups paired according to different reading accuracy (D-accuracy; LBLD-accuracy). All of the children read an expository text and orally retold the story as they understood it. The analysis quantified propositions (main ideas and details) and retold links. A retelling reference standard (3–0) was also established from the best to the worst performance. We compared both clinical groups (D and LBLD) with their respective control groups by means of Mann–Whitney tests. Results: D showed the same total of propositions, links and reference standards as D-control, but performed better than D-accuracy in macro structural (total of links) and super structural (retelling reference standard) measures. Results suggest that dyslexic children are able to use their linguistic competence and their own background knowledge to minimize the effects of their decoding deficit, especially at the highest text processing levels. LBLD performed worse than LBLD-control in all of the retelling measures and LBLD showed worse performance than LBLD-accuracy in the total retold links and retelling reference standard. Those results suggest that both decoding and linguistic difficulties affect reading comprehension. Moreover, the linguistic deficits presented by LBLD students do not allow these pupils to perform as competently in terms of text comprehension as the children with dyslexia do. Thus, failure in the macro and super-structural information processing of the expository text were evidenced. Conclusion: Each clinical group showed a different retelling profile. Such findings support the view that there are differences between these two clinical populations in the non-phonological dimensions of language. PMID:27313551
Reference intervals: current status, recent developments and future considerations.

PubMed

Ozarda, Yesim

2016-01-01

Reliable and accurate reference intervals (RIs) for laboratory analyses are an integral part of the process of correct interpretation of clinical laboratory test results. RIs given in laboratory reports have an important role in aiding the clinician in interpreting test results in reference to values for healthy populations. Since the 1980s, the International Federation of Clinical Chemistry (IFCC) has been proactive in establishing recommendations to clarify the true significance of the term 'RIs, to select the appropriate reference population and statistically analyse the data. The C28-A3 guideline published by the Clinical and Laboratory Standards Institute (CLSI) and IFCC is still the most widely-used source of reference in this area. In recent years, protocols additional to the Guideline have been published by the IFCC, Committee on Reference Intervals and Decision Limits (C-RIDL), including all details of multicenter studies on RIs to meet the requirements in this area. Multicentric RIs studies are the most important development in the area of RIs. Recently, the C-RIDL has performed many multicentric studies to obtain common RIs. Confusion of RIs and clinical decision limits (CDLs) remains an issue and pediatric and geriatric age groups are a significant problem. For future studies of RIs, the genetic effect would seem to be the most challenging area.  The aim of the review is to present the current theory and practice of RIs, with special emphasis given to multicenter RIs studies, RIs studies for pediatric and geriatric age groups, clinical decision limits and partitioning by genetic effects on RIs.
Reference intervals: current status, recent developments and future considerations

PubMed Central

Ozarda, Yesim

2016-01-01

Reliable and accurate reference intervals (RIs) for laboratory analyses are an integral part of the process of correct interpretation of clinical laboratory test results. RIs given in laboratory reports have an important role in aiding the clinician in interpreting test results in reference to values for healthy populations. Since the 1980s, the International Federation of Clinical Chemistry (IFCC) has been proactive in establishing recommendations to clarify the true significance of the term ‘RIs, to select the appropriate reference population and statistically analyse the data. The C28-A3 guideline published by the Clinical and Laboratory Standards Institute (CLSI) and IFCC is still the most widely-used source of reference in this area. In recent years, protocols additional to the Guideline have been published by the IFCC, Committee on Reference Intervals and Decision Limits (C-RIDL), including all details of multicenter studies on RIs to meet the requirements in this area. Multicentric RIs studies are the most important development in the area of RIs. Recently, the C-RIDL has performed many multicentric studies to obtain common RIs. Confusion of RIs and clinical decision limits (CDLs) remains an issue and pediatric and geriatric age groups are a significant problem. For future studies of RIs, the genetic effect would seem to be the most challenging area. The aim of the review is to present the current theory and practice of RIs, with special emphasis given to multicenter RIs studies, RIs studies for pediatric and geriatric age groups, clinical decision limits and partitioning by genetic effects on RIs. PMID:26981015
An administrative data validation study of the accuracy of algorithms for identifying rheumatoid arthritis: the influence of the reference standard on algorithm performance.

PubMed

Widdifield, Jessica; Bombardier, Claire; Bernatsky, Sasha; Paterson, J Michael; Green, Diane; Young, Jacqueline; Ivers, Noah; Butt, Debra A; Jaakkimainen, R Liisa; Thorne, J Carter; Tu, Karen

2014-06-23

We have previously validated administrative data algorithms to identify patients with rheumatoid arthritis (RA) using rheumatology clinic records as the reference standard. Here we reassessed the accuracy of the algorithms using primary care records as the reference standard. We performed a retrospective chart abstraction study using a random sample of 7500 adult patients under the care of 83 family physicians contributing to the Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Using physician-reported diagnoses as the reference standard, we computed and compared the sensitivity, specificity, and predictive values for over 100 administrative data algorithms for RA case ascertainment. We identified 69 patients with RA for a lifetime RA prevalence of 0.9%. All algorithms had excellent specificity (>97%). However, sensitivity varied (75-90%) among physician billing algorithms. Despite the low prevalence of RA, most algorithms had adequate positive predictive value (PPV; 51-83%). The algorithm of "[1 hospitalization RA diagnosis code] or [3 physician RA diagnosis codes with ≥1 by a specialist over 2 years]" had a sensitivity of 78% (95% CI 69-88), specificity of 100% (95% CI 100-100), PPV of 78% (95% CI 69-88) and NPV of 100% (95% CI 100-100). Administrative data algorithms for detecting RA patients achieved a high degree of accuracy amongst the general population. However, results varied slightly from our previous report, which can be attributed to differences in the reference standards with respect to disease prevalence, spectrum of disease, and type of comparator group.
Defining overweight and obesity among Greek children living in Thessaloniki: International versus local reference standards.

PubMed

Christoforidis, A; Dimitriadou, M; Papadopolou, E; Stilpnopoulou, D; Katzos, G; Athanassiou-Metaxa, M

2011-04-01

Body Mass Index (BMI) offers a simple and reasonable measure of obesity that, with the use of the appropriate reference, can help in the early detection of children with weight problems. Our aim was to compare the two most commonly used international BMI references and the national Greek BMI reference in identifying Greek children being overweight and obese. A group of 1557 children (820 girls and 737 boys, mean age: 11.42 ± 3.51 years) were studied. Weight and height was measured using standard methods, and BMI was calculated. Overweight and obesity were determined using the International Obesity Task Force (IOTF) standards, the Centers for Disease Control and Prevention (CDC) BMI-forage curves and the most recent Greek BMI-for-age curves. RESULTS showed that the IOTF's cut-off limits identifies a significantly higher prevalence of overweight (22.4%) compared with both the CDC's (11.8%, p=0.03) and the Greek's (7.4%, p=0.002) cut-off limits. However, the prevalence of obesity was generally increased when it was determined using the CDC's cut-off limits (13.9%) compared to the prevalence calculated with both the IOTF's (6.5%, p=0.05) and the Greek's (6.9%, n.s.) cut off limits. The use of the national Greek reference standards for BMI underestimates the true prevalence of overweight and obesity. On the contrary, both the IOTF and the CDC standards, although independently, detect an increased number of overweight and obese children and thus they should be adopted in the clinical practice for an earlier identification and a timelier intervention.
Thoracic surgeons' perception of frail behavior in videos of standardized patients.

PubMed

Ferguson, Mark K; Thompson, Katherine; Huisingh-Scheetz, Megan; Farnan, Jeanne; Hemmerich, Josh A; Slawinski, Kris; Acevedo, Julissa; Lee, Sang Mee; Rojnica, Marko; Small, Stephen

2014-01-01

Frailty is a predictor of poor outcomes following many types of operations. We measured thoracic surgeons' accuracy in assessing patient frailty using videos of standardized patients demonstrating signs of physical frailty. We compared their performance to that of geriatrics specialists. We developed an anchored scale for rating degree of frailty. Reference categories were assigned to 31 videos of standardized patients trained to exhibit five levels of activity ranging from "vigorous" to "frail." Following an explanation of frailty, thoracic surgeons and geriatrics specialists rated the videos. We evaluated inter-rater agreement and tested differences between ratings and reference categories. The influences of clinical specialty, clinical experience, and self-rated expertise were examined. Inter-rater rank correlation among all participants was high (Kendall's W 0.85) whereas exact agreement (Fleiss' kappa) was only moderate (0.47). Better inter-rater agreement was demonstrated for videos exhibiting extremes of behavior. Exact agreement was better for thoracic surgeons (n = 32) than geriatrics specialists (n = 9; p = 0.045), whereas rank correlation was similar for both groups. More clinical years of experience and self-reported expertise were not associated with better inter-rater agreement. Videos of standardized patients exhibiting varying degrees of frailty are rated with internal consistency by thoracic surgeons as accurately as geriatrics specialists when referenced to an anchored scale. Ratings were less consistent for moderate degrees of frailty, suggesting that physicians require training to recognize early frailty. Such videos may be useful in assessing and teaching frailty recognition.
Exploring the utility of narrative analysis in diagnostic decision making: picture-bound reference, elaboration, and fetal alcohol spectrum disorders.

PubMed

Thorne, John C; Coggins, Truman E; Carmichael Olson, Heather; Astley, Susan J

2007-04-01

To evaluate classification accuracy and clinical feasibility of a narrative analysis tool for identifying children with a fetal alcohol spectrum disorder (FASD). Picture-elicited narratives generated by 16 age-matched pairs of school-aged children (FASD vs. typical development [TD]) were coded for semantic elaboration and reference strategy by judges who were unaware of age, gender, and group membership of the participants. Receiver operating characteristic (ROC) curves were used to examine the classification accuracy of the resulting set of narrative measures for making 2 classifications: (a) for the 16 children diagnosed with FASD, low performance (n = 7) versus average performance (n = 9) on a standardized expressive language task and (b) FASD (n = 16) versus TD (n = 16). Combining the rates of semantic elaboration and pragmatically inappropriate reference perfectly matched a classification based on performance on the standardized language task. More importantly, the rate of ambiguous nominal reference was highly accurate in classifying children with an FASD regardless of their performance on the standardized language task (area under the ROC curve = .863, confidence interval = .736-.991). Results support further study of the diagnostic utility of narrative analysis using discourse level measures of elaboration and children's strategic use of reference.

Malaysian growth centiles for children under six years old.

PubMed

Bong, Yiibonn; Shariff, Asma Ahmad; Mohamed, Abdul Majid; Merican, Amir Feisal

2015-03-01

Growth references are useful for the screening, assessment and monitoring of individual children as well as for evaluating various growth promoting interventions that could possibly affect a child in early life. To determine the growth centiles of Malaysian children and to establish contemporary cross-sectional growth reference charts for height and weight from birth to 6 years of age based on a representative sample of children from Malaysia. Gender- and age-specific centile curves for height and weight were derived using the Cole's LMS method. Data for this study were retrieved from Malaysian government health clinics using a two-stage stratified random sampling technique. Assessment of nutritional status was done with the SD scores (Z-scores) of WHO 2006 standards. Boys were found to be taller and heavier than girls in this study. The median length of Malaysian children was higher than the WHO 2006 standards and CDC 2000 reference. The overall prevalence of stunting and underweight were 8.3% and 9.3%, respectively. This study presents the first large-scale initiative for local reference charts. The growth reference would enable the growth assessment of a Malaysian child compared to the average growth of children in the country. It is suggested that the use of WHO 2006 Child Growth Standards should be complemented with local reference charts for a more wholesome growth assessment.
Impact of a dedicated cancer-associated thrombosis service on clinical outcomes: a mixed-methods evaluation of a clinical improvement exercise.

PubMed

Noble, Simon; Pease, Nikki; Sui, Jessica; Davies, James; Lewis, Sarah; Malik, Usman; Alikhan, Raza; Prout, Hayley; Nelson, Annmarie

2016-11-28

Cancer-associated thrombosis (CAT) complex condition, which may present to any healthcare professional and at any point during the cancer journey. As such, patients may be managed by a number of specialties, resulting in inconsistent practice and suboptimal care. We describe the development of a dedicated CAT service and its evaluation. Specialist cancer centre, district general hospital and primary care. Patients with CAT and their referring clinicians. A cross specialty team developed a dedicated CAT service , including clear referral pathways, consistent access to medicines, patient's information and a specialist clinic. The service was evaluated using a mixed-methods evaluation , including audits of clinical practice, clinical outcomes, staff surveys and qualitative interviewing of patients and healthcare professionals. Data from 457 consecutive referrals over an 18-month period were evaluated. The CAT service has led to an 88% increase in safe and consistent community prescribing of low-molecular-weight heparin, with improved access to specialist advice and information. Patients reported improved understanding of their condition, enabling better self-management as well as better access to support and information. Referring clinicians reported better care standards for their patients with improved access to expertise and appropriate management. A dedicated CAT service improves overall standards of care and is viewed positively by patients and clinicians alike. Further health economic evaluation would enhance the case for establishing this as the standard model of care. 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/.
Standardization, evaluation and early-phase method validation of an analytical scheme for batch-consistency N-glycosylation analysis of recombinant produced glycoproteins.

PubMed

Zietze, Stefan; Müller, Rainer H; Brecht, René

2008-03-01

In order to set up a batch-to-batch-consistency analytical scheme for N-glycosylation analysis, several sample preparation steps including enzyme digestions and fluorophore labelling and two HPLC-methods were established. The whole method scheme was standardized, evaluated and validated according to the requirements on analytical testing in early clinical drug development by usage of a recombinant produced reference glycoprotein (RGP). The standardization of the methods was performed by clearly defined standard operation procedures. During evaluation of the methods, the major interest was in the loss determination of oligosaccharides within the analytical scheme. Validation of the methods was performed with respect to specificity, linearity, repeatability, LOD and LOQ. Due to the fact that reference N-glycan standards were not available, a statistical approach was chosen to derive accuracy from the linearity data. After finishing the validation procedure, defined limits for method variability could be calculated and differences observed in consistency analysis could be separated into significant and incidental ones.
Rapid Bacterial Whole-Genome Sequencing to Enhance Diagnostic and Public Health Microbiology

PubMed Central

Reuter, Sandra; Ellington, Matthew J.; Cartwright, Edward J. P.; Köser, Claudio U.; Török, M. Estée; Gouliouris, Theodore; Harris, Simon R.; Brown, Nicholas M.; Holden, Matthew T. G.; Quail, Mike; Parkhill, Julian; Smith, Geoffrey P.; Bentley, Stephen D.; Peacock, Sharon J.

2014-01-01

IMPORTANCE The latest generation of benchtop DNA sequencing platforms can provide an accurate whole-genome sequence (WGS) for a broad range of bacteria in less than a day. These could be used to more effectively contain the spread of multidrug-resistant pathogens. OBJECTIVE To compare WGS with standard clinical microbiology practice for the investigation of nosocomial outbreaks caused by multidrug-resistant bacteria, the identification of genetic determinants of antimicrobial resistance, and typing of other clinically important pathogens. DESIGN, SETTING, AND PARTICIPANTS A laboratory-based study of hospital inpatients with a range of bacterial infections at Cambridge University Hospitals NHS Foundation Trust, a secondary and tertiary referral center in England, comparing WGS with standard diagnostic microbiology using stored bacterial isolates and clinical information. MAIN OUTCOMES AND MEASURES Specimens were taken and processed as part of routine clinical care, and cultured isolates stored and referred for additional reference laboratory testing as necessary. Isolates underwent DNA extraction and library preparation prior to sequencing on the Illumina MiSeq platform. Bioinformatic analyses were performed by persons blinded to the clinical, epidemiologic, and antimicrobial susceptibility data. RESULTS We investigated 2 putative nosocomial outbreaks, one caused by vancomycin-resistant Enterococcus faecium and the other by carbapenem-resistant Enterobacter cloacae; WGS accurately discriminated between outbreak and nonoutbreak isolates and was superior to conventional typing methods. We compared WGS with standard methods for the identification of the mechanism of carbapenem resistance in a range of gram-negative bacteria (Acinetobacter baumannii, E cloacae, Escherichia coli, and Klebsiella pneumoniae). This demonstrated concordance between phenotypic and genotypic results, and the ability to determine whether resistance was attributable to the presence of carbapenemases or other resistance mechanisms. Whole-genome sequencing was used to recapitulate reference laboratory typing of clinical isolates of Neisseria meningitidis and to provide extended phylogenetic analyses of these. CONCLUSIONS AND RELEVANCE The speed, accuracy, and depth of information provided by WGS platforms to confirm or refute outbreaks in hospitals and the community, and to accurately define transmission of multidrug-resistant and other organisms, represents an important advance. PMID:23857503
Methodologic quality and relevance of references in pharmaceutical advertisements in a Canadian medical journal.

PubMed

Lexchin, J; Holbrook, A

1994-07-01

To evaluate the methodologic quality and relevance of references in pharmaceutical advertisements in the Canadian Medical Association Journal (CMAJ). Analytic study. All 114 references cited in the first 22 distinct pharmaceutical advertisements in volume 146 of CMAJ. Mean methodologic quality score (modified from the 6-point scale used to assess articles in the American College of Physicians' Journal Club) and mean relevance score (based on a new 5-point scale) for all references in each advertisement. Twenty of the 22 companies responded, sending 78 (90%) of the 87 references requested. The mean methodologic quality score was 58% (95% confidence limits [CL] 51% and 65%) and the mean relevance score 76% (95% CL 72% and 80%). The two mean scores were statistically lower than the acceptable score of 80% (p < 0.05), and the methodologic quality score was outside the preset clinically significant difference of 15%. The poor rating for methodologic quality was primarily because of the citation of references to low-quality review articles and "other" sources (i.e., other than reports of clinical trials). Half of the advertisements had a methodologic quality score of less than 65%, but only five had a relevance score of less than 65%. Although the relevance of most of the references was within minimal acceptable limits, the methodologic quality was often unacceptable. Because advertisements are an important part of pharmaceutical marketing and education, we suggest that companies develop written standards for their advertisements and monitor their advertisements for adherence to these standards. We also suggest that the Pharmaceutical Advertising Advisory Board develop more stringent guidelines for advertising and that it enforce these guidelines in a consistent, rigorous fashion.
Methodologic quality and relevance of references in pharmaceutical advertisements in a Canadian medical journal.

PubMed Central

Lexchin, J; Holbrook, A

1994-01-01

OBJECTIVE: To evaluate the methodologic quality and relevance of references in pharmaceutical advertisements in the Canadian Medical Association Journal (CMAJ). DESIGN: Analytic study. DATA SOURCE: All 114 references cited in the first 22 distinct pharmaceutical advertisements in volume 146 of CMAJ. MAIN OUTCOME MEASURES: Mean methodologic quality score (modified from the 6-point scale used to assess articles in the American College of Physicians' Journal Club) and mean relevance score (based on a new 5-point scale) for all references in each advertisement. MAIN RESULTS: Twenty of the 22 companies responded, sending 78 (90%) of the 87 references requested. The mean methodologic quality score was 58% (95% confidence limits [CL] 51% and 65%) and the mean relevance score 76% (95% CL 72% and 80%). The two mean scores were statistically lower than the acceptable score of 80% (p < 0.05), and the methodologic quality score was outside the preset clinically significant difference of 15%. The poor rating for methodologic quality was primarily because of the citation of references to low-quality review articles and "other" sources (i.e., other than reports of clinical trials). Half of the advertisements had a methodologic quality score of less than 65%, but only five had a relevance score of less than 65%. CONCLUSIONS: Although the relevance of most of the references was within minimal acceptable limits, the methodologic quality was often unacceptable. Because advertisements are an important part of pharmaceutical marketing and education, we suggest that companies develop written standards for their advertisements and monitor their advertisements for adherence to these standards. We also suggest that the Pharmaceutical Advertising Advisory Board develop more stringent guidelines for advertising and that it enforce these guidelines in a consistent, rigorous fashion. PMID:8004560
Metrological approaches to organic chemical purity: primary reference materials for vitamin D metabolites.

PubMed

Nelson, Michael A; Bedner, Mary; Lang, Brian E; Toman, Blaza; Lippa, Katrice A

2015-11-01

Given the critical role of pure, organic compound primary reference standards used to characterize and certify chemical Certified Reference Materials (CRMs), it is essential that associated mass purity assessments be fit-for-purpose, represented by an appropriate uncertainty interval, and metrologically sound. The mass fraction purities (% g/g) of 25-hydroxyvitamin D (25(OH)D) reference standards used to produce and certify values for clinical vitamin D metabolite CRMs were investigated by multiple orthogonal quantitative measurement techniques. Quantitative (1)H-nuclear magnetic resonance spectroscopy (qNMR) was performed to establish traceability of these materials to the International System of Units (SI) and to directly assess the principal analyte species. The 25(OH)D standards contained volatile and water impurities, as well as structurally-related impurities that are difficult to observe by chromatographic methods or to distinguish from the principal 25(OH)D species by one-dimensional NMR. These impurities have the potential to introduce significant biases to purity investigations in which a limited number of measurands are quantified. Combining complementary information from multiple analytical methods, using both direct and indirect measurement techniques, enabled mitigation of these biases. Purities of 25(OH)D reference standards and associated uncertainties were determined using frequentist and Bayesian statistical models to combine data acquired via qNMR, liquid chromatography with UV absorbance and atmospheric pressure-chemical ionization mass spectrometric detection (LC-UV, LC-ACPI-MS), thermogravimetric analysis (TGA), and Karl Fischer (KF) titration.
Description and status update on GELLO: a proposed standardized object-oriented expression language for clinical decision support.

PubMed

Sordo, Margarita; Boxwala, Aziz A; Ogunyemi, Omolola; Greenes, Robert A

2004-01-01

A major obstacle to sharing computable clinical knowledge is the lack of a common language for specifying expressions and criteria. Such a language could be used to specify decision criteria, formulae, and constraints on data and action. Al-though the Arden Syntax addresses this problem for clinical rules, its generalization to HL7's object-oriented data model is limited. The GELLO Expression language is an object-oriented language used for expressing logical conditions and computations in the GLIF3 (GuideLine Interchange Format, v. 3) guideline modeling language. It has been further developed under the auspices of the HL7 Clinical Decision Support Technical Committee, as a proposed HL7 standard., GELLO is based on the Object Constraint Language (OCL), because it is vendor-independent, object-oriented, and side-effect-free. GELLO expects an object-oriented data model. Although choice of model is arbitrary, standardization is facilitated by ensuring that the data model is compatible with the HL7 Reference Information Model (RIM).
Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2014 edition.

PubMed

Minakami, Hisanori; Maeda, Tsugio; Fujii, Tomoyuki; Hamada, Hiromi; Iitsuka, Yoshinori; Itakura, Atsuo; Itoh, Hiroaki; Iwashita, Mitsutoshi; Kanagawa, Takeshi; Kanai, Makoto; Kasuga, Yoshio; Kawabata, Masakiyo; Kobayashi, Kosuke; Kotani, Tomomi; Kudo, Yoshiki; Makino, Yasuo; Matsubara, Shigeki; Matsuda, Hideo; Miura, Kiyonori; Murakoshi, Takeshi; Murotsuki, Jun; Ohkuchi, Akihide; Ohno, Yasumasa; Ohshiba, Yoko; Satoh, Shoji; Sekizawa, Akihiko; Sugiura, Mayumi; Suzuki, Shunji; Takahashi, Tsuneo; Tsukahara, Yuki; Unno, Nobuya; Yoshikawa, Hiroyuki

2014-06-01

The 'Clinical Guidelines for Obstetrical Practice, 2011 edition' were revised and published as a 2014 edition (in Japanese) in April 2014 by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction of burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. The number of Clinical Questions and Answers items increased from 87 in the 2011 edition to 104 in the 2014 edition. The Japanese 2014 version included a Discussion, a List of References, and some Tables and Figures following the Answers to the 104 Clinical Questions; these additional sections covered common problems and questions encountered in obstetrical practice, helping Japanese readers to achieve a comprehensive understanding. Each answer with a recommendation level of A, B or C was prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' was weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 104 Clinical Questions and Answers items, with the omission of the Discussion, List of References, and Tables and Figures, are presented herein to promote a better understanding among English readers of the current standard care practices for pregnant women in Japan. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.
Using a Standardized Clinical Quantitative Sensory Testing Battery to Judge the Clinical Relevance of Sensory Differences Between Adjacent Body Areas.

PubMed

Dimova, Violeta; Oertel, Bruno G; Lötsch, Jörn

2017-01-01

Skin sensitivity to sensory stimuli varies among different body areas. A standardized clinical quantitative sensory testing (QST) battery, established for the diagnosis of neuropathic pain, was used to assess whether the magnitude of differences between test sites reaches clinical significance. Ten different sensory QST measures derived from thermal and mechanical stimuli were obtained from 21 healthy volunteers (10 men) and used to create somatosensory profiles bilateral from the dorsum of the hands (the standard area for the assessment of normative values for the upper extremities as proposed by the German Research Network on Neuropathic Pain) and bilateral at volar forearms as a neighboring nonstandard area. The parameters obtained were statistically compared between test sites. Three of the 10 QST parameters differed significantly with respect to the "body area," that is, warmth detection, thermal sensory limen, and mechanical pain thresholds. After z-transformation and interpretation according to the QST battery's standard instructions, 22 abnormal values were obtained at the hand. Applying the same procedure to parameters assessed at the nonstandard site forearm, that is, z-transforming them to the reference values for the hand, 24 measurements values emerged as abnormal, which was not significantly different compared with the hand (P=0.4185). Sensory differences between neighboring body areas are statistically significant, reproducing prior knowledge. This has to be considered in scientific assessments where a small variation of the tested body areas may not be an option. However, the magnitude of these differences was below the difference in sensory parameters that is judged as abnormal, indicating a robustness of the QST instrument against protocol deviations with respect to the test area when using the method of comparison with a 95 % confidence interval of a reference dataset.
Reference values assessment in a Mediterranean population for small dense low-density lipoprotein concentration isolated by an optimized precipitation method.

PubMed

Fernández-Cidón, Bárbara; Padró-Miquel, Ariadna; Alía-Ramos, Pedro; Castro-Castro, María José; Fanlo-Maresma, Marta; Dot-Bach, Dolors; Valero-Politi, José; Pintó-Sala, Xavier; Candás-Estébanez, Beatriz

2017-01-01

High serum concentrations of small dense low-density lipoprotein cholesterol (sd-LDL-c) particles are associated with risk of cardiovascular disease (CVD). Their clinical application has been hindered as a consequence of the laborious current method used for their quantification. Optimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population. Forty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg 2+ precipitation method. sd-LDL-c concentration was calculated by subtracting high-density lipoprotein cholesterol (HDL-c) from the total cholesterol measured in the supernatant. This method was compared with the reference method (ultracentrifugation). Reference values were estimated according to the Clinical and Laboratory Standards Institute and The International Federation of Clinical Chemistry and Laboratory Medicine recommendations. sd-LDL-c concentration was measured in serums from 79 subjects with no lipid metabolism abnormalities. The Passing-Bablok regression equation is y = 1.52 (0.72 to 1.73) + 0.07 x (-0.1 to 0.13), demonstrating no significant statistical differences between the modified precipitation method and the ultracentrifugation reference method. Similarly, no differences were detected when considering only sd-LDL-c from dyslipidemic patients, since the modifications added to the precipitation method facilitated the proper sedimentation of triglycerides and other lipoproteins. The reference interval for sd-LDL-c concentration estimated in a Mediterranean population was 0.04-0.47 mmol/L. An optimization of the heparin-Mg 2+ precipitation method for sd-LDL particle isolation was performed, and reference intervals were established in a Spanish Mediterranean population. Measured values were equivalent to those obtained with the reference method, assuring its clinical application when tested in both normolipidemic and dyslipidemic subjects.
Construction of a New Growth References for China Based on Urban Chinese Children: Comparison with the WHO Growth Standards

PubMed Central

Zong, Xin-Nan; Li, Hui

2013-01-01

Introduction Growth references for Chinese children should be updated due to the positive secular growth trends and the progress of the smoothing techniques. Human growth differs among the various ethnic groups, so comparison of the China references with the WHO standards helps to understand such differences. Methods The China references, including weight, length/height, head circumference, weight-for-length/height and body mass index (BMI) aged 0–18 years, were constructed based on 69,760 urban infants and preschool children under 7 years and 24,542 urban school children aged 6–20 years derived from two cross-sectional national surveys. The Cole’s LMS method is employed for smoothing the growth curves. Results The merged data sets resulted in a smooth transition at age 6–7 years and continuity of curves from 0 to 18 years. Varying differences were found on the empirical standard deviation (SD) curves in each indicator at nearly all ages between China and WHO. The most noticeable differences occurred in genders, final height and boundary centiles curves. Chinese boys’ weight is strikingly heavier than that of the WHO at age 6–10 years. The height is taller than that of the WHO for boys below 15 years and for girls below 13, but is significantly lower when boys over 15 years and girls over 13. BMI is generally higher than that of the WHO for boys at age 6–16 years but appreciably lower for girls at 3–18 years. Conclusions The differences between China and WHO are mainly caused by the reference populations of different ethnic backgrounds. For practitioners, the choices of the standards/references depend on the population to be assessed and the purpose of the study. The new China references could be applied to facilitate the standardization assessment of growth and nutrition for Chinese children and adolescents in clinical pediatric and public health. PMID:23527219
Measurement uncertainty: Friend or foe?

PubMed

Infusino, Ilenia; Panteghini, Mauro

2018-02-02

The definition and enforcement of a reference measurement system, based on the implementation of metrological traceability of patients' results to higher order reference methods and materials, together with a clinically acceptable level of measurement uncertainty, are fundamental requirements to produce accurate and equivalent laboratory results. The uncertainty associated with each step of the traceability chain should be governed to obtain a final combined uncertainty on clinical samples fulfilling the requested performance specifications. It is important that end-users (i.e., clinical laboratory) may know and verify how in vitro diagnostics (IVD) manufacturers have implemented the traceability of their calibrators and estimated the corresponding uncertainty. However, full information about traceability and combined uncertainty of calibrators is currently very difficult to obtain. Laboratory professionals should investigate the need to reduce the uncertainty of the higher order metrological references and/or to increase the precision of commercial measuring systems. Accordingly, the measurement uncertainty should not be considered a parameter to be calculated by clinical laboratories just to fulfil the accreditation standards, but it must become a key quality indicator to describe both the performance of an IVD measuring system and the laboratory itself. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Recommendations for designing and conducting veterinary clinical pathology biologic variation studies.

PubMed

Freeman, Kathleen P; Baral, Randolph M; Dhand, Navneet K; Nielsen, Søren Saxmose; Jensen, Asger L

2017-06-01

The recent creation of a veterinary clinical pathology biologic variation website has highlighted the need to provide recommendations for future studies of biologic variation in animals in order to help standardize and improve the quality of published information and to facilitate review and selection of publications as standard references. The following recommendations are provided in the format and order commonly found in veterinary publications. A checklist is provided to aid in planning, implementing, and evaluating veterinary studies on biologic variation (Appendix S1). These recommendations provide a valuable resource for clinicians, laboratorians, and researchers interested in conducting studies of biologic variation and in determining the quality of studies of biologic variation in veterinary laboratory testing. © 2017 American Society for Veterinary Clinical Pathology.
ASVCP guidelines: quality assurance for point-of-care testing in veterinary medicine.

PubMed

Flatland, Bente; Freeman, Kathleen P; Vap, Linda M; Harr, Kendal E

2013-12-01

Point-of-care testing (POCT) refers to any laboratory testing performed outside the conventional reference laboratory and implies close proximity to patients. Instrumental POCT systems consist of small, handheld or benchtop analyzers. These have potential utility in many veterinary settings, including private clinics, academic veterinary medical centers, the community (eg, remote area veterinary medical teams), and for research applications in academia, government, and industry. Concern about the quality of veterinary in-clinic testing has been expressed in published veterinary literature; however, little guidance focusing on POCT is available. Recognizing this void, the ASVCP formed a subcommittee in 2009 charged with developing quality assurance (QA) guidelines for veterinary POCT. Guidelines were developed through literature review and a consensus process. Major recommendations include (1) taking a formalized approach to POCT within the facility, (2) use of written policies, standard operating procedures, forms, and logs, (3) operator training, including periodic assessment of skills, (4) assessment of instrument analytical performance and use of both statistical quality control and external quality assessment programs, (5) use of properly established or validated reference intervals, (6) and ensuring accurate patient results reporting. Where possible, given instrument analytical performance, use of a validated 13s control rule for interpretation of control data is recommended. These guidelines are aimed at veterinarians and veterinary technicians seeking to improve management of POCT in their clinical or research setting, and address QA of small chemistry and hematology instruments. These guidelines are not intended to be all-inclusive; rather, they provide a minimum standard for maintenance of POCT instruments in the veterinary setting. © 2013 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.
Poor symptom and performance validity in regularly referred Hospital outpatients: Link with standard clinical measures, and role of incentives.

PubMed

Dandachi-FitzGerald, Brechje; van Twillert, Björn; van de Sande, Peter; van Os, Yindee; Ponds, Rudolf W H M

2016-05-30

We investigated the frequency of symptom validity test (SVT) failure and its clinical correlates in a large, heterogeneous sample of hospital outpatients referred for psychological assessment for clinical purposes. We studied patients (N=469), who were regularly referred for assessment to the psychology departments of five hospitals. Background characteristics, including information about incentives, were obtained with a checklist completed by the clinician. As a measure of over-reporting, the Structured Inventory of Malingered Symptomatology (SIMS) was administered to all patients. The Amsterdam Short-Term Memory test (ASTM), a cognitive underperformance measure, was only administered to patients who were referred for a neuropsychological assessment. Symptom over-reporting occurred in a minority of patients, ranging from 12% to 19% in the main diagnostic patient groups. Patients with morbid obesity had a low rate of over-reporting (1%). The SIMS was positively associated with levels of self-reported psychological symptoms. Cognitive underperformance occurred in 29.3% of the neuropsychological assessments. The ASTM was negatively associated with memory test performance. We found no association between SVT failure and financial incentives. Our results support the recommendation to routinely evaluate symptom validity in clinical assessments of hospital patients. The dynamics behind invalid symptom reporting need to be further elucidated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
FDA's Approach to Regulating Biosimilars.

PubMed

Lemery, Steven J; Ricci, M Stacey; Keegan, Patricia; McKee, Amy E; Pazdur, Richard

2017-04-15

The Biologics Price Competition and Innovation (BPCI) Act, enacted as part of the Affordable Care Act, created a new licensure pathway for biological products demonstrated to be biosimilar with or interchangeable with an FDA-licensed biological product (the "reference product"). The FDA's approach to the regulation of biosimilars is based on the requirements set forth in the BPCI Act. A biosimilar product is highly similar to the reference product, notwithstanding minor differences in clinically inactive components, and there are no clinically meaningful differences between products in terms of safety, purity, and potency. The foundation of a biosimilar development program is an analytic similarity assessment that directly compares the structural/physiochemical and functional properties of the proposed biosimilar with the reference product. Data from clinical studies, which include an assessment of immunogenicity and pharmacokinetics/pharmacodynamics, are used to assess for clinically meaningful differences and not to independently establish the safety and effectiveness of the biosimilar. Like all products that the FDA regulates, the FDA requires that biosimilar products meet the agency's rigorous standards of safety and efficacy for approval. That means patients and health care professionals are able to rely upon the safety and effectiveness of biosimilar products in the same manner as for the reference product. Clin Cancer Res; 23(8); 1882-5. ©2016 AACR . ©2016 American Association for Cancer Research.
Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism.

PubMed

Domínguez Jiménez, José Luis; Fernández Suárez, Antonio; Muñoz Colmenero, Aurora Úrsula; Fatela Cantillo, Daniel; López Pelayo, Iratxe

2017-04-01

There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Implementation of a National Reference Laboratory for Buruli Ulcer Disease in Togo

PubMed Central

Badziklou, Kossi; Halatoko, Wemboo Afiwa; Maman, Issaka; Vogel, Felix; Bidjada, Bawimodom; Awoussi, Koffi Somenou; Piten, Ebekalisai; Helfrich, Kerstin; Mengele, Carolin; Nitschke, Jörg; Amekuse, Komi; Wiedemann, Franz Xaver; Diefenhardt, Adolf; Kobara, Basile; Herbinger, Karl–Heinz; Kere, Abiba Banla; Prince-David, Mireille; Löscher, Thomas; Bretzel, Gisela

2013-01-01

Background In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo. Methodology Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions “Maritime” and “Central,” standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory. Principal Findings The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%. Conclusions High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory. PMID:23359828
Implementation of a national reference laboratory for Buruli ulcer disease in Togo.

PubMed

Beissner, Marcus; Huber, Kristina Lydia; Badziklou, Kossi; Halatoko, Wemboo Afiwa; Maman, Issaka; Vogel, Felix; Bidjada, Bawimodom; Awoussi, Koffi Somenou; Piten, Ebekalisai; Helfrich, Kerstin; Mengele, Carolin; Nitschke, Jörg; Amekuse, Komi; Wiedemann, Franz Xaver; Diefenhardt, Adolf; Kobara, Basile; Herbinger, Karl-Heinz; Kere, Abiba Banla; Prince-David, Mireille; Löscher, Thomas; Bretzel, Gisela

2013-01-01

In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo. Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions "Maritime" and "Central," standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory. The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%. High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory.

Fully automated motion correction in first-pass myocardial perfusion MR image sequences.

PubMed

Milles, Julien; van der Geest, Rob J; Jerosch-Herold, Michael; Reiber, Johan H C; Lelieveldt, Boudewijn P F

2008-11-01

This paper presents a novel method for registration of cardiac perfusion magnetic resonance imaging (MRI). The presented method is capable of automatically registering perfusion data, using independent component analysis (ICA) to extract physiologically relevant features together with their time-intensity behavior. A time-varying reference image mimicking intensity changes in the data of interest is computed based on the results of that ICA. This reference image is used in a two-pass registration framework. Qualitative and quantitative validation of the method is carried out using 46 clinical quality, short-axis, perfusion MR datasets comprising 100 images each. Despite varying image quality and motion patterns in the evaluation set, validation of the method showed a reduction of the average right ventricle (LV) motion from 1.26+/-0.87 to 0.64+/-0.46 pixels. Time-intensity curves are also improved after registration with an average error reduced from 2.65+/-7.89% to 0.87+/-3.88% between registered data and manual gold standard. Comparison of clinically relevant parameters computed using registered data and the manual gold standard show a good agreement. Additional tests with a simulated free-breathing protocol showed robustness against considerable deviations from a standard breathing protocol. We conclude that this fully automatic ICA-based method shows an accuracy, a robustness and a computation speed adequate for use in a clinical environment.
International Standardization of the Clinical Dosimetry of Beta Radiation Brachytherapy Sources: Progress of an ISO Standard

NASA Astrophysics Data System (ADS)

Soares, Christopher

2006-03-01

In 2004 a new work item proposal (NWIP) was accepted by the International Organization for Standardization (ISO) Technical Committee 85 (TC85 -- Nuclear Energy), Subcommittee 2 (Radiation Protection) for the development of a standard for the clinical dosimetry of beta radiation sources used for brachytherapy. To develop this standard, a new Working Group (WG 22 - Ionizing Radiation Dosimetry and Protocols in Medical Applications) was formed. The standard is based on the work of an ad-hoc working group initiated by the Dosimetry task group of the Deutsches Insitiut für Normung (DIN). Initially the work was geared mainly towards the needs of intravascular brachytherapy, but with the decline of this application, more focus has been placed on the challenges of accurate dosimetry for the concave eye plaques used to treat ocular melanoma. Guidance is given for dosimetry formalisms, reference data to be used, calibrations, measurement methods, modeling, uncertainty determinations, treatment planning and reporting, and clinical quality control. The document is currently undergoing review by the ISO member bodies for acceptance as a Committee Draft (CD) with publication of the final standard expected by 2007. There are opportunities for other ISO standards for medical dosimetry within the framework of WG22.
Standards for testing and clinical validation of seizure detection devices.

PubMed

Beniczky, Sándor; Ryvlin, Philippe

2018-06-01

To increase the quality of studies on seizure detection devices, we propose standards for testing and clinical validation of such devices. We identified 4 key features that are important for studies on seizure detection devices: subjects, recordings, data analysis and alarms, and reference standard. For each of these features, we list the specific aspects that need to be addressed in the studies, and depending on these, studies are classified into 5 phases (0-4). We propose a set of outcome measures that need to be reported, and we propose standards for reporting the results. These standards will help in designing and reporting studies on seizure detection devices, they will give readers clear information on the level of evidence provided by the studies, and they will help regulatory bodies in assessing the quality of the validation studies. These standards are flexible, allowing classification of the studies into one of the 5 phases. We propose actions that can facilitate development of novel methods and devices. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.
Glycosylated haemoglobin: measurement and clinical use.

PubMed

Peacock, I

1984-08-01

The discovery, biochemistry, laboratory determination, and clinical application of glycosylated haemoglobins are reviewed. Sources of error are discussed in detail. No single assay method is suitable for all purposes, and in the foreseeable future generally acceptable standards and reference ranges are unlikely to be agreed. Each laboratory must establish its own. Nevertheless, the development of glycosylated haemoglobin assays is an important advance. They offer the best available means of assessing diabetic control.
Analytical and Clinical Performance Evaluation of the Abbott Architect PIVKA Assay.

PubMed

Ko, Dae-Hyun; Hyun, Jungwon; Kim, Hyun Soo; Park, Min-Jeong; Kim, Jae-Seok; Park, Ji-Young; Shin, Dong Hoon; Cho, Hyoun Chan

2018-01-01

Protein induced by vitamin K absence (PIVKA) is measured using various assays and is used to help diagnose hepatocellular carcinoma. The present study evaluated the analytical and clinical performances of the recently released Abbott Architect PIVKA assay. Precision, linearity, and correlation tests were performed in accordance with the Clinical Laboratory Standardization Institute guidelines. Sample type suitability was assessed using serum and plasma samples from the same patients, and the reference interval was established using sera from 204 healthy individuals. The assay had coefficients of variation of 3.2-3.5% and intra-laboratory variation of 3.6-5.5%. Linearity was confirmed across the entire measurable range. The Architect PIVKA assay was comparable to the Lumipulse PIVKA assay, and the plasma and serum samples provided similar results. The lower reference limit was 13.0 mAU/mL and the upper reference limit was 37.4 mAU/mL. The ability of the Architect PIVKA assay to detect hepatocellular carcinoma was comparable to that of the alpha-fetoprotein test and the Lumipulse PIVKA assay. The Architect PIVKA assay provides excellent analytical and clinical performance, is simple for clinical laboratories to adopt, and has improved sample type suitability that could broaden the assay's utility. © 2018 by the Association of Clinical Scientists, Inc.
The Clinical Utility of ASRS-v1.1 for Identifying ADHD in Alcoholics Using PRISM as the Reference Standard.

PubMed

Reyes, Maria M; Schneekloth, Terry D; Hitschfeld, Mario J; Geske, Jennifer R; Atkinson, David L; Karpyak, Victor M

2016-05-02

The objective was to assess the clinical utility of the Adult ADHD Self-Report Scale (ASRS-v1.1) in identifying ADHD in alcoholics using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) as the diagnostic "gold standard." We performed a secondary analysis of data from 379 treatment-seeking alcoholics who completed the ASRS-v1.1 and the ADHD module of the PRISM. Data analysis included descriptive statistics. The prevalence of ADHD was 7.7% (95% CI = [5.4, 10.8]). The positive predictive value (PPV) of the ASRS-v1.1 was 18.1% (95% CI = [12.4, 25.7]) and the negative predictive value (NPV) was 97.6% (95% CI = [94.9, 98.9]). The ASRS-v1.1 demonstrated a sensitivity of 79.3% (95% CI = [61.6, 90.2]) and a specificity of 70.3% (95% CI = [65.3, 74.8]). The ASRS-v1.1 demonstrated acceptable sensitivity and specificity in a sample of treatment-seeking alcoholics when compared with the PRISM as the reference standard for ADHD diagnosis. © The Author(s) 2016.
Methodological Issues in Antifungal Susceptibility Testing of Malassezia pachydermatis

PubMed Central

Peano, Andrea; Pasquetti, Mario; Tizzani, Paolo; Chiavassa, Elisa; Guillot, Jacques; Johnson, Elizabeth

2017-01-01

Reference methods for antifungal susceptibility testing of yeasts have been developed by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antibiotic Susceptibility Testing (EUCAST). These methods are intended to test the main pathogenic yeasts that cause invasive infections, namely Candida spp. and Cryptococcus neoformans, while testing other yeast species introduces several additional problems in standardization not addressed by these reference procedures. As a consequence, a number of procedures have been employed in the literature to test the antifungal susceptibility of Malassezia pachydermatis. This has resulted in conflicting results. The aim of the present study is to review the procedures and the technical parameters (growth media, inoculum preparation, temperature and length of incubation, method of reading) employed for susceptibility testing of M. pachydermatis, and when possible, to propose recommendations for or against their use. Such information may be useful for the future development of a reference assay. PMID:29371554
Defining overweight and obesity among Greek children living in Thessaloniki: International versus local reference standards

PubMed Central

Christoforidis, A; Dimitriadou, M; Papadopolou, E; Stilpnopoulou, D; Katzos, G; Athanassiou-Metaxa, M

2011-01-01

Background: Body Mass Index (BMI) offers a simple and reasonable measure of obesity that, with the use of the appropriate reference, can help in the early detection of children with weight problems. Our aim was to compare the two most commonly used international BMI references and the national Greek BMI reference in identifying Greek children being overweight and obese. Methods: A group of 1557 children (820 girls and 737 boys, mean age: 11.42 ± 3.51 years) were studied. Weight and height was measured using standard methods, and BMI was calculated. Overweight and obesity were determined using the International Obesity Task Force (IOTF) standards, the Centers for Disease Control and Prevention (CDC) BMI-forage curves and the most recent Greek BMI-for-age curves. Results: Results showed that the IOTF's cut-off limits identifies a significantly higher prevalence of overweight (22.4%) compared with both the CDC's (11.8%, p=0.03) and the Greek's (7.4%, p=0.002) cut-off limits. However, the prevalence of obesity was generally increased when it was determined using the CDC's cut-off limits (13.9%) compared to the prevalence calculated with both the IOTF's (6.5%, p=0.05) and the Greek's (6.9%, n.s.) cut off limits. Conclusions: The use of the national Greek reference standards for BMI underestimates the true prevalence of overweight and obesity. On the contrary, both the IOTF and the CDC standards, although independently, detect an increased number of overweight and obese children and thus they should be adopted in the clinical practice for an earlier identification and a timelier intervention. PMID:22110296
[Reference values for lead levels in blood for the urban population].

PubMed

Paolielo, M M; Gutierrez, P R; Turini, C A; Matsuo, T; Mezzaroba, L; Barbosa, D S; Alvarenga, A L; Carvalho, S R; Figueiroa, G A; Leite, V G; Gutierrez, A C; Nogueira, K B; Inamine, W A; Zavatti, A M

1997-04-01

The lead reference values for blood used in Brazil come from studies conducted in other countries, where socioeconomic, clinical, nutritional and occupational conditions are significantly different. In order to guarantee an accurate biomonitoring of the population which is occupationally exposed to lead, a major health concern of the studied community, reference values for individuals who are not occupationally exposed and who live in the southern region of the city were established. The sample was composed of 206 subjects of at least 15 years of age. Various strategies were employed to assure good-quality sampling. Subjects who presented values outside clinical or laboratory norms were excluded, as well as those whose specific activities might interfere with the results. Lead reference values for blood were found to be from 2.40 to 16.6 micrograms.dL-1, obtained by the interval x +/- 2s (where x is the mean and s is the standard deviation form observed values) and the median was 7.9 micrograms.dL-1.
Reference values for pulmonary diffusing capacity for adult native Finns.

PubMed

Kainu, Annette; Toikka, Jyri; Vanninen, Esko; Timonen, Kirsi L

2017-04-01

Measurement standards for pulmonary diffusing capacity were updated in 2005 by the ATS/ERS Task Force. However, in Finland reference values published in 1982 by Viljanen et al. have been used to date. The main aim of this study was to produce updated reference models for single-breath diffusing capacity for carbon monoxide for Finnish adults. Single-breath diffusing capacity for carbon monoxide was measured in 631 healthy non-smoking volunteers (41.5% male). Reference values for diffusing capacity (DLCO), alveolar volume (VA), diffusing capacity per unit of lung volume (DLCO/VA), and lung volumes were calculated using a linear regression model. Previously used Finnish reference values were found to produce too low predicted values, with mean predicted DLCO 111.0 and 104.4%, and DLCO/VA of 103.5 and 102.7% in males and females, respectively. With the European Coalition for Steel and Coal (ECSC) reference values there was a significant sex difference in DLCO/VA with mean predicted 105.4% in males and 92.8% in females (p < .001). New reference values for DLCO, DLCO/VA, VA, vital capacity (VC), inspiratory vital capacity (IVC), and inspiratory capacity (IC) are suggested for clinical use to replace technically outdated reference values for clinical applications.
Computer-Based Image Analysis for Plus Disease Diagnosis in Retinopathy of Prematurity: Performance of the "i-ROP" System and Image Features Associated With Expert Diagnosis.

PubMed

Ataer-Cansizoglu, Esra; Bolon-Canedo, Veronica; Campbell, J Peter; Bozkurt, Alican; Erdogmus, Deniz; Kalpathy-Cramer, Jayashree; Patel, Samir; Jonas, Karyn; Chan, R V Paul; Ostmo, Susan; Chiang, Michael F

2015-11-01

We developed and evaluated the performance of a novel computer-based image analysis system for grading plus disease in retinopathy of prematurity (ROP), and identified the image features, shapes, and sizes that best correlate with expert diagnosis. A dataset of 77 wide-angle retinal images from infants screened for ROP was collected. A reference standard diagnosis was determined for each image by combining image grading from 3 experts with the clinical diagnosis from ophthalmoscopic examination. Manually segmented images were cropped into a range of shapes and sizes, and a computer algorithm was developed to extract tortuosity and dilation features from arteries and veins. Each feature was fed into our system to identify the set of characteristics that yielded the highest-performing system compared to the reference standard, which we refer to as the "i-ROP" system. Among the tested crop shapes, sizes, and measured features, point-based measurements of arterial and venous tortuosity (combined), and a large circular cropped image (with radius 6 times the disc diameter), provided the highest diagnostic accuracy. The i-ROP system achieved 95% accuracy for classifying preplus and plus disease compared to the reference standard. This was comparable to the performance of the 3 individual experts (96%, 94%, 92%), and significantly higher than the mean performance of 31 nonexperts (81%). This comprehensive analysis of computer-based plus disease suggests that it may be feasible to develop a fully-automated system based on wide-angle retinal images that performs comparably to expert graders at three-level plus disease discrimination. Computer-based image analysis, using objective and quantitative retinal vascular features, has potential to complement clinical ROP diagnosis by ophthalmologists.
Detailed clinical models: a review.

PubMed

Goossen, William; Goossen-Baremans, Anneke; van der Zel, Michael

2010-12-01

Due to the increasing use of electronic patient records and other health care information technology, we see an increase in requests to utilize these data. A highly level of standardization is required during the gathering of these data in the clinical context in order to use it for analyses. Detailed Clinical Models (DCM) have been created toward this purpose and several initiatives have been implemented in various parts of the world to create standardized models. This paper presents a review of DCM. Two types of analyses are presented; one comparing DCM against health care information architectures and a second bottom up approach from concept analysis to representation. In addition core parts of the draft ISO standard 13972 on DCM are used such as clinician involvement, data element specification, modeling, meta information, and repository and governance. SIX INITIATIVES WERE SELECTED: Intermountain Healthcare, 13606/OpenEHR Archetypes, Clinical Templates, Clinical Contents Models, Health Level 7 templates, and Dutch Detailed Clinical Models. Each model selected was reviewed for their overall development, involvement of clinicians, use of data types, code bindings, expressing semantics, modeling, meta information, use of repository and governance. Using both a top down and bottom up approach to comparison reveals many commonalties and differences between initiatives. Important differences include the use of or lack of a reference model and expressiveness of models. Applying clinical data element standards facilitates the use of conceptual DCM models in different technical representations.
The application of disease management to clinical trial designs.

PubMed

Puterman, Jared; Alter, David A

2009-08-01

The utilization of disease management (DM) as a minimum standard of care is believed to facilitate pronounced benefits in overall patient outcome and cost management. Randomized clinical trials remain the gold standard evaluative tool in clinical medicine. However, the extent to which contemporary cardiovascular clinical trials incorporate DM components into their treatment or control arms is unknown. Our study is the first to evaluate the extent to which clinical trials incorporate DM as a minimum standard of care for both the intervention and control groups. In total, 386 clinical trials published in 3 leading medical journals between 2003 and 2006 were evaluated. For each study, elements related to DM care, as defined using the American Heart Association Taxonomy, were abstracted and characterized. Our results demonstrate that while the application of DM has increased over time, only 3.4% of the clinical trials examined incorporated all 8 DM elements (and only 11% of such trials incorporated 4 DM elements). A significant association was found between study year and the inclusion of more than 3 elements of DM (chi(2) = 10.10 (3); p = 0.018). In addition, associations were found between study objective and DM criteria, as well as between cohort type and domains described. Our study serves as a baseline reference for the tracking of DM within, and its application to, randomized clinical trials. Moreover, our results underscore the need for broader implementation and evaluation of DM as a minimum care standard within clinical trial research.
Verification of chemistry reference ranges using a simple method in sub-Saharan Africa

PubMed Central

Taylor, Douglas; Mandala, Justin; Nanda, Kavita; Van Campenhout, Christel; Agingu, Walter; Madurai, Lorna; Barsch, Eva-Maria; Deese, Jennifer; Van Damme, Lut; Crucitti, Tania

2016-01-01

Background Chemistry safety assessments are interpreted by using chemistry reference ranges (CRRs). Verification of CRRs is time consuming and often requires a statistical background. Objectives We report on an easy and cost-saving method to verify CRRs. Methods Using a former method introduced by Sigma Diagnostics, three study sites in sub-Saharan Africa, Bondo, Kenya, and Pretoria and Bloemfontein, South Africa, verified the CRRs for hepatic and renal biochemistry assays performed during a clinical trial of HIV antiretroviral pre-exposure prophylaxis. The aspartate aminotransferase/alanine aminotransferase, creatinine and phosphorus results from 10 clinically-healthy participants at the screening visit were used. In the event the CRRs did not pass the verification, new CRRs had to be calculated based on 40 clinically-healthy participants. Results Within a few weeks, the study sites accomplished verification of the CRRs without additional costs. The aspartate aminotransferase reference ranges for the Bondo, Kenya site and the alanine aminotransferase reference ranges for the Pretoria, South Africa site required adjustment. The phosphorus CRR passed verification and the creatinine CRR required adjustment at every site. The newly-established CRR intervals were narrower than the CRRs used previously at these study sites due to decreases in the upper limits of the reference ranges. As a result, more toxicities were detected. Conclusion To ensure the safety of clinical trial participants, verification of CRRs should be standard practice in clinical trials conducted in settings where the CRR has not been validated for the local population. This verification method is simple, inexpensive, and can be performed by any medical laboratory. PMID:28879112
Verification of chemistry reference ranges using a simple method in sub-Saharan Africa.

PubMed

De Baetselier, Irith; Taylor, Douglas; Mandala, Justin; Nanda, Kavita; Van Campenhout, Christel; Agingu, Walter; Madurai, Lorna; Barsch, Eva-Maria; Deese, Jennifer; Van Damme, Lut; Crucitti, Tania

2016-01-01

Chemistry safety assessments are interpreted by using chemistry reference ranges (CRRs). Verification of CRRs is time consuming and often requires a statistical background. We report on an easy and cost-saving method to verify CRRs. Using a former method introduced by Sigma Diagnostics, three study sites in sub-Saharan Africa, Bondo, Kenya, and Pretoria and Bloemfontein, South Africa, verified the CRRs for hepatic and renal biochemistry assays performed during a clinical trial of HIV antiretroviral pre-exposure prophylaxis. The aspartate aminotransferase/alanine aminotransferase, creatinine and phosphorus results from 10 clinically-healthy participants at the screening visit were used. In the event the CRRs did not pass the verification, new CRRs had to be calculated based on 40 clinically-healthy participants. Within a few weeks, the study sites accomplished verification of the CRRs without additional costs. The aspartate aminotransferase reference ranges for the Bondo, Kenya site and the alanine aminotransferase reference ranges for the Pretoria, South Africa site required adjustment. The phosphorus CRR passed verification and the creatinine CRR required adjustment at every site. The newly-established CRR intervals were narrower than the CRRs used previously at these study sites due to decreases in the upper limits of the reference ranges. As a result, more toxicities were detected. To ensure the safety of clinical trial participants, verification of CRRs should be standard practice in clinical trials conducted in settings where the CRR has not been validated for the local population. This verification method is simple, inexpensive, and can be performed by any medical laboratory.
Electrical safety Q&A. A reference guide for the clinical engineer.

PubMed

2005-02-01

This guide, which ECRI developed to answer the electrical safety questions most frequently asked by member hospitals, features practical advice for addressing electrical safety concerns in the healthcare environment. Questions addressed include: STANDARDS AND APPROVALS: What electrical safety standards apply? How do NFPA 99 and IEC 60601-1 differ? What organizations approve medical devices? LEAKAGE CURRENT LIMITS AND TESTING: How are leakage current limits established? What limits apply to equipment used in the hospital? And how should the limits be applied in special cases, such as the use of PCs in the patient care area or equipment used in the clinical laboratory? ISOLATED POWER: What are its advantages and disadvantages, and is isolated power needed in the operating room? Other topics addressed include double insulation, ground-fault circuit interrupters (GFCIs), and requirements for medical devices used in the home. Supplementary articles discuss acceptable alternatives to UL listing, the use of Hospital Grade plugs, the limitations of leakage current testing of devices connected to isolated power systems, and the debate about whether to designate ORs as wet locations. Experienced clinical engineers should find this guide to be a handy reference, while those new to the field should find it to be a helpful educational resource.
Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. Fourth Edition

ERIC Educational Resources Information Center

Barkley, Russell A., Ed.

2014-01-01

Widely regarded as the standard clinical reference, this volume provides the best current knowledge about attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. The field's leading authorities address all aspects of assessment, diagnosis, and treatment, including psychological therapies and pharmacotherapy. Core…
[Evaluation of the standard application of Delphi in the diagnosis of chronic obstructive pulmonary disease caused by occupational irritant chemicals].

PubMed

Zhao, L; Yan, Y J

2017-11-20

Objective: To investigate the problems encountered in the application of the standard (hereinafter referred to as standard) for the diagnosis of chronic obstructive pulmonary disease caused by occu-pational irritant chemicals, to provide reference for the revision of the new standard, to reduce the number of missed patients in occupational COPD, and to get rid of the working environment of those who suffer from chronic respiratory diseases due to long-term exposure to poisons., slowing the progression of the disease. Methods: Using Delphi (Delphi) Expert research method, after the senior experts to demonstrate, to under-stand the GBZ 237-2011 "occupational irritant chemicals to the diagnosis of chronic obstructive pulmonary dis-ease" standard evaluation of the system encountered problems, to seek expert advice, The problems encoun-tered during the clinical implementation of the standards promulgated in 2011 are presented. Results: Through the Delphi Expert investigation method, it is found that experts agree on the content evaluation and implemen-tation evaluation in the standard, but the operational evaluation of the standard is disputed. According to the clinical experience, the experts believe that the range of occupational irritant gases should be expanded, and the operation of the problem of smoking, seniority determination and occupational contact history should be challenged during the diagnosis. Conclusions: Since the promulgation in 2011 of the criteria for the diagnosis of chronic obstructive pulmonary disease caused by occupational stimulant chemicals, there have been some problems in the implementation process, which have caused many occupationally exposed to irritating gases to suffer from "occupational chronic respiratory Diseases" without a definitive diagnosis.
Accuracy of the MacArthur competence assessment tool for clinical research (MacCAT-CR) for measuring children's competence to consent to clinical research.

PubMed

Hein, Irma M; Troost, Pieter W; Lindeboom, Robert; Benninga, Marc A; Zwaan, C Michel; van Goudoever, Johannes B; Lindauer, Ramón J L

2014-12-01

An objective assessment of children's competence to consent to research participation is currently not possible. Age limits for asking children's consent vary considerably between countries, and, to our knowledge, the correlation between competence and children's age has never been systematically investigated. To test a standardized competence assessment instrument for children by modifying the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), to investigate its reliability and validity, and to examine the correlation of its assessment with age and estimate cutoff ages. This prospective study included children and adolescents aged 6 to 18 years in the inpatient and outpatient departments of allergology, gastroenterology, oncology, ophthalmology, and pulmonology from January 1, 2012, through January 1, 2014. Participants were eligible for clinical research studies, including observational studies and randomized clinical trials. Competence judgments by experts aware of the 4 relevant criteria-understanding, appreciation, reasoning, and choice-were used to establish the reference standard. The index test was the MacCAT-CR, which used a semistructured interview format. Interrater reliability, validity, and dimensionality of the MacCAT-CR and estimated cutoff ages for competence. Of 209 eligible patients, we included 161 (mean age, 10.6 years; 47.2% male). Good reproducibility of MacCAT-CR total and subscale scores was observed (intraclass correlation coefficient range, 0.68-0.92). We confirmed unidimensionality of the MacCAT-CR. By the reference standard, we judged 54 children (33.5%) to be incompetent; by the MacCAT-CR, 61 children (37.9%). Criterion-related validity of MacCAT-CR scores was supported by high overall accuracy in correctly classifying children as competent against the reference standard (area under the receiver operating characteristics curve, 0.78). Age was a good predictor of competence on the MacCAT-CR (area under the receiver operating characteristics curve, 0.90). In children younger than 9.6 years, competence was unlikely (sensitivity, 90%); in those older than 11.2 years, competence was probable (specificity, 90%). The optimal cutoff age was 10.4 years (sensitivity, 81%; specificity, 84%). The MacCAT-CR demonstrated strong psychometric properties. In children aged 9.6 to 11.2 years, consent may be justified when competence can be demonstrated in individual cases by the MacCAT-CR. The results contribute to a scientific underpinning of regulations for clinical research directed toward children.
Device and methods for "gold standard" registration of clinical 3D and 2D cerebral angiograms

NASA Astrophysics Data System (ADS)

Madan, Hennadii; Likar, Boštjan; Pernuš, Franjo; Å piclin, Žiga

2015-03-01

Translation of any novel and existing 3D-2D image registration methods into clinical image-guidance systems is limited due to lack of their objective validation on clinical image datasets. The main reason is that, besides the calibration of the 2D imaging system, a reference or "gold standard" registration is very difficult to obtain on clinical image datasets. In the context of cerebral endovascular image-guided interventions (EIGIs), we present a calibration device in the form of a headband with integrated fiducial markers and, secondly, propose an automated pipeline comprising 3D and 2D image processing, analysis and annotation steps, the result of which is a retrospective calibration of the 2D imaging system and an optimal, i.e., "gold standard" registration of 3D and 2D images. The device and methods were used to create the "gold standard" on 15 datasets of 3D and 2D cerebral angiograms, whereas each dataset was acquired on a patient undergoing EIGI for either aneurysm coiling or embolization of arteriovenous malformation. The use of the device integrated seamlessly in the clinical workflow of EIGI. While the automated pipeline eliminated all manual input or interactive image processing, analysis or annotation. In this way, the time to obtain the "gold standard" was reduced from 30 to less than one minute and the "gold standard" of 3D-2D registration on all 15 datasets of cerebral angiograms was obtained with a sub-0.1 mm accuracy.

CPTC and NIST-sponsored Yeast Reference Material Now Publicly Available | Office of Cancer Clinical Proteomics Research

Cancer.gov

The yeast protein extract (RM8323) developed by National Institute of Standards and Technology (NIST) under the auspices of NCI's CPTC initiative is currently available to the public at https://www-s.nist.gov/srmors/view_detail.cfm?srm=8323. The yeast proteome offers researchers a unique biological reference material. RM8323 is the most extensively characterized complex biological proteome and the only one associated with several large-scale studies to estimate protein abundance across a wide concentration range.
Digital antimicrobial susceptibility testing using the MilliDrop technology.

PubMed

Jiang, L; Boitard, L; Broyer, P; Chareire, A-C; Bourne-Branchu, P; Mahé, P; Tournoud, M; Franceschi, C; Zambardi, G; Baudry, J; Bibette, J

2016-03-01

We present the MilliDrop Analyzer (MDA), a droplet-based millifluidic system for digital antimicrobial susceptibility testing (D-AST), which enables us to determine minimum inhibitory concentrations (MICs) precisely and accurately. The MilliDrop technology was validated by using resazurin for fluorescence readout, for comparison with standard methodology, and for conducting reproducibility studies. In this first assessment, the susceptibility of a reference Gram-negative strain Escherichia coli ATCC 25922 to gentamicin, chloramphenicol, and nalidixic acid were tested by the MDA, VITEK®2, and broth microdilution as a reference standard. We measured the susceptibility of clinically relevant Gram-positive strains of Staphylococcus aureus to vancomycin, including vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-susceptible S. aureus (VSSA) strains. The MDA provided results which were much more accurate than those of VITEK®2 and standard broth microdilution. The enhanced accuracy enabled us to reliably discriminate between VSSA and hVISA strains.
The gallium melting-point standard: its application and evaluation for temperature measurements in the clinical laboratory.

PubMed

Bowers, G N; Inman, S R

1977-01-01

We are impressed with the ease and certainty of calibration electronic thermometers with thermistor probes to +/- 0.01 degree C at the gallium melting point, 29.771(4) degrees C. The IFCC reference method for measuring aspartate aminotransferase activity in serum was run at the reaction temperature of 29.771(4) degrees C. By constantly referencing to gallium as an integral part of the assay procedure, we determined the absolute reaction temperature to IPTS-68 (International Practical Temperature Scale of 1968) to +/- 0.02 degrees C. This unique temperature calibration standard near the center of the range of temperatures commonly used in the clinical laboratory is a valuable addition and can be expected to improve the accuracy of measurements, especially in clinical enzymology.
A logical foundation for representation of clinical data.

PubMed Central

Campbell, K E; Das, A K; Musen, M A

1994-01-01

OBJECTIVE: A general framework for representation of clinical data that provides a declarative semantics of terms and that allows developers to define explicitly the relationships among both terms and combinations of terms. DESIGN: Use of conceptual graphs as a standard representation of logic and of an existing standardized vocabulary, the Systematized Nomenclature of Medicine (SNOMED International), for lexical elements. Concepts such as time, anatomy, and uncertainty must be modeled explicitly in a way that allows relation of these foundational concepts to surface-level clinical descriptions in a uniform manner. RESULTS: The proposed framework was used to model a simple radiology report, which included temporal references. CONCLUSION: Formal logic provides a framework for formalizing the representation of medical concepts. Actual implementations will be required to evaluate the practicality of this approach. PMID:7719805
A height-for-age growth reference for children with achondroplasia: Expanded applications and comparison with original reference data.

PubMed

Hoover-Fong, Julie; McGready, John; Schulze, Kerry; Alade, Adekemi Yewande; Scott, Charles I

2017-05-01

The height-for-age (HA) reference currently used for children with achondroplasia is not adaptable for electronic records or calculation of HA Z-scores. We report new HA curves and tables of mean and standard deviation (SD) HA, for calculating Z-scores, from birth-16 years in achondroplasia. Mixed longitudinal data were abstracted from medical records of achondroplasia patients from a single clinical practice (CIS, 1967-2004). Gender-specific height percentiles (5, 25, 50, 75, 95th) were estimated across the age continuum, using a 2 month window per time point smoothed by a quadratic smoothing algorithm. HA curves were constructed for 0-36 months and 2-16 years to optimize resolution for younger children. Mean monthly height (SD) was tabulated. These novel HA curves were compared to reference data currently in use for children with achondroplasia. 293 subjects (162 male/131 female) contributed 1,005 and 932 height measures, with greater data paucity with age. Mean HA tracked with original achondroplasia norms, particularly through mid-childhood (2-9 years), but with no evidence of a pubertal growth spurt. Standard deviation of height at each month interval increased from birth through 16 years. Birth length was lower in achondroplasia than average stature and, as expected, height deficits increased with age. A new HA reference is available for longitudinal growth assessment in achondroplasia, taking advantage of statistical modeling techniques and allowing for Z-score calculations. This is an important contribution to clinical care and research endeavors for the achondroplasia population. © 2017 Wiley Periodicals, Inc.
Practical utilization of recombinant AAV vector reference standards: focus on vector genomes titration by free ITR qPCR.

PubMed

D'Costa, Susan; Blouin, Veronique; Broucque, Frederic; Penaud-Budloo, Magalie; François, Achille; Perez, Irene C; Le Bec, Christine; Moullier, Philippe; Snyder, Richard O; Ayuso, Eduard

2016-01-01

Clinical trials using recombinant adeno-associated virus (rAAV) vectors have demonstrated efficacy and a good safety profile. Although the field is advancing quickly, vector analytics and harmonization of dosage units are still a limitation for commercialization. AAV reference standard materials (RSMs) can help ensure product safety by controlling the consistency of assays used to characterize rAAV stocks. The most widely utilized unit of vector dosing is based on the encapsidated vector genome. Quantitative polymerase chain reaction (qPCR) is now the most common method to titer vector genomes (vg); however, significant inter- and intralaboratory variations have been documented using this technique. Here, RSMs and rAAV stocks were titered on the basis of an inverted terminal repeats (ITRs) sequence-specific qPCR and we found an artificial increase in vg titers using a widely utilized approach. The PCR error was introduced by using single-cut linearized plasmid as the standard curve. This bias was eliminated using plasmid standards linearized just outside the ITR region on each end to facilitate the melting of the palindromic ITR sequences during PCR. This new "Free-ITR" qPCR delivers vg titers that are consistent with titers obtained with transgene-specific qPCR and could be used to normalize in-house product-specific AAV vector standards and controls to the rAAV RSMs. The free-ITR method, including well-characterized controls, will help to calibrate doses to compare preclinical and clinical data in the field.
Protein quantification using a cleavable reporter peptide.

PubMed

Duriez, Elodie; Trevisiol, Stephane; Domon, Bruno

2015-02-06

Peptide and protein quantification based on isotope dilution and mass spectrometry analysis are widely employed for the measurement of biomarkers and in system biology applications. The accuracy and reliability of such quantitative assays depend on the quality of the stable-isotope labeled standards. Although the quantification using stable-isotope labeled peptides is precise, the accuracy of the results can be severely biased by the purity of the internal standards, their stability and formulation, and the determination of their concentration. Here we describe a rapid and cost-efficient method to recalibrate stable isotope labeled peptides in a single LC-MS analysis. The method is based on the equimolar release of a protein reference peptide (used as surrogate for the protein of interest) and a universal reporter peptide during the trypsinization of a concatenated polypeptide standard. The quality and accuracy of data generated with such concatenated polypeptide standards are highlighted by the quantification of two clinically important proteins in urine samples and compared with results obtained with conventional stable isotope labeled reference peptides. Furthermore, the application of the UCRP standards in complex samples is described.
Differences in serum thyroglobulin measurements by 3 commercial immunoradiometric assay kits and laboratory standardization using Certified Reference Material 457 (CRM-457).

PubMed

Lee, Ji In; Kim, Ji Young; Choi, Joon Young; Kim, Hee Kyung; Jang, Hye Won; Hur, Kyu Yeon; Kim, Jae Hyeon; Kim, Kwang-Won; Chung, Jae Hoon; Kim, Sun Wook

2010-09-01

Serum thyroglobulin (Tg) is essential in the follow-up of patients with differentiated thyroid carcinoma (DTC). However, interchangeability and standardization between Tg assays have not yet been achieved, even with the development of an international Tg standard (Certified Reference Material 457 [CRM-457]). Serum Tg from 30 DTC patients and serially diluted CRM-457 were measured using 3 different immunoradiometric assays (IRMA-1, IRMA-2, IRMA-3). The intraclass correlation coefficient (ICC) method was used to describe the concordance of each IRMA to CRM-457. The serum Tg measured by 3 different IRMAs correlated well (r > .85, p < .0001), but clinically relevant discrepancies were found in 13.3% of patients. IRMA-3, which claims to be standardized to CRM-457, showed the best ICC (p(1) = .98) for the CRM-457. Hospitals caring for patients with DTC should either set their own cutoffs for IRMAs for Tg based on their patient pools, or adopt IRMAs standardized to CRM-457 and calibrate their laboratory using CRM-457.
The "Good Enough" Parent: Implications for Child Protection

ERIC Educational Resources Information Center

Choate, Peter W.; Engstrom, Sandra

2014-01-01

Child protection workers must determine under what conditions a child should be sustained within the family system. A standard that is often referred to is "good enough" parenting or minimal parenting competence. Research and clinical literature fails to offer workers guidance on the practical application of this terminology. Such…
Influence of Paternal Age on Assisted Reproduction Outcome

ClinicalTrials.gov

2017-04-27

We Will Retrospectively Assess Our Databases in Our Clinic; Instituto Valenciano de Infertilidad in Valencia (Spain); Searching for Assisted Reproduction Procedures; IUI Standard IVF/ICSI Cycles and Ovum Donation IVF/ICSI Cycles; Who Were Referred to Our Unit to Cryopreserve Sperm During the Period; From January 2000 to December 2006
CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa.

PubMed

Karita, Etienne; Ketter, Nzeera; Price, Matt A; Kayitenkore, Kayitesi; Kaleebu, Pontiano; Nanvubya, Annet; Anzala, Omu; Jaoko, Walter; Mutua, Gaudensia; Ruzagira, Eugene; Mulenga, Joseph; Sanders, Eduard J; Mwangome, Mary; Allen, Susan; Bwanika, Agnes; Bahemuka, Ubaldo; Awuondo, Ken; Omosa, Gloria; Farah, Bashir; Amornkul, Pauli; Birungi, Josephine; Yates, Sarah; Stoll-Johnson, Lisa; Gilmour, Jill; Stevens, Gwynn; Shutes, Erin; Manigart, Olivier; Hughes, Peter; Dally, Len; Scott, Janet; Stevens, Wendy; Fast, Pat; Kamali, Anatoli

2009-01-01

Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S. -derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.
SENIORLAB: a prospective observational study investigating laboratory parameters and their reference intervals in the elderly.

PubMed

Risch, Martin; Nydegger, Urs; Risch, Lorenz

2017-01-01

In clinical practice, laboratory results are often important for making diagnostic, therapeutic, and prognostic decisions. Interpreting individual results relies on accurate reference intervals and decision limits. Despite the considerable amount of resources in clinical medicine spent on elderly patients, accurate reference intervals for the elderly are rarely available. The SENIORLAB study set out to determine reference intervals in the elderly by investigating a large variety of laboratory parameters in clinical chemistry, hematology, and immunology. The SENIORLAB study is an observational, prospective cohort study. Subjectively healthy residents of Switzerland aged 60 years and older were included for baseline examination (n = 1467), where anthropometric measurements were taken, medical history was reviewed, and a fasting blood sample was drawn under optimal preanalytical conditions. More than 110 laboratory parameters were measured, and a biobank was set up. The study participants are followed up every 3 to 5 years for quality of life, morbidity, and mortality. The primary aim is to evaluate different laboratory parameters at age-related reference intervals. The secondary aims of this study include the following: identify associations between different parameters, identify diagnostic characteristics to diagnose different circumstances, identify the prevalence of occult disease in subjectively healthy individuals, and identify the prognostic factors for the investigated outcomes, including mortality. To obtain better grounds to justify clinical decisions, specific reference intervals for laboratory parameters of the elderly are needed. Reference intervals are obtained from healthy individuals. A major obstacle when obtaining reference intervals in the elderly is the definition of health in seniors because individuals without any medical condition and any medication are rare in older adulthood. Reference intervals obtained from such individuals cannot be considered representative for seniors in a status of age-specific normal health. In addition to the established methods for determining reference intervals, this longitudinal study utilizes a unique approach, in that survival and long-term well-being are taken as indicators of health in seniors. This approach is expected to provide robust and representative reference intervals that are obtained from an adequate reference population and not a collective of highly selected individuals. The present study was registered under International Standard Randomized Controlled Trial Number registry: ISRCTN53778569.
Standardized evaluation framework for evaluating coronary artery stenosis detection, stenosis quantification and lumen segmentation algorithms in computed tomography angiography.

PubMed

Kirişli, H A; Schaap, M; Metz, C T; Dharampal, A S; Meijboom, W B; Papadopoulou, S L; Dedic, A; Nieman, K; de Graaf, M A; Meijs, M F L; Cramer, M J; Broersen, A; Cetin, S; Eslami, A; Flórez-Valencia, L; Lor, K L; Matuszewski, B; Melki, I; Mohr, B; Oksüz, I; Shahzad, R; Wang, C; Kitslaar, P H; Unal, G; Katouzian, A; Örkisz, M; Chen, C M; Precioso, F; Najman, L; Masood, S; Ünay, D; van Vliet, L; Moreno, R; Goldenberg, R; Vuçini, E; Krestin, G P; Niessen, W J; van Walsum, T

2013-12-01

Though conventional coronary angiography (CCA) has been the standard of reference for diagnosing coronary artery disease in the past decades, computed tomography angiography (CTA) has rapidly emerged, and is nowadays widely used in clinical practice. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms devised to detect and quantify the coronary artery stenoses, and to segment the coronary artery lumen in CTA data. The objective of this evaluation framework is to demonstrate the feasibility of dedicated algorithms to: (1) (semi-)automatically detect and quantify stenosis on CTA, in comparison with quantitative coronary angiography (QCA) and CTA consensus reading, and (2) (semi-)automatically segment the coronary lumen on CTA, in comparison with expert's manual annotation. A database consisting of 48 multicenter multivendor cardiac CTA datasets with corresponding reference standards are described and made available. The algorithms from 11 research groups were quantitatively evaluated and compared. The results show that (1) some of the current stenosis detection/quantification algorithms may be used for triage or as a second-reader in clinical practice, and that (2) automatic lumen segmentation is possible with a precision similar to that obtained by experts. The framework is open for new submissions through the website, at http://coronary.bigr.nl/stenoses/. Copyright © 2013 Elsevier B.V. All rights reserved.
Towards Standardizing the Alcoholism Evaluation Of Potential Liver Transplant Recipients.

PubMed

Beresford, Thomas P; Lucey, Michael R

2018-03-01

For teams around the world, alcoholic liver disease patients comprise the largest, and clinically most controversial, group applying for liver transplant. And yet evaluation decisions for them remain highly variable by locale. Targeting standardized assessment, we provide guidelines on what information the transplant team should seek, from what sources, and how best to make use of it. This report focuses on 'what to do and how to do it' in providing appropriate assessments for this complex patient group. Proper evaluation includes (a) taking the clinical history from the patient and a required, corroborating third person, (b) assessing patient cognition, (c) establishing alcohol/substance use diagnosis to differentiate alcohol dependence, abuse and polysubstance dependence, (d) assessing ambivalence in primary alcohol addiction, (e) measuring social stability and (f) using Vaillant's factors for abstinence prognosis. Properly applied, these six factors will allow standardized selection in most cases taken across programs despite differences in resources, available expertise and decision practices. This report focuses on the essentials of the psychiatric/behavioral evaluation for 'alcoholic' persons referred for liver transplant. Attention to those essentials offers clinical standardization across transplant programs in different locales.
Cross-mapping clinical notes between hospitals: an application of the LOINC Document Ontology.

PubMed

Li, Li; Morrey, C Paul; Baorto, David

2011-01-01

Standardization of document titles is essential for management as the volume of electronic clinical notes increases. The two campuses of the New York Presbyterian Hospital have over 2,700 distinct document titles. The LOINC Document Ontology (DO) provides a standard for the naming of clinical documents in a multi-axis structure. We have represented the latest LOINC DO structure in the MED, and developed an automated process mapping the clinical documents from both the West (Columbia) and East (Cornell) campuses to the LOINC DO. We find that the LOINC DO can represent the majority of our documents, and about half of the documents map between campuses using the LOINC DO as a reference. We evaluated the possibility of using current LOINC codes in document exchange between different institutions. While there is clear success in the ability of the LOINC DO to represent documents and facilitate exchange we find there are granularity issues.
Multicentre evaluation of stable reference whole blood for enumeration of lymphocyte subsets by flow cytometry.

PubMed

Edwards, Cherry; Belgrave, Danielle; Janossy, George; Bradley, Nicholas J; Stebbings, Richard; Gaines-Das, Rose; Thorpe, Robin; Sawle, Alex; Arroz, Maria Jorge; Brando, Bruno; Gratama, Jan Willem; Orfao de Matos, Alberto; Papa, Stephano; Papamichail, Michael; Lenkei, Rodica; Rothe, Gregor; Barnett, David

2005-06-22

BACKGROUND: Clinical indications for lymphocyte subset enumeration by flow cytometry include monitoring of disease progression and timing of therapeutic intervention in infection with human immunodeficiency virus. Until recently international standardisation has not been possible due to a lack of suitable stable reference material. METHODS: This study consisted of two trials of a stabilised whole blood preparation. Eleven participants were sent two standard protocols for staining plus gating strategy and asked to report absolute counts for lymphocyte subsets. RESULTS: No significant difference was detected between the two methods when results from the two assays and all partners were pooled. Significant differences in results from the different partners were observed. However, representative mean counts were obtained for geometric means, geometric coefficient of variation, and 95% confidence interval for CD3 910 cells/mul, 9%, and 888 to 933, respectively), CD4 (495 cells/mul, 12%, and 483 to 507), and CD8 (408 cells/mul, 13%, and 393 to 422). CONCLUSION: We have introduced a stabilised blood preparation and a well-characterized biological standard. The availability of this reference material greatly simplifies the validation of new techniques for CD4(+) T-cell enumeration and the expansion of external quality assurance programmes for clinical laboratories, including those that operate in resource-restricted environments. (c) 2005 Wiley-Liss, Inc.
Clinical laboratory accreditation in India.

PubMed

Handoo, Anil; Sood, Swaroop Krishan

2012-06-01

Test results from clinical laboratories must ensure accuracy, as these are crucial in several areas of health care. It is necessary that the laboratory implements quality assurance to achieve this goal. The implementation of quality should be audited by independent bodies,referred to as accreditation bodies. Accreditation is a third-party attestation by an authoritative body, which certifies that the applicant laboratory meets quality requirements of accreditation body and has demonstrated its competence to carry out specific tasks. Although in most of the countries,accreditation is mandatory, in India it is voluntary. The quality requirements are described in standards developed by many accreditation organizations. The internationally acceptable standard for clinical laboratories is ISO15189, which is based on ISO/IEC standard 17025. The accreditation body in India is the National Accreditation Board for Testing and Calibration Laboratories, which has signed Mutual Recognition Agreement with the regional cooperation the Asia Pacific Laboratory Accreditation Cooperation and with the apex cooperation the International Laboratory Accreditation Cooperation.
Repeat testing of low-level HIV-1 RNA: assay performance and implementation in clinical trials.

PubMed

White, Kirsten; Garner, Will; Wei, Lilian; Eron, Joseph J; Zhong, Lijie; Miller, Michael D; Martin, Hal; Plummer, Andrew; Tran-Muchowski, Cecilia; Lindstrom, Kim; Porter, James; Piontkowsky, David; Light, Angela; Reiske, Heinz; Quirk, Erin

2018-05-15

Assess the performance of HIV-1 RNA repeat testing of stored samples in cases of low-level viremia during clinical trials. Prospective and retrospective analysis of randomized clinical trial samples and reference standards. To evaluate assay variability of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, v2.0, three separate sources of samples were utilized: the World Health Organization (WHO) HIV reference standard (assayed using 50 independent measurements at six viral loads <200 copies/ml), retrospective analysis of four to six aliquots of plasma samples from four clinical trial participants, and prospective repeat testing of 120 samples from participants in randomized trials with low-level viremia. The TaqMan assay on the WHO HIV-1 RNA standards at viral loads <200 copies/ml performed within the expected variability according to assay specifications. However, standards with low viral loads of 36 and 18 copies/ml reported values of ≥ 50 copies/ml in 66 and 18% of tests, respectively. In participants treated with antiretrovirals who had unexpected viremia of 50-200 copies/ml after achieving <50 copies/ml, retesting of multiple aliquots of stored plasma found <50 copies/ml in nearly all cases upon retesting (14/15; 93%). Repeat testing was prospectively implemented in four clinical trials for all samples with virologic rebound of 50-200 copies/ml (n = 120 samples from 92 participants) from which 42% (50/120) had a retest result of less than 50 copies/ml and 58% (70/120) retested ≥ 50 copies/ml. The TaqMan HIV-1 RNA assay shows variability around 50 copies/ml that affects clinical trial results and may impact clinical practice. In participants with a history of viral load suppression, unexpected low-level viremia may be because of assay variability rather than low drug adherence or true virologic failure. Retesting a stored aliquot of the same sample may differentiate between assay variability and virologic failure as the source of viremia. This retesting strategy could save time, money, and anxiety for patients and their providers, as well as decrease follow-up clinic visits without increasing the risk of virologic failure and resistance development.
Clinical utility of a single-item test for DSM-5 alcohol use disorder among outpatients with anxiety and depressive disorders.

PubMed

Bartoli, Francesco; Crocamo, Cristina; Biagi, Enrico; Di Carlo, Francesco; Parma, Francesca; Madeddu, Fabio; Capuzzi, Enrico; Colmegna, Fabrizia; Clerici, Massimo; Carrà, Giuseppe

2016-08-01

There is a lack of studies testing accuracy of fast screening methods for alcohol use disorder in mental health settings. We aimed at estimating clinical utility of a standard single-item test for case finding and screening of DSM-5 alcohol use disorder among individuals suffering from anxiety and mood disorders. We recruited adults consecutively referred, in a 12-month period, to an outpatient clinic for anxiety and depressive disorders. We assessed the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single-item test, using the Mini- International Neuropsychiatric Interview (MINI), plus an additional item of Composite International Diagnostic Interview (CIDI) for craving, as reference standard to diagnose a current DSM-5 alcohol use disorder. We estimated sensitivity and specificity of the single-item test, as well as positive and negative Clinical Utility Indexes (CUIs). 242 subjects with anxiety and mood disorders were included. The NIAAA single-item test showed high sensitivity (91.9%) and specificity (91.2%) for DSM-5 alcohol use disorder. The positive CUI was 0.601, whereas the negative one was 0.898, with excellent values also accounting for main individual characteristics (age, gender, diagnosis, psychological distress levels, smoking status). Testing for relevant indexes, we found an excellent clinical utility of the NIAAA single-item test for screening true negative cases. Our findings support a routine use of reliable methods for rapid screening in similar mental health settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Using Natural Language Processing to Improve Efficiency of Manual Chart Abstraction in Research: The Case of Breast Cancer Recurrence

PubMed Central

Carrell, David S.; Halgrim, Scott; Tran, Diem-Thy; Buist, Diana S. M.; Chubak, Jessica; Chapman, Wendy W.; Savova, Guergana

2014-01-01

The increasing availability of electronic health records (EHRs) creates opportunities for automated extraction of information from clinical text. We hypothesized that natural language processing (NLP) could substantially reduce the burden of manual abstraction in studies examining outcomes, like cancer recurrence, that are documented in unstructured clinical text, such as progress notes, radiology reports, and pathology reports. We developed an NLP-based system using open-source software to process electronic clinical notes from 1995 to 2012 for women with early-stage incident breast cancers to identify whether and when recurrences were diagnosed. We developed and evaluated the system using clinical notes from 1,472 patients receiving EHR-documented care in an integrated health care system in the Pacific Northwest. A separate study provided the patient-level reference standard for recurrence status and date. The NLP-based system correctly identified 92% of recurrences and estimated diagnosis dates within 30 days for 88% of these. Specificity was 96%. The NLP-based system overlooked 5 of 65 recurrences, 4 because electronic documents were unavailable. The NLP-based system identified 5 other recurrences incorrectly classified as nonrecurrent in the reference standard. If used in similar cohorts, NLP could reduce by 90% the number of EHR charts abstracted to identify confirmed breast cancer recurrence cases at a rate comparable to traditional abstraction. PMID:24488511

[Error prevention through management of complications in urology: standard operating procedures from commercial aviation as a model].

PubMed

Kranz, J; Sommer, K-J; Steffens, J

2014-05-01

Patient safety and risk/complication management rank among the current megatrends in modern medicine, which has undoubtedly become more complex. In time-critical, error-prone and difficult situations, which often occur repeatedly in everyday clinical practice, guidelines are inappropriate for acting rapidly and intelligently. With the establishment and consistent use of standard operating procedures like in commercial aviation, a possible strategic approach is available. These medical aids to decision-making - quick reference cards - are short, optimized instructions that enable a standardized procedure in case of medical claims.
Development of Lentivirus-Based Reference Materials for Ebola Virus Nucleic Acid Amplification Technology-Based Assays.

PubMed

Mattiuzzo, Giada; Ashall, James; Doris, Kathryn S; MacLellan-Gibson, Kirsty; Nicolson, Carolyn; Wilkinson, Dianna E; Harvey, Ruth; Almond, Neil; Anderson, Robert; Efstathiou, Stacey; Minor, Philip D; Page, Mark

2015-01-01

The 2013-present Ebola virus outbreak in Western Africa has prompted the production of many diagnostic assays, mostly based on nucleic acid amplification technologies (NAT). The calibration and performance assessment of established assays and those under evaluation requires reference materials that can be used in parallel with the clinical sample to standardise or control for every step of the procedure, from extraction to the final qualitative/quantitative result. We have developed safe and stable Ebola virus RNA reference materials by encapsidating anti sense viral RNA into HIV-1-like particles. The lentiviral particles are replication-deficient and non-infectious due to the lack of HIV-1 genes and Envelope protein. Ebola virus genes were subcloned for encapsidation into two lentiviral preparations, one containing NP-VP35-GP and the other VP40 and L RNA. Each reference material was formulated as a high-titre standard for use as a calibrator for secondary or internal standards, and a 10,000-fold lower titre preparation to serve as an in-run control. The preparations have been freeze-dried to maximise stability. These HIV-Ebola virus RNA reference materials were suitable for use with in-house and commercial quantitative RT-PCR assays and with digital RT-PCR. The HIV-Ebola virus RNA reference materials are stable at up to 37°C for two weeks, allowing the shipment of the material worldwide at ambient temperature. These results support further evaluation of the HIV-Ebola virus RNA reference materials as part of an International collaborative study for the establishment of the 1st International Standard for Ebola virus RNA.
The Australian radiation protection and nuclear safety agency megavoltage photon thermoluminescence dosimetry postal audit service 2007-2010.

PubMed

Oliver, C P; Butler, D J; Webb, D V

2012-03-01

The Australian radiation protection and nuclear safety agency (ARPANSA) has continuously provided a level 1 mailed thermoluminescence dosimetry audit service for megavoltage photons since 2007. The purpose of the audit is to provide an independent verification of the reference dose output of a radiotherapy linear accelerator in a clinical environment. Photon beam quality measurements can also be made as part of the audit in addition to the output measurements. The results of all audits performed between 2007 and 2010 are presented. The average of all reference beam output measurements calculated as a clinically stated dose divided by an ARPANSA measured dose is 0.9993. The results of all beam quality measurements calculated as a clinically stated quality divided by an ARPANSA measured quality is 1.0087. Since 2011 the provision of all auditing services has been transferred from the Ionizing Radiation Standards section to the Australian Clinical Dosimetry Service (ACDS) which is currently housed within ARPANSA.
A proposed protocol for acceptance and constancy control of computed tomography systems: a Nordic Association for Clinical Physics (NACP) work group report.

PubMed

Kuttner, Samuel; Bujila, Robert; Kortesniemi, Mika; Andersson, Henrik; Kull, Love; Østerås, Bjørn Helge; Thygesen, Jesper; Tarp, Ivanka Sojat

2013-03-01

Quality assurance (QA) of computed tomography (CT) systems is one of the routine tasks for medical physicists in the Nordic countries. However, standardized QA protocols do not yet exist and the QA methods, as well as the applied tolerance levels, vary in scope and extent at different hospitals. To propose a standardized protocol for acceptance and constancy testing of CT scanners in the Nordic Region. Following a Nordic Association for Clinical Physics (NACP) initiative, a group of medical physicists, with representatives from four Nordic countries, was formed. Based on international literature and practical experience within the group, a comprehensive standardized test protocol was developed. The proposed protocol includes tests related to the mechanical functionality, X-ray tube, detector, and image quality for CT scanners. For each test, recommendations regarding the purpose, equipment needed, an outline of the test method, the measured parameter, tolerance levels, and the testing frequency are stated. In addition, a number of optional tests are briefly discussed that may provide further information about the CT system. Based on international references and medical physicists' practical experiences, a comprehensive QA protocol for CT systems is proposed, including both acceptance and constancy tests. The protocol may serve as a reference for medical physicists in the Nordic countries.
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.
Preliminary development of an ultrabrief two-item bedside test for delirium.

PubMed

Fick, Donna M; Inouye, Sharon K; Guess, Jamey; Ngo, Long H; Jones, Richard N; Saczynski, Jane S; Marcantonio, Edward R

2015-10-01

Delirium is common, morbid, and costly, yet is greatly under-recognized among hospitalized older adults. To identify the best single and pair of mental status test items that predict the presence of delirium. Diagnostic test evaluation study that enrolled medicine inpatients aged 75 years or older at an academic medical center. Patients underwent a clinical reference standard assessment involving a patient interview, medical record review, and interviews with family members and nurses to determine the presence or absence of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition defined delirium. Participants also underwent the three-dimensional Confusion Assessment Method (3D-CAM), a brief, validated assessment for delirium. Individual items and pairs of items from the 3D-CAM were evaluated to determine sensitivity and specificity relative to the reference standard delirium diagnosis. Of the 201 participants (mean age 84 years, 62% female), 42 (21%) had delirium based on the clinical reference standard. The single item with the best test characteristics was "months of the year backwards" with a sensitivity of 83% (95% confidence interval [CI]: 69%-93%) and specificity of 69% (95% CI: 61%-76%). The best 2-item screen was the combination of "months of the year backwards" and "what is the day of the week?" with a sensitivity of 93% (95% CI: 81%-99%) and specificity of 64% (95% CI: 56%-70%). We identified a single item with >80% and pair of items with >90% sensitivity for delirium. If validated prospectively, these items will serve as an initial innovative screening step for delirium identification in hospitalized older adults. © 2015 Society of Hospital Medicine.
Interpretability of the PedsQL™ Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales in Pediatric Patients With Functional and Organic Gastrointestinal Diseases

PubMed Central

Bendo, Cristiane B.; Shulman, Robert J.; Self, Mariella M.; Nurko, Samuel; Franciosi, James P.; Saps, Miguel; Saeed, Shehzad; Zacur, George M.; Vaughan Dark, Chelsea; Pohl, John F.

2015-01-01

Objective The present study investigates the clinical interpretability of the Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and Worry Scales in pediatric patients with functional gastrointestinal disorders or organic gastrointestinal diseases in comparison with healthy controls. Methods The PedsQL™ Gastrointestinal Scales were completed by 587 patients with gastrointestinal disorders/diseases and 685 parents, and 513 healthy children and 337 parents. Minimal important difference (MID) scores were derived from the standard error of measurement (SEM). Cut-points were derived based on one and two standard deviations (SDs) from the healthy reference means. Results The percentages of patients below the scales’ cut-points were significantly greater than the healthy controls (most p values ≤ .001). Scale scores 2 SDs from the healthy reference means were within the range of scores for pediatric patients with a gastrointestinal disorder. MID values were generated using the SEM. Conclusions The findings support the clinical interpretability of the new PedsQL™ Gastrointestinal Symptoms Scales and Worry Scales. PMID:25682210
Terminology for contrast-enhanced sonography: a practical glossary.

PubMed

Catalano, Orlando; Migaleddu, Vincenzo; Quaia, Emilio; Caruso, Giuseppe

2007-06-01

The purpose of this glossary is to offer an updated guide to the correct terminology for contrast-enhanced sonography. This report was prepared by a panel of radiologists from the Sonography Section of the Italian Association of Medical Radiology. A leading author prepared a list of terms based on a comprehensive literature survey. The draft was analyzed by 3 experts on the topic of contrast-enhanced sonography. These reviewers reached a consensus and prepared the final version. A list of 137 terms is included. These terms are briefly defined. Their proper application is discussed, with special reference to potential misleading uses. Contrast-enhanced sonography is a relatively new diagnostic tool, now entering clinical practice in several countries. Use of appropriate, universal terminology is mandatory in the scientific setting to allow comparison between different published experiences. Additionally, use of clear, standardized terminology is necessary in the clinical setting to facilitate report understanding by the referring physician. Standardized, nonequivocal nomenclature may also help future diffusion of sonographic contrast media in countries where their application is still not approved.
[Evidence-based quality assessment of 10-year orthodontic clinical trials in 4 major dental journals].

PubMed

Sun, Yan-nan; Lei, Fei-fei; Cao, Yan-li; Fu, Min-kui

2010-02-01

To assess the quality of orthodontic clinical trials published in 4 major dental journals in the past 10 years and establish the reference standard for orthodontic clinical trials and quality control of dental journals. All the clinical trials published in Chinese Journal of Stomatology, West China Journal of Stomatology, Journal of Practice Stomatology and Chinese Journal of Orthodontics from 1999 to 2008 were searched. The demographic information of the papers was extracted and the quality of the clinical trials according to the consolidated standards of reporting trials (CONSORT) was assessed. Four hundred and ninety-four clinical trials were retrieved, and 21.3% (105/494) of them were supported by grants. For the study design, only 26.1% (129/494) were prospective studies, and 3.8% (19/494) were randomized clinical trials. It was hard to evaluate precisely due to the lack of information about the details of the study designs. For the randomized clinical trials, the lack of details for randomization, allocation concealment, blinding and intention to treat compromised the quality. The general quality of clinical trials in orthodontics is poor. It needs to be improved both in the clinical study design and the paper writing.
Understanding the 'Silver Book' - An important reference for standardised nomenclature in clinical laboratory sciences.

PubMed

Flatman, Robert; Férard, Georges; Dybkaer, René

2017-04-01

Clinical laboratories perform a wide menu of testing (examinations). Successful requesting, examination, and ordering in this environment requires clear standardised nomenclature. The Silver Book (SB) is an IUPAC (International Union of Pure and Applied Chemistry) publication, produced with the support of both IUPAC and the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine), that makes recommendations on logical standardised nomenclature, symbols, properties, and units in many disciplines of the clinical laboratory sciences. These recommendations are founded on and in agreement with the principles and work of the International Organization for Standardization (ISO), Bureau International des Poids et Mesures (BIPM), IUPAC, and the IFCC. Practical applications described are based on those scientific principles. The SB recommendations apply to all types of examination, not only to measurement of quantities but also examination of nominal properties where no magnitude is involved. The SB is applicable not only to clinical chemistry, but to many other clinical laboratory disciplines. For examples, reports regarding haemostasis, toxicology, clinical microbiology, reproduction and fertility, clinical pharmacology, clinical allergology, clinical molecular biology, and clinical immunohaematology have been published by the IUPAC and the IFCC. Peak scientific bodies such as the IUPAC and the IFCC have important roles in the development of sound international standards for nomenclature of examinations. Such standards support safe and effective representation of patient health information, foster portability, and empower future decision support systems. Copyright © 2016. Published by Elsevier B.V.
Source localization of rhythmic ictal EEG activity: a study of diagnostic accuracy following STARD criteria.

PubMed

Beniczky, Sándor; Lantz, Göran; Rosenzweig, Ivana; Åkeson, Per; Pedersen, Birthe; Pinborg, Lars H; Ziebell, Morten; Jespersen, Bo; Fuglsang-Frederiksen, Anders

2013-10-01

Although precise identification of the seizure-onset zone is an essential element of presurgical evaluation, source localization of ictal electroencephalography (EEG) signals has received little attention. The aim of our study was to estimate the accuracy of source localization of rhythmic ictal EEG activity using a distributed source model. Source localization of rhythmic ictal scalp EEG activity was performed in 42 consecutive cases fulfilling inclusion criteria. The study was designed according to recommendations for studies on diagnostic accuracy (STARD). The initial ictal EEG signals were selected using a standardized method, based on frequency analysis and voltage distribution of the ictal activity. A distributed source model-local autoregressive average (LAURA)-was used for the source localization. Sensitivity, specificity, and measurement of agreement (kappa) were determined based on the reference standard-the consensus conclusion of the multidisciplinary epilepsy surgery team. Predictive values were calculated from the surgical outcome of the operated patients. To estimate the clinical value of the ictal source analysis, we compared the likelihood ratios of concordant and discordant results. Source localization was performed blinded to the clinical data, and before the surgical decision. Reference standard was available for 33 patients. The ictal source localization had a sensitivity of 70% and a specificity of 76%. The mean measurement of agreement (kappa) was 0.61, corresponding to substantial agreement (95% confidence interval (CI) 0.38-0.84). Twenty patients underwent resective surgery. The positive predictive value (PPV) for seizure freedom was 92% and the negative predictive value (NPV) was 43%. The likelihood ratio was nine times higher for the concordant results, as compared with the discordant ones. Source localization of rhythmic ictal activity using a distributed source model (LAURA) for the ictal EEG signals selected with a standardized method is feasible in clinical practice and has a good diagnostic accuracy. Our findings encourage clinical neurophysiologists assessing ictal EEGs to include this method in their armamentarium. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Current status of antifungal susceptibility testing methods.

PubMed

Arikan, Sevtap

2007-11-01

Antifungal susceptibility testing is a very dynamic field of medical mycology. Standardization of in vitro susceptibility tests by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST), and current availability of reference methods constituted the major remarkable steps in the field. Based on the established minimum inhibitory concentration (MIC) breakpoints, it is now possible to determine the susceptibilities of Candida strains to fluconazole, itraconazole, voriconazole, and flucytosine. Moreover, utility of fluconazole antifungal susceptibility tests as an adjunct in optimizing treatment of candidiasis has now been validated. While the MIC breakpoints and clinical significance of susceptibility testing for the remaining fungi and antifungal drugs remain yet unclear, modifications of the available methods as well as other methodologies are being intensively studied to overcome the present drawbacks and limitations. Among the other methods under investigation are Etest, colorimetric microdilution, agar dilution, determination of fungicidal activity, flow cytometry, and ergosterol quantitation. Etest offers the advantage of practical application and favorable agreement rates with the reference methods that are frequently above acceptable limits. However, MIC breakpoints for Etest remain to be evaluated and established. Development of commercially available, standardized colorimetric panels that are based on CLSI method parameters has added more to the antifungal susceptibility testing armamentarium. Flow cytometry, on the other hand, appears to offer rapid susceptibility testing but requires specified equipment and further evaluation for reproducibility and standardization. Ergosterol quantitation is another novel approach, which appears potentially beneficial particularly in discrimination of azole-resistant isolates from heavy trailers. The method is yet investigational and requires to be further studied. Developments in methodology and applications of antifungal susceptibility testing will hopefully provide enhanced utility in clinical guidance of antifungal therapy. However, and particularly in immunosuppressed host, in vitro susceptibility is and will remain only one of several factors that influence clinical outcome.
Agreement between gastrointestinal panel testing and standard microbiology methods for detecting pathogens in suspected infectious gastroenteritis: Test evaluation and meta-analysis in the absence of a reference standard.

PubMed

Freeman, Karoline; Tsertsvadze, Alexander; Taylor-Phillips, Sian; McCarthy, Noel; Mistry, Hema; Manuel, Rohini; Mason, James

2017-01-01

Multiplex gastrointestinal pathogen panel (GPP) tests simultaneously identify bacterial, viral and parasitic pathogens from the stool samples of patients with suspected infectious gastroenteritis presenting in hospital or the community. We undertook a systematic review to compare the accuracy of GPP tests with standard microbiology techniques. Searches in Medline, Embase, Web of Science and the Cochrane library were undertaken from inception to January 2016. Eligible studies compared GPP tests with standard microbiology techniques in patients with suspected gastroenteritis. Quality assessment of included studies used tailored QUADAS-2. In the absence of a reference standard we analysed test performance taking GPP tests and standard microbiology techniques in turn as the benchmark test, using random effects meta-analysis of proportions. No study provided an adequate reference standard with which to compare the test accuracy of GPP and conventional tests. Ten studies informed a meta-analysis of positive and negative agreement. Positive agreement across all pathogens was 0.93 (95% CI 0.90 to 0.96) when conventional methods were the benchmark and 0.68 (95% CI: 0.58 to 0.77) when GPP provided the benchmark. Negative agreement was high in both instances due to the high proportion of negative cases. GPP testing produced a greater number of pathogen-positive findings than conventional testing. It is unclear whether these additional 'positives' are clinically important. GPP testing has the potential to simplify testing and accelerate reporting when compared to conventional microbiology methods. However the impact of GPP testing upon the management, treatment and outcome of patients is poorly understood and further studies are needed to evaluate the health economic impact of GPP testing compared with standard methods. The review protocol is registered with PROSPERO as CRD42016033320.
Better infrastructure for critical care trials: nomenclature, etymology, and informatics.

PubMed

Singh, Jeffrey M; Ferguson, Niall D

2009-01-01

The goals of this review article are to review the importance and value of standardized definitions in clinical research, as well as to propose the necessary tools and infrastructure needed to advance nosology and medial taxonomy to improve the quality of clinical trials in the field of critical care. We searched MEDLINE for relevant articles, reviewed those selected and their reference lists, and consulted personal files for relevant information. When the pathobiology of diseases is well understood, standard disease definitions can be extremely specific and precise; however, when the pathobiology of the disease is less well understood or more complex, biological markers may not be diagnostically useful or even available. In these cases, syndromic definitions effectively classify and group illnesses with similar symptoms and clinical signs. There is no clear gold standard for the diagnosis of many clinical entities in the intensive care unit, including notably both acute respiratory distress syndrome and sepsis. There are several types of consensus methods that can be used to explicate the judgmental approach that is often needed in these cases, including interactive or consensus groups, the nominal group technique, and the Delphi technique. Ideally, the definition development process will create clear and unambiguous language in which each definition accurately reflects the current understanding of the disease state. The development, implementation, evaluation, revision, and reevaluation of standardized definitions are keys for advancing the quality of clinical trials in the critical care arena.
[Brief on the standardization of the practitioner's posture in acupuncture operation].

PubMed

Lu, Yonghui

2015-07-01

To discuss the standardization of the practitioner's posture in acupuncture operation. Based on the relevant discussion on 'way to holding needle' recorded in Lingshu (Miraculous Pivot) and in association with the clinical acupuncture practice, it was required to standardize the practitioner's posture in acupuncture operation in reference to Lingshu (Miraculous Pivot). The standard standing posture of the practitioner is the precondition of acupuncture operation; the standard holding needle with the puncture hand is the key to the exercise of acupuncture technique and the regular standing orientation is the need of acupuncture operation. The three aspects are complemented each other, which is the coordinative procedure in acupuncture operation and enable the practitioner's high concentration with the body, qi and mind involved.
[Comparison and review on specifications of fermented Cordyceps sinensis products].

PubMed

Yang, Ping; Zhao, Xiao-Xia; Zhang, Yong-Wen

2018-02-01

There are five kinds of fermented Cordyceps crude drug and their preparations that have been approved as medicine on the market. Since the initial strains of the crude drug were all isolated from natural Cordyceps sinensis， they have similar names， chemical components and even clinical applications. However， because of the different strain species and fermentation processes， there was significant difference in quality. As a result， they should be clearly distinguished in clinical use. Most of the products were researched and developed during the 1980s and 1990s， so there was difference in quality standards for different products， and their quality control levels of some products were not perfect. At present， some of the products are approved as Chinese medicine， others are approved as chemical drugs， with a confusion in products name， management and clinical application. In this paper， the approval numbers， quality standards and clinical applications， and current problems of these products were summarized and compared; some suggestions were put forward， such as standardizing the product name， unifying the management of approval number category， and increasing the specific quality control attributes， in order to provide reference for standard implementation， quality control and drug regulation for fermented Cordyceps crude drugs and their preparations. Copyright© by the Chinese Pharmaceutical Association.
Adherence to Standards for Reporting Diagnostic Accuracy in Emergency Medicine Research.

PubMed

Gallo, Lucas; Hua, Nadia; Mercuri, Mathew; Silveira, Angela; Worster, Andrew

2017-08-01

Diagnostic tests are used frequently in the emergency department (ED) to guide clinical decision making and, hence, influence clinical outcomes. The Standards for Reporting of Diagnostic Accuracy (STARD) criteria were developed to ensure that diagnostic test studies are performed and reported to best inform clinical decision making in the ED. The objective was to determine the extent to which diagnostic studies published in emergency medicine journals adhered to STARD 2003 criteria. Diagnostic studies published in eight MEDLINE-listed, peer-reviewed, emergency medicine journals over a 5-year period were reviewed for compliance to STARD criteria. A total of 12,649 articles were screened and 114 studies were included in our study. Twenty percent of these were randomly selected for assessment using STARD 2003 criteria. Adherence to STARD 2003 reporting standards for each criteria ranged from 8.7% adherence (criteria-reporting adverse events from performing index test or reference standard) to 100% (multiple criteria). Just over half of STARD criteria are reported in more than 80% studies. As poorly reported studies may negatively impact their clinical usefulness, it is essential that studies of diagnostic test accuracy be performed and reported adequately. Future studies should assess whether studies have improved compliance with the STARD 2015 criteria amendment. © 2017 by the Society for Academic Emergency Medicine.
Valid analytical performance specifications for combined analytical bias and imprecision for the use of common reference intervals.

PubMed

Hyltoft Petersen, Per; Lund, Flemming; Fraser, Callum G; Sandberg, Sverre; Sölétormos, György

2018-01-01

Background Many clinical decisions are based on comparison of patient results with reference intervals. Therefore, an estimation of the analytical performance specifications for the quality that would be required to allow sharing common reference intervals is needed. The International Federation of Clinical Chemistry (IFCC) recommended a minimum of 120 reference individuals to establish reference intervals. This number implies a certain level of quality, which could then be used for defining analytical performance specifications as the maximum combination of analytical bias and imprecision required for sharing common reference intervals, the aim of this investigation. Methods Two methods were investigated for defining the maximum combination of analytical bias and imprecision that would give the same quality of common reference intervals as the IFCC recommendation. Method 1 is based on a formula for the combination of analytical bias and imprecision and Method 2 is based on the Microsoft Excel formula NORMINV including the fractional probability of reference individuals outside each limit and the Gaussian variables of mean and standard deviation. The combinations of normalized bias and imprecision are illustrated for both methods. The formulae are identical for Gaussian and log-Gaussian distributions. Results Method 2 gives the correct results with a constant percentage of 4.4% for all combinations of bias and imprecision. Conclusion The Microsoft Excel formula NORMINV is useful for the estimation of analytical performance specifications for both Gaussian and log-Gaussian distributions of reference intervals.
Interoperability of medical device information and the clinical applications: an HL7 RMIM based on the ISO/IEEE 11073 DIM.

PubMed

Yuksel, Mustafa; Dogac, Asuman

2011-07-01

Medical devices are essential to the practice of modern healthcare services. Their benefits will increase if clinical software applications can seamlessly acquire the medical device data. The need to represent medical device observations in a format that can be consumable by clinical applications has already been recognized by the industry. Yet, the solutions proposed involve bilateral mappings from the ISO/IEEE 11073 Domain Information Model (DIM) to specific message or document standards. Considering that there are many different types of clinical applications such as the electronic health record and the personal health record systems, the clinical workflows, and the clinical decision support systems each conforming to different standard interfaces, detailing a mapping mechanism for every one of them introduces significant work and, thus, limits the potential health benefits of medical devices. In this paper, to facilitate the interoperability of clinical applications and the medical device data, we use the ISO/IEEE 11073 DIM to derive an HL7 v3 Refined Message Information Model (RMIM) of the medical device domain from the HL7 v3 Reference Information Mode (RIM). This makes it possible to trace the medical device data back to a standard common denominator, that is, HL7 v3 RIM from which all the other medical domains under HL7 v3 are derived. Hence, once the medical device data are obtained in the RMIM format, it can easily be transformed into HL7-based standard interfaces through XML transformations because these interfaces all have their building blocks from the same RIM. To demonstrate this, we provide the mappings from the developed RMIM to some of the widely used HL7 v3-based standard interfaces.
Comprehensive reference ranges for hematology and clinical chemistry laboratory parameters derived from normal Nigerian adults.

PubMed

Miri-Dashe, Timzing; Osawe, Sophia; Tokdung, Monday; Daniel, Monday Tokdung Nenbammun; Daniel, Nenbammun; Choji, Rahila Pam; Mamman, Ille; Deme, Kurt; Damulak, Dapus; Abimiku, Alash'le

2014-01-01

Interpretation of laboratory test results with appropriate diagnostic accuracy requires reference or cutoff values. This study is a comprehensive determination of reference values for hematology and clinical chemistry in apparently healthy voluntary non-remunerated blood donors and pregnant women. Consented clients were clinically screened and counseled before testing for HIV, Hepatitis B, Hepatitis C and Syphilis. Standard national blood donors' questionnaire was administered to consented blood donors. Blood from qualified volunteers was used for measurement of complete hematology and chemistry parameters. Blood samples were analyzed from a total of 383 participants, 124 (32.4%) males, 125 (32.6%) non-pregnant females and 134 pregnant females (35.2%) with a mean age of 31 years. Our results showed that the red blood cells count (RBC), Hemoglobin (HB) and Hematocrit (HCT) had significant gender difference (p = 0.000) but not for total white blood count (p>0.05) which was only significantly higher in pregnant verses non-pregnant women (p = 0.000). Hemoglobin and Hematocrit values were lower in pregnancy (P = 0.000). Platelets were significantly higher in females than men (p = 0.001) but lower in pregnant women (p = .001) with marked difference in gestational period. For clinical chemistry parameters, there was no significant difference for sodium, potassium and chloride (p>0.05) but gender difference exists for Bicarbonate (HCO3), Urea nitrogen, Creatinine as well as the lipids (p<0.05). Total bilirubin was significantly higher in males than females (p = 0.000). Significant differences exist for all chemistry parameters between pregnant and non-pregnant women in this study (p<0.05), except Amylase and total cholesterol (p>0.05). Hematological and Clinical Chemistry reference ranges established in this study showed significant gender differences. Pregnant women also differed from non-pregnant females and during pregnancy. This is the first of such comprehensive study to establish reference values among adult Nigerians and difference observed underscore the need to establish reference values for different populations.

Validation of no-reference image quality index for the assessment of digital mammographic images

NASA Astrophysics Data System (ADS)

de Oliveira, Helder C. R.; Barufaldi, Bruno; Borges, Lucas R.; Gabarda, Salvador; Bakic, Predrag R.; Maidment, Andrew D. A.; Schiabel, Homero; Vieira, Marcelo A. C.

2016-03-01

To ensure optimal clinical performance of digital mammography, it is necessary to obtain images with high spatial resolution and low noise, keeping radiation exposure as low as possible. These requirements directly affect the interpretation of radiologists. The quality of a digital image should be assessed using objective measurements. In general, these methods measure the similarity between a degraded image and an ideal image without degradation (ground-truth), used as a reference. These methods are called Full-Reference Image Quality Assessment (FR-IQA). However, for digital mammography, an image without degradation is not available in clinical practice; thus, an objective method to assess the quality of mammograms must be performed without reference. The purpose of this study is to present a Normalized Anisotropic Quality Index (NAQI), based on the Rényi entropy in the pseudo-Wigner domain, to assess mammography images in terms of spatial resolution and noise without any reference. The method was validated using synthetic images acquired through an anthropomorphic breast software phantom, and the clinical exposures on anthropomorphic breast physical phantoms and patient's mammograms. The results reported by this noreference index follow the same behavior as other well-established full-reference metrics, e.g., the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). Reductions of 50% on the radiation dose in phantom images were translated as a decrease of 4dB on the PSNR, 25% on the SSIM and 33% on the NAQI, evidencing that the proposed metric is sensitive to the noise resulted from dose reduction. The clinical results showed that images reduced to 53% and 30% of the standard radiation dose reported reductions of 15% and 25% on the NAQI, respectively. Thus, this index may be used in clinical practice as an image quality indicator to improve the quality assurance programs in mammography; hence, the proposed method reduces the subjectivity inter-observers in the reporting of image quality assessment.
Poor peer relations predict parent- and self-reported behavioral and emotional problems of adolescents with gender dysphoria: a cross-national, cross-clinic comparative analysis.

PubMed

de Vries, Annelou L C; Steensma, Thomas D; Cohen-Kettenis, Peggy T; VanderLaan, Doug P; Zucker, Kenneth J

2016-06-01

This study is the third in a series to examine behavioral and emotional problems in children and adolescents with gender dysphoria in a comparative analysis between two clinics in Toronto, Ontario, Canada and Amsterdam, the Netherlands. In the present study, we report Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) data on adolescents assessed in the Toronto clinic (n = 177) and the Amsterdam clinic (n = 139). On the CBCL and the YSR, we found that the percentage of adolescents with clinical range behavioral and emotional problems was higher when compared to the non-referred standardization samples but similar to the referred adolescents. On both the CBCL and the YSR, the Toronto adolescents had a significantly higher Total Problem score than the Amsterdam adolescents. Like our earlier studies of CBCL data of children and Teacher's Report Form data of children and adolescents, a measure of poor peer relations was the strongest predictor of CBCL and YSR behavioral and emotional problems in gender dysphoric adolescents.
Whole body MRI, including diffusion-weighted imaging in follow-up of patients with testicular cancer.

PubMed

Mosavi, Firas; Laurell, Anna; Ahlström, Håkan

2015-11-01

Whole body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) has become increasingly utilized in cancer imaging, yet the clinical utility of these techniques in follow-up of testicular cancer patients has not been evaluated. The purpose of this study was to evaluate the feasibility of WB MRI with continuous table movement (CTM) technique, including multistep DWI in follow-up of patients with testicular cancer. WB MRI including DWI was performed in follow-up of 71 consecutive patients (median age, 37 years; range 19-84) with histologically confirmed testicular cancer. WB MRI protocol included axial T1-Dixon and T2-BLADE sequences using CTM technique. Furthermore, multi-step DWI was performed using b-value 50 and 1000 s/mm(2). One criterion for feasibility was patient tolerance and satisfactory image quality. Another criterion was the accuracy in detection of any pathological mass, compared to standard of reference. Signal intensity in DWI was used for evaluation of residual mass activity. Clinical, laboratory and imaging follow-up were applied as standard of reference for the evaluation of WB MRI. WB MRI was tolerated in nearly all patients (69/71 patients, 97%) and the image quality was satisfactory. Metal artifacts deteriorated the image quality in six patients, but it did not influence the overall results. No case of clinical relapse was observed during the follow-up time. There was a good agreement between conventional WB MRI and standard of reference in all patients. Three patients showed residual masses and DWI signal was not restricted in these patients. Furthermore, DWI showed abnormally high signal intensity in a normal-sized retroperitoneal lymph node indicating metastasis. The subsequent (18)F-FDG PET/CT could verify the finding. WB MRI with CTM technique including multi-step DWI is feasible in follow-up of patients with testicular cancer. DWI may contribute to important added-value data to conventional MRI sequences regarding the activity of residual masses.
Effect of Transitioning from Standard Reference Material 2806a to Standard Reference Material 2806b for Light Obscuration Particle Countering

DTIC Science & Technology

2016-04-01

Reference Material 2806b for Light Obscuration Particle Countering April 2016 UNCLASSIFIED UNCLASSIFIED Joel Schmitigal 27809 Standard Form 298 (Rev...Standard Reference Material 2806b for Light Obscuration Particle Countering 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Reference Material 2806a to Standard Reference Material 2806b for Light Obscuration Particle Countering Joel Schmitigal Force Projection
[When should a patient with musculoskeletal trauma be referred to emergency ward?].

PubMed

Feiner, Adam-Scott; Duruz, Henri

2010-08-25

Standardized clinical examination can obviate the need for osteoarticular radiographs for trauma. This paper summarizes a number of decision rules that allow clinical exclusion of significant fracture of the cervical spine, elbow, knee or ankle, making radiographs unnecessary. These criteria were all derived from large cohort studies (Nexus, Ottawa, CCS, etc..., and have been prospectively validated. The rigorous use of these criteria in daily practice improves treatment times and costs with no adverse effect on treatment quality.
A Simple Strategy for Implementing Standard Reference Terminologies in a Distributed Healthcare Delivery System with Minimal Impact to Existing Applications

PubMed Central

Bouhaddou, Omar; Lincoln, Michael J.; Maulden, Sarah; Murphy, Holli; Warnekar, Pradnya; Nguyen, Viet; Lam, Siew; Brown, Steven H; Frankson, Ferdinand J.; Crandall, Glen; Hughes, Carla; Sigley, Roger; Insley, Marcia; Graham, Gail

2006-01-01

The Veterans Administration (VA) has adopted an ambitious program to standardize its clinical terminology to comply with industry-wide standards. The VA is using commercially available tools and in-house software to create a high-quality reference terminology system. The terminology will be used by current and future applications with no planned disruption to operational systems. The first large customer of the group is the national VA Health Data Repository (HDR). Unique enterprise identifiers are assigned to each standard term, and a rich network of semantic relationships makes the resulting data not only recognizable, but highly computable and reusable in a variety of applications, including decision support and data sharing with partners such as the Department of Defense (DoD). This paper describes the specific methods and approaches that the VA has employed to develop and implement this innovative program in existing information system. The goal is to share with others our experience with key issues that face our industry as we move toward an electronic health record for every individual. PMID:17238306
The Joint Committee for Traceability in Laboratory Medicine (JCTLM) - its history and operation.

PubMed

Jones, Graham R D; Jackson, Craig

2016-01-30

The Joint Committee for Traceability in Laboratory Medicine (JCTLM) was formed to bring together the sciences of metrology, laboratory medicine and laboratory quality management. The aim of this collaboration is to support worldwide comparability and equivalence of measurement results in clinical laboratories for the purpose of improving healthcare. The JCTLM has its origins in the activities of international metrology treaty organizations, professional societies and federations devoted to improving measurement quality in physical, chemical and medical sciences. The three founding organizations, the International Committee for Weights and Measures (CIPM), the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the International Laboratory Accreditation Cooperation (ILAC) are the leaders of this activity. The main service of the JCTLM is a web-based database with a list of reference materials, reference methods and reference measurement services meeting appropriate international standards. This database allows manufacturers to select references for assay traceability and provides support for suppliers of these services. As of mid 2015 the database lists 295 reference materials for 162 analytes, 170 reference measurement procedures for 79 analytes and 130 reference measurement services for 39 analytes. There remains a need for the development and implementation of metrological traceability in many areas of laboratory medicine and the JCTLM will continue to promote these activities into the future. Copyright © 2015 Elsevier B.V. All rights reserved.
Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.

PubMed

French, Anna; Bravery, Christopher; Smith, James; Chandra, Amit; Archibald, Peter; Gold, Joseph D; Artzi, Natalie; Kim, Hae-Won; Barker, Richard W; Meissner, Alexander; Wu, Joseph C; Knowles, Jonathan C; Williams, David; García-Cardeña, Guillermo; Sipp, Doug; Oh, Steve; Loring, Jeanne F; Rao, Mahendra S; Reeve, Brock; Wall, Ivan; Carr, Andrew J; Bure, Kim; Stacey, Glyn; Karp, Jeffrey M; Snyder, Evan Y; Brindley, David A

2015-03-01

There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify "signatures" for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes. ©AlphaMed Press.
Enabling Consistency in Pluripotent Stem Cell-Derived Products for Research and Development and Clinical Applications Through Material Standards

PubMed Central

Bravery, Christopher; Smith, James; Chandra, Amit; Archibald, Peter; Gold, Joseph D.; Artzi, Natalie; Kim, Hae-Won; Barker, Richard W.; Meissner, Alexander; Wu, Joseph C.; Knowles, Jonathan C.; Williams, David; García-Cardeña, Guillermo; Sipp, Doug; Oh, Steve; Loring, Jeanne F.; Rao, Mahendra S.; Reeve, Brock; Wall, Ivan; Carr, Andrew J.; Bure, Kim; Stacey, Glyn; Karp, Jeffrey M.

2015-01-01

Summary There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify “signatures” for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes. PMID:25650438
The effect of cone beam CT (CBCT) on therapeutic decision-making in endodontics.

PubMed

Mota de Almeida, F J; Knutsson, K; Flygare, L

2014-01-01

The aim was to assess to what extent cone beam CT (CBCT) used in accordance with current European Commission guidelines in a normal clinical setting has an impact on therapeutic decisions in a population referred for endodontic problems. The study includes data of consecutively examined patients collected from October 2011 to December 2012. From 2 different endodontic specialist clinics, 57 patients were referred for a CBCT examination using criteria in accordance with current European guidelines. The CBCT examinations were performed using similar equipment and standardized among clinics. After a thorough clinical examination, but before CBCT, the examiner made a preliminary therapy plan which was recorded. After the CBCT examination, the same examiner made a new therapy plan. Therapy plans both before and after the CBCT examination were plotted for 53 patients and 81 teeth. As four patients had incomplete protocols, they were not included in the final analysis. 4% of the patients referred to endodontic clinics during the study period were examined with CBCT. The most frequent reason for referral to CBCT examination was to differentiate pathology from normal anatomy, this was the case in 24 patients (45% of the cases). The primary outcome was therapy plan changes that could be attributed to CBCT examination. There were changes in 28 patients (53%). CBCT has a significant impact on therapeutic decision efficacy in endodontics when used in concordance with the current European Commission guidelines.
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.
Multicenter evaluation of stress-first myocardial perfusion image triage by nuclear technologists and automated quantification.

PubMed

Chaudhry, Waseem; Hussain, Nasir; Ahlberg, Alan W; Croft, Lori B; Fernandez, Antonio B; Parker, Mathew W; Swales, Heather H; Slomka, Piotr J; Henzlova, Milena J; Duvall, W Lane

2017-06-01

A stress-first myocardial perfusion imaging (MPI) protocol saves time, is cost effective, and decreases radiation exposure. A limitation of this protocol is the requirement for physician review of the stress images to determine the need for rest images. This hurdle could be eliminated if an experienced technologist and/or automated computer quantification could make this determination. Images from consecutive patients who were undergoing a stress-first MPI with attenuation correction at two tertiary care medical centers were prospectively reviewed independently by a technologist and cardiologist blinded to clinical and stress test data. Their decision on the need for rest imaging along with automated computer quantification of perfusion results was compared with the clinical reference standard of an assessment of perfusion images by a board-certified nuclear cardiologist that included clinical and stress test data. A total of 250 patients (mean age 61 years and 55% female) who underwent a stress-first MPI were studied. According to the clinical reference standard, 42 (16.8%) and 208 (83.2%) stress-first images were interpreted as "needing" and "not needing" rest images, respectively. The technologists correctly classified 229 (91.6%) stress-first images as either "needing" (n = 28) or "not needing" (n = 201) rest images. Their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 66.7%, 96.6%, 80.0%, and 93.5%, respectively. An automated stress TPD score ≥1.2 was associated with optimal sensitivity and specificity and correctly classified 179 (71.6%) stress-first images as either "needing" (n = 31) or "not needing" (n = 148) rest images. Its sensitivity, specificity, PPV, and NPV were 73.8%, 71.2%, 34.1%, and 93.1%, respectively. In a model whereby the computer or technologist could correct for the other's incorrect classification, 242 (96.8%) stress-first images were correctly classified. The composite sensitivity, specificity, PPV, and NPV were 83.3%, 99.5%, 97.2%, and 96.7%, respectively. Technologists and automated quantification software had a high degree of agreement with the clinical reference standard for determining the need for rest images in a stress-first imaging protocol. Utilizing an experienced technologist and automated systems to screen stress-first images could expand the use of stress-first MPI to sites where the cardiologist is not immediately available for interpretation.
Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study.

PubMed

Bulla, O; Poncet, A; Alberio, L; Asmis, L M; Gähler, A; Graf, L; Nagler, M; Studt, J-D; Tsakiris, D A; Fontana, P

2017-07-01

Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue. Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories. Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard. When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard. In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard. © 2017 John Wiley & Sons Ltd.
CLSI-based transference and verification of CALIPER pediatric reference intervals for 29 Ortho VITROS 5600 chemistry assays.

PubMed

Higgins, Victoria; Truong, Dorothy; Woroch, Amy; Chan, Man Khun; Tahmasebi, Houman; Adeli, Khosrow

2018-03-01

Evidence-based reference intervals (RIs) are essential to accurately interpret pediatric laboratory test results. To fill gaps in pediatric RIs, the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) project developed an age- and sex-specific pediatric RI database based on healthy pediatric subjects. Originally established for Abbott ARCHITECT assays, CALIPER RIs were transferred to assays on Beckman, Roche, Siemens, and Ortho analytical platforms. This study provides transferred reference intervals for 29 biochemical assays for the Ortho VITROS 5600 Chemistry System (Ortho). Based on Clinical Laboratory Standards Institute (CLSI) guidelines, a method comparison analysis was performed by measuring approximately 200 patient serum samples using Abbott and Ortho assays. The equation of the line of best fit was calculated and the appropriateness of the linear model was assessed. This equation was used to transfer RIs from Abbott to Ortho assays. Transferred RIs were verified using 84 healthy pediatric serum samples from the CALIPER cohort. RIs for most chemistry analytes successfully transferred from Abbott to Ortho assays. Calcium and CO 2 did not meet statistical criteria for transference (r 2 <0.70). Of the 32 transferred reference intervals, 29 successfully verified with approximately 90% of results from reference samples falling within transferred confidence limits. Transferred RIs for total bilirubin, magnesium, and LDH did not meet verification criteria and are not reported. This study broadens the utility of the CALIPER pediatric RI database to laboratories using Ortho VITROS 5600 biochemical assays. Clinical laboratories should verify CALIPER reference intervals for their specific analytical platform and local population as recommended by CLSI. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
A candidate reference method for serum potassium measurement by inductively coupled plasma mass spectrometry.

PubMed

Yan, Ying; Han, Bingqing; Zeng, Jie; Zhou, Weiyan; Zhang, Tianjiao; Zhang, Jiangtao; Chen, Wenxiang; Zhang, Chuanbao

2017-08-28

Potassium is an important serum ion that is frequently assayed in clinical laboratories. Quality assurance requires reference methods; thus, the establishment of a candidate reference method for serum potassium measurements is important. An inductively coupled plasma mass spectrometry (ICP-MS) method was developed. Serum samples were gravimetrically spiked with an aluminum internal standard, digested with 69% ultrapure nitric acid, and diluted to the required concentration. The 39K/27Al ratios were measured by ICP-MS in hydrogen mode. The method was calibrated using 5% nitric acid matrix calibrators, and the calibration function was established using the bracketing method. The correlation coefficients between the measured 39K/27Al ratios and the analyte concentration ratios were >0.9999. The coefficients of variation were 0.40%, 0.68%, and 0.22% for the three serum samples, and the analytical recovery was 99.8%. The accuracy of the measurement was also verified by measuring certified reference materials, SRM909b and SRM956b. Comparison with the ion selective electrode routine method and international inter-laboratory comparisons gave satisfied results. The new ICP-MS method is specific, precise, simple, and low-cost, and it may be used as a candidate reference method for standardizing serum potassium measurements.
SU-F-BRD-10: Lung IMRT Planning Using Standardized Beam Bouquet Templates

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

Yuan, L; Wu, Q J.; Yin, F

2014-06-15

Purpose: We investigate the feasibility of choosing from a small set of standardized templates of beam bouquets (i.e., entire beam configuration settings) for lung IMRT planning to improve planning efficiency and quality consistency, and also to facilitate automated planning. Methods: A set of beam bouquet templates is determined by learning from the beam angle settings in 60 clinical lung IMRT plans. A k-medoids cluster analysis method is used to classify the beam angle configuration into clusters. The value of the average silhouette width is used to determine the ideal number of clusters. The beam arrangements in each medoid of themore » resulting clusters are taken as the standardized beam bouquet for the cluster, with the corresponding case taken as the reference case. The resulting set of beam bouquet templates was used to re-plan 20 cases randomly selected from the database and the dosimetric quality of the plans was evaluated against the corresponding clinical plans by a paired t-test. The template for each test case was manually selected by a planner based on the match between the test and reference cases. Results: The dosimetric parameters (mean±S.D. in percentage of prescription dose) of the plans using 6 beam bouquet templates and those of the clinical plans, respectively, and the p-values (in parenthesis) are: lung Dmean: 18.8±7.0, 19.2±7.0 (0.28), esophagus Dmean: 32.0±16.3, 34.4±17.9 (0.01), heart Dmean: 19.2±16.5, 19.4±16.6 (0.74), spinal cord D2%: 47.7±18.8, 52.0±20.3 (0.01), PTV dose homogeneity (D2%-D99%): 17.1±15.4, 20.7±12.2 (0.03).The esophagus Dmean, cord D02 and PTV dose homogeneity are statistically better in the plans using the standardized templates, but the improvements (<5%) may not be clinically significant. The other dosimetric parameters are not statistically different. Conclusion: It's feasible to use a small number of standardized beam bouquet templates (e.g. 6) to generate plans with quality comparable to that of clinical plans. Partially supported by NIH/NCI under grant #R21CA161389 and a master research grant by Varian Medical System.« less
Evidence-Based Diagnosis and Treatment of the Painful Sacroiliac Joint

PubMed Central

Laslett, Mark

2008-01-01

Sacroiliac joint (SIJ) pain refers to the pain arising from the SIJ joint structures. SIJ dysfunction generally refers to aberrant position or movement of SIJ structures that may or may not result in pain. This paper aims to clarify the difference between these clinical concepts and present current available evidence regarding diagnosis and treatment of SIJ disorders. Tests for SIJ dysfunction generally have poor inter-examiner reliability. A reference standard for SIJ dysfunction is not readily available, so validity of the tests for this disorder is unknown. Tests that stress the SIJ in order to provoke familiar pain have acceptable inter-examiner reliability and have clinically useful validity against an acceptable reference standard. It is unknown if provocation tests can reliably identify extra-articular SIJ sources of pain. Three or more positive pain provocation SIJ tests have sensitivity and specificity of 91% and 78%, respectively. Specificity of three or more positive tests increases to 87% in patients whose symptoms cannot be made to move towards the spinal midline, i.e., centralize. In chronic back pain populations, patients who have three or more positive provocation SIJ tests and whose symptoms cannot be made to centralize have a probability of having SIJ pain of 77%, and in pregnant populations with back pain, a probability of 89%. This combination of test findings could be used in research to evaluate the efficacy of specific treatments for SIJ pain. Treatments most likely to be effective are specific lumbopelvic stabilization training and injections of corticosteroid into the intra-articular space. PMID:19119403
Clinical Impact of Wordless Picture Storybooks on Bilingual Narrative Language Production: A Comparison of the "Frog" Stories

ERIC Educational Resources Information Center

Heilmann, John J.; Rojas, Raúl; Iglesias, Aquiles; Miller, Jon F.

2016-01-01

Background: Language sampling, recognized as a gold standard for expressive language assessment, is often elicited using wordless picture storybooks. A series of wordless storybooks, commonly referred to as "Frog" stories, have been frequently used in language-based research with children from around the globe. Aims: To examine the…
Autism Spectrum Disorders in Gender Dysphoric Children and Adolescents

ERIC Educational Resources Information Center

de Vries, Annelou L. C.; Noens, Ilse L. J.; Cohen-Kettenis, Peggy T.; van Berckelaer-Onnes, Ina A.; Doreleijers, Theo A.

2010-01-01

Only case reports have described the co-occurrence of gender identity disorder (GID) and autism spectrum disorders (ASD). This study examined this co-occurrence using a systematic approach. Children and adolescents (115 boys and 89 girls, mean age 10.8, SD = 3.58) referred to a gender identity clinic received a standardized assessment during which…
Accuracy of Blood Loss Measurement during Cesarean Delivery.

PubMed

Doctorvaladan, Sahar V; Jelks, Andrea T; Hsieh, Eric W; Thurer, Robert L; Zakowski, Mark I; Lagrew, David C

2017-04-01

Objective This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland-Altman method. Results Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R 2 = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R 2 = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R 2 = 0.304). Conclusion During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes.

Accuracy of Blood Loss Measurement during Cesarean Delivery

PubMed Central

Doctorvaladan, Sahar V.; Jelks, Andrea T.; Hsieh, Eric W.; Thurer, Robert L.; Zakowski, Mark I.; Lagrew, David C.

2017-01-01

Objective This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland–Altman method. Results Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R2 = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes. PMID:28497007
Biophysical characterization and structure of the Fab fragment from the NIST reference antibody, RM 8671.

PubMed

Karageorgos, Ioannis; Gallagher, Elyssia S; Galvin, Connor; Gallagher, D Travis; Hudgens, Jeffrey W

2017-11-01

Monoclonal antibody pharmaceuticals are the fastest-growing class of therapeutics, with a wide range of clinical applications. To assure their safety, these protein drugs must demonstrate highly consistent purity and stability. Key to these objectives is higher order structure measurements validated by calibration to reference materials. We describe preparation, characterization, and crystal structure of the Fab fragment prepared from the NIST Reference Antibody RM 8671 (NISTmAb). NISTmAb is a humanized IgG1κ antibody, produced in murine cell culture and purified by standard biopharmaceutical production methods, developed at the National Institute of Standards and Technology (NIST) to serve as a reference material. The Fab fragment was derived from NISTmAb through papain cleavage followed by protein A based purification. The purified Fab fragment was characterized by SDS-PAGE, capillary gel electrophoresis, multi-angle light scattering, size exclusion chromatography, mass spectrometry, and x-ray crystallography. The crystal structure at 0.2 nm resolution includes four independent Fab molecules with complete light chains and heavy chains through Cys 223, enabling assessment of conformational variability and providing a well-characterized reference structure for research and engineering applications. This nonproprietary, publically available reference material of known higher-order structure can support metrology in biopharmaceutical applications, and it is a suitable platform for validation of molecular modeling studies. Published by Elsevier Ltd.
Children with Chronic Lung Disease: Facilitating Smoking Cessation for their Caregivers.

PubMed

Bacewicz, Aleksandra; Wang, Wei; Ashouri, Judy; ElMallah, Mai K

2015-06-01

Through a QI project at a tertiary referral pediatric pulmonary center, our objective was to establish a methodical approach to identify and engage smoking parents of children with chronic lung disease in a smoking cessation program. We hypothesized that smoking caregivers of children with chronic lung disease would be more motivated to enroll in a smoking cessation program when referred from tertiary pediatric pulmonary center. We assessed smoking habits and interest in quitting of parents with surveys. Parents ready to quit within 30 days were referred to the Florida Quitline from clinic. Pulmonary function tests, exacerbations, hospitalizations and need for prednisone or antibiotics were obtained from the patient charts and surveys. Follow-up two to 6 months later assessed the quit rate and child's clinical well-being and lung function. A standard mechanism to identify caregivers who smoked was established by engaging our medical assistants through a prompt in our EMR system. Out of those caregivers who were identified as smokers and accompanied their children to clinic, 52% were interested in a referral to the Florida Quitline. Out of those, only 12% successfully completed the program and ceased to smoke. The Florida Quitline was unable to reach the majority of parents who were referred to them. The majority of those referred to the Ouitline were not successfully contacted or enrolled in the program. The current procedure for referring and enrolling individuals to the Quitline is not effective for our population, but compares to the national average.
Reference intervals and allometric scaling of two-dimensional echocardiographic measurements in 150 healthy cats.

PubMed

Karsten, Schober; Stephanie, Savino; Vedat, Yildiz

2017-11-10

The objective of the study was to evaluate the effects of body weight (BW), breed, and sex on two-dimensional (2D) echocardiographic measures, reference ranges, and prediction intervals using allometrically-scaled data of left atrial (LA) and left ventricular (LV) size and LV wall thickness in healthy cats. Study type was retrospective, observational, and clinical cohort. 150 healthy cats were enrolled and 2D echocardiograms analyzed. LA diameter, LV wall thickness, and LV dimension were quantified using three different imaging views. The effect of BW, breed, sex, age, and interaction (BW*sex) on echocardiographic variables was assessed using univariate and multivariate regression and linear mixed model analysis. Standard (using raw data) and allometrically scaled (Y=a × M b ) reference intervals and prediction intervals were determined. BW had a significant (P<0.05) independent effect on 2D variables whereas breed, sex, and age did not. There were clinically relevant differences between reference intervals using mean ± 2SD of raw data and mean and 95% prediction interval of allometrically-scaled variables, most prominent in larger (>6 kg) and smaller (<3 kg) cats. A clinically relevant difference between thickness of the interventricular septum (IVS) and dimension of the LV posterior wall (LVPW) was identified. In conclusion, allometric scaling and BW-based 95% prediction intervals should be preferred over conventional 2D echocardiographic reference intervals in cats, in particular in small and large cats. These results are particularly relevant to screening examinations for feline hypertrophic cardiomyopathy.
Accurate detection of low prevalence AKT1 E17K mutation in tissue or plasma from advanced cancer patients

PubMed Central

de Bruin, Elza C.; Whiteley, Jessica L.; Corcoran, Claire; Kirk, Pauline M.; Fox, Jayne C.; Armisen, Javier; Lindemann, Justin P. O.; Schiavon, Gaia; Ambrose, Helen J.; Kohlmann, Alexander

2017-01-01

Personalized healthcare relies on accurate companion diagnostic assays that enable the most appropriate treatment decision for cancer patients. Extensive assay validation prior to use in a clinical setting is essential for providing a reliable test result. This poses a challenge for low prevalence mutations with limited availability of appropriate clinical samples harboring the mutation. To enable prospective screening for the low prevalence AKT1 E17K mutation, we have developed and validated a competitive allele-specific TaqMan® PCR (castPCR™) assay for mutation detection in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Analysis parameters of the castPCR™ assay were established using an FFPE DNA reference standard and its analytical performance was assessed using 338 breast cancer and gynecological cancer FFPE samples. With recent technical advances for minimally invasive mutation detection in circulating tumor DNA (ctDNA), we subsequently also evaluated the OncoBEAM™ assay to enable plasma specimens as additional diagnostic opportunity for AKT1 E17K mutation testing. The analysis performance of the OncoBEAM™ test was evaluated using a novel AKT1 E17K ctDNA reference standard consisting of sheared genomic DNA spiked into human plasma. Both assays are employed at centralized testing laboratories operating according to quality standards for prospective identification of the AKT1 E17K mutation in ER+ breast cancer patients in the context of a clinical trial evaluating the AKT inhibitor AZD5363 in combination with endocrine (fulvestrant) therapy. PMID:28472036
A hand‐carried cardiac ultrasound device in the outpatient cardiology clinic reduces the need for standard echocardiography

PubMed Central

Trambaiolo, P; Papetti, F; Posteraro, A; Amici, E; Piccoli, M; Cerquetani, E; Pastena, G; Gambelli, G; Salustri, A

2007-01-01

Objective To assess the potential value and cost‐effectiveness of a hand‐carried ultrasound (HCU) device in an outpatient cardiology clinic. Methods 222 consecutive patients were prospectively enrolled in the study. When standard echocardiography (SE) was specifically indicated on the basis of clinical history, electrocardiogram and physical examination, the same cardiologist (level‐2 or level‐3 trained) immediately performed an HCU examination. The cardiologist then reassessed the clinical situation to confirm or cancel the SE request according to the information provided by HCU. The SE examination was performed by a sonographer and examined in a blinded fashion by a cardiologist expert in echocardiography. Findings from the two examinations were compared. Results HCU was performed in 108/222 patients, and a definite diagnosis was established in 34 of them (31%), making SE examination potentially avoidable. In the 74 patients with inconclusive HCU results and for whom SE was still indicated, the decision was mainly dictated by the lack of spectral Doppler modality in the HCU system. The overall agreement between HCU and SE for diagnosis of normal/abnormal echocardiograms was 73% (κ = 0.4). On the basis of the potentially avoided SE examinations and the obviated need for a second cardiac consultation, a total cost saving of €2142 per 100 patients referred for echocardiography was estimated. Conclusions The use of a simple HCU device in the outpatient cardiology clinic allowed reliable diagnosis in one third of the patients referred for echocardiography, which translates into cost and time saving benefits. PMID:16940393
Clinical biochemistry, haematology and body weight in piglets.

PubMed

Egeli, A K; Framstad, T; Morberg, H

1998-01-01

Reference ranges for clinical biochemical parameters commonly investigated in pigs were determined in one- (day 1), 21- and 35-day old piglets. The mean and standard deviation were also estimated for body weight, and haematological and clinical biochemical parameters at these ages. The piglets were divided into 2 investigation groups according to whether they had a haemoglobin concentration < or = 80 g/l ("anaemic group") or > 80 g/l ("normal group") on days 14, 21 and 28. The "anaemic group" was compared to the "normal group" on days 21 and 35. Many of the clinical biochemical parameters varied according to age. Some of the enzymes had high average values and wide reference ranges in piglets, especially on day 1, compared to the reference ranges for sows given in the literature. The reference ranges for some of the metabolic parameters were broader on day 1 than later in the preweaning period. The reference ranges for albumin, total iron-binding capacity and serum iron were, however, lower and more narrow on day 1. On days 21 and 35, relatively high values for phosphorus must be considered "normal" compared to the figures given in the literature for adult pigs. The other minerals seemed to be quite unaffected of age, but some were affected by anaemia. The anaemic piglets had lower average serum iron but higher total iron-binding capacity than the "normal" piglets on days 21 and 35. However, variation between piglets gave wide reference ranges, indicating that these parameters will only have limited usefulness in detecting iron deficiency anaemia in piglets. The electrolytes seemed also to be affected by the existence of anaemia. The body weight and leukocyte counts were significantly lower in the "anaemic group" than the "normal group" on day 35, while the greatest differences in clinical biochemical parameters between the groups were found on day 21, when the piglets in the "anaemic group" were most severely anaemic. Although these piglets suffered from severe iron-deficiency anaemia, only a few clinical biochemical parameters were affected, and the differences between groups were mostly small.
Normative Standards for HRpQCT Parameters in Chinese Men and Women.

PubMed

Zhu, Tracy Y; Yip, Benjamin Hk; Hung, Vivian Wy; Choy, Carol Wy; Cheng, Ka-Lo; Kwok, Timothy Cy; Cheng, Jack Cy; Qin, Ling

2018-06-12

Assessing bone architecture using high resolution peripheral quantitative computed tomography (HRpQCT) has the potential to improve fracture risk assessment. The Normal Reference Study aimed to establish sex-specific reference centile curves for HRpQCT parameters. This was an age-stratified cross-sectional study and 1,072 ambulatory Chinese men (n = 544) and women (n = 528) aged 20-79yrs, who were free from conditions and medications that could affect bone metabolism and had no history of fragility fracture, were recruited from local communities of Hong Kong. Reference centile curves for each HRpQCT parameter were constructed using Generalized Additive Models for Location, Scale and Shape with age as the only explanatory variable. Patterns of reference centile curves reflected age-related changes of bone density, microarchitecture, and estimated bone strength. In both sexes, loss of cortical bone was only evident in mid-adulthood, particularly in women with a more rapid fashion probably concurrent with the onset of menopause. In contrast, loss of trabecular bone was subtle or gradual or occurred at an earlier age. Expected values of HRpQCT parameters for a defined sex and age, and a defined percentile or z-score were obtained from these curves. T-scores were calculated using the population with the peak values as the reference and reflected age- or menopause-related bone loss in an older individual or the room to reach the peak potential in a younger individual. These reference centile curves produced a standard describing a norm or desirable target that enables value clinical judgements. Percentiles, z-scores and T-scores would be helpful in detecting abnormalities in bone density and microarchitecture arising from various conditions and establishing entry criteria for clinical trials. They also hold the potential to refine the diagnosis of osteoporosis and assessment of fracture risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Non-invasive prediction of forthcoming cirrhosis-related complications

PubMed Central

Kang, Wonseok; Kim, Seung Up; Ahn, Sang Hoon

2014-01-01

In patients with chronic liver diseases, identification of significant liver fibrosis and cirrhosis is essential for determining treatment strategies, assessing therapeutic response, and stratifying long-term prognosis. Although liver biopsy remains the reference standard for evaluating the extent of liver fibrosis in patients with chronic liver diseases, several non-invasive methods have been developed as alternatives to liver biopsies. Some of these non-invasive methods have demonstrated clinical accuracy for diagnosing significant fibrosis or cirrhosis in many cross-sectional studies with the histological fibrosis stage as a reference standard. However, non-invasive methods cannot be fully validated through cross-sectional studies since liver biopsy is not a perfect surrogate endpoint marker. Accordingly, recent studies have focused on assessing the performance of non-invasive methods through long-term, longitudinal, follow-up studies with solid clinical endpoints related to advanced stages of liver fibrosis and cirrhosis. As a result, current view is that these alternative methods can independently predict future cirrhosis-related complications, such as hepatic decompensation, liver failure, hepatocellular carcinoma, or liver-related death. The clinical role of non-invasive models seems to be shifting from a simple tool for predicting the extent of fibrosis to a surveillance tool for predicting future liver-related events. In this article, we will summarize recent longitudinal studies of non-invasive methods for predicting forthcoming complications related to liver cirrhosis and discuss the clinical value of currently available non-invasive methods based on evidence from the literature. PMID:24627597
Clinical value of 18 FDG PET/CT in screening for distant metastases in head and neck squamous cell carcinoma.

PubMed

Deurvorst, S E; Hoekstra, O S; Castelijns, J A; Witte, B I; Leemans, C R; de Bree, R

2018-06-01

The detection of distant metastases is of major importance in management of head and neck squamous cell carcinoma patients. All patients underwent 18 FDG PET/CT for the detection of distant metastases. Retrospective single-centre study. Head and neck squamous cell carcinoma patients with high-risk factors for distant metastases. Accuracy of 18 FDG PET/CT for the detection of distant metastases using clinical development of distant metastases and a minimal follow-up of twelve months as reference standard. Comparison of overall survival between patients diagnosed with distant metastases during initial screening and patients diagnosed with distant metastases during follow-up. In 23 (12%) of the 190 patients, 18 FDG PET/CT detected distant metastases at screening. Sensitivity and negative predictive value were 46.2% (95% CI 32.6-59.7) and 82.6% (95% CI 76.8-88.5). No difference in median overall survival from the time of distant metastases detection was found between patients diagnosed with DM during work-up or during follow-up. In head and neck squamous cell carcinoma patients with high-risk factors, 18 FDG PET/CT has a high negative predictive value for the detection of distant metastases and should be used in daily clinical practice, although the sensitivity is limited when long-term follow-up is used as reference standard. © 2018 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.
Guidelines for Assessment of Gait and Reference Values for Spatiotemporal Gait Parameters in Older Adults: The Biomathics and Canadian Gait Consortiums Initiative

PubMed Central

Beauchet, Olivier; Allali, Gilles; Sekhon, Harmehr; Verghese, Joe; Guilain, Sylvie; Steinmetz, Jean-Paul; Kressig, Reto W.; Barden, John M.; Szturm, Tony; Launay, Cyrille P.; Grenier, Sébastien; Bherer, Louis; Liu-Ambrose, Teresa; Chester, Vicky L.; Callisaya, Michele L.; Srikanth, Velandai; Léonard, Guillaume; De Cock, Anne-Marie; Sawa, Ryuichi; Duque, Gustavo; Camicioli, Richard; Helbostad, Jorunn L.

2017-01-01

Background: Gait disorders, a highly prevalent condition in older adults, are associated with several adverse health consequences. Gait analysis allows qualitative and quantitative assessments of gait that improves the understanding of mechanisms of gait disorders and the choice of interventions. This manuscript aims (1) to give consensus guidance for clinical and spatiotemporal gait analysis based on the recorded footfalls in older adults aged 65 years and over, and (2) to provide reference values for spatiotemporal gait parameters based on the recorded footfalls in healthy older adults free of cognitive impairment and multi-morbidities. Methods: International experts working in a network of two different consortiums (i.e., Biomathics and Canadian Gait Consortium) participated in this initiative. First, they identified items of standardized information following the usual procedure of formulation of consensus findings. Second, they merged databases including spatiotemporal gait assessments with GAITRite® system and clinical information from the “Gait, cOgnitiOn & Decline” (GOOD) initiative and the Generation 100 (Gen 100) study. Only healthy—free of cognitive impairment and multi-morbidities (i.e., ≤ 3 therapeutics taken daily)—participants aged 65 and older were selected. Age, sex, body mass index, mean values, and coefficients of variation (CoV) of gait parameters were used for the analyses. Results: Standardized systematic assessment of three categories of items, which were demographics and clinical information, and gait characteristics (clinical and spatiotemporal gait analysis based on the recorded footfalls), were selected for the proposed guidelines. Two complementary sets of items were distinguished: a minimal data set and a full data set. In addition, a total of 954 participants (mean age 72.8 ± 4.8 years, 45.8% women) were recruited to establish the reference values. Performance of spatiotemporal gait parameters based on the recorded footfalls declined with increasing age (mean values and CoV) and demonstrated sex differences (mean values). Conclusions: Based on an international multicenter collaboration, we propose consensus guidelines for gait assessment and spatiotemporal gait analysis based on the recorded footfalls, and reference values for healthy older adults. PMID:28824393
Use of Fat Mass and Fat Free Mass Standard Deviation Scores Obtained Using Simple Measurement Methods in Healthy Children and Patients: Comparison with the Reference 4-Component Model

PubMed Central

Atherton, Rachel R.; Williams, Jane E.; Wells, Jonathan C. K.; Fewtrell, Mary S.

2013-01-01

Background Clinical application of body composition (BC) measurements for individual children has been limited by lack of appropriate reference data. Objectives (1) To compare fat mass (FM) and fat free mass (FFM) standard deviation scores (SDS) generated using new body composition reference data and obtained using simple measurement methods in healthy children and patients with those obtained using the reference 4-component (4-C) model; (2) To determine the extent to which scores from simple methods agree with those from the 4-C model in identification of abnormal body composition. Design FM SDS were calculated for 4-C model, dual-energy X-ray absorptiometry (DXA; GE Lunar Prodigy), BMI and skinfold thicknesses (SFT); and FFM SDS for 4CM, DXA and bioelectrical impedance analysis (BIA; height2/Z)) in 927 subjects aged 3.8–22.0 y (211 healthy, 716 patients). Results DXA was the most accurate method for both FM and FFM SDS in healthy subjects and patients (mean bias (limits of agreement) FM SDS 0.03 (±0.62); FFM SDS −0.04 (±0.72)), and provided best agreement with the 4-C model in identifying abnormal BC (SDS ≤−2 or ≥2). BMI and SFTs were reasonable predictors of abnormal FM SDS, but poor in providing an absolute value. BIA was comparable to DXA for FFM SDS and in identifying abnormal subjects. Conclusions DXA may be used both for research and clinically to determine FM and FFM SDS. BIA may be used to assess FFM SDS in place of DXA. BMI and SFTs can be used to measure adiposity for groups but not individuals. The performance of simpler techniques in monitoring longitudinal BC changes requires investigation. Ultimately, the most appropriate method should be determined by its predictive value for clinical outcome. PMID:23690932
Use of fat mass and fat free mass standard deviation scores obtained using simple measurement methods in healthy children and patients: comparison with the reference 4-component model.

PubMed

Atherton, Rachel R; Williams, Jane E; Wells, Jonathan C K; Fewtrell, Mary S

2013-01-01

Clinical application of body composition (BC) measurements for individual children has been limited by lack of appropriate reference data. (1) To compare fat mass (FM) and fat free mass (FFM) standard deviation scores (SDS) generated using new body composition reference data and obtained using simple measurement methods in healthy children and patients with those obtained using the reference 4-component (4-C) model; (2) To determine the extent to which scores from simple methods agree with those from the 4-C model in identification of abnormal body composition. FM SDS were calculated for 4-C model, dual-energy X-ray absorptiometry (DXA; GE Lunar Prodigy), BMI and skinfold thicknesses (SFT); and FFM SDS for 4CM, DXA and bioelectrical impedance analysis (BIA; height(2)/Z)) in 927 subjects aged 3.8-22.0 y (211 healthy, 716 patients). DXA was the most accurate method for both FM and FFM SDS in healthy subjects and patients (mean bias (limits of agreement) FM SDS 0.03 (± 0.62); FFM SDS -0.04 (± 0.72)), and provided best agreement with the 4-C model in identifying abnormal BC (SDS ≤-2 or ≥ 2). BMI and SFTs were reasonable predictors of abnormal FM SDS, but poor in providing an absolute value. BIA was comparable to DXA for FFM SDS and in identifying abnormal subjects. DXA may be used both for research and clinically to determine FM and FFM SDS. BIA may be used to assess FFM SDS in place of DXA. BMI and SFTs can be used to measure adiposity for groups but not individuals. The performance of simpler techniques in monitoring longitudinal BC changes requires investigation. Ultimately, the most appropriate method should be determined by its predictive value for clinical outcome.
Comparison of the Vitek 2 Antifungal Susceptibility System with the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) Broth Microdilution Reference Methods and with the Sensititre YeastOne and Etest Techniques for In Vitro Detection of Antifungal Resistance in Yeast Isolates ▿ ‖

PubMed Central

Cuenca-Estrella, Manuel; Gomez-Lopez, Alicia; Alastruey-Izquierdo, Ana; Bernal-Martinez, Leticia; Cuesta, Isabel; Buitrago, Maria J.; Rodriguez-Tudela, Juan L.

2010-01-01

The commercial technique Vitek 2 system for antifungal susceptibility testing of yeast species was evaluated. A collection of 154 clinical yeast isolates, including amphotericin B- and azole-resistant organisms, was tested. Results were compared with those obtained by the reference procedures of both the CLSI and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Two other commercial techniques approved for clinical use, the Etest and the Sensititre YeastOne, were included in the comparative exercise as well. The average essential agreement (EA) between the Vitek 2 system and the reference procedures was >95%, comparable with the average EAs observed between the reference procedures and the Sensititre YeastOne and Etest. The EA values were >97% for Candida spp. and stood at 92% for Cryptococcus neoformans. Intraclass correlation coefficients (ICC) between the commercial techniques and the reference procedures were statistically significant (P < 0.01). Percentages of very major errors were 2.6% between Vitek 2 and the EUCAST technique and 1.6% between Vitek 2 and the CLSI technique. The Vitek 2 MIC results were available after 14 to 18 h of incubation for all Candida spp. (average time to reading, 15.5 h). The Vitek 2 system was shown to be a reliable technique to determine antifungal susceptibility testing of yeast species and a more rapid and easier alternative for clinical laboratories than the procedures developed by either the CLSI or EUCAST. PMID:20220169
1000 Norms Project: protocol of a cross-sectional study cataloging human variation.

PubMed

McKay, Marnee J; Baldwin, Jennifer N; Ferreira, Paulo; Simic, Milena; Vanicek, Natalie; Hiller, Claire E; Nightingale, Elizabeth J; Moloney, Niamh A; Quinlan, Kate G; Pourkazemi, Fereshteh; Sman, Amy D; Nicholson, Leslie L; Mousavi, Seyed J; Rose, Kristy; Raymond, Jacqueline; Mackey, Martin G; Chard, Angus; Hübscher, Markus; Wegener, Caleb; Fong Yan, Alycia; Refshauge, Kathryn M; Burns, Joshua

2016-03-01

Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or 'normal' values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. In 2012 the 1000 Norms Project Consortium defined the concept of 'normal', established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype ('gene for speed'). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.
Preparation and value assignment of standard reference material 968e fat-soluble vitamins, carotenoids, and cholesterol in human serum.

PubMed

Thomas, Jeanice B; Duewer, David L; Mugenya, Isaac O; Phinney, Karen W; Sander, Lane C; Sharpless, Katherine E; Sniegoski, Lorna T; Tai, Susan S; Welch, Michael J; Yen, James H

2012-01-01

Standard Reference Material 968e Fat-Soluble Vitamins, Carotenoids, and Cholesterol in Human Serum provides certified values for total retinol, γ- and α-tocopherol, total lutein, total zeaxanthin, total β-cryptoxanthin, total β-carotene, 25-hydroxyvitamin D(3), and cholesterol. Reference and information values are also reported for nine additional compounds including total α-cryptoxanthin, trans- and total lycopene, total α-carotene, trans-β-carotene, and coenzyme Q(10). The certified values for the fat-soluble vitamins and carotenoids in SRM 968e were based on the agreement of results from the means of two liquid chromatographic methods used at the National Institute of Standards and Technology (NIST) and from the median of results of an interlaboratory comparison exercise among institutions that participate in the NIST Micronutrients Measurement Quality Assurance Program. The assigned values for cholesterol and 25-hydroxyvitamin D(3) in the SRM are the means of results obtained using the NIST reference method based upon gas chromatography-isotope dilution mass spectrometry and liquid chromatography-isotope dilution tandem mass spectrometry, respectively. SRM 968e is currently one of two available health-related NIST reference materials with concentration values assigned for selected fat-soluble vitamins, carotenoids, and cholesterol in human serum matrix. This SRM is used extensively by laboratories worldwide primarily to validate methods for determining these analytes in human serum and plasma and for assigning values to in-house control materials. The value assignment of the analytes in this SRM will help support measurement accuracy and traceability for laboratories performing health-related measurements in the clinical and nutritional communities.
Physical tests for shoulder impingements and local lesions of bursa, tendon or labrum that may accompany impingement.

PubMed

Hanchard, Nigel C A; Lenza, Mário; Handoll, Helen H G; Takwoingi, Yemisi

2013-04-30

Impingement is a common cause of shoulder pain. Impingement mechanisms may occur subacromially (under the coraco-acromial arch) or internally (within the shoulder joint), and a number of secondary pathologies may be associated. These include subacromial-subdeltoid bursitis (inflammation of the subacromial portion of the bursa, the subdeltoid portion, or both), tendinopathy or tears affecting the rotator cuff or the long head of biceps tendon, and glenoid labral damage. Accurate diagnosis based on physical tests would facilitate early optimisation of the clinical management approach. Most people with shoulder pain are diagnosed and managed in the primary care setting. To evaluate the diagnostic accuracy of physical tests for shoulder impingements (subacromial or internal) or local lesions of bursa, rotator cuff or labrum that may accompany impingement, in people whose symptoms and/or history suggest any of these disorders. We searched electronic databases for primary studies in two stages. In the first stage, we searched MEDLINE, EMBASE, CINAHL, AMED and DARE (all from inception to November 2005). In the second stage, we searched MEDLINE, EMBASE and AMED (2005 to 15 February 2010). Searches were delimited to articles written in English. We considered for inclusion diagnostic test accuracy studies that directly compared the accuracy of one or more physical index tests for shoulder impingement against a reference test in any clinical setting. We considered diagnostic test accuracy studies with cross-sectional or cohort designs (retrospective or prospective), case-control studies and randomised controlled trials. Two pairs of review authors independently performed study selection, assessed the study quality using QUADAS, and extracted data onto a purpose-designed form, noting patient characteristics (including care setting), study design, index tests and reference standard, and the diagnostic 2 x 2 table. We presented information on sensitivities and specificities with 95% confidence intervals (95% CI) for the index tests. Meta-analysis was not performed. We included 33 studies involving 4002 shoulders in 3852 patients. Although 28 studies were prospective, study quality was still generally poor. Mainly reflecting the use of surgery as a reference test in most studies, all but two studies were judged as not meeting the criteria for having a representative spectrum of patients. However, even these two studies only partly recruited from primary care.The target conditions assessed in the 33 studies were grouped under five main categories: subacromial or internal impingement, rotator cuff tendinopathy or tears, long head of biceps tendinopathy or tears, glenoid labral lesions and multiple undifferentiated target conditions. The majority of studies used arthroscopic surgery as the reference standard. Eight studies utilised reference standards which were potentially applicable to primary care (local anaesthesia, one study; ultrasound, three studies) or the hospital outpatient setting (magnetic resonance imaging, four studies). One study used a variety of reference standards, some applicable to primary care or the hospital outpatient setting. In two of these studies the reference standard used was acceptable for identifying the target condition, but in six it was only partially so. The studies evaluated numerous standard, modified, or combination index tests and 14 novel index tests. There were 170 target condition/index test combinations, but only six instances of any index test being performed and interpreted similarly in two studies. Only two studies of a modified empty can test for full thickness tear of the rotator cuff, and two studies of a modified anterior slide test for type II superior labrum anterior to posterior (SLAP) lesions, were clinically homogenous. Due to the limited number of studies, meta-analyses were considered inappropriate. Sensitivity and specificity estimates from each study are presented on forest plots for the 170 target condition/index test combinations grouped according to target condition. There is insufficient evidence upon which to base selection of physical tests for shoulder impingements, and local lesions of bursa, tendon or labrum that may accompany impingement, in primary care. The large body of literature revealed extreme diversity in the performance and interpretation of tests, which hinders synthesis of the evidence and/or clinical applicability.
Individual and Joint Expert Judgments as Reference Standards in Artifact Detection

PubMed Central

Verduijn, Marion; Peek, Niels; de Keizer, Nicolette F.; van Lieshout, Erik-Jan; de Pont, Anne-Cornelie J.M.; Schultz, Marcus J.; de Jonge, Evert; de Mol, Bas A.J.M.

2008-01-01

Objective To investigate the agreement among clinical experts in their judgments of monitoring data with respect to artifacts, and to examine the effect of reference standards that consist of individual and joint expert judgments on the performance of artifact filters. Design Individual judgments of four physicians, a majority vote judgment, and a consensus judgment were obtained for 30 time series of three monitoring variables: mean arterial blood pressure (ABPm), central venous pressure (CVP), and heart rate (HR). The individual and joint judgments were used to tune three existing automated filtering methods and to evaluate the performance of the resulting filters. Measurements The interrater agreement was calculated in terms of positive specific agreement (PSA). The performance of the artifact filters was quantified in terms of sensitivity and positive predictive value (PPV). Results PSA values between 0.33 and 0.85 were observed among clinical experts in their selection of artifacts, with relatively high values for CVP data. Artifact filters developed using judgments of individual experts were found to moderately generalize to new time series and other experts; sensitivity values ranged from 0.40 to 0.60 for ABPm and HR filters (PPV: 0.57–0.84), and from 0.63 to 0.80 for CVP filters (PPV: 0.71–0.86). A higher performance value for the filters was found for the three variable types when joint judgments were used for tuning the filtering methods. Conclusion Given the disagreement among experts in their individual judgment of monitoring data with respect to artifacts, the use of joint reference standards obtained from multiple experts is recommended for development of automatic artifact filters. PMID:18096912
Delirium diagnosis methodology used in research: a survey-based study.

PubMed

Neufeld, Karin J; Nelliot, Archana; Inouye, Sharon K; Ely, E Wesley; Bienvenu, O Joseph; Lee, Hochang Benjamin; Needham, Dale M

2014-12-01

To describe methodology used to diagnose delirium in research studies evaluating delirium detection tools. The authors used a survey to address reference rater methodology for delirium diagnosis, including rater characteristics, sources of patient information, and diagnostic process, completed via web or telephone interview according to respondent preference. Participants were authors of 39 studies included in three recent systematic reviews of delirium detection instruments in hospitalized patients. Authors from 85% (N = 33) of the 39 eligible studies responded to the survey. The median number of raters per study was 2.5 (interquartile range: 2-3); 79% were physicians. The raters' median duration of clinical experience with delirium diagnosis was 7 years (interquartile range: 4-10), with 5% having no prior clinical experience. Inter-rater reliability was evaluated in 70% of studies. Cognitive tests and delirium detection tools were used in the delirium reference rating process in 61% (N = 21) and 45% (N = 15) of studies, respectively, with 33% (N = 11) using both and 27% (N = 9) using neither. When patients were too drowsy or declined to participate in delirium evaluation, 70% of studies (N = 23) used all available information for delirium diagnosis, whereas 15% excluded such patients. Significant variability exists in reference standard methods for delirium diagnosis in published research. Increasing standardization by documenting inter-rater reliability, using standardized cognitive and delirium detection tools, incorporating diagnostic expert consensus panels, and using all available information in patients declining or unable to participate with formal testing may help advance delirium research by increasing consistency of case detection and improving generalizability of research results. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
European Society of Clinical Pharmacy (ESCP) glossary of scientific terms: a tool for standardizing scientific jargon.

PubMed

Carollo, Anna; Rieutord, André; Launay-Vacher, Vincent

2012-04-01

This glossary is a tool for clinicians who have to confront topics in which medical, scientific and technical jargon is closely linked. It provides definitions for the key concepts and terms of pharmaceutical care, clinical pharmacy, and research in the health care system in clinical settings. It includes items that are not particularly technical, but that should be part of the know-how of staff working in medical and scientific fields. In fact, the glossary can also help clinical technicians who want to understand the precise definition of scientific terms, which often do not coincide with the ones used in the practice setting. PRINCIPAL GOALS AND OBJECTIVES: The aim of this glossary is to aid in the development of more standardized and established terminology for clinical pharmacy, facilitate communication among different stakeholders and, ultimately, contribute to a higher-quality health care system. The glossary contains 165 definitions of concepts and principles in clinical pharmacy, and terms widely used in this field. The criteria for the inclusion of terms were specific applications in health promotion, or terms used in other fields that have a specific meaning or application when used in reference to clinical activity. The glossary arose from the need to standardize terminology in the scientific field. It was not intended as a comprehensive listing that would include all medical terms, but as a useful tool for clinical pharmacists working in this area, and for users who occasionally encounter unusual, often hard to understand, terminology.

Trace element reference values in tissues from inhabitants of the EU. XII. Development of BioReVa program for statistical treatment.

PubMed

Iversen, B S; Sabbioni, E; Fortaner, S; Pietra, R; Nicolotti, A

2003-01-20

Statistical data treatment is a key point in the assessment of trace element reference values being the conclusive stage of a comprehensive and organized evaluation process of metal concentration in human body fluids. The EURO TERVIHT project (Trace Elements Reference Values in Human Tissues) was started for evaluating, checking and suggesting harmonized procedures for the establishment of trace element reference intervals in body fluids and tissues. Unfortunately, different statistical approaches are being used in this research field making data comparison difficult and in some cases impossible. Although international organizations such as International Federation of Clinical Chemistry (IFCC) or International Union of Pure and Applied Chemistry (IUPAC) have issued recommended guidelines for reference values assessment, including the statistical data treatment, a unique format and a standardized data layout is still missing. The aim of the present study is to present a software (BioReVa) running under Microsoft Windows platform suitable for calculating the reference intervals of trace elements in body matrices. The main scope for creating an ease-of-use application was to control the data distribution, to establish the reference intervals according to the accepted recommendation, on the base of the simple statistic, to get a standard presentation of experimental data and to have an application to which further need could be integrated in future. BioReVa calculates the IFCC reference intervals as well as the coverage intervals recommended by IUPAC as a supplement to the IFCC intervals. Examples of reference values and reference intervals calculated with BioReVa software concern Pb and Se in blood; Cd, In and Cr in urine, Hg and Mo in hair of different general European populations. University of Michigan
Identifying appropriate reference data models for comparative effectiveness research (CER) studies based on data from clinical information systems.

PubMed

Ogunyemi, Omolola I; Meeker, Daniella; Kim, Hyeon-Eui; Ashish, Naveen; Farzaneh, Seena; Boxwala, Aziz

2013-08-01

The need for a common format for electronic exchange of clinical data prompted federal endorsement of applicable standards. However, despite obvious similarities, a consensus standard has not yet been selected in the comparative effectiveness research (CER) community. Using qualitative metrics for data retrieval and information loss across a variety of CER topic areas, we compare several existing models from a representative sample of organizations associated with clinical research: the Observational Medical Outcomes Partnership (OMOP), Biomedical Research Integrated Domain Group, the Clinical Data Interchange Standards Consortium, and the US Food and Drug Administration. While the models examined captured a majority of the data elements that are useful for CER studies, data elements related to insurance benefit design and plans were most detailed in OMOP's CDM version 4.0. Standardized vocabularies that facilitate semantic interoperability were included in the OMOP and US Food and Drug Administration Mini-Sentinel data models, but are left to the discretion of the end-user in Biomedical Research Integrated Domain Group and Analysis Data Model, limiting reuse opportunities. Among the challenges we encountered was the need to model data specific to a local setting. This was handled by extending the standard data models. We found that the Common Data Model from the OMOP met the broadest complement of CER objectives. Minimal information loss occurred in mapping data from institution-specific data warehouses onto the data models from the standards we assessed. However, to support certain scenarios, we found a need to enhance existing data dictionaries with local, institution-specific information.
Flexible add-on solution for MR image-guided interventions in a closed-bore scanner environment.

PubMed

Busse, Harald; Garnov, Nikita; Thörmer, Gregor; Zajonz, Dirk; Gründer, Wilfried; Kahn, Thomas; Moche, Michael

2010-09-01

MRI is of great clinical utility for the guidance of various diagnostic and therapeutic procedures. In a standard closed-bore scanner, the simplest approach is to manipulate the instrument outside the bore and move the patient into the bore for reference and control imaging only. Without navigational assistance, however, such an approach can be difficult, inaccurate, and time consuming. Therefore, an add-on navigation solution is described that addresses these limitations. Patient registration is established by an automatic, robust, and fast (<30 sec) localization of table-mounted MR reference markers and the instrument is tracked optically. Good hand-eye coordination is provided by following the virtual instrument on MR images that are reconstructed in real time from the reference data. Needle displacements of 2.2 +/- 0.6 mm and 3.9 +/- 2.4 mm were determined in a phantom (P < 0.05), depending on whether the reference markers were placed at smaller (98-139 mm) or larger (147-188 mm) distances from the isocenter. Clinical functionality of the navigation concept is demonstrated by a double oblique, subscapular hook-wire insertion in a patient with a body mass index of 30.1 kg/m(2). Ease of use, compactness, and flexibility of this technique suggest that it can be used for many other procedures in different body regions. More patient cases are needed to evaluate clinical performance and workflow. 2010 Wiley-Liss, Inc.
[Application of traditional Chinese medicine reference standards in quality control of Chinese herbal pieces].

PubMed

Lu, Tu-Lin; Li, Jin-Ci; Yu, Jiang-Yong; Cai, Bao-Chang; Mao, Chun-Qin; Yin, Fang-Zhou

2014-01-01

Traditional Chinese medicine (TCM) reference standards plays an important role in the quality control of Chinese herbal pieces. This paper overviewed the development of TCM reference standards. By analyzing the 2010 edition of Chinese pharmacopoeia, the application of TCM reference standards in the quality control of Chinese herbal pieces was summarized, and the problems exiting in the system were put forward. In the process of improving the quality control level of Chinese herbal pieces, various kinds of advanced methods and technology should be used to research the characteristic reference standards of Chinese herbal pieces, more and more reasonable reference standards should be introduced in the quality control system of Chinese herbal pieces. This article discussed the solutions in the aspect of TCM reference standards, and future development of quality control on Chinese herbal pieces is prospected.
An HL7-CDA wrapper for facilitating semantic interoperability to rule-based Clinical Decision Support Systems.

PubMed

Sáez, Carlos; Bresó, Adrián; Vicente, Javier; Robles, Montserrat; García-Gómez, Juan Miguel

2013-03-01

The success of Clinical Decision Support Systems (CDSS) greatly depends on its capability of being integrated in Health Information Systems (HIS). Several proposals have been published up to date to permit CDSS gathering patient data from HIS. Some base the CDSS data input on the HL7 reference model, however, they are tailored to specific CDSS or clinical guidelines technologies, or do not focus on standardizing the CDSS resultant knowledge. We propose a solution for facilitating semantic interoperability to rule-based CDSS focusing on standardized input and output documents conforming an HL7-CDA wrapper. We define the HL7-CDA restrictions in a HL7-CDA implementation guide. Patient data and rule inference results are mapped respectively to and from the CDSS by means of a binding method based on an XML binding file. As an independent clinical document, the results of a CDSS can present clinical and legal validity. The proposed solution is being applied in a CDSS for providing patient-specific recommendations for the care management of outpatients with diabetes mellitus. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Use of the VITEK 2 system to identify and test the antifungal susceptibility of clinically relevant yeast species

PubMed Central

Melhem, MSC; Bertoletti, A; Lucca, HRL; Silva, RBO; Meneghin, FA; Szeszs, MW

2013-01-01

Eleven quality control isolates (Candida albicans ATCC 64548, C. tropicalis ATCC 200956, C. glabrata ATCC 90030, C. lusitaniae ATCC 200951, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, C. dubliniensis ATCC 6330, Saccharomyces cerevisiae ATCC 9763, Cryptococcus neoformans ATCC 90012, C. gattii FIOCRUZ-CPF 60, and Trichosporon mucoides ATCC 204094) and 32 bloodstream isolates, including C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, C. guilliermondii, C. pelliculosa (Pichia anomala), C. haemulonii, C. lusitaniae, and C. kefyr were identified at the species level by the VITEK 2 system. A set of clinical isolates (32 total) were used as challenge strains to evaluate the ability of the VITEK 2 system to determine the antifungal susceptibility of yeasts compared with the CLSI and EUCAST BMD reference standards. The VITEK 2 system correctly identified 100% of the challenge strains. The identification of yeast species and the evaluation of their susceptibility profiles were performed in an automated manner by the VITEK 2 system after approximately 15 h of growth for most species of Candida. The VITEK 2 system ensures that each test is performed in a standardized manner and provides quantitative MIC results that are reproducible and accurate when compared with the BMD reference methods. This system was able to determine the MICs of amphotericin B, flucytosine, voriconazole, and fluconazole in 15 h or less for the most common clinically relevant Candida species. In addition, the VITEK 2 system could reliably identify resistance to flucytosine, voriconazole, and fluconazole and exhibits excellent quantitative and qualitative agreement with the CLSI or EUCAST broth microdilution reference methods. PMID:24688520
The performance of flash glucose monitoring in critically ill patients with diabetes.

PubMed

Ancona, Paolo; Eastwood, Glenn M; Lucchetta, Luca; Ekinci, Elif I; Bellomo, Rinaldo; Mårtensson, Johan

2017-06-01

Frequent glucose monitoring may improve glycaemic control in critically ill patients with diabetes. We aimed to assess the accuracy of a novel subcutaneous flash glucose monitor (FreeStyle Libre [Abbott Diabetes Care]) in these patients. We applied the FreeStyle Libre sensor to the upper arm of eight patients with diabetes in the intensive care unit and obtained hourly flash glucose measurements. Duplicate recordings were obtained to assess test-retest reliability. The reference glucose level was measured in arterial or capillary blood. We determined numerical accuracy using Bland- Altman methods, the mean absolute relative difference (MARD) and whether the International Organization for Standardization (ISO) and Clinical and Laboratory Standards Institute Point of Care Testing (CLSI POCT) criteria were met. Clarke error grid (CEG) and surveillance error grid (SEG) analyses were used to determine clinical accuracy. We compared 484 duplicate flash glucose measurements and observed a Pearson correlation coefficient of 0.97 and a coefficient of repeatability of 1.6 mmol/L. We studied 185 flash readings paired with arterial glucose levels, and 89 paired with capillary glucose levels. Using the arterial glucose level as the reference, we found a mean bias of 1.4 mmol/L (limits of agreement, -1.7 to 4.5 mmol/L). The MARD was 14% (95% CI, 12%-16%) and the proportion of measurements meeting ISO and CLSI POCT criteria was 64.3% and 56.8%, respectively. The proportions of values within a low-risk zone on CEG and SEG analyses were 97.8% and 99.5%, respectively. Using capillary glucose levels as the reference, we found that numerical and clinical accuracy were lower. The subcutaneous FreeStyle Libre blood glucose measurement system showed high test-retest reliability and acceptable accuracy when compared with arterial blood glucose measurement in critically ill patients with diabetes.
Quality management and accreditation in a mixed research and clinical hair testing analytical laboratory setting-a review.

PubMed

Fulga, Netta

2013-06-01

Quality management and accreditation in the analytical laboratory setting are developing rapidly and becoming the standard worldwide. Quality management refers to all the activities used by organizations to ensure product or service consistency. Accreditation is a formal recognition by an authoritative regulatory body that a laboratory is competent to perform examinations and report results. The Motherisk Drug Testing Laboratory is licensed to operate at the Hospital for Sick Children in Toronto, Ontario. The laboratory performs toxicology tests of hair and meconium samples for research and clinical purposes. Most of the samples are involved in a chain of custody cases. Establishing a quality management system and achieving accreditation became mandatory by legislation for all Ontario clinical laboratories since 2003. The Ontario Laboratory Accreditation program is based on International Organization for Standardization 15189-Medical laboratories-Particular requirements for quality and competence, an international standard that has been adopted as a national standard in Canada. The implementation of a quality management system involves management commitment, planning and staff education, documentation of the system, validation of processes, and assessment against the requirements. The maintenance of a quality management system requires control and monitoring of the entire laboratory path of workflow. The process of transformation of a research/clinical laboratory into an accredited laboratory, and the benefits of maintaining an effective quality management system, are presented in this article.
Direct and indirect forms of childhood maltreatment and nonsuicidal self-injury among clinically-referred children and youth.

PubMed

Armiento, Jenna; Hamza, Chloe A; Stewart, Shannon L; Leschied, Alan

2016-08-01

Although exposure to direct forms of childhood maltreatment is among the most widely studied risk factors for nonsuicidal self-injury (NSSI), research on NSSI has largely overlooked the role of exposure to indirect forms of child maltreatment (i.e., witnessing domestic violence). To address this gap in the literature, the present study examined associations among both direct and indirect forms of child maltreatment and NSSI among clinically-referred children and youth. Data was collected using the interRAI Child and Youth Mental Health Assessment (ChYMH) at ten mental health agencies. The ChYMH is a comprehensive standardized clinical assessment tool completed by trained assessors using multiple sources. The study included a convenience sample of 747 children and youth (68% male) between ages 8-18 with complex mental health histories referred for inpatient or outpatient care in Ontario, Canada. Univariate chi-square analyses indicated positive associations with NSSI and both direct (i.e., physical, sexual) and indirect child maltreatment (i.e., witnessing domestic violence). In a binary multivariate logistic regression analysis controlling for participant age and sex, only exposure to indirect child maltreatment emerged as multivariate predictor of NSSI. The sample was limited to only 10 mental health agencies and only consenting parents/guardians referred to mental health services suggesting the study may not be generalizable to all clinical samples. The present study provides evidence that witnessing domestic violence in childhood is an important risk factor for NSSI. Clinical relevance includes implications for clinicians to develop targeted intervention and prevention strategies for NSSI for children who have witnessed domestic violence. Copyright © 2016 Elsevier B.V. All rights reserved.
The relationship between clinical and standardized tests for hand-arm vibration syndrome.

PubMed

Poole, C J M; Mason, H; Harding, A-H

2016-06-01

Standardized laboratory tests are undertaken to assist the diagnosis and staging of hand-arm vibration syndrome (HAVS), but the strength of the relationship between the tests and clinical stages of HAVS is unknown. To assess the relationship between the results of thermal aesthesiometry (TA), vibrotactile (VT) thresholds and cold provocation (CP) tests with the modified Stockholm scales for HAVS and to determine whether the relationship is affected by finger skin temperature. Consecutive records of workers referred to a Tier 5 HAVS assessment centre from 2006 to 2015 were identified. The diagnosis and staging of cases was undertaken from the clinical information contained in the records. Cases with alternative or mixed diagnoses were excluded and staging performed according to the modified Stockholm scale without knowledge of the results of the standardized laboratory tests. A total of 279 cases of HAVS were analysed. Although there was a significant trend for sensorineural (SN) and vascular scores to increase with clinical stage (P < 0.01), there was no significant difference in scores between 2SN early and 2SN late or between 2SN late and 3SN. There was moderate correlation between the TA and VT scores and the clinical SN stages (r = 0.6). This correlation did not change when subjects were divided into those with a finger skin temperature <30 and >30°C. CP scores distributed bimodally and correlated poorly with clinical staging (r = 0.2). Standardized SN tests distinguish between the lower Stockholm stages, but not above 2SN early. This has implications for health surveillance and UK policy. © Crown copyright 2016.
Development of Standard Reference Materials to support assessment of iodine status for nutritional and public health purposes.

PubMed

Long, Stephen E; Catron, Brittany L; Boggs, Ashley Sp; Tai, Susan Sc; Wise, Stephen A

2016-09-01

The use of urinary iodine as an indicator of iodine status relies in part on the accuracy of the analytical measurement of iodine in urine. Likewise, the use of dietary iodine intake as an indicator of iodine status relies in part on the accuracy of the analytical measurement of iodine in dietary sources, including foods and dietary supplements. Similarly, the use of specific serum biomarkers of thyroid function to screen for both iodine deficiency and iodine excess relies in part on the accuracy of the analytical measurement of those biomarkers. The National Institute of Standards and Technology has been working with the NIH Office of Dietary Supplements for several years to develop higher-order reference measurement procedures and Standard Reference Materials to support the validation of new routine analytical methods for iodine in foods and dietary supplements, for urinary iodine, and for several serum biomarkers of thyroid function including thyroid-stimulating hormone, thyroglobulin, total and free thyroxine, and total and free triiodothyronine. These materials and methods have the potential to improve the assessment of iodine status and thyroid function in observational studies and clinical trials, thereby promoting public health efforts related to iodine nutrition. © 2016 American Society for Nutrition.
[Clinical efficacy of cycloferon in complex therapy of infectious mononucleosis in pediatrics].

PubMed

Kasymova, E B; Bashkina, O A; Galimzianov, Kh M

2011-01-01

The results of the cycloferon use in therapy of 80 children at the age of 1 to 15 years with infectious mononucleosis are presented. The children were divided by chance sampling into two comparable groups of 40 subjects each. In the first group the children in addition to the standard therapy were treated with cycloferon for 10 days, intramuscularly or orally depending on the age. The reference group included the patients under the standard therapy alone. The efficacy of the drug was evaluated by reduction and more rapid disappearance of the main clinical symptoms of the disease. The improvement of certain laboratory indices, including those of the liver protein synthesis function were recorded, that allowed to reduce the hospitalization term. No side effects of the cycloferon use were observed.
Fundamentals of nuclear pharmacy, 3rd Ed

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

Saha, G.B.

1992-01-01

This book is a standard text/reference of nuclear pharmacy. New sections in the Third Edition include: instruments used for radiation detection and measurement; disposal of radioactive materials; clinical uses of all new and existing radiopharmaceuticals; 99m Tc and 123I-labeled radiopharmaceuticals, as well as radiolabeled leukocytes, platelets, and antibodies; and up-to-date descriptions of the latest FDA regulations.
Evaluation and clinical implementation of in vivo dosimetry for kV radiotherapy using radiochromic film and micro-silica bead thermoluminescent detectors.

PubMed

Palmer, Antony L; Jafari, Shakardokht M; Mone, Ioanna; Muscat, Sarah

2017-10-01

kV radiotherapy treatment calculations are based on flat, homogenous, full-scatter reference conditions. However, clinical treatments often include surface irregularities and inhomogeneities, causing uncertainty. Therefore, confirmation of actual delivered doses in vivo is valuable. The current study evaluates, and implements, radiochromic film and micro silica bead TLD for in vivo kV dosimetry. The kV energy and dose response of EBT3 film and silica bead TLD was established and uncertainty budgets determined. In vivo dosimetry measurements were made for a consecutive series of 30 patients using the two dosimetry systems. Energy dependent calibration factors were required for both dosimetry systems. The standard uncertainty estimate for in vivo measurement with film was 1.7% and for beads was 1.5%. The mean measured dose was -2.1% for film and -2.6% for beads compared to prescription. Deviations up to -9% were found in cases of large surface irregularity, or with underlying air cavities or bone. Dose shielding by beads could be clinically relevant at low kV energies and superficial depths. Both film and beads may be used to provide in vivo verification of delivered doses in kV radiotherapy, particularly for complex situations that are not well represented by standard reference condition calculations. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Comparative evaluation of the Aptima HIV-1 Quant Dx assay and COBAS TaqMan HIV-1 v2.0 assay using the Roche High Pure System for the quantification of HIV-1 RNA in plasma.

PubMed

Schalasta, Gunnar; Börner, Anna; Speicher, Andrea; Enders, Martin

2016-03-01

Quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma has become the standard of care in the management of HIV-infected patients. There are several commercially available assays that have been implemented for the detection of HIV-1 RNA in plasma. Here, the new Hologic Aptima® HIV-1 Quant Dx assay (Aptima HIV) was compared to the Roche COBAS® TaqMan® HIV-1 Test v2.0 for use with the High Pure System (HPS/CTM). The performance characteristics of the assays were assessed using commercially available HIV reference panels, dilution of the WHO 3rd International HIV-1 RNA International Standard (WHO-IS) and plasma from clinical specimens. Assay performance was determined by linear regression, Deming correlation analysis and Bland-Altman analysis. Testing of HIV-1 reference panels revealed excellent agreement. The 61 clinical specimens quantified in both assays were linearly associated and strongly correlated. The Aptima HIV assay offers performance comparable to that of the HPS/CTM assay and, as it is run on a fully automated platform, a significantly improved workflow.
Expression and purification of a functional recombinant aspartate aminotransferase (AST) from Escherichia coli.

PubMed

Zou, Lihui; Zhao, Haijian; Wang, Daguang; Wang, Meng; Zhang, Chuanbao; Xiao, Fei

2014-07-01

Aspartate aminotransferase (AST; E.C. 2.6.1.1), a vitamin B6-dependent enzyme, preferentially promotes the mutual transformation of aspartate and α-ketoglutarate to oxaloacetate and glutamate. It plays a key role in amino acid metabolism and has been widely recommended as a biomarker of liver and heart damage. Our study aimed to evaluate the extensive preparation of AST and its application in quality control in clinical laboratories. We describe a scheme to express and purify the 6His-AST fusion protein. An optimized sequence coding AST was synthesized and transformed into Escherichia coli BL21 (DE3) strain for protein expression. Ideally, the fusion protein has a volumetric productivity achieving 900 mg/l cultures. After affinity chromatography, the enzyme activity of purified AST reached 150,000 U/L. Commutability assessment between the engineered AST and standard AST from Roche suggested that the engineered AST was the better candidate for the reference material. Moreover, the AST showed high stability during long-term storage at -20ºC. In conclusion, the highly soluble 6His-tagged AST can become a convenient tool for supplying a much better and cheaper standard or reference material for the clinical laboratory.
The definition of insulin resistance using HOMA-IR for Americans of Mexican descent using machine learning.

PubMed

Qu, Hui-Qi; Li, Quan; Rentfro, Anne R; Fisher-Hoch, Susan P; McCormick, Joseph B

2011-01-01

The lack of standardized reference range for the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index has limited its clinical application. This study defines the reference range of HOMA-IR index in an adult Hispanic population based with machine learning methods. This study investigated a Hispanic population of 1854 adults, randomly selected on the basis of 2000 Census tract data in the city of Brownsville, Cameron County. Machine learning methods, support vector machine (SVM) and Bayesian Logistic Regression (BLR), were used to automatically identify measureable variables using standardized values that correlate with HOMA-IR; K-means clustering was then used to classify the individuals by insulin resistance. Our study showed that the best cutoff of HOMA-IR for identifying those with insulin resistance is 3.80. There are 39.1% individuals in this Hispanic population with HOMA-IR>3.80. Our results are dramatically different using the popular clinical cutoff of 2.60. The high sensitivity and specificity of HOMA-IR>3.80 for insulin resistance provide a critical fundamental for our further efforts to improve the public health of this Hispanic population.
The Definition of Insulin Resistance Using HOMA-IR for Americans of Mexican Descent Using Machine Learning

PubMed Central

Qu, Hui-Qi; Li, Quan; Rentfro, Anne R.; Fisher-Hoch, Susan P.; McCormick, Joseph B.

2011-01-01

Objective The lack of standardized reference range for the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index has limited its clinical application. This study defines the reference range of HOMA-IR index in an adult Hispanic population based with machine learning methods. Methods This study investigated a Hispanic population of 1854 adults, randomly selected on the basis of 2000 Census tract data in the city of Brownsville, Cameron County. Machine learning methods, support vector machine (SVM) and Bayesian Logistic Regression (BLR), were used to automatically identify measureable variables using standardized values that correlate with HOMA-IR; K-means clustering was then used to classify the individuals by insulin resistance. Results Our study showed that the best cutoff of HOMA-IR for identifying those with insulin resistance is 3.80. There are 39.1% individuals in this Hispanic population with HOMA-IR>3.80. Conclusions Our results are dramatically different using the popular clinical cutoff of 2.60. The high sensitivity and specificity of HOMA-IR>3.80 for insulin resistance provide a critical fundamental for our further efforts to improve the public health of this Hispanic population. PMID:21695082
Comparison of four different techniques to evaluate the elastic properties of phantom in elastography: is there a gold standard?

NASA Astrophysics Data System (ADS)

Oudry, Jennifer; Lynch, Ted; Vappou, Jonathan; Sandrin, Laurent; Miette, Véronique

2014-10-01

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young’s modulus over the range of normal and cirrhotic liver stiffnesses. The Young’s modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.
Comparison of four different techniques to evaluate the elastic properties of phantom in elastography: is there a gold standard?

PubMed

Oudry, Jennifer; Lynch, Ted; Vappou, Jonathan; Sandrin, Laurent; Miette, Véronique

2014-10-07

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young's modulus over the range of normal and cirrhotic liver stiffnesses. The Young's modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.

Standardised anatomical alignment of the head in a clinical photography studio. A comparison between the Frankfort Horizontal and the natural head position.

PubMed

Capon, Thomas

The Frankfort Horizontal (FH) is used by clinical photographers as a reference plane to help maintain Standardised Representational Photography (SRP) when photographing a patients head. A comparative method of alignment is the Natural Head Position (NHP). For this study a survey was created that asked consultants and clinical photographers which method of alignment they considered to be the most effective. The survey found that 77% of respondents thought the FH was the most effective method of alignment. This high figure is due to some confirmation bias as the FH is the industry standard.
Calibration of helical tomotherapy machine using EPR/alanine dosimetry.

PubMed

Perichon, Nicolas; Garcia, Tristan; François, Pascal; Lourenço, Valérie; Lesven, Caroline; Bordy, Jean-Marc

2011-03-01

Current codes of practice for clinical reference dosimetry of high-energy photon beams in conventional radiotherapy recommend using a 10 x 10 cm2 square field, with the detector at a reference depth of 10 cm in water and 100 cm source to surface distance (SSD) (AAPM TG-51) or 100 cm source-to-axis distance (SAD) (IAEA TRS-398). However, the maximum field size of a helical tomotherapy (HT) machine is 40 x 5 cm2 defined at 85 cm SAD. These nonstandard conditions prevent a direct implementation of these protocols. The purpose of this study is twofold: To check the absorbed dose in water and dose rate calibration of a tomotherapy unit as well as the accuracy of the tomotherapy treatment planning system (TPS) calculations for a specific test case. Both topics are based on the use of electron paramagnetic resonance (EPR) using alanine as transfer dosimeter between the Laboratoire National Henri Becquerel (LNHB) 60Co-gamma-ray reference beam and the Institut Curie's HT beam. Irradiations performed in the LNHB reference 60Co-gamma-ray beam allowed setting up the calibration method, which was then implemented and tested at the LNHB 6 MV linac x-ray beam, resulting in a deviation of 1.6% (at a 1% standard uncertainty) relative to the reference value determined with the standard IAEA TRS-398 protocol. HT beam dose rate estimation shows a difference of 2% with the value stated by the manufacturer at a 2% standard uncertainty. A 4% deviation between measured dose and the calculation from the tomotherapy TPS was found. The latter was originated by an inadequate representation of the phantom CT-scan values and, consequently, mass densities within the phantom. This difference has been explained by the mass density values given by the CT-scan and used by the TPS which were not the true ones. Once corrected using Monte Carlo N-Particle simulations to validate the accuracy of this process, the difference between corrected TPS calculations and alanine measured dose values was then found to be around 2% (with 2% standard uncertainty on TPS doses and 1.5% standard uncertainty on EPR measurements). Beam dose rate estimation results were found to be in good agreement with the reference value given by the manufacturer at 2% standard uncertainty. Moreover, the dose determination method was set up with a deviation around 2% (at a 2% standard uncertainty).
Evaluation of four commercial biuret reagent kits of serum total protein by the American Association for Clinical Chemistry reference measurement procedure.

PubMed

He, Meilin; Zhang, Jie

2011-06-01

In China, the traceability of clinical chemistry methods is still immature. Therefore, it is necessary to establish a reference measurement procedure and evaluate commercial reagent kits using such established procedures. We reproduced the reference measurement procedure for serum total protein, as recommended by the American Association for Clinical Chemistry (AACC). We evaluated the performance by Clinical Laboratory Standard Institute (CLSI) guidelines EP15-A and EP6-A. Subsequently, four commercial reagent kits were evaluated by the reproduced reference procedure following CLSI guideline EP9-A2. The performance of the reproduced reference procedure was as follows: CVs ranged from 0.47% to 0.85% at medical decision levels (X(c)) of 45 g/L, 60 g/L and 80 g/L. Linearity was Y=1.0022X-0.2121 (r=0.9999), and recovery ranged from 100.2% to 102.4%. The External Quality Assessment Scheme for Reference Laboratories in Laboratory Medicine (RELA) was applied, and the result was within the limit of equivalence. The linear relationships of four commercial reagent kits, Merit Choice, KHB, Leadman, and Olympus, were, respectively: Y=0.9922X+0.5776 (r=0.9961); Y=0.9936X+0.4316 (r=0.9992); Y=0.9949X+0.9129 (r=0.9987) and Y=0.9923X+0.8876 (r=0.9989). KHB showed slight negative bias, and the mean±SD was -0.03±0.60 g/L. Merit Choice, Leadman, and Olympus all showed positive bias, and the mean±SDs were 0.02±0.63 g/L, 0.55±0.77 g/L and 0.34±0.71 g/L, respectively. The correlation and bias of four commercial reagent kits for serum total protein were found to be acceptable. Thus, these reagent kits can be used reliably in China.
Accuracy of Referring Provider and Endoscopist Impressions of Colonoscopy Indication.

PubMed

Naveed, Mariam; Clary, Meredith; Ahn, Chul; Kubiliun, Nisa; Agrawal, Deepak; Cryer, Byron; Murphy, Caitlin; Singal, Amit G

2017-07-01

Background: Referring provider and endoscopist impressions of colonoscopy indication are used for clinical care, reimbursement, and quality reporting decisions; however, the accuracy of these impressions is unknown. This study assessed the sensitivity, specificity, positive and negative predictive value, and overall accuracy of methods to classify colonoscopy indication, including referring provider impression, endoscopist impression, and administrative algorithm compared with gold standard chart review. Methods: We randomly sampled 400 patients undergoing a colonoscopy at a Veterans Affairs health system between January 2010 and December 2010. Referring provider and endoscopist impressions of colonoscopy indication were compared with gold-standard chart review. Indications were classified into 4 mutually exclusive categories: diagnostic, surveillance, high-risk screening, or average-risk screening. Results: Of 400 colonoscopies, 26% were performed for average-risk screening, 7% for high-risk screening, 26% for surveillance, and 41% for diagnostic indications. Accuracy of referring provider and endoscopist impressions of colonoscopy indication were 87% and 84%, respectively, which were significantly higher than that of the administrative algorithm (45%; P <.001 for both). There was substantial agreement between endoscopist and referring provider impressions (κ=0.76). All 3 methods showed high sensitivity (>90%) for determining screening (vs nonscreening) indication, but specificity of the administrative algorithm was lower (40.3%) compared with referring provider (93.7%) and endoscopist (84.0%) impressions. Accuracy of endoscopist, but not referring provider, impression was lower in patients with a family history of colon cancer than in those without (65% vs 84%; P =.001). Conclusions: Referring provider and endoscopist impressions of colonoscopy indication are both accurate and may be useful data to incorporate into algorithms classifying colonoscopy indication. Copyright © 2017 by the National Comprehensive Cancer Network.
CSAHi study-2: Validation of multi-electrode array systems (MEA60/2100) for prediction of drug-induced proarrhythmia using human iPS cell-derived cardiomyocytes: Assessment of reference compounds and comparison with non-clinical studies and clinical information.

PubMed

Nozaki, Yumiko; Honda, Yayoi; Watanabe, Hitoshi; Saiki, Shota; Koyabu, Kiyotaka; Itoh, Tetsuji; Nagasawa, Chiho; Nakamori, Chiaki; Nakayama, Chiaki; Iwasaki, Hiroshi; Suzuki, Shinobu; Tanaka, Kohji; Takahashi, Etsushi; Miyamoto, Kaori; Morimura, Kaoru; Yamanishi, Atsuhiro; Endo, Hiroko; Shinozaki, Junko; Nogawa, Hisashi; Shinozawa, Tadahiro; Saito, Fumiyo; Kunimatsu, Takeshi

2017-08-01

With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In this study, we evaluated the responses of hiPS-CMs/MEA to another 31 reference compounds associated with cardiac toxicities, and gene expression to further clarify the electrophysiological characteristics over the course of culture period. The hiPS-CMs/MEA assay accurately predicted reference compounds potential for arrhythmogenesis, and yielded results that showed better correlation with target concentrations of QTc prolongation or TdP in clinical setting than other current in vitro and in vivo assays. Gene expression analyses revealed consistent profiles in all samples within and among the testing facilities. This report would provide CiPA with informative guidance on the use of the hiPS-CMs/MEA assay, and promote the establishment of a new paradigm, beyond conventional in vitro and in vivo assays for cardiac safety assessment of new drugs. Copyright © 2017 Elsevier Inc. All rights reserved.
The effect of cone beam CT (CBCT) on therapeutic decision-making in endodontics

PubMed Central

Knutsson, K; Flygare, L

2014-01-01

Objectives: The aim was to assess to what extent cone beam CT (CBCT) used in accordance with current European Commission guidelines in a normal clinical setting has an impact on therapeutic decisions in a population referred for endodontic problems. Methods: The study includes data of consecutively examined patients collected from October 2011 to December 2012. From 2 different endodontic specialist clinics, 57 patients were referred for a CBCT examination using criteria in accordance with current European guidelines. The CBCT examinations were performed using similar equipment and standardized among clinics. After a thorough clinical examination, but before CBCT, the examiner made a preliminary therapy plan which was recorded. After the CBCT examination, the same examiner made a new therapy plan. Therapy plans both before and after the CBCT examination were plotted for 53 patients and 81 teeth. As four patients had incomplete protocols, they were not included in the final analysis. Results: 4% of the patients referred to endodontic clinics during the study period were examined with CBCT. The most frequent reason for referral to CBCT examination was to differentiate pathology from normal anatomy, this was the case in 24 patients (45% of the cases). The primary outcome was therapy plan changes that could be attributed to CBCT examination. There were changes in 28 patients (53%). Conclusions: CBCT has a significant impact on therapeutic decision efficacy in endodontics when used in concordance with the current European Commission guidelines. PMID:24766060
Stroke Caused by Atherosclerosis of the Major Intracranial Arteries

PubMed Central

Banerjee, Chirantan; Chimowitz, Marc I.

2017-01-01

Our goal in this review is to discuss the pathophysiology, diagnosis and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms “intracranial stenosis” and “intracranial atherosclerosis”. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease (ICAD) is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics and Asians compared with whites. Diabetes, hypertension, metabolic syndrome, smoking, hyperlipidemia and a sedentary lifestyle are the major modifiable risk factors associated with ICAD. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with ICAD. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serologic, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients. PMID:28154100
A reference architecture for integrated EHR in Colombia.

PubMed

de la Cruz, Edgar; Lopez, Diego M; Uribe, Gustavo; Gonzalez, Carolina; Blobel, Bernd

2011-01-01

The implementation of national EHR infrastructures has to start by a detailed definition of the overall structure and behavior of the EHR system (system architecture). Architectures have to be open, scalable, flexible, user accepted and user friendly, trustworthy, based on standards including terminologies and ontologies. The GCM provides an architectural framework created with the purpose of analyzing any kind of system, including EHR system´s architectures. The objective of this paper is to propose a reference architecture for the implementation of an integrated EHR in Colombia, based on the current state of system´s architectural models, and EHR standards. The proposed EHR architecture defines a set of services (elements) and their interfaces, to support the exchange of clinical documents, offering an open, scalable, flexible and semantically interoperable infrastructure. The architecture was tested in a pilot tele-consultation project in Colombia, where dental EHR are exchanged.
Recommendations for the Generation, Quantification, Storage, and Handling of Peptides Used for Mass Spectrometry-Based Assays.

PubMed

Hoofnagle, Andrew N; Whiteaker, Jeffrey R; Carr, Steven A; Kuhn, Eric; Liu, Tao; Massoni, Sam A; Thomas, Stefani N; Townsend, R Reid; Zimmerman, Lisa J; Boja, Emily; Chen, Jing; Crimmins, Daniel L; Davies, Sherri R; Gao, Yuqian; Hiltke, Tara R; Ketchum, Karen A; Kinsinger, Christopher R; Mesri, Mehdi; Meyer, Matthew R; Qian, Wei-Jun; Schoenherr, Regine M; Scott, Mitchell G; Shi, Tujin; Whiteley, Gordon R; Wrobel, John A; Wu, Chaochao; Ackermann, Brad L; Aebersold, Ruedi; Barnidge, David R; Bunk, David M; Clarke, Nigel; Fishman, Jordan B; Grant, Russ P; Kusebauch, Ulrike; Kushnir, Mark M; Lowenthal, Mark S; Moritz, Robert L; Neubert, Hendrik; Patterson, Scott D; Rockwood, Alan L; Rogers, John; Singh, Ravinder J; Van Eyk, Jennifer E; Wong, Steven H; Zhang, Shucha; Chan, Daniel W; Chen, Xian; Ellis, Matthew J; Liebler, Daniel C; Rodland, Karin D; Rodriguez, Henry; Smith, Richard D; Zhang, Zhen; Zhang, Hui; Paulovich, Amanda G

2016-01-01

For many years, basic and clinical researchers have taken advantage of the analytical sensitivity and specificity afforded by mass spectrometry in the measurement of proteins. Clinical laboratories are now beginning to deploy these work flows as well. For assays that use proteolysis to generate peptides for protein quantification and characterization, synthetic stable isotope-labeled internal standard peptides are of central importance. No general recommendations are currently available surrounding the use of peptides in protein mass spectrometric assays. The Clinical Proteomic Tumor Analysis Consortium of the National Cancer Institute has collaborated with clinical laboratorians, peptide manufacturers, metrologists, representatives of the pharmaceutical industry, and other professionals to develop a consensus set of recommendations for peptide procurement, characterization, storage, and handling, as well as approaches to the interpretation of the data generated by mass spectrometric protein assays. Additionally, the importance of carefully characterized reference materials-in particular, peptide standards for the improved concordance of amino acid analysis methods across the industry-is highlighted. The alignment of practices around the use of peptides and the transparency of sample preparation protocols should allow for the harmonization of peptide and protein quantification in research and clinical care. © 2015 American Association for Clinical Chemistry.
Copy Number Heterogeneity, Large Origin Tandem Repeats, and Interspecies Recombination in Human Herpesvirus 6A (HHV-6A) and HHV-6B Reference Strains

PubMed Central

Roychoudhury, Pavitra; Makhsous, Negar; Hanson, Derek; Chase, Jill; Krueger, Gerhard; Xie, Hong; Huang, Meei-Li; Saunders, Lindsay; Ablashi, Dharam; Koelle, David M.; Cook, Linda; Jerome, Keith R.

2018-01-01

ABSTRACT Quantitative PCR is a diagnostic pillar for clinical virology testing, and reference materials are necessary for accurate, comparable quantitation between clinical laboratories. Accurate quantitation of human herpesvirus 6A/B (HHV-6A/B) is important for detection of viral reactivation and inherited chromosomally integrated HHV-6A/B in immunocompromised patients. Reference materials in clinical virology commonly consist of laboratory-adapted viral strains that may be affected by the culture process. We performed next-generation sequencing to make relative copy number measurements at single nucleotide resolution of eight candidate HHV-6A and seven HHV-6B reference strains and DNA materials from the HHV-6 Foundation and Advanced Biotechnologies Inc. Eleven of 17 (65%) HHV-6A/B candidate reference materials showed multiple copies of the origin of replication upstream of the U41 gene by next-generation sequencing. These large tandem repeats arose independently in culture-adapted HHV-6A and HHV-6B strains, measuring 1,254 bp and 983 bp, respectively. The average copy number measured was between 5 and 10 times the number of copies of the rest of the genome. We also report the first interspecies recombinant HHV-6A/B strain with a HHV-6A backbone and a >5.5-kb region from HHV-6B, from U41 to U43, that covered the origin tandem repeat. Specific HHV-6A reference strains demonstrated duplication of regions at U1/U2, U87, and U89, as well as deletion in the U12-to-U24 region and the U94/U95 genes. HHV-6A/B strains derived from cord blood mononuclear cells from different laboratories on different continents with fewer passages revealed no copy number differences throughout the viral genome. These data indicate that large origin tandem duplications are an adaptation of both HHV-6A and HHV-6B in culture and show interspecies recombination is possible within the Betaherpesvirinae. IMPORTANCE Anything in science that needs to be quantitated requires a standard unit of measurement. This includes viruses, for which quantitation increasingly determines definitions of pathology and guidelines for treatment. However, the act of making standard or reference material in virology can alter its very accuracy through genomic duplications, insertions, and rearrangements. We used deep sequencing to examine candidate reference strains for HHV-6, a ubiquitous human virus that can reactivate in the immunocompromised population and is integrated into the human genome in every cell of the body for 1% of people worldwide. We found large tandem repeats in the origin of replication for both HHV-6A and HHV-6B that are selected for in culture. We also found the first interspecies recombinant between HHV-6A and HHV-6B, a phenomenon that is well known in alphaherpesviruses but to date has not been seen in betaherpesviruses. These data critically inform HHV-6A/B biology and the standard selection process. PMID:29491155
Diagnostic accuracy research in glaucoma is still incompletely reported: An application of Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015.

PubMed

Michelessi, Manuele; Lucenteforte, Ersilia; Miele, Alba; Oddone, Francesco; Crescioli, Giada; Fameli, Valeria; Korevaar, Daniël A; Virgili, Gianni

2017-01-01

Research has shown a modest adherence of diagnostic test accuracy (DTA) studies in glaucoma to the Standards for Reporting of Diagnostic Accuracy Studies (STARD). We have applied the updated 30-item STARD 2015 checklist to a set of studies included in a Cochrane DTA systematic review of imaging tools for diagnosing manifest glaucoma. Three pairs of reviewers, including one senior reviewer who assessed all studies, independently checked the adherence of each study to STARD 2015. Adherence was analyzed on an individual-item basis. Logistic regression was used to evaluate the effect of publication year and impact factor on adherence. We included 106 DTA studies, published between 2003-2014 in journals with a median impact factor of 2.6. Overall adherence was 54.1% for 3,286 individual rating across 31 items, with a mean of 16.8 (SD: 3.1; range 8-23) items per study. Large variability in adherence to reporting standards was detected across individual STARD 2015 items, ranging from 0 to 100%. Nine items (1: identification as diagnostic accuracy study in title/abstract; 6: eligibility criteria; 10: index test (a) and reference standard (b) definition; 12: cut-off definitions for index test (a) and reference standard (b); 14: estimation of diagnostic accuracy measures; 21a: severity spectrum of diseased; 23: cross-tabulation of the index and reference standard results) were adequately reported in more than 90% of the studies. Conversely, 10 items (3: scientific and clinical background of the index test; 11: rationale for the reference standard; 13b: blinding of index test results; 17: analyses of variability; 18; sample size calculation; 19: study flow diagram; 20: baseline characteristics of participants; 28: registration number and registry; 29: availability of study protocol; 30: sources of funding) were adequately reported in less than 30% of the studies. Only four items showed a statistically significant improvement over time: missing data (16), baseline characteristics of participants (20), estimates of diagnostic accuracy (24) and sources of funding (30). Adherence to STARD 2015 among DTA studies in glaucoma research is incomplete, and only modestly increasing over time.
[Diagnostic kits in parasitology: which controls?].

PubMed

Rossi, P

2004-06-01

The development of new diagnostic tools particularly for some parasitic "neglected diseases", is slowed or even hindered by limited resources assigned for basic and applied research in public institution and private sector. Even if the time-line and costs needed for developing a new In Vitro Diagnostic (IVD) test are generally lower compared to vaccines or new drugs, industry is poorly engaged in investing resources due to the perception of limited markets. To accelerate the development of diagnostics for the world's most deadly diseases, the World Health Organization's (WHO) Special Programme for Research and Training in Tropical Diseases (TDR), the United Nations Development Programme, the World Bank and the Gates Foundation, last year launched a new initiative, FIND (Foundation for Innovative New Diagnostics, www.finddiagnostics.org). The aim is to "apply the latest biotechnology innovations to develop and validate affordable diagnostic tests for diseases of the developing world". Ideally, a new diagnostic test should be accurately evaluated prior to use in medical practice. The first step would be a pre-clinical evaluation, an analytic study to determine its laboratory performance. A crucial point in this phase is the calibration of reagents (antigens, antibodies, DNA probes, etc.) against a standard reference preparation. WHO, through the WHO International Laboratories for Biological Standards, "provides International Biological Reference Preparations which serve as reference sources of defined biological activity expressed in an internationally agreed unit" (www.who.int/biologicals/IBRP/index.htm). Standardization allows "comparison of biological measurements worldwide" and ensures the reliability of diagnostic procedures. These preparations are generally intended for use in the characterization of the activity of secondary reference preparations (regional, national or in-house working standards). Unfortunately, international reference standards for parasitic diseases are not available at present, except for Toxoplasma antibodies. The first international standard reagent for Anti-Toxoplasma Serum was established in 1968 and at present, an international standard reference serum, Anti-toxoplasma serum, human TOXM is available at the National Institute for Biological Standards and Control (NIBSC) in UK. Several collaborative, multicenter studies were carried out to assess the performance of different methods and commercial tests for the diagnosis of toxoplasmosis, by providing to participating laboratories a panel of well-defined sera to be tested. A four-phase process following well-accepted methodological standards for the development of diagnostics, analogous to those internationally accepted for drugs and vaccines was recently proposed. The pre-clinical evaluation, the analytic study to assess sensitivity, specificity, predictive values in laboratory (phase I), should be followed by a proof of principle study to distinguish diseased from healthy persons in easily accessible populations (phase II). The evaluation of test performance in populations of intended use (phase III), and finally the delineation of cost-effectiveness and societal impact of new tests in comparison with existing tools (phase IV) should complete the validation procedure. In this context, national regulatory agencies play a major role in pre-market approval and post-market surveillance of IVDs. The European Community in 1998 approved a directive (Directive 98/79/EC) which rules the marketing of IVD medical devices, in order to harmonise the performance levels and standards in European countries. But, among IVDs for parasitic diseases, only those to detect congenital toxoplasmosis are submitted to defined procedures to provide the verification of products before their placing on the market and the surveillance after their marketing by a notified body, which perform appropriate examinations, tests and inspections to production facilities to verify if the device meets the requirements of the directive. In U.S.A., the Food and Drug Administration (FDA), through the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), provides a comprehensive and regulatory activity for IVDs through pre-market evaluation and post-market surveillance. In developing countries, the scarcity of resources limits the procedures through which the national control authority can assure safety, quality and efficacy of products marketed, both imported and locally manufactured.
Pulse Wave Velocity as Marker of Preclinical Arterial Disease: Reference Levels in a Uruguayan Population Considering Wave Detection Algorithms, Path Lengths, Aging, and Blood Pressure

PubMed Central

Farro, Ignacio; Bia, Daniel; Zócalo, Yanina; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Alallón, Walter; Lluberas, Ricardo; Armentano, Ricardo L.

2012-01-01

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the “reference population”; the group of subjects with optimal/normal blood pressures levels at study time represented the “normal population.” Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes. PMID:22666551
Reference Values for Human Posture Measurements Based on Computerized Photogrammetry: A Systematic Review.

PubMed

Macedo Ribeiro, Ana Freire; Bergmann, Anke; Lemos, Thiago; Pacheco, Antônio Guilherme; Mello Russo, Maitê; Santos de Oliveira, Laura Alice; de Carvalho Rodrigues, Erika

The main objective of this study was to review the literature to identify reference values for angles and distances of body segments related to upright posture in healthy adult women with the Postural Assessment Software (PAS/SAPO). Electronic databases (BVS, PubMed, SciELO and Scopus) were assessed using the following descriptors: evaluation, posture, photogrammetry, physical therapy, postural alignment, postural assessment, and physiotherapy. Studies that performed postural evaluation in healthy adult women with PAS/SAPO and were published in English, Portuguese and Spanish, between the years 2005 and 2014 were included. Four studies met the inclusion criteria. Data from the included studies were grouped to establish the statistical descriptors (mean, variance, and standard deviation) of the body angles and distances. A total of 29 variables were assessed (10 in the anterior views, 16 in the lateral right and left views, and 3 in the posterior views), and its respective mean and standard deviation were calculated. Reference values for the anterior and posterior views showed no symmetry between the right and left sides of the body in the frontal plane. There were also small differences in the calculated reference values for the lateral view. The proposed reference values for quantitative evaluation of the upright posture in healthy adult women estimated in the present study using PAS/SAPO could guide future studies and help clinical practice. Copyright © 2017. Published by Elsevier Inc.
Normative Bone Mineral Density Z-Scores for Canadians Aged 16 to 24 Years: The Canadian Multicenter Osteoporosis Study

PubMed Central

Zhou, Wei; Langsetmo, Lisa; Berger, Claudie; Adachi, Jonathan D.; Papaioannou, Alexandra; Ioannidis, George; Webber, Colin; Atkinson, Stephanie A.; Olszynski, Wojciech P.; Brown, Jacques P.; Hanley, David A.; Josse, Robert; Kreiger, Nancy; Prior, Jerilynn; Kaiser, Stephanie; Kirkland, Susan; Goltzman, David; Davison, Kenneth Shawn

2016-01-01

The objectives of the study were to develop bone mineral density (BMD) reference norms and BMD Z-scores at various skeletal sites, to determine whether prior fracture and/or asthma were related to BMD, and to assess possible geographic variation of BMD among Canadian youth aged 16–24 yr. Z-Scores were defined as the number of standard deviations from the mean BMD of a healthy population of the same age, race, and sex. Z-Scores were calculated using the reference sample defined as Canadian Caucasian participants without asthma or prior fracture. Reference standards were created for lumbar spine (L1–L4), femoral neck, total hip, and greater trochanter, by each year of age (16–24 yr), and by sex. The Z-score norms were developed for groups noted earlier. Mean Z-scores between the asthma or fracture subgroups compared with the mean Z-scores in the reference sample were not different. There were minor differences in mean BMD across different Canadian geographic regions. This study provides age, sex, and skeletal site-specific Caucasian reference norms and formulae for the calculation of BMD Z-scores for Canadian youth aged 16–24 yr. This information will be valuable to help to identify individuals with clinically meaningful low BMD. PMID:20554232
CR softcopy display presets based on optimum visualization of specific findings

NASA Astrophysics Data System (ADS)

Andriole, Katherine P.; Gould, Robert G.; Webb, W. R.

1999-07-01

The purpose of this research is to assess the utility of providing presets for computed radiography (CR) softcopy display, based not on the window/level settings, but on image processing applied to the image based on optimization for visualization of specific findings, pathologies, etc. Clinical chest images are acquired using an Agfa ADC 70 CR scanner, and transferred over the PACS network to an image processing station which has the capability to perform multiscale contrast equalization. The optimal image processing settings per finding are developed in conjunction with a thoracic radiologist by manipulating the multiscale image contrast amplification algorithm parameters. Softcopy display of images processed with finding-specific settings are compared with the standard default image presentation for fifty cases of each category. Comparison is scored using a five point scale with positive one and two denoting the standard presentation is preferred over the finding-specific presets, negative one and two denoting the finding-specific preset is preferred over the standard presentation, and zero denoting no difference. Presets have been developed for pneumothorax and clinical cases are currently being collected in preparation for formal clinical trials. Subjective assessments indicate a preference for the optimized-preset presentation of images over the standard default, particularly by inexperienced radiology residents and referring clinicians.
Micronutrient content in enteral nutrition formulas: comparison with the dietary reference values for healthy populations.

PubMed

Iacone, Roberto; Scanzano, Clelia; Santarpia, Lidia; D'Isanto, Anna; Contaldo, Franco; Pasanisi, Fabrizio

2016-03-31

The micronutrient content in standard enteral mixtures should be closer to the dietary reference values for a healthy population since standard enteral diets are formulated for subjects with no special nutritional needs. This study compares the micronutrient content of the most common enteral nutrition (EN) formulas with European dietary reference values (DRVs) for healthy population. Sixty-two nutritionally complete enteral formulas were considered. The micronutrient content was calculated by multiplying the value reported on the nutritional information panel of each formula by the daily dose usually prescribed. The comparison between the micronutrient content of all enteral formulas evaluated and the DRVs indicates that daily fluoride and vitamin K requirements were not covered, while an oversupply of many other micronutrients was provided. Moreover, in some enteral formulas, at a dose of 2000 Kcal/day, zinc and vitamin A content exceeded the tolerable upper limits and, for one diabetes-specific enteral formula, the chromium content exceeded the relevant European standards in both 1500 and 2000 Kcal/day diets. Most enteral formulas evaluated are generally suitable for patients on long-term total EN and formulas with higher content of a specific micronutrient may be a useful tool for patients affected by specific clinical conditions, at least for a period of time, then switching to standard enteral mixtures. The availability of nutritional enteral formulas, well balanced also for micronutrient intake, will further improve individualized treatments, particularly for patients on long-term total EN.
Simultaneous identification and quantification of new psychoactive substances in blood by GC-APCI-QTOFMS coupled to nitrogen chemiluminescence detection without authentic reference standards.

PubMed

Ojanperä, Ilkka; Mesihää, Samuel; Rasanen, Ilpo; Pelander, Anna; Ketola, Raimo A

2016-05-01

A novel platform is introduced for simultaneous identification and quantification of new psychoactive substances (NPS) in blood matrix, without the necessity of using authentic reference standards. The instrumentation consisted of gas chromatography (GC) coupled to nitrogen chemiluminescence detection (NCD) and atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (APCI-QTOFMS). In this concept, the GC flow is divided in appropriate proportions between NCD for single-calibrant quantification, utilizing the detector's equimolar response to nitrogen, and QTOFMS for accurate mass-based identification. The principle was proven by analyzing five NPS, bupropion, desoxypipradrol (2-DPMP), mephedrone, methylone, and naphyrone, in sheep blood. The samples were spiked with the analytes post-extraction to avoid recovery considerations at this point. All the NPS studies produced a protonated molecule in APCI resulting in predictable fragmentation with high mass accuracy. The N-equimolarity of quantification by NCD was investigated by using external calibration with the secondary standard caffeine at five concentration levels between 0.17 and 1.7 mg/L in blood matrix as five replicates. The equimolarity was on average 98.7%, and the range of individual equimolarity determinations was 76.7-130.1%. The current analysis platform affords a promising approach to instant simultaneous qualitative and quantitative analysis of drugs in the absence of authentic reference standards, not only in forensic and clinical toxicology but also in other bioanalytical applications.
Standardization of Laboratory Methods for the PERCH Study

PubMed Central

Karron, Ruth A.; Morpeth, Susan C.; Bhat, Niranjan; Levine, Orin S.; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Howie, Stephen R. C.; Knoll, Maria Deloria; Kotloff, Karen L.; Madhi, Shabir A.; Scott, J. Anthony G.; Thea, Donald M.; Adrian, Peter V.; Ahmed, Dilruba; Alam, Muntasir; Anderson, Trevor P.; Antonio, Martin; Baillie, Vicky L.; Dione, Michel; Endtz, Hubert P.; Gitahi, Caroline; Karani, Angela; Kwenda, Geoffrey; Maiga, Abdoul Aziz; McClellan, Jessica; Mitchell, Joanne L.; Morailane, Palesa; Mugo, Daisy; Mwaba, John; Mwansa, James; Mwarumba, Salim; Nyongesa, Sammy; Panchalingam, Sandra; Rahman, Mustafizur; Sawatwong, Pongpun; Tamboura, Boubou; Toure, Aliou; Whistler, Toni; O’Brien, Katherine L.; Murdoch, David R.

2017-01-01

Abstract The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1–59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites. Site laboratories received uniform training, equipment, and reagents for core testing methods. Standardization was further assured by routine teleconferences, in-person meetings, site monitoring visits, and internal and external quality assurance testing. Targeted confirmatory testing and testing by specialized assays were done at a central reference laboratory. PMID:28575358
Guidelines Regarding §16 of the German Transplantation Act - Initial Experiences with Structured Reporting.

PubMed

Pinto Dos Santos, Daniel; Arnhold, Gordon; Mildenberger, Peter; Düber, Christoph; Kloeckner, Roman

2017-12-01

Purpose To transfer the report sheet from the guidelines regarding the German Transplantation Act to a standards-compliant report template and to evaluate it in the clinical routine. Materials and Methods The template was developed using the freely available software brackets.io. It was implemented in the clinical routine using a reporting platform developed in-house. Interfaces to the department RIS and PACS allowed for integration into the usual reporting workflow. The evaluation period was 70 days. Results Developing the template for implementation of the guidelines was possible without any difficulties. The content of the report sheet provided in the guidelines was transferred one to one. Additionally, a text field was included to allow for further remarks. In the period under review, 7 radiologists performed 44 evaluations in line with § 16 of the German Transplantation Act. Users of the template, referring physicians and the employees of the transplantation office reported a high degree of satisfaction. Conclusion Implementing report sheets that are required by law (e. g. in the guidelines regarding § 16 of the German Transplantation Act) in the clinical routine electronically is easy and achieves a high degree of acceptance. The standard supported by the German Radiological Society (IHE - "Management of radiology report templates") allows for a quick response to the growing demand for structured and standardized reporting. Key Points · Report sheets as required by law can easily be incorporated electronically into the clinical routine.. · Templates for structured reporting as supported by the German Radiological Society allow for a quick response to the growing demand for standardized reporting.. · Radiologists as well as referring physicians report a high degree of satisfaction with the electronic version of the report sheet.. Citation Format · Pinto dos Santos D, Arnhold G, Mildenberger P et al. Guidelines Regarding §16 of the German Transplantation Act - Initial Experiences with Structured Reporting. Fortschr Röntgenstr 2017; 189: 1145 - 1151. © Georg Thieme Verlag KG Stuttgart · New York.

Performance and standards for the process of head and neck cancer care: South and West audit of head and neck cancer 1996-1997 (SWAHN I). South and West Regional Cancer Organisation Tumour Panel for Head and Neck Cancer.

PubMed

Birchall, M A; Bailey, D; Lennon, A

2000-08-01

Evidence suggests wide variation in cancer care between different hospitals in the UK. To establish bench-marking data, we designed a prospective, 1 year regional study comparing key performance measures with established standards for the 28 hospital Trusts in the South and West of England involved in head and neck cancer care. 566 sequential patients with a newly-diagnosed head and neck cancer were included. Numbers referred and treated per hospital Trust were 1-58 and 1-65 respectively. 59% of patients received a pretreatment chest X-ray (standard 95%). 45% of patients were seen in a multidisciplinary clinic pretreatment (standard 95%), and this was proportional to the frequency of clinics held (P<0.0001). Median number of cases treated per surgeon was 4 (1-26), and by radiotherapist was 10 (1-51). Times between parts of the process of oral cancer care were closer to the standards than those for laryngeal cancer. Two patients were entered into a clinical trial. One had a quality-of-life score. Thus, in 1996-1997, in the South and West of England, there were major discrepancies between actual performance and established standards in many fundamental aspects of head and neck cancer care. Re-audit is essential to determine if the implementation of the Calman-Hine report has resulted in improvements.
Performance and standards for the process of head and neck cancer care: South and West audit of head and neck cancer 1996–1997 (SWAHN I)

PubMed Central

Birchall, M A; Bailey, D; Lennon, A

2000-01-01

Evidence suggests wide variation in cancer care between different hospitals in the UK. To establish bench-marking data, we designed a prospective, 1 year regional study comparing key performance measures with established standards for the 28 hospital Trusts in the South and West of England involved in head and neck cancer care. 566 sequential patients with a newly-diagnosed head and neck cancer were included. Numbers referred and treated per hospital Trust were 1–58 and 1–65 respectively. 59% of patients received a pretreatment chest X-ray (standard 95%). 45% of patients were seen in a multidisciplinary clinic pretreatment (standard 95%), and this was proportional to the frequency of clinics held (P< 0.0001). Median number of cases treated per surgeon was 4 (1–26), and by radiotherapist was 10 (1–51). Times between parts of the process of oral cancer care were closer to the standards than those for laryngeal cancer. Two patients were entered into a clinical trial. One had a quality-of-life score. Thus, in 1996–1997, in the South and West of England, there were major discrepancies between actual performance and established standards in many fundamental aspects of head and neck cancer care. Re-audit is essential to determine if the implementation of the Calman–Hine report has resulted in improvements. © 2000 Cancer Research Campaign PMID:10945484
Seven-Year Clinical Surveillance Program Demonstrates Consistent MARD Accuracy Performance of a Blood Glucose Test Strip.

PubMed

Setford, Steven; Grady, Mike; Mackintosh, Stephen; Donald, Robert; Levy, Brian

2018-05-01

MARD (mean absolute relative difference) is increasingly used to describe performance of glucose monitoring systems, providing a single-value quantitative measure of accuracy and allowing comparisons between different monitoring systems. This study reports MARDs for the OneTouch Verio® glucose meter clinical data set of 80 258 data points (671 individual batches) gathered as part of a 7.5-year self-surveillance program Methods: Test strips were routinely sampled from randomly selected manufacturer's production batches and sent to one of 3 clinic sites for clinical accuracy assessment using fresh capillary blood from patients with diabetes, using both the meter system and standard laboratory reference instrument. Evaluation of the distribution of strip batch MARD yielded a mean value of 5.05% (range: 3.68-6.43% at ±1.96 standard deviations from mean). The overall MARD for all clinic data points (N = 80 258) was also 5.05%, while a mean bias of 1.28 was recorded. MARD by glucose level was found to be consistent, yielding a maximum value of 4.81% at higher glucose (≥100 mg/dL) and a mean absolute difference (MAD) of 5.60 mg/dL at low glucose (<100 mg/dL). MARD by year of manufacture varied from 4.67-5.42% indicating consistent accuracy performance over the surveillance period. This 7.5-year surveillance program showed that this meter system exhibits consistently low MARD by batch, glucose level and year, indicating close agreement with established reference methods whilste exhibiting lower MARD values than continuous glucose monitoring (CGM) systems and providing users with confidence in the performance when transitioning to each new strip batch.
Performance of lung ultrasonography for the diagnosis of communityacquired pneumonia in hospitalized children.

PubMed

Man, Sorin Claudiu; Fufezan, Otilia; Sas, Valentina; Schnell, Cristina

2017-05-10

The objective of the study was to assess the performance of lung ultrasonography (LUS) as compared to chest radiography and the clinical criteria for the diagnosis of pneumonia in children. This was a retrospective study in which data were collected from medical files of 81 children admitted with a clinical suspicion of pneumonia in which both an LUS and a chest radiograph during the hospitalization were performed. Reference standard used for the diagnosis of pneumonia were chest radiographs (consolidation, parenchymal infiltrates, and interstitial infiltrate) and clinical criteria. LUSfindings were reported as normal, parenchymal consolidations and pleural effusions. Radiological pneumonia was reported in 72 of the 81 patients (88.9%). LUS identified parenchymal consolidations in 62 cases. LUS correctly identified radiological pneumonia with a sensitivity of 79.2% and a specificity of 44.4%. The positive predictive value (PPV) was 91.9% and the negative predictive value (NPV) was 21.0%. When clinical criteria were used as reference standard, the sensitivity, specificity, PPV and NPV of correctly identifying clinical pneumonia cases by LUS (only consolidations) were 80.0%, 66.7%, 96.8% and 21.0%. When indicative for the presence of pneumonia either the ultrasound consolidation or the ultrasound detected pleural effusion were considered when the sensitivity, PPV and NPV increased to 96.0% (95%CI: 88.8-99.2), 97.3% (95%CI: 92.0-99.1), and 57.1% (95%CI: 27.7-82.2), respectively. In our opinion, our findings together withprevious ones available in the literature recommend LUS as a valuable investigation for the diagnosis of community-acquiredpneumonia in children.
Eddy-Current Reference Standard

NASA Technical Reports Server (NTRS)

Ambrose, H. H., Jr.

1985-01-01

Magnetic properties of metallic reference standards duplicated and stabilized for eddy-current coil measurements over long times. Concept uses precisely machined notched samples of known annealed materials as reference standards.
Rabies vaccine standards: comparison of the 5th and 6th WHO international reference standards to the USDA veterinary reference standard.

PubMed

Hermann, J; Fry, A; Reising, M; Patterson, P; Siev, D; Gatewood, D

2012-11-06

Ensuring rabies vaccines are potent and effective is paramount in preventing transmission of this deadly disease and safeguarding public health. Efficacy of human and veterinary vaccines is ensured by evaluating relative potency estimates of the vaccine compared to a rabies reference standard using the National Institutes of Health (NIH) test. Reference vaccines are based on the International Standard for Rabies Vaccine provided by the World Health Organization (WHO). A comparison study was conducted to determine the relative potency of the 5th WHO, 6th WHO, and United States Department of Agriculture's (USDA) 08-14 reference standards using the NIH test. Results from the study demonstrate that the 6th WHO reference standard is approximately twice as potent as the 5th WHO reference when reconstituted to contain 1 IU per ml. Based on these results, the Center for Veterinary Biologics (CVB) doubled the reconstitution volume of USDA veterinary reference 08-14 from 13 ml to 26 ml, for an initial use dilution of 0.7 IU per ml for use by veterinary biologics manufacturers in the NIH test. This study emphasizes the importance of reference standard calibration for use in the National Institutes of Health test. Published by Elsevier Ltd.
IFCC approved HPLC reference measurement procedure for the alcohol consumption biomarker carbohydrate-deficient transferrin (CDT): Its validation and use.

PubMed

Schellenberg, François; Wielders, Jos; Anton, Raymond; Bianchi, Vincenza; Deenmamode, Jean; Weykamp, Cas; Whitfield, John; Jeppsson, Jan-Olof; Helander, Anders

2017-02-01

Carbohydrate-deficient transferrin (CDT) is used as a biomarker of sustained high alcohol consumption. The currently available measurement procedures for CDT are based on various analytical techniques (HPLC, capillary electrophoresis, nephelometry), some differing in the definition of the analyte and using different reference intervals and cut-off values. The Working Group on Standardization of CDT (WG-CDT), initiated by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), has validated an HPLC candidate reference measurement procedure (cRMP) for CDT (% disialotransferrin to total transferrin based on peak areas), demonstrating that it is suitable as a reference measurement procedure (RMP) for CDT. Presented is a detailed description of the cRMP and its calibration. Practical aspects on how to treat genetic variant and so-called di-tri bridge samples are described. Results of method performance characteristics, as demanded by ISO 15189 and ISO 15193, are given, as well as the reference interval and measurement uncertainty and how to deal with that in routine use. The correlation of the cRMP with commercial CDT procedures and the performance of the cRMP in a network of laboratories are also presented. The performance of the CDT cRMP in combination with previously developed commutable calibrators allows for standardization of the currently available commercial measurement procedures for CDT. The cRMP has recently been approved by the IFCC and will be from now on be known as the IFCC-RMP for CDT, while CDT results standardized according to this RMP should be indicated as CDT IFCC . Copyright © 2016 Elsevier B.V. All rights reserved.
Age and sex variation in serum albumin concentration: an observational study.

PubMed

Weaving, Gary; Batstone, Gifford F; Jones, Richard G

2016-01-01

In the UK, a common reference interval for serum albumin is widely used irrespective of age or sex. Implicit in this is that laboratories produce analytically similar results. This paper challenges the validity of this approach. A three-week collection of results sent to all primary care centres in England has been analysed by age, sex and laboratory. In all, 1,079,193 serum albumin reports were included in this analysis. The mean population serum albumin concentration increases to peak at around age 20 years and then decreases with increasing age. Values in females decrease more rapidly but become close to male values at 60 years. The variation between laboratories was large and potentially clinically significant. Reference intervals for serum albumin should be stratified by age and sex. Until there is greater methodological standardization, laboratories should determine their own reference intervals and not accept a single consensus reference interval. © The Author(s) 2015.
Hematology and plasma chemistry reference intervals for cultured tilapia (Oreochromis hybrid).

PubMed

Hrubec, Terry C.; Cardinale, Jenifer L.; Smith, Stephen A.

2000-01-01

Tilapia are a commonly aquacultured fish yet little is known about their normal physiology and response to disease. In this study we determined the results of complete hematologic (n=40) and plasma biochemical profiles (n=63) in production tilapia (Oreochromis hybrids). The fish were raised in recirculating systems with a high stocking density (120 g/L), and were in the middle of a 15-month production cycle. Blood was analyzed using standard techniques, and reference intervals were determined using nonparametric methods. Non-production tilapia (n=15) from low-density tanks (4 g/L) also were sampled; the clinical chemistry results were compared to reference intervals from the fish raised in high-density tanks. Differences were noted in plasma protein, calcium and phosphorus concentrations, such that reference intervals for high-density production tilapia were not applicable to fish raised under different environmental and management conditions.
Linear time-dependent reference intervals where there is measurement error in the time variable-a parametric approach.

PubMed

Gillard, Jonathan

2015-12-01

This article re-examines parametric methods for the calculation of time specific reference intervals where there is measurement error present in the time covariate. Previous published work has commonly been based on the standard ordinary least squares approach, weighted where appropriate. In fact, this is an incorrect method when there are measurement errors present, and in this article, we show that the use of this approach may, in certain cases, lead to referral patterns that may vary with different values of the covariate. Thus, it would not be the case that all patients are treated equally; some subjects would be more likely to be referred than others, hence violating the principle of equal treatment required by the International Federation for Clinical Chemistry. We show, by using measurement error models, that reference intervals are produced that satisfy the requirement for equal treatment for all subjects. © The Author(s) 2011.
Direct calibration of a reference standard against the air kerma strength primary standard, at 192Ir HDR energy.

PubMed

Rajan, K N Govinda; Selvam, T Palani; Bhatt, B C; Vijayam, M; Patki, V S; Vinatha; Pendse, A M; Kannan, V

2002-04-07

The primary standard of low air kerma rate sources or beams, maintained at the Radiological Standards Laboratory (RSL) of the Bhabha Atomic Research Centre (BARC), is a 60 cm3 spherical graphite ionization chamber. A 192Ir HDR source was standardized at the hospital site in units of air kerma strength (AKS) using this primary standard. A 400 cm3 bakelite chamber, functioning as a reference standard at the RSL for a long period, at low air kerma rates (compared to external beam dose rates), was calibrated against the primary standard. It was seen that the primary standard and the reference standard, both being of low Z, showed roughly the same scatter response and yielded the same calibration factor for the 400 cm3 reference chamber, with or without room scatter. However, any likelihood of change in the reference chamber calibration factor would necessitate the re-transport of the primary standard to the hospital site for re-calibration. Frequent transport of the primary standard can affect the long-term stability of the primary standard, due to its movement or other extraneous causes. The calibration of the reference standard against the primary standard at the RSL, for an industrial type 192Ir source maintained at the laboratory, showed excellent agreement with the hospital calibration, making it possible to check the reference chamber calibration at RSL itself. Further calibration procedures have been developed to offer traceable calibration of the hospital well ionization chambers.
Undertaking clinical audit, with reference to a Prescribing Observatory for Mental Health audit of lithium monitoring.

PubMed

Paton, Carol; Barnes, Thomas R E

2014-06-01

Audit is an important tool for quality improvement. The collection of data on clinical performance against evidence-based and clinically relevant standards, which are considered by clinicians to be realistic in routine practice, can usefully prompt reflective practice and the implementation of change. Evidence of participation in clinical audit is required to achieve intended learning outcomes for trainees in psychiatry and revalidation for those who are members of the Royal College of Psychiatrists. This article addresses some of the practical steps involved in conducting an audit project, and, to illustrate key points, draws on lessons learnt from a national, audit-based, quality improvement programme of lithium prescribing and monitoring conducted through the Prescribing Observatory for Mental Health.
Selection of reference standard during method development using the analytical hierarchy process.

PubMed

Sun, Wan-yang; Tong, Ling; Li, Dong-xiang; Huang, Jing-yi; Zhou, Shui-ping; Sun, Henry; Bi, Kai-shun

2015-03-25

Reference standard is critical for ensuring reliable and accurate method performance. One important issue is how to select the ideal one from the alternatives. Unlike the optimization of parameters, the criteria of the reference standard are always immeasurable. The aim of this paper is to recommend a quantitative approach for the selection of reference standard during method development based on the analytical hierarchy process (AHP) as a decision-making tool. Six alternative single reference standards were assessed in quantitative analysis of six phenolic acids from Salvia Miltiorrhiza and its preparations by using ultra-performance liquid chromatography. The AHP model simultaneously considered six criteria related to reference standard characteristics and method performance, containing feasibility to obtain, abundance in samples, chemical stability, accuracy, precision and robustness. The priority of each alternative was calculated using standard AHP analysis method. The results showed that protocatechuic aldehyde is the ideal reference standard, and rosmarinic acid is about 79.8% ability as the second choice. The determination results successfully verified the evaluation ability of this model. The AHP allowed us comprehensive considering the benefits and risks of the alternatives. It was an effective and practical tool for optimization of reference standards during method development. Copyright © 2015 Elsevier B.V. All rights reserved.
WE-A-BRD-01: Innovation in Radiation Therapy Planning I: Knowledge Guided Treatment Planning

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

Wu, Q; Olsen, L

2014-06-15

Intensity modulated radiation therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) offer the capability of normal tissues and organs sparing. However, the exact amount of sparing is often unknown until the plan is complete. This lack of prior guidance has led to the iterative, trial and-error approach in current planning practice. Even with this effort the search for patient-specific optimal organ sparing is still strongly influenced by planner's experience. While experience generally helps in maximizing the dosimetric advantages of IMRT/VMAT, there have been several reports showing unnecessarily high degree of plan quality variability at individual institutions and amongst different institutions,more » even with a large amount of experience and the best available tools. Further, when physician and physicist evaluate a plan, the dosimetric quality of the plan is often compared with a standard protocol that ignores individual patient anatomy and tumor characteristic variations. In recent years, developments of knowledge models for clinical IMRT/VMAT planning guidance have shown promising clinical potentials. These knowledge models extract past expert clinical experience into mathematical models that predict dose sparing references at patient-specific level. For physicians and planners, these references provide objective values that reflect best achievable dosimetric constraints. For quality assurance, applying patient-specific dosimetry requirements will enable more quantitative and objective assessment of protocol compliance for complex IMRT planning. Learning Objectives: Modeling and representation of knowledge for knowledge-guided treatment planning. Demonstrations of knowledge-guided treatment planning with a few clinical caanatomical sites. Validation and evaluation of knowledge models for cost and quality effective standardization of plan optimization.« less
[The International Classification of Functioning, Disability and Health (ICF) : The implementation of the ICF Core Sets for Hand Conditions in clinical routine as an example of application].

PubMed

Coenen, Michaela; Rudolf, Klaus-Dieter; Kus, Sandra; Dereskewitz, Caroline

2018-05-24

The International Classification of Functioning, Disability and Health (ICF) provides a standardized language of almost 1500 ICF categories for coding information about functioning and contextual factors. Short lists (ICF Core Sets) are helpful tools to support the implementation of the ICF in clinical routine. In this paper we report on the implementation of ICF Core Sets in clinical routine using the "ICF Core Sets for Hand Conditions" and the "Lighthouse Project Hand" as an example. Based on the ICF categories of the "Brief ICF Core Set for Hand Conditions", the ICF-based assessment tool (ICF Hand A ) was developed aiming to guide the assessment and treatment of patients with injuries and diseases located at the hand. The ICF Hand A facilitates the standardized assessment of functioning - taking into consideration of a holistic view of the patients - along the continuum of care ranging from acute care to rehabilitation and return to work. Reference points for the assessment of the ICF Hand A are determined in treatment guidelines for selected injuries and diseases of the hand along with recommendations for acute treatment and care, procedures and interventions of subsequent treatment and rehabilitation. The assessment of the ICF Hand A according to the defined reference points can be done using electronic clinical assessment tools and allows for an automatic generation of a timely medical report of a patient's functioning. In the future, the ICF Hand A can be used to inform the coding of functioning in ICD-11.
Assessing children’s competence to consent in research by a standardized tool: a validity study

PubMed Central

2012-01-01

Background Currently over 50% of drugs prescribed to children have not been evaluated properly for use in their age group. One key reason why children have been excluded from clinical trials is that they are not considered able to exercise meaningful autonomy over the decision to participate. Dutch law states that competence to consent can be presumed present at the age of 12 and above; however, in pediatric practice children’s competence is not that clearly presented and the transition from assent to active consent is gradual. A gold standard for competence assessment in children does not exist. In this article we describe a study protocol on the development of a standardized tool for assessing competence to consent in research in children and adolescents. Methods/design In this study we modified the MacCAT-CR, the best evaluated competence assessment tool for adults, for use in children and adolescents. We will administer the tool prospectively to a cohort of pediatric patients from 6 to18 years during the selection stages of ongoing clinical trials. The outcomes of the MacCAT-CR interviews will be compared to a reference standard, established by the judgments of clinical investigators, and an expert panel consisting of child psychiatrists, child psychologists and medical ethicists. The reliability, criterion-related validity and reproducibility of the tool will be determined. As MacCAT-CR is a multi-item scale consisting of 13 items, power was justified at 130–190 subjects, providing a minimum of 10–15 observations per item. MacCAT-CR outcomes will be correlated with age, life experience, IQ, ethnicity, socio-economic status and competence judgment of the parent(s). It is anticipated that 160 participants will be recruited over 2 years to complete enrollment. Discussion A validity study on an assessment tool of competence to consent is strongly needed in research practice, particularly in the child and adolescent population. In this study we will establish a reference standard of children’s competence to consent, combined with validation of an assessment instrument. Results can facilitate responsible involvement of children in clinical trials by further development of guidelines, health-care policies and legal policies. PMID:23009102
Performance analysis of the OneTouch UltraVue blood glucose monitoring system.

PubMed

Chang, Anna; Orth, Alice; Le, Bryan; Menchavez, Perla; Miller, Lupe

2009-09-01

OneTouch UltraVue is a new meter for self-monitoring of blood glucose that includes a color display, used-strip ejector, and no-button interface. The system uses an electrochemical biosensor technology based on glucose oxidase chemistry to detect glucose concentrations from 20 to 600 mg/dl (1.1 to 33.3 mmol/liter). Accuracy and reproducibility were evaluated over a wide range of glucose concentrations according to standard criteria. Clinical accuracy was assessed by health care providers (HCPs) in two studies and by diabetes patients in the second study. Reference glucose levels were determined by a YSI 2300 analyzer. Same-day reproducibility and day-to-day reproducibility were also evaluated. In the accuracy studies, 99.7% and 98.7% of tests by HCPs and 97.0% of tests by patients were within +/-15 mg/dl (+/-0.8 mmol/liter) of the YSI reference for blood glucose <75 mg/dl (<4.2 mmol/liter), and within +/-20% for blood glucose > or =75 mg/dl (> or =4.2 mmol/liter), respectively. Consensus error grid analysis showed that 99.7% and 95.3% of tests by HCPs and 97.0% of tests by patients fell within zone A (i.e., has no effect on clinical action); all other results were in zone B (i.e., altered clinical action, little or no effect on clinical outcome). In the reproducibility studies, the standard deviation was <1.5 mg/dl (<0.1 mmol/liter) for glucose concentrations <100 mg/dl (<5.6 mmol/liter), and the coefficient of variation was <2% for concentrations > or = 100 mg/dl (> or =5.6 mmol/liter). OneTouch UltraVue meets standard acceptability criteria for accuracy and reproducibility across a wide range of glucose concentrations. Its simple interface and lack of contact with used strips make it a viable option for older patients and their caregivers. 2009 Diabetes Technology Society.
Performance Analysis of the OneTouch® UltraVue™ Blood Glucose Monitoring System

PubMed Central

Chang, Anna; Orth, Alice; Le, Bryan; Menchavez, Perla; Miller, Lupe

2009-01-01

Background OneTouch® UltraVue™ is a new meter for self-monitoring of blood glucose that includes a color display, used-strip ejector, and no-button interface. The system uses an electrochemical biosensor technology based on glucose oxidase chemistry to detect glucose concentrations from 20 to 600 mg/dl (1.1 to 33.3 mmol/liter). Methods Accuracy and reproducibility were evaluated over a wide range of glucose concentrations according to standard criteria. Clinical accu-racy was assessed by health care providers (HCPs) in two studies and by diabetes patients in the second study. Reference glucose lev-els were determined by a YSI 2300 analyzer. Same-day reproducibility and day-to-day reproducibility were also evaluated. Results In the accuracy studies, 99.7% and 98.7% of tests by HCPs and 97.0% of tests by patients were within ±15 mg/dl (±0.8 mmol/liter) of the YSI reference for blood glucose <75 mg/dl (<4.2 mmol/liter), and within ±20% for blood glucose ≥75 mg/dl (≥4.2 mmol/liter), respectively. Consensus error grid analysis showed that 99.7% and 95.3% of tests by HCPs and 97.0% of tests by patients fell within zone A (i.e., has no effect on clinical action); all other results were in zone B (i.e., altered clinical action, little or no effect on clini-cal outcome). In the reproducibility studies, the standard deviation was <1.5 mg/dl (<0.1 mmol/liter) for glucose concentra-tions <100 mg/dl (<5.6 mmol/liter), and the coefficient of variation was <2% for concentrations ≥100 mg/dl (≥5.6 mmol/liter). Conclusions OneTouch UltraVue meets standard acceptability criteria for accuracy and reproducibility across a wide range of glucose concentra-tions. Its simple interface and lack of contact with used strips make it a viable option for older patients and their caregivers. PMID:20144431
Audit of child maltreatment medical assessments in a culturally diverse, metropolitan setting

PubMed Central

Hotton, Paul Rex

2017-01-01

Objective Child maltreatment (CM) is a major public health problem globally. While there is evidence for the value of medical examination in the assessment of CM, little is known about the quality of clinical assessments for CM. South Western Sydney (SWS) has a large metropolitan population with many vulnerable subgroups. We aimed to describe acute presentations of CM in SWS over a 3-year period—with a focus on the quality of the clinical assessments. We wanted to determine whether the cases assessed fulfilled established minimum standards for clinical assessment of CM and whether the assessments were performed in a child-friendly manner. Design We gathered data from the acute child protection database on all children <16 years referred for assessment between 2013 and 2015. We performed simple descriptive analysis on the data. We measured the assessment, report writing and follow-up against criteria for minimum standards for CM assessments, and identified whether assessments were child-friendly from available clinical information. Results There were 304 children referred; 279 seen for acute assessment; most (73%) were for sexual abuse, 75 (27%) were for physical abuse/neglect. Over half the assessments identified other health concerns; joint assessments performed by paediatric and forensic doctors were better at identifying these health concerns than solo assessments. Most assessments were multidisciplinary and used protocols; half were not followed up; a third were performed after-hours and a third had no carer present during assessments. Conclusions We identified strengths and weaknesses in current CM assessments in our service. Locally relevant standards for CM assessments are achievable in the acute setting, more challenging is addressing appropriate medical and psychosocial follow-up for these children. While we have established baseline domains for measuring a child-friendly approach to CM assessments, more should be done to ensure these vulnerable children are assessed in a timely, child-friendly manner, with appropriate follow-up. PMID:29637146
Audit of child maltreatment medical assessments in a culturally diverse, metropolitan setting.

PubMed

Raman, Shanti; Hotton, Paul Rex

2017-01-01

Child maltreatment (CM) is a major public health problem globally. While there is evidence for the value of medical examination in the assessment of CM, little is known about the quality of clinical assessments for CM. South Western Sydney (SWS) has a large metropolitan population with many vulnerable subgroups. We aimed to describe acute presentations of CM in SWS over a 3-year period-with a focus on the quality of the clinical assessments. We wanted to determine whether the cases assessed fulfilled established minimum standards for clinical assessment of CM and whether the assessments were performed in a child-friendly manner. We gathered data from the acute child protection database on all children <16 years referred for assessment between 2013 and 2015. We performed simple descriptive analysis on the data. We measured the assessment, report writing and follow-up against criteria for minimum standards for CM assessments, and identified whether assessments were child-friendly from available clinical information. There were 304 children referred; 279 seen for acute assessment; most (73%) were for sexual abuse, 75 (27%) were for physical abuse/neglect. Over half the assessments identified other health concerns; joint assessments performed by paediatric and forensic doctors were better at identifying these health concerns than solo assessments. Most assessments were multidisciplinary and used protocols; half were not followed up; a third were performed after-hours and a third had no carer present during assessments. We identified strengths and weaknesses in current CM assessments in our service. Locally relevant standards for CM assessments are achievable in the acute setting, more challenging is addressing appropriate medical and psychosocial follow-up for these children. While we have established baseline domains for measuring a child-friendly approach to CM assessments, more should be done to ensure these vulnerable children are assessed in a timely, child-friendly manner, with appropriate follow-up.

Identification and antimicrobial susceptibility testing of Staphylococcus vitulinus by the BD phoenix automated microbiology system.

PubMed

Cirković, Ivana; Hauschild, Tomasz; Jezek, Petr; Dimitrijević, Vladimir; Vuković, Dragana; Stepanović, Srdjan

2008-08-01

This study evaluated the performance of the BD Phoenix system for the identification (ID) and antimicrobial susceptibility testing (AST) of Staphylococcus vitulinus. Of the 10 S. vitulinus isolates included in the study, 2 were obtained from the Czech Collection of Microorganisms, 5 from the environment, 2 from human clinical samples, and 1 from an animal source. The results of conventional biochemical and molecular tests were used for the reference method for ID, while antimicrobial susceptibility testing performed in accordance with Clinical and Laboratory Standards Institute recommendations and PCR for the mecA gene were the reference for AST. Three isolates were incorrectly identified by the BD Phoenix system; one of these was incorrectly identified to the genus level, and two to the species level. The results of AST by the BD Phoenix system were in agreement with those by the reference method used. While the results of susceptibility testing compared favorably, the 70% accuracy of the Phoenix system for identification of this unusual staphylococcal species was not fully satisfactory.
[Quality standards for duplex ultrasonographic assessment (duplex us) of abdominal aortic stent grafts].

PubMed

Diard, A; Becker, F; Pichot, O

2017-05-01

The quality standards of the French Society of Vascular Medicine for the ultrasound assessment of lower limb arteries in vascular medicine practice are based on the principle that these examinations have to meet two requirements: technical know-how (knowledge of devices and methodologies); medical know-how (level of examination matching the indication and purpose of the examination, interpretation and critical analysis of results). To describe an optimal level of examination adjusted to the indication or clinical hypothesis; to establish harmonious practices, methodologies, terminologies, results description and report; to provide good practice reference points and to promote a high quality process. The three levels of examination, indications and objectives for each level; the reference standard examination (level 2) and its variants according to indications; the minimal content of the exam report, the medical conclusion letter to the corresponding physician (synthesis, conclusion and management suggestions); commented glossary (anatomy, hemodynamics, signs and symptoms); technical basis; device settings. Here, we discuss duplex ultrasound for the supervision of the aortic stent grafts. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Reference tissue modeling with parameter coupling: application to a study of SERT binding in HIV

NASA Astrophysics Data System (ADS)

Endres, Christopher J.; Hammoud, Dima A.; Pomper, Martin G.

2011-04-01

When applicable, it is generally preferred to evaluate positron emission tomography (PET) studies using a reference tissue-based approach as that avoids the need for invasive arterial blood sampling. However, most reference tissue methods have been shown to have a bias that is dependent on the level of tracer binding, and the variability of parameter estimates may be substantially affected by noise level. In a study of serotonin transporter (SERT) binding in HIV dementia, it was determined that applying parameter coupling to the simplified reference tissue model (SRTM) reduced the variability of parameter estimates and yielded the strongest between-group significant differences in SERT binding. The use of parameter coupling makes the application of SRTM more consistent with conventional blood input models and reduces the total number of fitted parameters, thus should yield more robust parameter estimates. Here, we provide a detailed evaluation of the application of parameter constraint and parameter coupling to [11C]DASB PET studies. Five quantitative methods, including three methods that constrain the reference tissue clearance (kr2) to a common value across regions were applied to the clinical and simulated data to compare measurement of the tracer binding potential (BPND). Compared with standard SRTM, either coupling of kr2 across regions or constraining kr2 to a first-pass estimate improved the sensitivity of SRTM to measuring a significant difference in BPND between patients and controls. Parameter coupling was particularly effective in reducing the variance of parameter estimates, which was less than 50% of the variance obtained with standard SRTM. A linear approach was also improved when constraining kr2 to a first-pass estimate, although the SRTM-based methods yielded stronger significant differences when applied to the clinical study. This work shows that parameter coupling reduces the variance of parameter estimates and may better discriminate between-group differences in specific binding.
Nutritional status in sick children and adolescents is not accurately reflected by BMI-SDS.

PubMed

Fusch, Gerhard; Raja, Preeya; Dung, Nguyen Quang; Karaolis-Danckert, Nadina; Barr, Ronald; Fusch, Christoph

2013-01-01

Nutritional status provides helpful information of disease severity and treatment effectiveness. Body mass index standard deviation scores (BMI-SDS) provide an approximation of body composition and thus are frequently used to classify nutritional status of sick children and adolescents. However, the accuracy of estimating body composition in this population using BMI-SDS has not been assessed. Thus, this study aims to evaluate the accuracy of nutritional status classification in sick infants and adolescents using BMI-SDS, upon comparison to classification using percentage body fat (%BF) reference charts. BMI-SDS was calculated from anthropometric measurements and %BF was measured using dual-energy x-ray absorptiometry (DXA) for 393 sick children and adolescents (5 months-18 years). Subjects were classified by nutritional status (underweight, normal weight, overweight, and obese), using 2 methods: (1) BMI-SDS, based on age- and gender-specific percentiles, and (2) %BF reference charts (standard). Linear regression and a correlation analysis were conducted to compare agreement between both methods of nutritional status classification. %BF reference value comparisons were also made between 3 independent sources based on German, Canadian, and American study populations. Correlation between nutritional status classification by BMI-SDS and %BF agreed moderately (r (2) = 0.75, 0.76 in boys and girls, respectively). The misclassification of nutritional status in sick children and adolescents using BMI-SDS was 27% when using German %BF references. Similar rates observed when using Canadian and American %BF references (24% and 23%, respectively). Using BMI-SDS to determine nutritional status in a sick population is not considered an appropriate clinical tool for identifying individual underweight or overweight children or adolescents. However, BMI-SDS may be appropriate for longitudinal measurements or for screening purposes in large field studies. When accurate nutritional status classification of a sick patient is needed for clinical purposes, nutritional status will be assessed more accurately using methods that accurately measure %BF, such as DXA.
Multicenter evaluation of stress-first myocardial perfusion image triage by nuclear technologists and automated quantification

PubMed Central

Chaudhry, Waseem; Hussain, Nasir; Ahlberg, Alan W.; Croft, Lori B.; Fernandez, Antonio B.; Parker, Mathew W.; Swales, Heather H.; Slomka, Piotr J.; Henzlova, Milena J.; Duvall, W. Lane

2016-01-01

Background A stress-first myocardial perfusion imaging (MPI) protocol saves time, is cost effective, and decreases radiation exposure. A limitation of this protocol is the requirement for physician review of the stress images to determine the need for rest images. This hurdle could be eliminated if an experienced technologist and/or automated computer quantification could make this determination. Methods Images from consecutive patients who were undergoing a stress-first MPI with attenuation correction at two tertiary care medical centers were prospectively reviewed independently by a technologist and cardiologist blinded to clinical and stress test data. Their decision on the need for rest imaging along with automated computer quantification of perfusion results was compared with the clinical reference standard of an assessment of perfusion images by a board-certified nuclear cardiologist that included clinical and stress test data. Results A total of 250 patients (mean age 61 years and 55% female) who underwent a stress-first MPI were studied. According to the clinical reference standard, 42 (16.8%) and 208 (83.2%) stress-first images were interpreted as “needing” and “not needing” rest images, respectively. The technologists correctly classified 229 (91.6%) stress-first images as either “needing” (n = 28) or “not needing” (n = 201) rest images. Their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 66.7%, 96.6%, 80.0%, and 93.5%, respectively. An automated stress TPD score ≥1.2 was associated with optimal sensitivity and specificity and correctly classified 179 (71.6%) stress-first images as either “needing” (n = 31) or “not needing” (n = 148) rest images. Its sensitivity, specificity, PPV, and NPV were 73.8%, 71.2%, 34.1%, and 93.1%, respectively. In a model whereby the computer or technologist could correct for the other's incorrect classification, 242 (96.8%) stress-first images were correctly classified. The composite sensitivity, specificity, PPV, and NPV were 83.3%, 99.5%, 97.2%, and 96.7%, respectively. Conclusion Technologists and automated quantification software had a high degree of agreement with the clinical reference standard for determining the need for rest images in a stress-first imaging protocol. Utilizing an experienced technologist and automated systems to screen stress-first images could expand the use of stress-first MPI to sites where the cardiologist is not immediately available for interpretation. PMID:26566774
Rapid Antimicrobial Susceptibility Testing Using Forward Laser Light Scatter Technology

PubMed Central

Clinton, Lani K.; Hewitt, Carolyn; Koyamatsu, Terri; Sun, Yilun; Jamison, Ginger; Perkins, Rosalie; Tang, Li; Pounds, Stanley; Bankowski, Matthew J.

2016-01-01

The delayed reporting of antimicrobial susceptibility testing remains a limiting factor in clinical decision-making in the treatment of bacterial infection. This study evaluates the use of forward laser light scatter (FLLS) to measure bacterial growth for the early determination of antimicrobial susceptibility. Three isolates each (two clinical isolates and one reference strain) of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were tested in triplicate using two commercial antimicrobial testing systems, the Vitek2 and the MicroScan MIC panel, to challenge the BacterioScan FLLS. The BacterioScan FLLS showed a high degree of categorical concordance with the commercial methods. Pairwise comparison with each commercial system serving as a reference standard showed 88.9% agreement with MicroScan (two minor errors) and 72.2% agreement with Vitek (five minor errors). FLLS using the BacterioScan system shows promise as a novel method for the rapid and accurate determination of antimicrobial susceptibility. PMID:27558176
15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...
15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...
15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...
15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...
Profile of referrals for early childhood developmental delay to ambulatory subspecialty clinics.

PubMed

Shevell, M I; Majnemer, A; Rosenbaum, P; Abrahamowicz, M

2001-09-01

The objective of this study was to determine the profile and pattern of referral to subspecialty clinics of young children with suspected developmental delay together with the factors prompting their referral. All children under 5 years of age referred to either developmental pediatrics or pediatric neurology clinics at a single tertiary hospital over an 18-month period were prospectively identified. Standardized demographic and referral information were collected at intake, final developmental delay subtype diagnosed was identified, and referring physicians were surveyed regarding factors prompting referral. A total of 224 children met study criteria. There was a marked male preponderance (166/224), especially among those with either cognitive or language delay. Two delay subtypes, global developmental delay and developmental language disorder, accounted for two thirds of the diagnoses made. For slightly more than one third of the children (75/224), the delay subtype diagnosed following specialty evaluation was different from that initially suspected by the referring physician. A mean delay of 15.5 months was observed for the cohort as a whole between initial parental concern and specialty assessment. For referring physicians, the major factor prompting referral was the severity of the observed delay. The most important aspects of the specialty evaluation according to referral sources were the identification of a possible etiology and confirmation of delay. A profile of referrals and the rationale thereof for a cohort of children with suspected developmental delay is presented that, although locale specific, has implications for service provision and training.
Fractional flow reserve guided revascularization in daily practice: clinical judgment does not always meet science.

PubMed

Rubinshtein, Ronen; Jaffe, Ronen

2013-09-01

Measurement of the fractional flow reserve (FFR) during invasive coronary angiography is the accepted ''gold standard'' for assessing the functional significance of coronary artery lesions by determination of the characteristics of blood flow proximal and distal to a coronary stenosis during pharmacologically-mediated hyperemia. Abnormal FFR is associated with higher cardiac event rate if the coronary lesion is left untreated. On the other hand, it was shown that patients derived no clinical benefit from revascularization of angiographically obstructive lesions which were hemodynamically insignificant according to FFR (>0.8). This editorial comment refers to an observational cohort study which reported that in approximately 20% of real world patients the treatment strategy chosen was discordant with FFR findings. Our comment discusses these findings and concludes that while the standard of care is to treat patients in accordance with their FFR results (when available), it should be recognized that there are some clinical scenarios that may require a treatment strategy that is discordant with FFR result.
Wechsler Adult Intelligence Scale-IV Dyads for Estimating Global Intelligence.

PubMed

Girard, Todd A; Axelrod, Bradley N; Patel, Ronak; Crawford, John R

2015-08-01

All possible two-subtest combinations of the core Wechsler Adult Intelligence Scale-IV (WAIS-IV) subtests were evaluated as possible viable short forms for estimating full-scale IQ (FSIQ). Validity of the dyads was evaluated relative to FSIQ in a large clinical sample (N = 482) referred for neuropsychological assessment. Sample validity measures included correlations, mean discrepancies, and levels of agreement between dyad estimates and FSIQ scores. In addition, reliability and validity coefficients were derived from WAIS-IV standardization data. The Coding + Information dyad had the strongest combination of reliability and validity data. However, several other dyads yielded comparable psychometric performance, albeit with some variability in their particular strengths. We also observed heterogeneity between validity coefficients from the clinical and standardization-based estimates for several dyads. Thus, readers are encouraged to also consider the individual psychometric attributes, their clinical or research goals, and client or sample characteristics when selecting among the dyadic short forms. © The Author(s) 2014.
Reference Standard Test and the Diagnostic Ability of Spectral Domain Optical Coherence Tomography in Glaucoma.

PubMed

Rao, Harsha L; Yadav, Ravi K; Addepalli, Uday K; Begum, Viquar U; Senthil, Sirisha; Choudhari, Nikhil S; Garudadri, Chandra S

2015-08-01

To evaluate the relationship between the reference standard used to diagnose glaucoma and the diagnostic ability of spectral domain optical coherence tomograph (SDOCT). In a cross-sectional study, 280 eyes of 175 consecutive subjects, referred to a tertiary eye care center for glaucoma evaluation, underwent optic disc photography, visual field (VF) examination, and SDOCT examination. The cohort was divided into glaucoma and control groups based on 3 reference standards for glaucoma diagnosis: first based on the optic disc classification (179 glaucoma and 101 control eyes), second on VF classification (glaucoma hemifield test outside normal limits and pattern SD with P-value of <5%, 130 glaucoma and 150 control eyes), and third on the presence of both glaucomatous optic disc and glaucomatous VF (125 glaucoma and 155 control eyes). Relationship between the reference standards and the diagnostic parameters of SDOCT were evaluated using areas under the receiver operating characteristic curve, sensitivity, and specificity. Areas under the receiver operating characteristic curve and sensitivities of most of the SDOCT parameters obtained with the 3 reference standards (ranging from 0.74 to 0.88 and 72% to 88%, respectively) were comparable (P>0.05). However, specificities of SDOCT parameters were significantly greater (P<0.05) with optic disc classification as reference standard (74% to 88%) compared with VF classification as reference standard (57% to 74%). Diagnostic parameters of SDOCT that was significantly affected by reference standard was the specificity, which was greater with optic disc classification as the reference standard. This has to be considered when comparing the diagnostic ability of SDOCT across studies.
Comprehensive Assessment of Struggling Learners Referred to a Graduate Medical Education Remediation Program.

PubMed

Warburton, Karen M; Goren, Eric; Dine, C Jessica

2017-12-01

Implementation of the Next Accreditation System has provided a standardized framework for identifying learners not meeting milestones, but there is as yet no corresponding framework for remediation. We developed a comprehensive assessment process that allows correct diagnosis of a struggling learner's deficit(s) to promote successful remediation. At the University of Pennsylvania, resident learners within the Department of Medicine who are not meeting milestones are referred to the Early Intervention Remediation Committee (EIRC). The EIRC, composed of 14 faculty members with expertise in remediation, uses a standardized process to assess learners' deficits. These faculty members categorize primary deficits as follows: medical knowledge, clinical reasoning, organization and efficiency, professionalism, and communication skills. The standardized process of assessment includes an analysis of the learner's file, direct communication with evaluators, an interview focused on learner perception of the problem, screening for underlying medical or psychosocial issues, and a review of systems for deficits in the 6 core competencies. Participants were surveyed after participating in this process. Over a 2-year period, the EIRC assessed and developed remediation plans for 4% of learners (14 of a total 342). Following remediation and reassessment, the identified problems were satisfactorily resolved in all cases with no disciplinary action. While the process was time intensive, an average of 45 hours per learner, the majority of faculty and residents rated it as positive and beneficial. This structured assessment process identifies targeted areas for remediation and adds to the tools available to Clinical Competency Committees.
34 CFR 73.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Cross-reference to employee ethical conduct standards... of Education STANDARDS OF CONDUCT § 73.1 Cross-reference to employee ethical conduct standards and... branch-wide Standards of Ethical Conduct at 5 CFR part 2635 and to the Department of Education regulation...
34 CFR 73.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Cross-reference to employee ethical conduct standards... of Education STANDARDS OF CONDUCT § 73.1 Cross-reference to employee ethical conduct standards and... branch-wide Standards of Ethical Conduct at 5 CFR part 2635 and to the Department of Education regulation...
34 CFR 73.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false Cross-reference to employee ethical conduct standards... of Education STANDARDS OF CONDUCT § 73.1 Cross-reference to employee ethical conduct standards and... branch-wide Standards of Ethical Conduct at 5 CFR part 2635 and to the Department of Education regulation...
34 CFR 73.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 false Cross-reference to employee ethical conduct standards... of Education STANDARDS OF CONDUCT § 73.1 Cross-reference to employee ethical conduct standards and... branch-wide Standards of Ethical Conduct at 5 CFR part 2635 and to the Department of Education regulation...
34 CFR 73.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false Cross-reference to employee ethical conduct standards... of Education STANDARDS OF CONDUCT § 73.1 Cross-reference to employee ethical conduct standards and... branch-wide Standards of Ethical Conduct at 5 CFR part 2635 and to the Department of Education regulation...

7 CFR 1728.97 - Incorporation by reference of electric standards and specifications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 11 2014-01-01 2014-01-01 false Incorporation by reference of electric standards and...) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC STANDARDS AND SPECIFICATIONS FOR MATERIALS AND CONSTRUCTION § 1728.97 Incorporation by reference of electric standards and specifications. The...
7 CFR 1728.97 - Incorporation by reference of electric standards and specifications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 11 2012-01-01 2012-01-01 false Incorporation by reference of electric standards and...) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC STANDARDS AND SPECIFICATIONS FOR MATERIALS AND CONSTRUCTION § 1728.97 Incorporation by reference of electric standards and specifications. The...
US Food and Drug Administration Perspectives on Clinical Mass Spectrometry.

PubMed

Lathrop, Julia Tait; Jeffery, Douglas A; Shea, Yvonne R; Scholl, Peter F; Chan, Maria M

2016-01-01

Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry-based devices and enhance their entry into the clinic. © 2015 American Association for Clinical Chemistry.
Longitudinal Analysis of New Information Types in Clinical Notes

PubMed Central

Zhang, Rui; Pakhomov, Serguei; Melton, Genevieve B.

2014-01-01

It is increasingly recognized that redundant information in clinical notes within electronic health record (EHR) systems is ubiquitous, significant, and may negatively impact the secondary use of these notes for research and patient care. We investigated several automated methods to identify redundant versus relevant new information in clinical reports. These methods may provide a valuable approach to extract clinically pertinent information and further improve the accuracy of clinical information extraction systems. In this study, we used UMLS semantic types to extract several types of new information, including problems, medications, and laboratory information. Automatically identified new information highly correlated with manual reference standard annotations. Methods to identify different types of new information can potentially help to build up more robust information extraction systems for clinical researchers as well as aid clinicians and researchers in navigating clinical notes more effectively and quickly identify information pertaining to changes in health states. PMID:25717418
Using Semantic Web technologies for the generation of domain-specific templates to support clinical study metadata standards.

PubMed

Jiang, Guoqian; Evans, Julie; Endle, Cory M; Solbrig, Harold R; Chute, Christopher G

2016-01-01

The Biomedical Research Integrated Domain Group (BRIDG) model is a formal domain analysis model for protocol-driven biomedical research, and serves as a semantic foundation for application and message development in the standards developing organizations (SDOs). The increasing sophistication and complexity of the BRIDG model requires new approaches to the management and utilization of the underlying semantics to harmonize domain-specific standards. The objective of this study is to develop and evaluate a Semantic Web-based approach that integrates the BRIDG model with ISO 21090 data types to generate domain-specific templates to support clinical study metadata standards development. We developed a template generation and visualization system based on an open source Resource Description Framework (RDF) store backend, a SmartGWT-based web user interface, and a "mind map" based tool for the visualization of generated domain-specific templates. We also developed a RESTful Web Service informed by the Clinical Information Modeling Initiative (CIMI) reference model for access to the generated domain-specific templates. A preliminary usability study is performed and all reviewers (n = 3) had very positive responses for the evaluation questions in terms of the usability and the capability of meeting the system requirements (with the average score of 4.6). Semantic Web technologies provide a scalable infrastructure and have great potential to enable computable semantic interoperability of models in the intersection of health care and clinical research.
Evaluation of treatment response and resistance in metastatic renal cell cancer (mRCC) using integrated 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI); The REMAP study.

PubMed

Kelly-Morland, Christian; Rudman, Sarah; Nathan, Paul; Mallett, Susan; Montana, Giovanni; Cook, Gary; Goh, Vicky

2017-06-02

Tyrosine kinase inhibitors are the first line standard of care for treatment of metastatic renal cell carcinoma (RCC). Accurate response assessment in the setting of antiangiogenic therapies remains suboptimal as standard size-related response criteria do not necessarily accurately reflect clinical benefit, as they may be less pronounced or occur later in therapy than devascularisation. The challenge for imaging is providing timely assessment of disease status allowing therapies to be tailored to ensure ongoing clinical benefit. We propose that combined assessment of morphological, physiological and metabolic imaging parameters using 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ( 18 F-FDG PET/MRI) will better reflect disease behaviour, improving assessment of response/non-response/relapse. The REMAP study is a single-centre prospective observational study. Eligible patients with metastatic renal cell carcinoma, planned for systemic therapy, with at least 2 lesions will undergo an integrated 18 F-FDG PET and MRI whole body imaging with diffusion weighted and contrast-enhanced multiphasic as well as standard anatomical MRI sequences at baseline, 12 weeks and 24 weeks of systemic therapy allowing 18 F-FDG standardised uptake value (SUV), apparent diffusion co-efficient (ADC) and normalised signal intensity (SI) parameters to be obtained. Standard of care contrast-enhanced computed tomography CT scans will be performed at equivalent time-points. CT response categorisation will be performed using RECIST 1.1 and alternative (modified)Choi and MASS criteria. The reference standard for disease status will be by consensus panel taking into account clinical, biochemical and conventional imaging parameters. Intra- and inter-tumoural heterogeneity in vascular, diffusion and metabolic response/non-response will be assessed by image texture analysis. Imaging will also inform the development of computational methods for automated disease status categorisation. The REMAP study will demonstrate the ability of integrated 18 F-FDG PET-MRI to provide a more personalised approach to therapy. We suggest that 18 F-FDG PET/MRI will provide superior sensitivity and specificity in early response/non-response categorisation when compared to standard CT (using RECIST 1.1 and alternative (modified)Choi or MASS criteria) thus facilitating more timely and better informed treatment decisions. The trial is approved by the Southeast London Research Ethics Committee reference 16/LO/1499 and registered on the NIHR clinical research network portfolio ISRCTN12114913 .
[Standardization of terminology in laboratory medicine I].

PubMed

Yoon, Soo Young; Yoon, Jong Hyun; Min, Won Ki; Lim, Hwan Sub; Song, Junghan; Chae, Seok Lae; Lee, Chang Kyu; Kwon, Jung Ah; Lee, Kap No

2007-04-01

Standardization of medical terminology is essential for data transmission between health-care institutions or clinical laboratories and for maximizing the benefits of information technology. Purpose of our study was to standardize the medical terms used in the clinical laboratory, such as test names, units, terms used in result descriptions, etc. During the first year of the study, we developed a standard database of concept names for laboratory terms, which covered the terms used in government health care centers, their branch offices, and primary health care units. Laboratory terms were collected from the electronic data interchange (EDI) codes from National Health Insurance Corporation (NHIC), Logical Observation Identifier Names and Codes (LOINC) database, community health centers and their branch offices, and clinical laboratories of representative university medical centers. For standard expression, we referred to the English-Korean/ Korean-English medical dictionary of Korean Medical Association and the rules for foreign language translation. Programs for mapping between LOINC DB and EDI code and for translating English to Korean were developed. A Korean standard laboratory terminology database containing six axial concept names such as components, property, time aspect, system (specimen), scale type, and method type was established for 7,508 test observations. Short names and a mapping table for EDI codes and Unified Medical Language System (UMLS) were added. Synonym tables for concept names, words used in the database, and six axial terms were prepared to make it easier to find the standard terminology with common terms used in the field of laboratory medicine. Here we report for the first time a Korean standard laboratory terminology database for test names, result description terms, result units covering most laboratory tests in primary healthcare centers.
Telemetry Standards, RCC Standard 106-17. Chapter 3. Frequency Division Multiplexing Telemetry Standards

DTIC Science & Technology

2017-07-01

any of the listed reference frequencies may be used provided the requirements for compensation rate of change are satisfied. If the reference...for in present discriminator systems when the nominal response rating of the channels is employed and a reference frequency is recorded with the...Telemetry Standards, RCC Standard 106-17 Chapter 3, July 2017 3-i CHAPTER 3 Frequency Division Multiplexing Telemetry Standards Acronyms
Developing standards for malaria microscopy: external competency assessment for malaria microscopists in the Asia-Pacific.

PubMed

Ashraf, Sania; Kao, Angie; Hugo, Cecilia; Christophel, Eva M; Fatunmbi, Bayo; Luchavez, Jennifer; Lilley, Ken; Bell, David

2012-10-24

Malaria diagnosis has received renewed interest in recent years, associated with the increasing accessibility of accurate diagnosis through the introduction of rapid diagnostic tests and new World Health Organization guidelines recommending parasite-based diagnosis prior to anti-malarial therapy. However, light microscopy, established over 100 years ago and frequently considered the reference standard for clinical diagnosis, has been neglected in control programmes and in the malaria literature and evidence suggests field standards are commonly poor. Microscopy remains the most accessible method for parasite quantitation, for drug efficacy monitoring, and as a reference of assessing other diagnostic tools. This mismatch between quality and need highlights the importance of the establishment of reliable standards and procedures for assessing and assuring quality. This paper describes the development, function and impact of a multi-country microscopy external quality assurance network set up for this purpose in Asia. Surveys were used for key informants and past participants for feedback on the quality assurance programme. Competency scores for each country from 14 participating countries were compiled for analyses using paired sample t-tests. In-depth interviews were conducted with key informants including the programme facilitators and national level microscopists. External assessments and limited retraining through a formalized programme based on a reference slide bank has demonstrated an increase in standards of competence of senior microscopists over a relatively short period of time, at a potentially sustainable cost. The network involved in the programme now exceeds 14 countries in the Asia-Pacific, and the methods are extended to other regions. While the impact on national programmes varies, it has translated in some instances into a strengthening of national microscopy standards and offers a possibility both for supporting revival of national microcopy programmes, and for the development of globally recognized standards of competency needed both for patient management and field research.
Developing standards for malaria microscopy: external competency assessment for malaria microscopists in the Asia-Pacific

PubMed Central

2012-01-01

Background Malaria diagnosis has received renewed interest in recent years, associated with the increasing accessibility of accurate diagnosis through the introduction of rapid diagnostic tests and new World Health Organization guidelines recommending parasite-based diagnosis prior to anti-malarial therapy. However, light microscopy, established over 100 years ago and frequently considered the reference standard for clinical diagnosis, has been neglected in control programmes and in the malaria literature and evidence suggests field standards are commonly poor. Microscopy remains the most accessible method for parasite quantitation, for drug efficacy monitoring, and as a reference of assessing other diagnostic tools. This mismatch between quality and need highlights the importance of the establishment of reliable standards and procedures for assessing and assuring quality. This paper describes the development, function and impact of a multi-country microscopy external quality assurance network set up for this purpose in Asia. Methods Surveys were used for key informants and past participants for feedback on the quality assurance programme. Competency scores for each country from 14 participating countries were compiled for analyses using paired sample t-tests. In-depth interviews were conducted with key informants including the programme facilitators and national level microscopists. Results External assessments and limited retraining through a formalized programme based on a reference slide bank has demonstrated an increase in standards of competence of senior microscopists over a relatively short period of time, at a potentially sustainable cost. The network involved in the programme now exceeds 14 countries in the Asia-Pacific, and the methods are extended to other regions. Conclusions While the impact on national programmes varies, it has translated in some instances into a strengthening of national microscopy standards and offers a possibility both for supporting revival of national microcopy programmes, and for the development of globally recognized standards of competency needed both for patient management and field research. PMID:23095668
Accuracy of magnetic resonance based susceptibility measurements

NASA Astrophysics Data System (ADS)

Erdevig, Hannah E.; Russek, Stephen E.; Carnicka, Slavka; Stupic, Karl F.; Keenan, Kathryn E.

2017-05-01

Magnetic Resonance Imaging (MRI) is increasingly used to map the magnetic susceptibility of tissue to identify cerebral microbleeds associated with traumatic brain injury and pathological iron deposits associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Accurate measurements of susceptibility are important for determining oxygen and iron content in blood vessels and brain tissue for use in noninvasive clinical diagnosis and treatment assessments. Induced magnetic fields with amplitude on the order of 100 nT, can be detected using MRI phase images. The induced field distributions can then be inverted to obtain quantitative susceptibility maps. The focus of this research was to determine the accuracy of MRI-based susceptibility measurements using simple phantom geometries and to compare the susceptibility measurements with magnetometry measurements where SI-traceable standards are available. The susceptibilities of paramagnetic salt solutions in cylindrical containers were measured as a function of orientation relative to the static MRI field. The observed induced fields as a function of orientation of the cylinder were in good agreement with simple models. The MRI susceptibility measurements were compared with SQUID magnetometry using NIST-traceable standards. MRI can accurately measure relative magnetic susceptibilities while SQUID magnetometry measures absolute magnetic susceptibility. Given the accuracy of moment measurements of tissue mimicking samples, and the need to look at small differences in tissue properties, the use of existing NIST standard reference materials to calibrate MRI reference structures is problematic and better reference materials are required.
Estimating A Reference Standard Segmentation With Spatially Varying Performance Parameters: Local MAP STAPLE

PubMed Central

Commowick, Olivier; Akhondi-Asl, Alireza; Warfield, Simon K.

2012-01-01

We present a new algorithm, called local MAP STAPLE, to estimate from a set of multi-label segmentations both a reference standard segmentation and spatially varying performance parameters. It is based on a sliding window technique to estimate the segmentation and the segmentation performance parameters for each input segmentation. In order to allow for optimal fusion from the small amount of data in each local region, and to account for the possibility of labels not being observed in a local region of some (or all) input segmentations, we introduce prior probabilities for the local performance parameters through a new Maximum A Posteriori formulation of STAPLE. Further, we propose an expression to compute confidence intervals in the estimated local performance parameters. We carried out several experiments with local MAP STAPLE to characterize its performance and value for local segmentation evaluation. First, with simulated segmentations with known reference standard segmentation and spatially varying performance, we show that local MAP STAPLE performs better than both STAPLE and majority voting. Then we present evaluations with data sets from clinical applications. These experiments demonstrate that spatial adaptivity in segmentation performance is an important property to capture. We compared the local MAP STAPLE segmentations to STAPLE, and to previously published fusion techniques and demonstrate the superiority of local MAP STAPLE over other state-of-the- art algorithms. PMID:22562727
PCA3 Reference Set Application: T2-Erg-Martin Sanda-Emory (2014) — EDRN Public Portal

Cancer.gov

We hypothesize that combining T2:erg (T2:erg) fusion and PCA3 detection in urine collected after digital rectal exam can improve the specificity of identifying clinically significant prostate cancer presence over the standard PSA and DRE. To address this hypothesis we propose to validate the performance of the urinary T2:erg in a multiplex model predicting the diagnosis of clinically significant prostate cancer on subsequent prostate biopsy using post-DRE pre biopsy urine specimens from a cohort of 900 men on the EDRN’s PCA3 trial.
Twenty-first-century medical microbiology services in the UK.

PubMed

Duerden, Brian

2005-12-01

With infection once again a high priority for the UK National Health Service (NHS), the medical microbiology and infection-control services require increased technology resources and more multidisciplinary staff. Clinical care and health protection need a coordinated network of microbiology services working to consistent standards, provided locally by NHS Trusts and supported by the regional expertise and national reference laboratories of the new Health Protection Agency. Here, I outline my thoughts on the need for these new resources and the ways in which clinical microbiology services in the UK can best meet the demands of the twenty-first century.
Creation of an Open Framework for Point-of-Care Computer-Assisted Reporting and Decision Support Tools for Radiologists.

PubMed

Alkasab, Tarik K; Bizzo, Bernardo C; Berland, Lincoln L; Nair, Sujith; Pandharipande, Pari V; Harvey, H Benjamin

2017-09-01

Decreasing unnecessary variation in radiology reporting and producing guideline-concordant reports is fundamental to radiology's success in value-based payment models and good for patient care. In this article, we present an open authoring system for point-of-care clinical decision support tools integrated into the radiologist reporting environment referred to as the computer-assisted reporting and decision support (CAR/DS) framework. The CAR/DS authoring system, described herein, includes: (1) a definition format for representing radiology clinical guidelines as structured, machine-readable Extensible Markup Language documents and (2) a user-friendly reference implementation to test the fidelity of the created definition files with the clinical guideline. The proposed definition format and reference implementation will enable content creators to develop CAR/DS tools that voice recognition software (VRS) vendors can use to extend the commercial tools currently in use. In making the definition format and reference implementation software freely available, we hope to empower individual radiologists, expert groups such as the ACR, and VRS vendors to develop a robust ecosystem of CAR/DS tools that can further improve the quality and efficiency of the patient care that our field provides. We hope that this initial effort can serve as the basis for a community-owned open standard for guideline definition that the imaging informatics and VRS vendor communities will embrace and strengthen. To this end, the ACR Assist™ initiative is intended to make the College's clinical content, including the Incidental Findings Committee White Papers, available for decision support tool creation based upon the herein described CAR/DS framework. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.
Occupational medicine specialist referral triggers: Mixed-methods analysis of teleconsult cases.

PubMed

Eaton, J L; Mohammad, A; Mohr, D C; Brustein, D J; Kirkhorn, S R

2017-12-30

Qualitative analyses can yield critical lessons for learning organizations in healthcare. Few studies have applied these techniques in the field of occupational and environmental medicine (OEM). To describe the characteristics of complex cases referred for OEM subspecialty evaluation and variation by referring provider's training. Using a mixed methods approach, we conducted a content analysis of clinical cases submitted to a national OEM teleconsult service. Consecutive cases entered between April 2014 and July 2015 were screened, coded and analysed. 108 cases were available for analysis. Local Veterans Health Administration (VHA) non-specialist providers entered a primary medical diagnosis in 96% of cases at the time of intake. OEM speciality physicians coded significant medical conditions based on free text comments. Coder inter-rater reliability was 84%. The most frequent medical diagnosis types associated with tertiary OEM referral by non-specialists were endocrine (19%), cardiovascular (18%) and mental health (16%). Concern for usage of controlled and/or sedating medications was cited in 1% of cases. Compared to referring non-specialists, OEM physicians were more likely to attribute case complexity to musculoskeletal (OR: 2.3, 1.68-3.14) or neurological (OR: 1.69, 1.28-2.24) conditions. Medication usage (OR: 2.2, 1.49-2.26) was more likely to be a source of clinical concern among referring providers. The findings highlight the range of triggers for OEM physician subspecialty referral in clinical practice with employee patients. The results of this study can be used to inform development of provider education, standardized clinical practice pathways, and quality review activities for occupational medicine practitioners. Published by Oxford University Press on behalf of The Society of Occupational Medicine 2017.
Soliciting Strategies for Developing Cell-Based Reference Materials to Advance Mesenchymal Stromal Cell Research and Clinical Translation

PubMed Central

Viswanathan, Sowmya; Keating, Armand; Deans, Robert; Hematti, Peiman; Prockop, Darwin; Stroncek, David F.; Stacey, Glyn; Weiss, Dan J.; Mason, Christopher

2014-01-01

The mesenchymal stromal cell (MSC) field continues to rapidly progress with a number of clinical trials initiated and completed, with some reported successes in multiple clinical indications, and a growing number of companies established. The field, nevertheless, faces several challenges. Persistent issues include the definition of a MSC and comparability between MSC preparations. This is because of inherent cell heterogeneity, the absence of markers that are unique to MSCs, and the difficulty in precisely defining them by developmental origin. Differences in the properties of MSCs also depend on the site of tissue harvest, phenotypic and genotypic characteristics of the donor and the isolation, and storage and expansion methods used. These differences may be sufficient to ensure that attributes of the final MSC product could differ in potentially significant ways. Since there are currently no gold standards, we propose using a reference material to establish methods of comparability among MSC preparations. We suggest four possible “ruler scenarios” and a method for global distribution. We further suggest that critical to establishing a reference material is the need to define protocols for comparing cells. The main purpose of this article is to solicit input in establishing a consensus-based comparison. A comparative approach will be critical to all stages of translation to better clarify mechanisms of MSC actions, define an optimal cell manufacturing process, ensure best practice clinical investigations, extend the use of an MSC product for new indications, protect an MSC product from imitators, and develop uniform reimbursement policies. Importantly, a reference material may enable a consensus on a practical definition of MSCs. PMID:24422625
Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs

PubMed Central

2010-01-01

Background Acute urinary tract infections (UTI) are one of the most common bacterial infections among women presenting to primary care. However, there is a lack of consensus regarding the optimal reference standard threshold for diagnosing UTI. The objective of this systematic review is to determine the diagnostic accuracy of symptoms and signs in women presenting with suspected UTI, across three different reference standards (102 or 103 or 105 CFU/ml). We also examine the diagnostic value of individual symptoms and signs combined with dipstick test results in terms of clinical decision making. Methods Searches were performed through PubMed (1966 to April 2010), EMBASE (1973 to April 2010), Cochrane library (1973 to April 2010), Google scholar and reference checking. Studies that assessed the diagnostic accuracy of symptoms and signs of an uncomplicated UTI using a urine culture from a clean-catch or catherised urine specimen as the reference standard, with a reference standard of at least ≥ 102 CFU/ml were included. Synthesised data from a high quality systematic review were used regarding dipstick results. Studies were combined using a bivariate random effects model. Results Sixteen studies incorporating 3,711 patients are included. The weighted prior probability of UTI varies across diagnostic threshold, 65.1% at ≥ 102 CFU/ml; 55.4% at ≥ 103 CFU/ml and 44.8% at ≥ 102 CFU/ml ≥ 105 CFU/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 102 CFU/ml is the reference standard. Presence of dysuria (+LR 1.30 95% CI 1.20-1.41), frequency (+LR 1.10 95% CI 1.04-1.16), hematuria (+LR 1.72 95%CI 1.30-2.27), nocturia (+LR 1.30 95% CI 1.08-1.56) and urgency (+LR 1.22 95% CI 1.11-1.34) all increase the probability of UTI. The presence of vaginal discharge (+LR 0.65 95% CI 0.51-0.83) decreases the probability of UTI. Presence of hematuria has the highest diagnostic utility, raising the post-test probability of UTI to 75.8% at ≥ 102 CFU/ml and 67.4% at ≥ 103 CFU/ml. Probability of UTI increases to 93.3% and 90.1% at ≥ 102 CFU/ml and ≥ 103 CFU/ml respectively when presence of hematuria is combined with a positive dipstick result for nitrites. Subgroup analysis shows improved diagnostic accuracy using lower reference standards ≥ 102 CFU/ml and ≥ 103 CFU/ml. Conclusions Individual symptoms and signs have a modest ability to raise the pretest-risk of UTI. Diagnostic accuracy improves considerably when combined with dipstick tests particularly tests for nitrites. PMID:20969801
Predicting acute uncomplicated urinary tract infection in women: a systematic review of the diagnostic accuracy of symptoms and signs.

PubMed

Giesen, Leonie G M; Cousins, Gráinne; Dimitrov, Borislav D; van de Laar, Floris A; Fahey, Tom

2010-10-24

Acute urinary tract infections (UTI) are one of the most common bacterial infections among women presenting to primary care. However, there is a lack of consensus regarding the optimal reference standard threshold for diagnosing UTI. The objective of this systematic review is to determine the diagnostic accuracy of symptoms and signs in women presenting with suspected UTI, across three different reference standards (10(2) or 10(3) or 10(5) CFU/ml). We also examine the diagnostic value of individual symptoms and signs combined with dipstick test results in terms of clinical decision making. Searches were performed through PubMed (1966 to April 2010), EMBASE (1973 to April 2010), Cochrane library (1973 to April 2010), Google scholar and reference checking.Studies that assessed the diagnostic accuracy of symptoms and signs of an uncomplicated UTI using a urine culture from a clean-catch or catherised urine specimen as the reference standard, with a reference standard of at least ≥ 10(2) CFU/ml were included. Synthesised data from a high quality systematic review were used regarding dipstick results. Studies were combined using a bivariate random effects model. Sixteen studies incorporating 3,711 patients are included. The weighted prior probability of UTI varies across diagnostic threshold, 65.1% at ≥ 10(2) CFU/ml; 55.4% at ≥ 10(3) CFU/ml and 44.8% at ≥ 10(2) CFU/ml ≥ 10(5) CFU/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 10(2) CFU/ml is the reference standard. Presence of dysuria (+LR 1.30 95% CI 1.20-1.41), frequency (+LR 1.10 95% CI 1.04-1.16), hematuria (+LR 1.72 95%CI 1.30-2.27), nocturia (+LR 1.30 95% CI 1.08-1.56) and urgency (+LR 1.22 95% CI 1.11-1.34) all increase the probability of UTI. The presence of vaginal discharge (+LR 0.65 95% CI 0.51-0.83) decreases the probability of UTI. Presence of hematuria has the highest diagnostic utility, raising the post-test probability of UTI to 75.8% at ≥ 10(2) CFU/ml and 67.4% at ≥ 10(3) CFU/ml. Probability of UTI increases to 93.3% and 90.1% at ≥ 10(2) CFU/ml and ≥ 10(3) CFU/ml respectively when presence of hematuria is combined with a positive dipstick result for nitrites. Subgroup analysis shows improved diagnostic accuracy using lower reference standards ≥ 10(2) CFU/ml and ≥ 10(3) CFU/ml. Individual symptoms and signs have a modest ability to raise the pretest-risk of UTI. Diagnostic accuracy improves considerably when combined with dipstick tests particularly tests for nitrites.
49 CFR 1019.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Cross-reference to employee ethical conduct... Cross-reference to employee ethical conduct standards and financial disclosure regulations. Members and employees of the Surface Transportation Board also should refer to the executive branch Standards of Ethical...

49 CFR 1019.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Cross-reference to employee ethical conduct... Cross-reference to employee ethical conduct standards and financial disclosure regulations. Members and employees of the Surface Transportation Board also should refer to the executive branch Standards of Ethical...
49 CFR 1019.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 false Cross-reference to employee ethical conduct... Cross-reference to employee ethical conduct standards and financial disclosure regulations. Members and employees of the Surface Transportation Board also should refer to the executive branch Standards of Ethical...
49 CFR 1019.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 false Cross-reference to employee ethical conduct... Cross-reference to employee ethical conduct standards and financial disclosure regulations. Members and employees of the Surface Transportation Board also should refer to the executive branch Standards of Ethical...
49 CFR 1019.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Cross-reference to employee ethical conduct... Cross-reference to employee ethical conduct standards and financial disclosure regulations. Members and employees of the Surface Transportation Board also should refer to the executive branch Standards of Ethical...
Automated ancillary cancer history classification for mesothelioma patients from free-text clinical reports

PubMed Central

Wilson, Richard A.; Chapman, Wendy W.; DeFries, Shawn J.; Becich, Michael J.; Chapman, Brian E.

2010-01-01

Background: Clinical records are often unstructured, free-text documents that create information extraction challenges and costs. Healthcare delivery and research organizations, such as the National Mesothelioma Virtual Bank, require the aggregation of both structured and unstructured data types. Natural language processing offers techniques for automatically extracting information from unstructured, free-text documents. Methods: Five hundred and eight history and physical reports from mesothelioma patients were split into development (208) and test sets (300). A reference standard was developed and each report was annotated by experts with regard to the patient’s personal history of ancillary cancer and family history of any cancer. The Hx application was developed to process reports, extract relevant features, perform reference resolution and classify them with regard to cancer history. Two methods, Dynamic-Window and ConText, for extracting information were evaluated. Hx’s classification responses using each of the two methods were measured against the reference standard. The average Cohen’s weighted kappa served as the human benchmark in evaluating the system. Results: Hx had a high overall accuracy, with each method, scoring 96.2%. F-measures using the Dynamic-Window and ConText methods were 91.8% and 91.6%, which were comparable to the human benchmark of 92.8%. For the personal history classification, Dynamic-Window scored highest with 89.2% and for the family history classification, ConText scored highest with 97.6%, in which both methods were comparable to the human benchmark of 88.3% and 97.2%, respectively. Conclusion: We evaluated an automated application’s performance in classifying a mesothelioma patient’s personal and family history of cancer from clinical reports. To do so, the Hx application must process reports, identify cancer concepts, distinguish the known mesothelioma from ancillary cancers, recognize negation, perform reference resolution and determine the experiencer. Results indicated that both information extraction methods tested were dependant on the domain-specific lexicon and negation extraction. We showed that the more general method, ConText, performed as well as our task-specific method. Although Dynamic- Window could be modified to retrieve other concepts, ConText is more robust and performs better on inconclusive concepts. Hx could greatly improve and expedite the process of extracting data from free-text, clinical records for a variety of research or healthcare delivery organizations. PMID:21031012
Multicenter Evaluation of Cystatin C Measurement after Assay Standardization.

PubMed

Bargnoux, Anne-Sophie; Piéroni, Laurence; Cristol, Jean-Paul; Kuster, Nils; Delanaye, Pierre; Carlier, Marie-Christine; Fellahi, Soraya; Boutten, Anne; Lombard, Christine; González-Antuña, Ana; Delatour, Vincent; Cavalier, Etienne

2017-04-01

Since 2010, a certified reference material ERM-DA471/IFCC has been available for cystatin C (CysC). This study aimed to assess the sources of uncertainty in results for clinical samples measured using standardized assays. This evaluation was performed in 2015 and involved 7 clinical laboratories located in France and Belgium. CysC was measured in a panel of 4 serum pools using 8 automated assays and a candidate isotope dilution mass spectrometry reference measurement procedure. Sources of uncertainty (imprecision and bias) were evaluated to calculate the relative expanded combined uncertainty for each CysC assay. Uncertainty was judged against the performance specifications derived from the biological variation model. Only Siemens reagents on the Siemens systems and, to a lesser extent, DiaSys reagents on the Cobas system, provided results that met the minimum performance criterion calculated according to the intraindividual and interindividual biological variations. Although the imprecision was acceptable for almost all assays, an increase in the bias with concentration was observed for Gentian reagents, and unacceptably high biases were observed for Abbott and Roche reagents on their own systems. This comprehensive picture of the market situation since the release of ERM-DA471/IFCC shows that bias remains the major component of the combined uncertainty because of possible problems associated with the implementation of traceability. Although some manufacturers have clearly improved their calibration protocols relative to ERM-DA471, most of them failed to meet the criteria for acceptable CysC measurements. © 2016 American Association for Clinical Chemistry.
Homemade thermometry instruments in the field.

PubMed

Pasquier, Mathieu; Rousson, Valentin; Zen Ruffinen, Grégoire; Hugli, Olivier

2012-03-01

Esophageal temperature is the gold standard for in-the-field temperature monitoring in hypothermic victims with cardiac arrest. For practical reasons, some mountain rescue teams use homemade esophageal thermometers to measure esophageal temperature; these consist of nonmedical inside/outside temperature monitoring instruments that have been modified to allow for esophageal insertion. We planned a study to determine the accuracy of such thermometers. Two of the same model of digital cabled indoor/outdoor thermometer were modified and tested in comparison with a reference thermometer. The thermometers were tested in a water bath at different temperatures between 10°C and 35.2°C. Three hundred measurements were taken with each thermometer. Our experimental study showed that both homemade thermometers provided a good correlation and a clinically acceptable agreement in comparison with the reference thermometer. Measurements were within 0.5°C in comparison with the reference thermometer 97.5% of the time. The homemade thermometers performed well in vitro, in comparison with a reference thermometer. However, because these devices in their original form are not designed for clinical use, their use should be restricted to situations when the use of a conventional esophageal thermometer is impossible. Copyright Â© 2012 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.
Research Diagnostic Criteria for Temporomandibular Disorders: Validity of Axis I Diagnoses

PubMed Central

Truelove, Edmond; Pan, Wei; Look, John O.; Mancl, Lloyd A.; Ohrbach, Richard K.; Velly, Ana; Huggins, Kimberly; Lenton, Patricia; Schiffman, Eric L.

2011-01-01

AIMS To estimate the criterion validity of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I TMD diagnoses. METHODS A combined total of 614 TMD community and clinic cases and 91 controls were examined at 3 study sites. RDC/TMD Axis I diagnoses were algorithmically derived from an examination performed by calibrated dental hygienists. Reference standards (Gold Standards) were established by means of consensus diagnoses rendered by 2 TMD experts using all available clinical data, including imaging studies. Validity of the RDC/TMD Axis I TMD diagnoses was estimated relative to reference-standard diagnoses (gold standard diagnoses). Target sensitivity and specificity were set a priori at ≥ 0.70 and ≥ 0.95, respectively. RESULTS Target sensitivity and specificity were not observed for any of the 8 RDC/TMD diagnoses. The highest validity was achieved for Group Ia myofascial pain (sensitivity 0.65, specificity 0.92) and Group Ib myofascial pain with limited opening (sensitivity 0.79, specificity 0.92). Target sensitivity and specificity were observed only when both Group I diagnoses were combined (0.87 and 0.98, respectively). For Group II (disc displacements) and Group III (arthralgia, arthritis, arthrosis) diagnoses, all estimates for sensitivity were below target (0.03 to 0.53), and specificity ranged from below to on target (0.86 to 0.99). CONCLUSION The RDC/TMD Axis I TMD diagnoses did not reach the targets set at sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Target validity was obtained only for myofascial pain without differentiation between normal and limited opening. Revision of the current Axis I TMD diagnostic algorithms is warranted to improve their validity. PMID:20213030
Traceability Assessment and Performance Evaluation of Results for Measurement of Abbott Clinical Chemistry Assays on 4 Chemistry Analyzers.

PubMed

Lim, Jinsook; Song, Kyung Eun; Song, Sang Hoon; Choi, Hyun-Jung; Koo, Sun Hoe; Kwon, Gye Choel

2016-05-01

-The traceability of clinical results to internationally recognized and accepted reference materials and reference measurement procedures has become increasingly important. Therefore, the establishment of traceability has become a mandatory requirement for all in vitro diagnostics devices. -To evaluate the traceability of the Abbott Architect c8000 system (Abbott Laboratories, Abbott Park, Illinois), consisting of calibrators and reagents, across 4 different chemistry analyzers, and to evaluate its general performance on the Toshiba 2000FR NEO (Toshiba Medical Systems Corporation, Otawara-shi, Tochigi-ken, Japan). -For assessment of traceability, secondary reference materials were evaluated 5 times, and then bias was calculated. Precision, linearity, and carryover were determined according to the guidelines of the Clinical and Laboratory Standards Institute (Wayne, Pennsylvania). -The biases from 4 different analyzers ranged from -2.33% to 2.70% on the Toshiba 2000FR NEO, -2.33% to 5.12% on the Roche Hitachi 7600 (Roche Diagnostics International, Basel, Switzerland), -0.93% to 2.87% on the Roche Modular, and -2.16% to 2.86% on the Abbott Architect c16000. The total coefficients of variance of all analytes were less than 5%. The coefficients of determination (R(2)) were more than 0.9900. The carryover rate ranged from -0.54% to 0.17%. -Abbott clinical chemistry assays met the performance criteria based on desirable biological variation for precision, bias, and total error. They also showed excellent linearity and carryover. Therefore, these clinical chemistry assays were found to be accurate and reliable and are readily applicable on the various platforms used in this study.
Open access gastroscopy: too much to swallow?

PubMed Central

Kerrigan, D D; Brown, S R; Hutchinson, G H

1990-01-01

OBJECTIVES--To ascertain the proportion of endoscopic examinations with normal findings in patients referred for gastroscopy through hospital medical staff or directly by their general practitioner and to assess the likely effect of targeting endoscopy in older patients. DESIGN--Retrospective audit of the gastroscopy practice of one consultant from 1986 to 1988 from information recorded on a standard form completed at the time of the examination, which contained details of patients, their endoscopic findings, and mode of referral (open access or clinic). SETTING--One district general hospital. PATIENTS--1545 Consecutive patients from primary catchment area attending for their first gastroscopy; 454 were referred through the outpatient clinic or by hospital colleagues (clinic group) and 1091 were accepted for endoscopy solely on their general practitioner's clinical diagnosis (open access group). RESULTS--Similar numbers (about 40%) of examinations with normal findings were performed in each group, although in patients aged over 40 the proportion with normal findings was significantly higher in the clinic group (p less than 0.03). Endoscopic evidence of gastro-oesophageal reflux disease, peptic ulceration, and gastroduodenal inflammation was equally common in each group; upper gastrointestinal malignancy, however, was significantly more common in patients referred through hospital doctors (5%, 23/454 v 2%, 22/1091 respectively; p less than 0.005) (although many of these patients had already been extensively investigated). IMPLICATIONS--Open access gastroscopy does not increase the number of unnecessary examinations and should become more widely available. Targeting this service to patients aged over 40 would reduce the number of requests but increase the diagnostic yield. PMID:2106992
The theory of reference values: an unfinished symphony.

PubMed

Siest, Gerard; Henny, Joseph; Gräsbeck, Ralph; Wilding, Peter; Petitclerc, Claude; Queraltó, Josep M; Hyltoft Petersen, Peter

2013-01-01

The history of the theory of reference values can be written as an unfinished symphony. The first movement, allegro con fuoco, played from 1960 to 1980: a mix of themes devoted to the study of biological variability (intra-, inter-individual, short- and long-term), preanalytical conditions, standardization of analytical methods, quality control, statistical tools for deriving reference limits, all of them complex variations developed on a central melody: the new concept of reference values that would replace the notion of normality whose definition was unclear. Additional contributions (multivariate reference values, use of reference limits from broad sets of patient data, drug interferences) conclude the movement on the variability of laboratory tests. The second movement, adagio, from 1980 to 2000, slowly develops and implements initial works. International and national recommendations were published by the IFCC-LM (International Federation of Clinical Chemistry and Laboratory Medicine) and scientific societies [French (SFBC), Spanish (SEQC), Scandinavian societies…]. Reference values are now topics of many textbooks and of several congresses, workshops, and round tables that are organized all over the world. Nowadays, reference values are part of current practice in all clinical laboratories, but not without difficulties, particularly for some laboratories to produce their own reference values and the unsuitability of the concept with respect to new technologies such as HPLC, GCMS, and PCR assays. Clinicians through consensus groups and practice guidelines have introduced their own tools, the decision limits, likelihood ratios and Reference Change Value (RCV), creating confusion among laboratorians and clinicians in substituting reference values and decision limits in laboratory reports. The rapid development of personalized medicine will eventually call for the use of individual reference values. The beginning of the second millennium is played allegro ma non-troppo from 2000 to 2012: the theory of reference values is back into fashion. The need to revise the concept is emerging. The manufacturers make a friendly pressure to facilitate the integration of Reference Intervals (RIs) in their technical documentation. Laboratorians are anxiously awaiting the solutions for what to do. The IFCC-LM creates Reference Intervals and Decision Limits Committee (C-RIDL) in 2005. Simultaneously, a joint working group IFCC-CLSI is created on the same topic. In 2008 the initial recommendations of IFCC-LM are revised and new guidelines are published by the Clinical and Laboratory Standards Institute (CLSI C28-A3). Fundamentals of the theory of reference values are not changed, but new avenues are explored: RIs transference, multicenter reference intervals, and a robust method for deriving RIs from small number of subjects. Concomitantly, other statistical methods are published such as bootstraps calculation and partitioning procedures. An alternative to recruiting healthy subjects proposes the use of biobanks conditional to the availability of controlled preanalytical conditions and of bioclinical data. The scope is also widening to include veterinary biology! During the early 2000s, several groups proposed the concept of 'Universal RIs' or 'Global RIs'. Still controversial, their applications await further investigations. The fourth movement, finale: beyond the methodological issues (statistical and analytical essentially), important questions remain unanswered. Do RIs intervene appropriately in medical decision-making? Are RIs really useful to the clinicians? Are evidence-based decision limits more appropriate? It should be appreciated that many laboratory tests represent a continuum that weakens the relevance of RIs. In addition, the boundaries between healthy and pathological states are shady areas influenced by many biological factors. In such a case the use of a single threshold is questionable. Wherever it will apply, individual reference values and reference change values have their place. A variation on an old theme! It is strange that in the period of personalized medicine (that is more stratified medicine), the concept of reference values which is based on stratification of homogeneous subgroups of healthy people could not be discussed and developed in conjunction with the stratification of sick patients. That is our message for the celebration of the 50th anniversary of Clinical Chemistry and Laboratory Medicine. Prospects are broad, enthusiasm is not lacking: much remains to be done, good luck for the new generations!
From plastic to gold: a unified classification scheme for reference standards in medical image processing

NASA Astrophysics Data System (ADS)

Lehmann, Thomas M.

2002-05-01

Reliable evaluation of medical image processing is of major importance for routine applications. Nonetheless, evaluation is often omitted or methodically defective when novel approaches or algorithms are introduced. Adopted from medical diagnosis, we define the following criteria to classify reference standards: 1. Reliance, if the generation or capturing of test images for evaluation follows an exactly determined and reproducible protocol. 2. Equivalence, if the image material or relationships considered within an algorithmic reference standard equal real-life data with respect to structure, noise, or other parameters of importance. 3. Independence, if any reference standard relies on a different procedure than that to be evaluated, or on other images or image modalities than that used routinely. This criterion bans the simultaneous use of one image for both, training and test phase. 4. Relevance, if the algorithm to be evaluated is self-reproducible. If random parameters or optimization strategies are applied, reliability of the algorithm must be shown before the reference standard is applied for evaluation. 5. Significance, if the number of reference standard images that are used for evaluation is sufficient large to enable statistically founded analysis. We demand that a true gold standard must satisfy the Criteria 1 to 3. Any standard only satisfying two criteria, i.e., Criterion 1 and Criterion 2 or Criterion 1 and Criterion 3, is referred to as silver standard. Other standards are termed to be from plastic. Before exhaustive evaluation based on gold or silver standards is performed, its relevance must be shown (Criterion 4) and sufficient tests must be carried out to found statistical analysis (Criterion 5). In this paper, examples are given for each class of reference standards.
Archetype Model-Driven Development Framework for EHR Web System.

PubMed

Kobayashi, Shinji; Kimura, Eizen; Ishihara, Ken

2013-12-01

This article describes the Web application framework for Electronic Health Records (EHRs) we have developed to reduce construction costs for EHR sytems. The openEHR project has developed clinical model driven architecture for future-proof interoperable EHR systems. This project provides the specifications to standardize clinical domain model implementations, upon which the ISO/CEN 13606 standards are based. The reference implementation has been formally described in Eiffel. Moreover C# and Java implementations have been developed as reference. While scripting languages had been more popular because of their higher efficiency and faster development in recent years, they had not been involved in the openEHR implementations. From 2007, we have used the Ruby language and Ruby on Rails (RoR) as an agile development platform to implement EHR systems, which is in conformity with the openEHR specifications. We implemented almost all of the specifications, the Archetype Definition Language parser, and RoR scaffold generator from archetype. Although some problems have emerged, most of them have been resolved. We have provided an agile EHR Web framework, which can build up Web systems from archetype models using RoR. The feasibility of the archetype model to provide semantic interoperability of EHRs has been demonstrated and we have verified that that it is suitable for the construction of EHR systems.
Plasma exogenous creatinine clearance in clinically healthy cats: comparison with urinary exogenous creatinine clearance, tentative reference intervals and indexation to bodyweight.

PubMed

Reynolds, B S; Massal, M R; Nguyen, P; Grégoire, L L; Périgaud, A E; Concordet, D; Biourge, V; Lefebvre, H P

2014-10-01

Glomerular filtration rate (GFR) is considered to be the best indicator of overall kidney function. The major objectives of this study were to compare plasma exogenous creatinine clearance (PECC) with a reference method, to establish reference intervals (RIs) for PECC and to assess the effects of indexation of GFR to bodyweight (BW) in cats. PECC was compared with urinary clearance of exogenous creatinine (UECC) in six clinically healthy domestic shorthair cats (experiment 1). Tentative RIs were determined according to current guidelines and the effects of indexation to BW and of covariables on GFR were assessed in 43 clinically healthy cats of various breeds (experiment 2). PECC was 15% higher than UECC (P <0.01), but the two estimates were strongly correlated (r(2)=0.97, P = 0.001). RIs for PECC were 6.4-21.3 mL/min or 1.2-4.9 mL/min/kg. The absolute (i.e. non-indexed) GFR value was not dependent on BW. Thus, indexation of GFR to BW in cats would not standardize the GFR value, but could introduce bias in clinical interpretation. Significant effects of breed, plasma protein concentration and plasma albumin concentration on GFR were demonstrated. Plasma concentrations of urea and creatinine, when assessed separately, were also weakly correlated with GFR in healthy cats. These combined findings contribute to a better understanding of renal function assessment in cats. Copyright © 2014 Elsevier Ltd. All rights reserved.
Comprehensive Characterization of Reference Standard Lots of HIV-1 Subtype C Gp120 Proteins for Clinical Trials in Southern African Regions

PubMed Central

Wang, Zihao; Lorin, Clarisse; Koutsoukos, Marguerite; Franco, David; Bayat, Babak; Zhang, Ying; Carfi, Andrea; Barnett, Susan W.; Porter, Frederick

2016-01-01

Two HIV-1 subtype C gp120 protein candidates were the selected antigens for several experimental vaccine regimens now under evaluation in HVTN 100 Phase I/II clinical trial aiming to support the start of the HVTN 702 Phase IIb/III trial in southern Africa, which is designed to confirm and extend the partial protection seen against HIV-1 infection in the RV144 Thai trial. Here, we report the comprehensive physicochemical characterization of the gp120 reference materials that are representative of the clinical trial materials. Gp120 proteins were stably expressed in Chinese Hamster Ovary (CHO) cells and subsequently purified and formulated. A panel of analytical techniques was used to characterize the physicochemical properties of the two protein molecules. When formulated in the AS01 Adjuvant System, the bivalent subtype C gp120 antigens elicited 1086.C- and TV1.C-specific binding antibody and CD4+ T cell responses in mice. All the characteristics were highly representative of the Clinical Trial Materials (CTM). Data from this report demonstrate the immunogenicity of the gp120 antigens, provide comprehensive characterization of the molecules, set the benchmark for assessment of current and future CTM lots, and lay the physicochemical groundwork for interpretation of future clinical trial data. PMID:27187483
28 CFR 45.1 - Cross-reference to ethical standards and financial disclosure regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Cross-reference to ethical standards and...) EMPLOYEE RESPONSIBILITIES § 45.1 Cross-reference to ethical standards and financial disclosure regulations. Employees of the Department of Justice are subject to the executive branch-wide Standards of Ethical Conduct...
10 CFR 1010.102 - Cross-references to employee ethical conduct standards, financial disclosure regulations, and...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Cross-references to employee ethical conduct standards... Cross-references to employee ethical conduct standards, financial disclosure regulations, and other conduct rules. Employees of DOE are subject to the Standards of Ethical Conduct for Employees of the...
28 CFR 45.1 - Cross-reference to ethical standards and financial disclosure regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Cross-reference to ethical standards and...) EMPLOYEE RESPONSIBILITIES § 45.1 Cross-reference to ethical standards and financial disclosure regulations. Employees of the Department of Justice are subject to the executive branch-wide Standards of Ethical Conduct...
10 CFR 1010.102 - Cross-references to employee ethical conduct standards, financial disclosure regulations, and...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Cross-references to employee ethical conduct standards... Cross-references to employee ethical conduct standards, financial disclosure regulations, and other conduct rules. Employees of DOE are subject to the Standards of Ethical Conduct for Employees of the...
10 CFR 1010.102 - Cross-references to employee ethical conduct standards, financial disclosure regulations, and...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Cross-references to employee ethical conduct standards... Cross-references to employee ethical conduct standards, financial disclosure regulations, and other conduct rules. Employees of DOE are subject to the Standards of Ethical Conduct for Employees of the...

28 CFR 45.1 - Cross-reference to ethical standards and financial disclosure regulations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Cross-reference to ethical standards and...) EMPLOYEE RESPONSIBILITIES § 45.1 Cross-reference to ethical standards and financial disclosure regulations. Employees of the Department of Justice are subject to the executive branch-wide Standards of Ethical Conduct...
10 CFR 1010.102 - Cross-references to employee ethical conduct standards, financial disclosure regulations, and...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Cross-references to employee ethical conduct standards... Cross-references to employee ethical conduct standards, financial disclosure regulations, and other conduct rules. Employees of DOE are subject to the Standards of Ethical Conduct for Employees of the...
28 CFR 45.1 - Cross-reference to ethical standards and financial disclosure regulations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Cross-reference to ethical standards and...) EMPLOYEE RESPONSIBILITIES § 45.1 Cross-reference to ethical standards and financial disclosure regulations. Employees of the Department of Justice are subject to the executive branch-wide Standards of Ethical Conduct...
28 CFR 45.1 - Cross-reference to ethical standards and financial disclosure regulations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Cross-reference to ethical standards and...) EMPLOYEE RESPONSIBILITIES § 45.1 Cross-reference to ethical standards and financial disclosure regulations. Employees of the Department of Justice are subject to the executive branch-wide Standards of Ethical Conduct...
A comparison of three infant skinfold reference standards: Tanner-Whitehouse, Cambridge Infant Growth Study, and WHO Child Growth Standards.

PubMed

Miller, Elizabeth M

2015-10-01

As researchers increasingly focus on early infancy as a critical period of development, there is a greater need for methodological tools that can address all aspects of infant growth. Infant skinfold measures, in particular, are measurements in need of reliable reference standards that encompass all ages of infants and provide an accurate assessment of the relative fatness of a population. This report evaluates three published reference standards for infant skinfold measurements: Tanner-Whitehouse, Cambridge Infant Growth Study, and the World Health Organization (WHO) Child Growth Standards. To assess these standards, triceps skinfolds from a population of rural Kenyan infants (n = 250) and triceps skinfolds and subscapular skinfolds from infants in the National Health and Nutrition Examination Survey 1999-2002 (NHANES; n = 1197) were calculated as z-scores from the lambda-mu-sigma curves provided by each reference population. The Tanner-Whitehouse standards represented both the Kenyan and US populations as lean, while the Cambridge standards represented both populations as overfat. The distribution of z-scores based on the WHO standards fell in the middle, but excluded infants from both populations who were below the age of 3 months. Based on these results, the WHO reference standard is the best skinfold reference standard for infants over the age of 3 months. For populations with infants of all ages, the Tanner-Whitehouse standards are recommended, despite representing both study populations as underfat. Ideally, the WHO will extend their reference standard to include infants between the ages of 0 and 3 months. © 2014 John Wiley & Sons Ltd.
Definition of osteoporosis by bone density criteria in men: effect of using female instead of male young reference data depends on skeletal site and densitometer manufacturer.

PubMed

Schousboe, John T; Tanner, S Bobo; Leslie, William D

2014-01-01

Whether to use young male or young female reference data to calculate bone mineral density (BMD) T-scores in men remains controversial. The third National Health and Nutrition Examination and Survey (NHANES III) data show that the mean and standard deviation of femoral neck and total hip BMD is greater in young men than young women, and therefore differences in T-scores at these sites using NHANES III female vs male norms becomes less as BMD decreases. In contrast, manufacturer-specific reference databases generally assume similar standard deviations of BMD in men and women. Using NHANES III reference data for the femoral neck and total hip, respectively we found that men with T-scores of -2.5 when young male norms are used have T-scores of -2.4 and -2.3 when young female norms are used. Using manufacturer-specific reference data, we found that men with T-scores of -2.5 when young male norms are used at the femoral neck, total hip, lumbar spine, or one-third of the forearm would have T-scores ranging from -2.4 to -0.4 when young female norms are used, depending on skeletal site and densitometer manufacturer. The change of proportions of men diagnosed with osteoporosis when young female norms are used instead of young male reference data differs substantially according to skeletal site and densitometer manufacturer. Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
Optically transmitted and inductively coupled electric reference to access in vivo concentrations for quantitative proton-decoupled ¹³C magnetic resonance spectroscopy.

PubMed

Chen, Xing; Pavan, Matteo; Heinzer-Schweizer, Susanne; Boesiger, Peter; Henning, Anke

2012-01-01

This report describes our efforts on quantification of tissue metabolite concentrations in mM by nuclear Overhauser enhanced and proton decoupled (13) C magnetic resonance spectroscopy and the Electric Reference To access In vivo Concentrations (ERETIC) method. Previous work showed that a calibrated synthetic magnetic resonance spectroscopy-like signal transmitted through an optical fiber and inductively coupled into a transmit/receive coil represents a reliable reference standard for in vivo (1) H magnetic resonance spectroscopy quantification on a clinical platform. In this work, we introduce a related implementation that enables simultaneous proton decoupling and ERETIC-based metabolite quantification and hence extends the applicability of the ERETIC method to nuclear Overhauser enhanced and proton decoupled in vivo (13) C magnetic resonance spectroscopy. In addition, ERETIC signal stability under the influence of simultaneous proton decoupling is investigated. The proposed quantification method was cross-validated against internal and external reference standards on human skeletal muscle. The ERETIC signal intensity stability was 100.65 ± 4.18% over 3 months including measurements with and without proton decoupling. Glycogen and unsaturated fatty acid concentrations measured with the ERETIC method were in excellent agreement with internal creatine and external phantom reference methods, showing a difference of 1.85 ± 1.21% for glycogen and 1.84 ± 1.00% for unsaturated fatty acid between ERETIC and creatine-based quantification, whereas the deviations between external reference and creatine-based quantification are 6.95 ± 9.52% and 3.19 ± 2.60%, respectively. Copyright © 2011 Wiley Periodicals, Inc.
Reference materials for molecular diagnostics: Current achievements and future strategies.

PubMed

Jing, Rongrong; Wang, Huimin; Ju, Shaoqing; Cui, Ming

2018-06-01

Molecular diagnoses have become more widespread in many areas of laboratory medicine where qualitative or quantitative approaches are used to detect nucleic acids. The increasing number of assay methods and the targets for molecular diagnostics contribute to variability in the test results among clinical laboratories. Thus, reference materials (RMs) are required to enhance the comparability of results. This review focuses on the definition of RMs as well as the production and characteristics of higher order RMs from different organizations and their future strategies. We describe the recent progress in RMs, including the definition of RMs by the Joint Committee for Guides in Metrology, as well as the production and characteristics of higher order RMs by international official bodies. There is an urgent need for RMs in nucleic acid testing, especially higher order RMs. To advance the harmonization and standardization of clinical nucleic acid detection, cooperation between the above organizations is proposed and different approaches to higher order RMs development are also needed. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
In vitro drug susceptibility of 40 international reference rapidly growing mycobacteria to 20 antimicrobial agents

PubMed Central

Pang, Hui; Li, Guilian; Wan, Li; Jiang, Yi; Liu, Haican; Zhao, Xiuqin; Zhao, Zhongfu; Wan, Kanglin

2015-01-01

Rapidly growing mycobacteria (RGM) are human pathogens that are relatively easily identified by acid-fast staining but are proving difficult to treat in the clinic. In this study, we performed susceptibility testing of 40 international reference RGM species against 20 antimicrobial agents using the cation-adjusted Mueller-Hinton (CAMH) broth microdilution based on the minimum inhibitory concentration (MIC) assay recommended by the guidelines of the Clinical and Laboratory Standards Institute (CLSI). The results demonstrated that RGM organisms were resistant to the majority of first-line antituberculous agents but not to second-line fluoroquinolones or aminoglycosides. Three drugs (amikacin, tigecycline and linezolid) displayed potent antimycobacterial activity against all tested strains. Capreomycin, levofloxacin and moxifloxacin emerged as promising candidates for the treatment of RGM infections, and cefoxitin and meropenem were active against most strains. Mycobacterium chelonae (M. chelonae), M. abscessus, M. bolletii, M. fortuitum, M. boenickei, M. conceptionense, M. pseudoshottsii, M. septicum and M. setense were the most resistant RGM species. These results provide significant insight into the treatment of RGM species and will assist optimization of clinical criteria. PMID:26629031
Blood lipid measurements. Variations and practical utility.

PubMed

Cooper, G R; Myers, G L; Smith, S J; Schlant, R C

1992-03-25

To describe the magnitude and impact of the major biological and analytical sources of variation in serum lipid and lipoprotein levels on risk of coronary heart disease; to present a way to qualitatively estimate the total intraindividual variation; and to demonstrate how to determine the number of specimens required to estimate, with 95% confidence, the "true" underlying total cholesterol value in the serum of a patient. Representative references on each source of variation were selected from more than 300 reviewed publications, most published within the past 5 years, to document current findings and concepts. Most articles reviewed were in English. Studies on biological sources of variation were selected using the following criteria: representative of published findings, clear statement of either significant or insignificant results, and acquisition of clinical and laboratory data under standardized conditions. Representative results for special populations such as women and children are reported when results differ from those of adult men. References were selected based on acceptable experimental design and use of standardized laboratory lipid measurements. The lipid levels considered representative for a selected source of variation arose from quantitative measurements by a suitably standardized laboratory. Statistical analysis of data was examined to assure reliability. The proposed method of estimating the biological coefficient of variation must be considered to give qualitative results, because only two or three serial specimens are collected in most cases for the estimation. Concern has arisen about the magnitude, impact, and interpretation of preanalytical as well as analytical sources of variation on reported results of lipid measurements of an individual. Preanalytical sources of variation from behavioral, clinical, and sampling sources constitute about 60% of the total variation in a reported lipid measurement of an individual. A technique is presented to allow physicians to qualitatively estimate the intraindividual biological variation of a patient from the results of two or more specimens reported from a standardized laboratory and to determine whether additional specimens are needed to meet the National Cholesterol Education Program recommendation that the intraindividual serum total cholesterol coefficient of variation not exceed 5.0. A National Reference Method Network has been established to help solve analytical problems.
Protocol for determining the diagnostic validity of physical examination maneuvers for shoulder pathology.

PubMed

Somerville, Lyndsay; Bryant, Dianne; Willits, Kevin; Johnson, Andrew

2013-02-08

Shoulder complaints are the third most common musculoskeletal problem in the general population. There are an abundance of physical examination maneuvers for diagnosing shoulder pathology. The validity of these maneuvers has not been adequately addressed. We propose a large Phase III study to investigate the accuracy of these tests in an orthopaedic setting. We will recruit consecutive new shoulder patients who are referred to two tertiary orthopaedic clinics. We will select which physical examination tests to include using a modified Delphi process. The physician will take a thorough history from the patient and indicate their certainty about each possible diagnosis (certain the diagnosis is absent, present or requires further testing). The clinician will only perform the physical examination maneuvers for diagnoses where uncertainty remains. We will consider arthroscopy the reference standard for patients who undergo surgery within 8 months of physical examination and magnetic resonance imaging with arthrogram for patients who do not. We will calculate the sensitivity, specificity and positive and negative likelihood ratios and investigate whether combinations of the top tests provide stronger predictions of the presence or absence of disease. There are several considerations when performing a diagnostic study to ensure that the results are applicable in a clinical setting. These include, 1) including a representative sample, 2) selecting an appropriate reference standard, 3) avoiding verification bias, 4) blinding the interpreters of the physical examination tests to the interpretation of the gold standard and, 5) blinding the interpreters of the gold standard to the interpretation of the physical examination tests. The results of this study will inform clinicians of which tests, or combination of tests, successfully reduce diagnostic uncertainty, which tests are misleading and how physical examination may affect the magnitude of the confidence the clinician feels about their diagnosis. The results of this study may reduce the number of costly and invasive imaging studies (MRI, CT or arthrography) that are requisitioned when uncertainty about diagnosis remains following history and physical exam. We also hope to reduce the variability between specialists in which maneuvers are used during physical examination and how they are used, all of which will assist in improving consistency of care between centres.
Evaluating the impact of a ‘virtual clinic’ on patient experience, personal and provider costs of care in urinary incontinence: A randomised controlled trial

PubMed Central

2018-01-01

Objective To evaluate the impact of using a ‘virtual clinic’ on patient experience and cost in the care of women with urinary incontinence. Materials and methods Women, aged > 18 years referred to a urogynaecology unit were randomised to either (1) A Standard Clinic or (2) A Virtual Clinic. Both groups completed a validated, web-based interactive, patient-reported outome measure (ePAQ-Pelvic Floor), in advance of their appointment followed by either a telephone consultation (Virtual Clinic) or face-to-face consultation (Standard Care). The primary outcome was the mean ‘short-term outcome scale’ score on the Patient Experience Questionnaire (PEQ). Secondary Outcome Measures included the other domains of the PEQ (Communications, Emotions and Barriers), Client Satisfaction Questionnaire (CSQ), Short-Form 12 (SF-12), personal, societal and NHS costs. Results 195 women were randomised: 98 received the intervention and 97 received standard care. The primary outcome showed a non-significant difference between the two study arms. No significant differences were also observed on the CSQ and SF-12. However, the intervention group showed significantly higher PEQ domain scores for Communications, Emotions and Barriers (including following adjustment for age and parity). Whilst standard care was overall more cost-effective, this was minimal (£38.04). The virtual clinic also significantly reduced consultation time (10.94 minutes, compared with a mean duration of 25.9 minutes respectively) and consultation costs compared to usual care (£31.75 versus £72.17 respectively), thus presenting potential cost-savings in out-patient management. Conclusions The virtual clinical had no impact on the short-term dimension of the PEQ and overall was not as cost-effective as standard care, due to greater clinic re-attendances in this group. In the virtual clinic group, consultation times were briefer, communication experience was enhanced and personal costs lower. For medical conditions of a sensitive or intimate nature, a virtual clinic has potential to support patients to communicate with health professionals about their condition. PMID:29346378
Increasing the accuracy and scalability of the Immunofluorescence Assay for Epstein Barr Virus by inferring continuous titers from a single sample dilution.

PubMed

Goh, Sherry Meow Peng; Swaminathan, Muthukaruppan; Lai, Julian U-Ming; Anwar, Azlinda; Chan, Soh Ha; Cheong, Ian

2017-01-01

High Epstein Barr Virus (EBV) titers detected by the indirect Immunofluorescence Assay (IFA) are a reliable predictor of Nasopharyngeal Carcinoma (NPC). Despite being the gold standard for serological detection of NPC, the IFA is limited by scaling bottlenecks. Specifically, 5 serial dilutions of each patient sample must be prepared and visually matched by an evaluator to one of 5 discrete titers. Here, we describe a simple method for inferring continuous EBV titers from IFA images acquired from NPC-positive patient sera using only a single sample dilution. In the first part of our study, 2 blinded evaluators used a set of reference titer standards to perform independent re-evaluations of historical samples with known titers. Besides exhibiting high inter-evaluator agreement, both evaluators were also in high concordance with historical titers, thus validating the accuracy of the reference titer standards. In the second part of the study, the reference titer standards were IFA-processed and assigned an 'EBV Score' using image analysis. A log-linear relationship between titers and EBV Score was observed. This relationship was preserved even when images were acquired and analyzed 3days post-IFA. We conclude that image analysis of IFA-processed samples can be used to infer a continuous EBV titer with just a single dilution of NPC-positive patient sera. This work opens new possibilities for improving the accuracy and scalability of IFA in the context of clinical screening. Copyright © 2016. Published by Elsevier B.V.
New standard measures for clinical voice analysis include high speed films

NASA Astrophysics Data System (ADS)

Pedersen, Mette; Munch, Kasper

2012-02-01

In the clinical work with patients in a medical voice clinic it is important to have a normal updated reference for the data used. Several new parameters have to be correlated to older traditional measures. The older ones are stroboscopy, eventually coordinated with electroglottography (EGG), the Multi- Dimensional-Voice Program and airflow rates. Long Time Averaged Spectrograms (LTAS) and phonetograms (voice profiles) are calculating the range and dynamics of tones of the patients. High-speed films, updated airflow measures as well as area calculations of phonotograms add information to the understanding of the glottis closure in single movements of the vocal cords. A multivariate analysis was made to study the connection between the measures. This information can be used in many connections, also in the otolaryngological clinic.
[Thinking on designation of sham acupuncture in clinical research].

PubMed

Pan, Li-Jia; Chen, Bo; Zhao, Xue; Guo, Yi

2014-01-01

Randomized controlled trials (RCT) is the source of the raw data of evidence-based medicine. Blind method is adopted in most of the high-quality RCT. Sham acupuncture is the main form of blinded in acupuncture clinical trial. In order to improve the quality of acupuncture clinical trail, based on the necessity of sham acupuncture in clinical research, the current situation as well as the existing problems of sham acupuncture, suggestions were put forward from the aspects of new way and new designation method which can be adopted as reference, and factors which have to be considered during the process of implementing. Various subjective and objective factors involving in the process of trial should be considered, and used of the current international standards, try to be quantification, and carry out strict quality monitoring.
Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: the CADDementia challenge.

PubMed

Bron, Esther E; Smits, Marion; van der Flier, Wiesje M; Vrenken, Hugo; Barkhof, Frederik; Scheltens, Philip; Papma, Janne M; Steketee, Rebecca M E; Méndez Orellana, Carolina; Meijboom, Rozanna; Pinto, Madalena; Meireles, Joana R; Garrett, Carolina; Bastos-Leite, António J; Abdulkadir, Ahmed; Ronneberger, Olaf; Amoroso, Nicola; Bellotti, Roberto; Cárdenas-Peña, David; Álvarez-Meza, Andrés M; Dolph, Chester V; Iftekharuddin, Khan M; Eskildsen, Simon F; Coupé, Pierrick; Fonov, Vladimir S; Franke, Katja; Gaser, Christian; Ledig, Christian; Guerrero, Ricardo; Tong, Tong; Gray, Katherine R; Moradi, Elaheh; Tohka, Jussi; Routier, Alexandre; Durrleman, Stanley; Sarica, Alessia; Di Fatta, Giuseppe; Sensi, Francesco; Chincarini, Andrea; Smith, Garry M; Stoyanov, Zhivko V; Sørensen, Lauge; Nielsen, Mads; Tangaro, Sabina; Inglese, Paolo; Wachinger, Christian; Reuter, Martin; van Swieten, John C; Niessen, Wiro J; Klein, Stefan

2015-05-01

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n=30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org. Copyright © 2015 Elsevier Inc. All rights reserved.
Measurement of blood pressure for the diagnosis and management of hypertension in different ethnic groups: one size fits all.

PubMed

Gill, Paramjit; Haque, M Sayeed; Martin, Una; Mant, Jonathan; Mohammed, Mohammed A; Heer, Gurdip; Johal, Amanpreet; Kaur, Ramandeep; Schwartz, Claire; Wood, Sally; Greenfield, Sheila M; McManus, Richard J

2017-02-08

Hypertension is a major risk factor for cardiovascular disease and prevalence varies by ethnic group. The diagnosis and management of blood pressure are informed by guidelines largely based on data from white populations. This study addressed whether accuracy of blood pressure measurement in terms of diagnosis of hypertension varies by ethnicity by comparing two measurement modalities (clinic blood pressure and home monitoring) with a reference standard of ambulatory BP monitoring in three ethnic groups. Cross-sectional population study (June 2010 - December 2012) with patients (40-75 years) of white British, South Asian and African Caribbean background with and without a previous diagnosis of hypertension recruited from 28 primary care practices. The study compared the test performance of clinic BP (using various protocols) and home-monitoring (1 week) with a reference standard of mean daytime ambulatory measurements using a threshold of 140/90 mmHg for clinic and 135/85 mmHg for out of office measurement. A total of 551 participants had complete data of whom 246 were white British, 147 South Asian and 158 African Caribbean. No consistent difference in accuracy of methods of blood pressure measurement was observed between ethnic groups with or without a prior diagnosis of hypertension: for people without hypertension, clinic measurement using three different methodologies had high specificity (75-97%) but variable sensitivity (33-65%) whereas home monitoring had sensitivity of 68-88% and specificity of 64-80%. For people with hypertension, detection of a raised blood pressure using clinic measurements had sensitivities of 34-69% with specificity of 73-92% and home monitoring had sensitivity (81-88%) and specificity (55-65%). For people without hypertension, ABPM remains the choice for diagnosing hypertension compared to the other modes of BP measurement regardless of ethnicity. Differences in accuracy of home monitoring and clinic monitoring (higher sensitivity of the former; higher specificity of the latter) were also not affected by ethnicity.
A Decade of Experience in Creating and Maintaining Data Elements for Structured Clinical Documentation in EHRs

PubMed Central

Zhou, Li; Collins, Sarah; Morgan, Stephen J.; Zafar, Neelam; Gesner, Emily J.; Fehrenbach, Martin; Rocha, Roberto A.

2016-01-01

Structured clinical documentation is an important component of electronic health records (EHRs) and plays an important role in clinical care, administrative functions, and research activities. Clinical data elements serve as basic building blocks for composing the templates used for generating clinical documents (such as notes and forms). We present our experience in creating and maintaining data elements for three different EHRs (one home-grown and two commercial systems) across different clinical settings, using flowsheet data elements as examples in our case studies. We identified basic but important challenges (including naming convention, links to standard terminologies, and versioning and change management) and possible solutions to address them. We also discussed more complicated challenges regarding governance, documentation vs. structured data capture, pre-coordination vs. post-coordination, reference information models, as well as monitoring, communication and training. PMID:28269927
An approach to an acute emotional stress reference scale.

PubMed

Garzon-Rey, J M; Arza, A; de-la-Camara, C; Lobo, A; Armario, A; Aguilo, J

2017-06-16

The clinical diagnosis aims to identify the degree of affectation of the psycho-physical state of the patient as a guide to therapeutic intervention. In stress, the lack of a measurement tool based on a reference makes it difficult to quantitatively assess this degree of affectation. To define and perform a primary assessment of a standard reference in order to measure acute emotional stress from the markers identified as indicators of the degree. Psychometric tests and biochemical variables are, in general, the most accepted stress measurements by the scientific community. Each one of them probably responds to different and complementary processes related to the reaction to a stress stimulus. The reference that is proposed is a weighted mean of these indicators by assigning them relative weights in accordance with a principal components analysis. An experimental study was conducted on 40 healthy young people subjected to the psychosocial stress stimulus of the Trier Social Stress Test in order to perform a primary assessment and consistency check of the proposed reference. The proposed scale clearly differentiates between the induced relax and stress states. Accepting the subjectivity of the definition and the lack of a subsequent validation with new experimental data, the proposed standard differentiates between a relax state and an emotional stress state triggered by a moderate stress stimulus, as it is the Trier Social Stress Test. The scale is robust. Although the variations in the percentage composition slightly affect the score, but they do not affect the valid differentiation between states.
Identifying Pediatric Severe Sepsis and Septic Shock: Accuracy of Diagnosis Codes.

PubMed

Balamuth, Fran; Weiss, Scott L; Hall, Matt; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Centkowski, Sierra; Baumer-Mouradian, Shannon; Weiser, Jason; Hayes, Katie; Shah, Samir S; Alpern, Elizabeth R

2015-12-01

To evaluate accuracy of 2 established administrative methods of identifying children with sepsis using a medical record review reference standard. Multicenter retrospective study at 6 US children's hospitals. Subjects were children >60 days to <19 years of age and identified in 4 groups based on International Classification of Diseases, Ninth Revision, Clinical Modification codes: (1) severe sepsis/septic shock (sepsis codes); (2) infection plus organ dysfunction (combination codes); (3) subjects without codes for infection, organ dysfunction, or severe sepsis; and (4) infection but not severe sepsis or organ dysfunction. Combination codes were allowed, but not required within the sepsis codes group. We determined the presence of reference standard severe sepsis according to consensus criteria. Logistic regression was performed to determine whether addition of codes for sepsis therapies improved case identification. A total of 130 out of 432 subjects met reference SD of severe sepsis. Sepsis codes had sensitivity 73% (95% CI 70-86), specificity 92% (95% CI 87-95), and positive predictive value 79% (95% CI 70-86). Combination codes had sensitivity 15% (95% CI 9-22), specificity 71% (95% CI 65-76), and positive predictive value 18% (95% CI 11-27). Slight improvements in model characteristics were observed when codes for vasoactive medications and endotracheal intubation were added to sepsis codes (c-statistic 0.83 vs 0.87, P = .008). Sepsis specific International Classification of Diseases, Ninth Revision, Clinical Modification codes identify pediatric patients with severe sepsis in administrative data more accurately than a combination of codes for infection plus organ dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

[Quality Management and Quality Specifications of Laboratory Tests in Clinical Studies--Challenges in Pre-Analytical Processes in Clinical Laboratories].

PubMed

Ishibashi, Midori

2015-01-01

The cost, speed, and quality are the three important factors recently indicated by the Ministry of Health, Labour and Welfare (MHLW) for the purpose of accelerating clinical studies. Based on this background, the importance of laboratory tests is increasing, especially in the evaluation of clinical study participants' entry and safety, and drug efficacy. To assure the quality of laboratory tests, providing high-quality laboratory tests is mandatory. For providing adequate quality assurance in laboratory tests, quality control in the three fields of pre-analytical, analytical, and post-analytical processes is extremely important. There are, however, no detailed written requirements concerning specimen collection, handling, preparation, storage, and shipping. Most laboratory tests for clinical studies are performed onsite in a local laboratory; however, a part of laboratory tests is done in offsite central laboratories after specimen shipping. As factors affecting laboratory tests, individual and inter-individual variations are well-known. Besides these factors, standardizing the factors of specimen collection, handling, preparation, storage, and shipping, may improve and maintain the high quality of clinical studies in general. Furthermore, the analytical method, units, and reference interval are also important factors. It is concluded that, to overcome the problems derived from pre-analytical processes, it is necessary to standardize specimen handling in a broad sense.
Generation of an annotated reference standard for vaccine adverse event reports.

PubMed

Foster, Matthew; Pandey, Abhishek; Kreimeyer, Kory; Botsis, Taxiarchis

2018-07-05

As part of a collaborative project between the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention for the development of a web-based natural language processing (NLP) workbench, we created a corpus of 1000 Vaccine Adverse Event Reporting System (VAERS) reports annotated for 36,726 clinical features, 13,365 temporal features, and 22,395 clinical-temporal links. This paper describes the final corpus, as well as the methodology used to create it, so that clinical NLP researchers outside FDA can evaluate the utility of the corpus to aid their own work. The creation of this standard went through four phases: pre-training, pre-production, production-clinical feature annotation, and production-temporal annotation. The pre-production phase used a double annotation followed by adjudication strategy to refine and finalize the annotation model while the production phases followed a single annotation strategy to maximize the number of reports in the corpus. An analysis of 30 reports randomly selected as part of a quality control assessment yielded accuracies of 0.97, 0.96, and 0.83 for clinical features, temporal features, and clinical-temporal associations, respectively and speaks to the quality of the corpus. Copyright © 2018 Elsevier Ltd. All rights reserved.
On the seamless, harmonized use of ISO/IEEE11073 and openEHR.

PubMed

Trigo, Jesús D; Kohl, Christian D; Eguzkiza, Aitor; Martínez-Espronceda, Miguel; Alesanco, Álvaro; Serrano, Luis; García, José; Knaup, Petra

2014-05-01

Standardized exchange of clinical information is a key factor in the provision of high quality health care systems. In this context, the openEHR specification facilitates the management of health data in electronic health records (EHRs), while the ISO/IEEE11073 (also referred to as X73PHD) family of standards provides a reference framework for medical device interoperability. Hospitals and health care providers using openEHR require flawless integration of data coming from external sources, such as X73PHD. Hence, a harmonization process is crucial for achieving a seamless, coherent use of those specifications in real scenarios. Such harmonization is the aim of this paper. Thus, the classes and attributes of a representative number of X73PHD specializations for medical devices--weight, temperature, blood pressure, pulse and heart rate, oximetry, and electrocardiograph--along with the X73PHD core document--ISO/IEEE11073-20601--have been analyzed and mapped to openEHR archetypes. The proposed methodology reuses the existing archetypes when possible and suggests new ones--or appropriate modifications--otherwise. As a result, this paper analyzes the inconsistencies found and the implications thereof in the coordinated use of these two standards. The procedure has also shown how existing standards are able to influence the archetype development process, enhancing the existing archetype corpus.
Lower reference limits of quantitative cord glucose-6-phosphate dehydrogenase estimated from healthy term neonates according to the clinical and laboratory standards institute guidelines: a cross sectional retrospective study

PubMed Central

2013-01-01

Background Previous studies have reported the lower reference limit (LRL) of quantitative cord glucose-6-phosphate dehydrogenase (G6PD), but they have not used approved international statistical methodology. Using common standards is expecting to yield more true findings. Therefore, we aimed to estimate LRL of quantitative G6PD detection in healthy term neonates by using statistical analyses endorsed by the International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI) for reference interval estimation. Methods This cross sectional retrospective study was performed at King Abdulaziz Hospital, Saudi Arabia, between March 2010 and June 2012. The study monitored consecutive neonates born to mothers from one Arab Muslim tribe that was assumed to have a low prevalence of G6PD-deficiency. Neonates that satisfied the following criteria were included: full-term birth (37 weeks); no admission to the special care nursery; no phototherapy treatment; negative direct antiglobulin test; and fathers of female neonates were from the same mothers’ tribe. The G6PD activity (Units/gram Hemoglobin) was measured spectrophotometrically by an automated kit. This study used statistical analyses endorsed by IFCC and CLSI for reference interval estimation. The 2.5th percentiles and the corresponding 95% confidence intervals (CI) were estimated as LRLs, both in presence and absence of outliers. Results 207 males and 188 females term neonates who had cord blood quantitative G6PD testing met the inclusion criteria. Method of Horn detected 20 G6PD values as outliers (8 males and 12 females). Distributions of quantitative cord G6PD values exhibited a normal distribution in absence of the outliers only. The Harris-Boyd method and proportion criteria revealed that combined gender LRLs were reliable. The combined bootstrap LRL in presence of the outliers was 10.0 (95% CI: 7.5-10.7) and the combined parametric LRL in absence of the outliers was 11.0 (95% CI: 10.5-11.3). Conclusion These results contribute to the LRL of quantitative cord G6PD detection in full-term neonates. They are transferable to another laboratory when pre-analytical factors and testing methods are comparable and the IFCC-CLSI requirements of transference are satisfied. We are suggesting using estimated LRL in absence of the outliers as mislabeling G6PD-deficient neonates as normal is intolerable whereas mislabeling G6PD-normal neonates as deficient is tolerable. PMID:24016342
A pilot study of reference vibrotactile perception thresholds on the fingertip obtained with Malaysian healthy people using ISO 13091-1 equipment.

PubMed

Daud, Roshada; Maeda, Setsuo; Kameel, Nur Nazmin Mustafa; Ripin, Muhamad Yunus; Bakrun, Norazman; Md Zein, Raemy; Kido, Masaharu; Higuchi, Kiyotaka

2004-04-01

The purpose of this paper is to clarify the reference vibrotactile perception thresholds (VPT) for healthy people in Malaysia. The measurement equipment standard, ISO 13091-1, of the vibrotactile perception thresholds for the assessment of nerve dysfunction and the analysis and interpretation of measurements at the fingertips standard, ISO 13091-2, were published in ISO/TC108/SC4/WG8 on 2001 and 2003 individually. In the ISO 13091-2 standard, the reference VPT data were obtained from few research papers. Malaysian people's VPT data don't include to this standard. In Malaysia, when the VPT is using to diagnose of the hand-arm vibration syndrome, the reference VPT data need to compare with the worker's ones. But, Malaysia does not have the reference VPT data yet. So, in this paper, the VPT was measured by using ISO 13091-1 standard equipment to obtain the reference data for Malaysian people. And these data were compared with the ISO reference data on the ISO 13091-2 standard. From the comparison of these data, it was clear that the Malaysian healthy people's VPT data were consistent with the reference data of the ISO 13091-2 standard.
The impact of US versus Indian BMD reference standards on the diagnosis of osteoporosis among South Asian Indians living in the United States

PubMed Central

Melamed, Alexander; Vittinghoff, Eric; Sriram, Usha; Schwartz, Ann V.; Kanaya, Alka M.

2010-01-01

The relationship between bone mineral density (BMD) and fracture risk is not well-established for non-white populations. There is no established BMD reference standard for South Asians. Dual energy x-ray absorptiometry (DXA) was used to measure BMD at total hip and lumbar spine in 150 US-based South Asian Indians. For each subject T-scores were calculated using BMD reference values based on US white, North Indian and South Indian populations, and the resulting WHO BMD category assignments were compared. Reference standards derived from Indian populations classified a larger proportion of US-based Indians as normal than did US white-based standards. The percentage of individuals reclassified when changing between reference standards varied by skeletal site and reference population origin, ranging from 13% (95% CI, 7–18%), when switching from US-white- to North Indian-based standard for total hip, to 40% (95% CI, 32–48%), when switching from US white to South Indian reference values for lumbar spine. These finding illustrate that choice of reference standard has a significant effect on the diagnosis of osteoporosis in South Asians, and underscore the importance of future research to quantify the relationship between BMD and fracture risk in this population. PMID:20663699
76 FR 8989 - Federal Acquisition Regulation; Updated Financial Accounting Standards Board Accounting References

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-16

... Acquisition Regulation; Updated Financial Accounting Standards Board Accounting References AGENCIES... Acquisition Regulation (FAR) to update references to authoritative accounting standards owing to the Financial... Accounting Principles (GAAP) (``Codification of GAAP''). DATES: Interested parties should submit written...
Simplified estimation of age-specific reference intervals for skewed data.

PubMed

Wright, E M; Royston, P

1997-12-30

Age-specific reference intervals are commonly used in medical screening and clinical practice, where interest lies in the detection of extreme values. Many different statistical approaches have been published on this topic. The advantages of a parametric method are that they necessarily produce smooth centile curves, the entire density is estimated and an explicit formula is available for the centiles. The method proposed here is a simplified version of a recent approach proposed by Royston and Wright. Basic transformations of the data and multiple regression techniques are combined to model the mean, standard deviation and skewness. Using these simple tools, which are implemented in almost all statistical computer packages, age-specific reference intervals may be obtained. The scope of the method is illustrated by fitting models to several real data sets and assessing each model using goodness-of-fit techniques.
Tighter accuracy standards within point-of-care blood glucose monitoring: how six commonly used systems compare.

PubMed

Robinson, Charlotte S; Sharp, Patrick

2012-05-01

Blood glucose monitoring systems (BGMS) are used in the hospital environment to manage blood glucose levels in patients at the bedside. The International Organization for Standardization (ISO) 15197:2003 standard is currently used by regulatory bodies as a minimum requirement for the performance of BGMS, specific to self-testing. There are calls for the tightening of accuracy requirements and implementation of a standard specifically for point-of-care (POC) BGMS. The accuracy of six commonly used BGMS was assessed in a clinical setting, with 108 patients' finger stick capillary samples. Using the accuracy criteria from the existing standard and a range of tightened accuracy criteria, system performance was compared. Other contributors to system performance have been measured, including hematocrit sensitivity and meter error rates encountered in the clinical setting. Five of the six BGMS evaluated met current accuracy criteria within the ISO 15197 standard. Only the Optium Xceed system had >95% of all readings within a tightened criteria of ±12.5% from the reference at glucose levels ≥72 mg/dl (4 mmol/liter) and ±9 mg/dl (0.5 mmol/liter) at glucose levels <72 mg/dl (4 mmol/liter). The Nova StatStrip Xpress had the greatest number of error messages observed; Optium Xceed the least. OneTouch Ultra2, Nova StatStrip Xpress, Accu-Chek Performa, and Contour TS products were all significantly influenced by blood hematocrit levels. From evidence obtained during this clinical evaluation, the Optium Xceed system is most likely to meet future anticipated accuracy standards for POC BGMS. In this clinical study, the results demonstrated the Optium Xceed product to have the highest level of accuracy, to have the lowest occurrence of error messages, and to be least influenced by blood hematocrit levels. © 2012 Diabetes Technology Society.
Fundamental Importance of Reference Glucose Analyzer Accuracy for Evaluating the Performance of Blood Glucose Monitoring Systems (BGMSs).

PubMed

Bailey, Timothy S; Klaff, Leslie J; Wallace, Jane F; Greene, Carmine; Pardo, Scott; Harrison, Bern; Simmons, David A

2016-07-01

As blood glucose monitoring system (BGMS) accuracy is based on comparison of BGMS and laboratory reference glucose analyzer results, reference instrument accuracy is important to discriminate small differences between BGMS and reference glucose analyzer results. Here, we demonstrate the important role of reference glucose analyzer accuracy in BGMS accuracy evaluations. Two clinical studies assessed the performance of a new BGMS, using different reference instrument procedures. BGMS and YSI analyzer results were compared for fingertip blood that was obtained by untrained subjects' self-testing and study staff testing, respectively. YSI analyzer accuracy was monitored using traceable serum controls. In study 1 (N = 136), 94.1% of BGMS results were within International Organization for Standardization (ISO) 15197:2013 accuracy criteria; YSI analyzer serum control results showed a negative bias (-0.64% to -2.48%) at the first site and a positive bias (3.36% to 6.91%) at the other site. In study 2 (N = 329), 97.8% of BGMS results were within accuracy criteria; serum controls showed minimal bias (<0.92%) at both sites. These findings suggest that the ability to demonstrate that a BGMS meets accuracy guidelines is influenced by reference instrument accuracy. © 2016 Diabetes Technology Society.
Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges.

PubMed

Pfeiffer, Christine M; Looker, Anne C

2017-12-01

Biochemical assessment of iron status relies on serum-based indicators, such as serum ferritin (SF), transferrin saturation, and soluble transferrin receptor (sTfR), as well as erythrocyte protoporphyrin. These indicators present challenges for clinical practice and national nutrition surveys, and often iron status interpretation is based on the combination of several indicators. The diagnosis of iron deficiency (ID) through SF concentration, the most commonly used indicator, is complicated by concomitant inflammation. sTfR concentration is an indicator of functional ID that is not an acute-phase reactant, but challenges in its interpretation arise because of the lack of assay standardization, common reference ranges, and common cutoffs. It is unclear which indicators are best suited to assess excess iron status. The value of hepcidin, non-transferrin-bound iron, and reticulocyte indexes is being explored in research settings. Serum-based indicators are generally measured on fully automated clinical analyzers available in most hospitals. Although international reference materials have been available for years, the standardization of immunoassays is complicated by the heterogeneity of antibodies used and the absence of physicochemical reference methods to establish "true" concentrations. From 1988 to 2006, the assessment of iron status in NHANES was based on the multi-indicator ferritin model. However, the model did not indicate the severity of ID and produced categorical estimates. More recently, iron status assessment in NHANES has used the total body iron stores (TBI) model, in which the log ratio of sTfR to SF is assessed. Together, sTfR and SF concentrations cover the full range of iron status. The TBI model better predicts the absence of bone marrow iron than SF concentration alone, and TBI can be analyzed as a continuous variable. Additional consideration of methodologies, interpretation of indicators, and analytic standardization is important for further improvements in iron status assessment. © 2017 American Society for Nutrition.
MTS dye based colorimetric CTLL-2 cell proliferation assay for product release and stability monitoring of interleukin-15: assay qualification, standardization and statistical analysis.

PubMed

Soman, Gopalan; Yang, Xiaoyi; Jiang, Hengguang; Giardina, Steve; Vyas, Vinay; Mitra, George; Yovandich, Jason; Creekmore, Stephen P; Waldmann, Thomas A; Quiñones, Octavio; Alvord, W Gregory

2009-08-31

A colorimetric cell proliferation assay using soluble tetrazolium salt [(CellTiter 96(R) Aqueous One Solution) cell proliferation reagent, containing the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) and an electron coupling reagent phenazine ethosulfate], was optimized and qualified for quantitative determination of IL-15 dependent CTLL-2 cell proliferation activity. An in-house recombinant Human (rHu)IL-15 reference lot was standardized (IU/mg) against an international reference standard. Specificity of the assay for IL-15 was documented by illustrating the ability of neutralizing anti-IL-15 antibodies to block the product specific CTLL-2 cell proliferation and the lack of blocking effect with anti-IL-2 antibodies. Under the defined assay conditions, the linear dose-response concentration range was between 0.04 and 0.17ng/ml of the rHuIL-15 produced in-house and 0.5-3.0IU/ml for the international standard. Statistical analysis of the data was performed with the use of scripts written in the R Statistical Language and Environment utilizing a four-parameter logistic regression fit analysis procedure. The overall variation in the ED(50) values for the in-house reference standard from 55 independent estimates performed over the period of 1year was 12.3% of the average. Excellent intra-plate and within-day/inter-plate consistency was observed for all four parameter estimates in the model. Different preparations of rHuIL-15 showed excellent intra-plate consistency in the parameter estimates corresponding to the lower and upper asymptotes as well as to the 'slope' factor at the mid-point. The ED(50) values showed statistically significant differences for different lots and for control versus stressed samples. Three R-scripts improve data analysis capabilities allowing one to describe assay variations, to draw inferences between data sets from formal statistical tests, and to set up improved assay acceptance criteria based on comparability and consistency in the four parameters of the model. The assay is precise, accurate and robust and can be fully validated. Applications of the assay were established including process development support, release of the rHuIL-15 product for pre-clinical and clinical studies, and for monitoring storage stability.
Diagnostic performance of short portable mental status questionnaire for screening dementia among patients attending cognitive assessment clinics in Singapore.

PubMed

Malhotra, Chetna; Chan, Angelique; Matchar, David; Seow, Dennis; Chuo, Adeline; Do, Young Kyung

2013-07-01

The Short Portable Mental Status Questionnaire (SPMSQ) is a brief cognitive screening instrument, which is easy to use by a healthcare worker with little training. However, the validity of this instrument has not been established in Singapore. Thus, the primary aim of this study was to determine the diagnostic performance of SPMSQ for screening dementia among patients attending outpatient cognitive assessment clinics and to assess whether the appropriate cut-off score varies by patient's age and education. A secondary aim of the study was to map the SPMSQ scores with Mini-Mental State Examination (MMSE) scores. SPMSQ and MMSE were administered by a trained interviewer to 127 patients visiting outpatient cognitive assessment clinics at the Singapore General Hospital, Changi General Hospital and Tan Tock Seng Hospital. The geriatricians at these clinics then diagnosed these patients with dementia or no dementia (reference standard). Sensitivity and specificity of SPMSQ with different cut-off points (number of errors) were calculated and compared to the reference standard using the Receiver Operator Characteristic (ROC) analysis. Correlation coefficient was also calculated between MMSE and SPMSQ scores. Based on the ROC analysis and a balance of sensitivity and specificity, the appropriate cut-off for SPMSQ was found to be 5 or more errors (sensitivity 78%, specificity 75%). The cut-off varied by education, but not by patient's age. There was a high correlation between SPMSQ and MMSE scores (r = 0.814, P <0.0001). Despite the advantage of being a brief screening instrument for dementia, the use of SPMSQ is limited by its low sensitivity and specificity, especially among patients with less than 6 years of education.
Availability of color calibration for consistent color display in medical images and optimization of reference brightness for clinical use

NASA Astrophysics Data System (ADS)

Iwai, Daiki; Suganami, Haruka; Hosoba, Minoru; Ohno, Kazuko; Emoto, Yutaka; Tabata, Yoshito; Matsui, Norihisa

2013-03-01

Color image consistency has not been accomplished yet except the Digital Imaging and Communication in Medicine (DICOM) Supplement 100 for implementing a color reproduction pipeline and device independent color spaces. Thus, most healthcare enterprises could not check monitor degradation routinely. To ensure color consistency in medical color imaging, monitor color calibration should be introduced. Using simple color calibration device . chromaticity of colors including typical color (Red, Green, Blue, Green and White) are measured as device independent profile connection space value called u'v' before and after calibration. In addition, clinical color images are displayed and visual differences are observed. In color calibration, monitor brightness level has to be set to quite lower value 80 cd/m2 according to sRGB standard. As Maximum brightness of most color monitors available currently for medical use have much higher brightness than 80 cd/m2, it is not seemed to be appropriate to use 80 cd/m2 level for calibration. Therefore, we propose that new brightness standard should be introduced while maintaining the color representation in clinical use. To evaluate effects of brightness to chromaticity experimentally, brightness level is changed in two monitors from 80 to 270cd/m2 and chromaticity value are compared with each brightness levels. As a result, there are no significant differences in chromaticity diagram when brightness levels are changed. In conclusion, chromaticity is close to theoretical value after color calibration. Moreover, chromaticity isn't moved when brightness is changed. The results indicate optimized reference brightness level for clinical use could be set at high brightness in current monitors .
Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 03: Energy dependence of a clinical probe-format calorimeter and its pertinence to absolute photon and electron beam dosimetry

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

Renaud, James; Seuntjens, Jan; Sarfehnia, Arman

Purpose: To evaluate the intrinsic and absorbed-dose energy dependence of a small-scale graphite calorimeter probe (GPC) developed for use as a routine clinical dosimeter. The influence of charge deposition on the response of the GPC was also assessed by performing absolute dosimetry in clinical linac-based electron beams. Methods: Intrinsic energy dependence was determined by performing constant-temperature calorimetry dose measurements in a water-equivalent solid phantom, under otherwise reference conditions, in five high-energy photon (63.5 < %dd(10){sub X} < 76.3), and five electron (2.3 cm < R{sub 50} < 8.3 cm) beams. Reference dosimetry was performed for all beams in question usingmore » an Exradin A19 ion chamber with a calibration traceable to national standards. The absorbed-dose component of the overall energy dependence was calculated using the EGSnrc egs-chamber user code. Results: A total of 72 measurements were performed with the GPC, resulting in a standard error on the mean absorbed dose of better than 0.3 % for all ten beams. For both the photon and electron beams, no statistically-significant energy dependence was observed experimentally. Peak-to-peak, variations in the relative response of the GPC across all beam qualities of a given radiation type were on the order of 1 %. No effects, either transient or permanent, were attributable to the charge deposited by the electron beams. Conclusions: The GPC’s apparent energy-independence, combined with its well-established linearity and dose rate independence, make it a potentially useful dosimetry system capable measuring photon and electron doses in absolute terms at the clinical level.« less
Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

PubMed

Korosoglou, G; Hansen, A; Bekeredjian, R; Filusch, A; Hardt, S; Wolf, D; Schellberg, D; Katus, H A; Kuecherer, H

2006-03-01

To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.
Turbulent Kinetic Energy Measurement Using Phase Contrast MRI for Estimating the Post-Stenotic Pressure Drop: In Vitro Validation and Clinical Application

PubMed Central

Ha, Hojin; Kim, Guk Bae; Kweon, Jihoon; Huh, Hyung Kyu; Lee, Sang Joon; Koo, Hyun Jung; Kang, Joon-Won; Lim, Tae-Hwan; Kim, Dae-Hee; Kim, Young-Hak

2016-01-01

Background Although the measurement of turbulence kinetic energy (TKE) by using magnetic resonance imaging (MRI) has been introduced as an alternative index for quantifying energy loss through the cardiac valve, experimental verification and clinical application of this parameter are still required. Objectives The goal of this study is to verify MRI measurements of TKE by using a phantom stenosis with particle image velocimetry (PIV) as the reference standard. In addition, the feasibility of measuring TKE with MRI is explored. Methods MRI measurements of TKE through a phantom stenosis was performed by using clinical 3T MRI scanner. The MRI measurements were verified experimentally by using PIV as the reference standard. In vivo application of MRI-driven TKE was explored in seven patients with aortic valve disease and one healthy volunteer. Transvalvular gradients measured by MRI and echocardiography were compared. Results MRI and PIV measurements of TKE are consistent for turbulent flow (0.666 < R2 < 0.738) with a mean difference of −11.13 J/m3 (SD = 4.34 J/m3). Results of MRI and PIV measurements differ by 2.76 ± 0.82 cm/s (velocity) and −11.13 ± 4.34 J/m3 (TKE) for turbulent flow (Re > 400). The turbulence pressure drop correlates strongly with total TKE (R2 = 0.986). However, in vivo measurements of TKE are not consistent with the transvalvular pressure gradient estimated by echocardiography. Conclusions These results suggest that TKE measurement via MRI may provide a potential benefit as an energy-loss index to characterize blood flow through the aortic valve. However, further clinical studies are necessary to reach definitive conclusions regarding this technique. PMID:26978529
Development of a One-Step Multiplex PCR Assay for Differential Detection of Major Mycobacterium Species

PubMed Central

Chae, Hansong; Han, Seung Jung; Kim, Su-Young; Ki, Chang-Seok; Huh, Hee Jae; Yong, Dongeun

2017-01-01

ABSTRACT The prevalence of tuberculosis continues to be high, and nontuberculous mycobacterial (NTM) infection has also emerged worldwide. Moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. Here, we developed a one-step multiplex PCR assay using whole-genome analysis and bioinformatics to identify novel molecular targets. The aims of this assay were to (i) discriminate between the Mycobacterium tuberculosis complex (MTBC) and NTM using rv0577 or RD750, (ii) differentiate M. tuberculosis (M. tuberculosis) from MTBC using RD9, (iii) selectively identify the widespread M. tuberculosis Beijing genotype by targeting mtbk_20680, and (iv) simultaneously detect five clinically important NTM (M. avium, M. intracellulare, M. abscessus, M. massiliense, and M. kansasii) by targeting IS1311, DT1, mass_3210, and mkan_rs12360. An initial evaluation of the multiplex PCR assay using reference strains demonstrated 100% specificity for the targeted Mycobacterium species. Analytical sensitivity ranged from 1 to 10 pg for extracted DNA and was 103 and 104 CFU for pure cultures and nonhomogenized artificial sputum cultures, respectively, of the targeted species. The accuracy of the multiplex PCR assay was further evaluated using 55 reference strains and 94 mycobacterial clinical isolates. Spoligotyping, multilocus sequence analysis, and a commercial real-time PCR assay were employed as standard assays to evaluate the multiplex PCR assay with clinical M. tuberculosis and NTM isolates. The PCR assay displayed 100% identification agreement with the standard assays. Our multiplex PCR assay is a simple, convenient, and reliable technique for differential identification of MTBC, M. tuberculosis, M. tuberculosis Beijing genotype, and major NTM species. PMID:28659320
Turbulent Kinetic Energy Measurement Using Phase Contrast MRI for Estimating the Post-Stenotic Pressure Drop: In Vitro Validation and Clinical Application.

PubMed

Ha, Hojin; Kim, Guk Bae; Kweon, Jihoon; Huh, Hyung Kyu; Lee, Sang Joon; Koo, Hyun Jung; Kang, Joon-Won; Lim, Tae-Hwan; Kim, Dae-Hee; Kim, Young-Hak; Kim, Namkug; Yang, Dong Hyun

2016-01-01

Although the measurement of turbulence kinetic energy (TKE) by using magnetic resonance imaging (MRI) has been introduced as an alternative index for quantifying energy loss through the cardiac valve, experimental verification and clinical application of this parameter are still required. The goal of this study is to verify MRI measurements of TKE by using a phantom stenosis with particle image velocimetry (PIV) as the reference standard. In addition, the feasibility of measuring TKE with MRI is explored. MRI measurements of TKE through a phantom stenosis was performed by using clinical 3T MRI scanner. The MRI measurements were verified experimentally by using PIV as the reference standard. In vivo application of MRI-driven TKE was explored in seven patients with aortic valve disease and one healthy volunteer. Transvalvular gradients measured by MRI and echocardiography were compared. MRI and PIV measurements of TKE are consistent for turbulent flow (0.666 < R2 < 0.738) with a mean difference of -11.13 J/m3 (SD = 4.34 J/m3). Results of MRI and PIV measurements differ by 2.76 ± 0.82 cm/s (velocity) and -11.13 ± 4.34 J/m3 (TKE) for turbulent flow (Re > 400). The turbulence pressure drop correlates strongly with total TKE (R2 = 0.986). However, in vivo measurements of TKE are not consistent with the transvalvular pressure gradient estimated by echocardiography. These results suggest that TKE measurement via MRI may provide a potential benefit as an energy-loss index to characterize blood flow through the aortic valve. However, further clinical studies are necessary to reach definitive conclusions regarding this technique.
Development of a One-Step Multiplex PCR Assay for Differential Detection of Major Mycobacterium Species.

PubMed

Chae, Hansong; Han, Seung Jung; Kim, Su-Young; Ki, Chang-Seok; Huh, Hee Jae; Yong, Dongeun; Koh, Won-Jung; Shin, Sung Jae

2017-09-01

The prevalence of tuberculosis continues to be high, and nontuberculous mycobacterial (NTM) infection has also emerged worldwide. Moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. Here, we developed a one-step multiplex PCR assay using whole-genome analysis and bioinformatics to identify novel molecular targets. The aims of this assay were to (i) discriminate between the Mycobacterium tuberculosis complex (MTBC) and NTM using rv0577 or RD750, (ii) differentiate M. tuberculosis ( M. tuberculosis ) from MTBC using RD9, (iii) selectively identify the widespread M. tuberculosis Beijing genotype by targeting mtbk_20680 , and (iv) simultaneously detect five clinically important NTM ( M. avium , M. intracellulare , M. abscessus , M. massiliense , and M. kansasii ) by targeting IS 1311 , DT1, mass_3210 , and mkan_rs12360 An initial evaluation of the multiplex PCR assay using reference strains demonstrated 100% specificity for the targeted Mycobacterium species. Analytical sensitivity ranged from 1 to 10 pg for extracted DNA and was 10 3 and 10 4 CFU for pure cultures and nonhomogenized artificial sputum cultures, respectively, of the targeted species. The accuracy of the multiplex PCR assay was further evaluated using 55 reference strains and 94 mycobacterial clinical isolates. Spoligotyping, multilocus sequence analysis, and a commercial real-time PCR assay were employed as standard assays to evaluate the multiplex PCR assay with clinical M. tuberculosis and NTM isolates. The PCR assay displayed 100% identification agreement with the standard assays. Our multiplex PCR assay is a simple, convenient, and reliable technique for differential identification of MTBC, M. tuberculosis , M. tuberculosis Beijing genotype, and major NTM species. Copyright © 2017 American Society for Microbiology.

Diagnostic accuracy of an identification tool for localized neuropathic pain based on the IASP criteria.

PubMed

Mayoral, Víctor; Pérez-Hernández, Concepción; Muro, Inmaculada; Leal, Ana; Villoria, Jesús; Esquivias, Ana

2018-04-27

Based on the clear neuroanatomical delineation of many neuropathic pain (NP) symptoms, a simple tool for performing a short structured clinical encounter based on the IASP diagnostic criteria was developed to identify NP. This study evaluated its accuracy and usefulness. A case-control study was performed in 19 pain clinics within Spain. A pain clinician used the experimental screening tool (the index test, IT) to assign the descriptions of non-neuropathic (nNP), non-localized neuropathic (nLNP), and localized neuropathic (LNP) to the patients' pain conditions. The reference standard was a formal clinical diagnosis provided by another pain clinician. The accuracy of the IT was compared with that of the Douleur Neuropathique en 4 questions (DN4) and the Leeds Assessment of Neuropathic Signs and Symptoms (LANSS). Six-hundred and sixty-six patients were analyzed. There was a good agreement between the IT and the reference standard (kappa =0.722). The IT was accurate in distinguishing between LNP and nLNP (83.2% sensitivity, 88.2% specificity), between LNP and the other pain categories (nLNP + nNP) (80.0% sensitivity, 90.7% specificity), and between NP and nNP (95.5% sensitivity, 89.1% specificity). The accuracy in distinguishing between NP and nNP was comparable with that of the DN4 and the LANSS. The IT took a median of 10 min to complete. A novel instrument based on an operationalization of the IASP criteria can not only discern between LNP and nLNP, but also provide a high level of diagnostic certainty about the presence of NP after a short clinical encounter.
Armored DNA in recombinant Baculoviruses as controls in molecular genetic assays.

PubMed

Freystetter, Andrea; Paar, Christian; Stekel, Herbert; Berg, Jörg

2017-10-01

The widespread use of molecular PCR-based assays in analytical and clinical laboratories brings about the need for test-specific, stable, and reliable external controls (EC) as well as standards and internal amplification controls (IC), in order to arrive at consistent test results. In addition, there is also a growing need to produce and provide stable, well-characterized molecular controls for quality assurance programs. In this study, we describe a novel approach to generate armored double-stranded DNA controls, which are encapsulated in baculovirus (BV) particles of the species Autographa californica multiple nucleopolyhedrovirus. We used the well-known BacPAK™ Baculovirus Expression System (Takara-Clontech), removed the polyhedrin promoter used for protein expression, and generated recombinant BV-armored DNAs. The obtained BV-armored DNAs were readily extracted by standard clinical DNA extraction methods, showed favorable linearity and performance in our clinical PCR assays, were resistant to DNase I digestion, and exhibited marked stability in human plasma and serum. BV-armored DNA ought to be used as ECs, quantification standards, and ICs in molecular assays, with the latter application allowing for the entire monitoring of clinical molecular assays for sample adequacy. BV-armored DNA may also be used to produce double-stranded DNA reference materials for, e.g., quality assurance programs. The ease to produce BV-armored DNA should make this approach feasible for a broad spectrum of molecular applications. Finally, as BV-armored DNAs are non-infectious to mammals, they may be even more conveniently shipped than clinical specimen.
In vitro vaccine potency testing: a proposal for reducing animal use for requalification testing.

PubMed

Brown, K; Stokes, W

2012-01-01

This paper proposes a program under which the use of animals for requalification of in vitro potency tests could be eliminated. Standard References (USDA/CVB nomenclature) would be developed, characterized, stored and monitored by selected reference laboratories worldwide. These laboratories would employ scientists skilled in protein and glycoprotein chemistry and equipped with state-of-the-art instruments for required analyses. After Standard References are established, the reference laboratories would provide them to the animal health industry as "gold standards". Companies would then establish and validate a correlation between the Standard Reference and the company Master Reference (USDA/CVB nomenclature) using an internal in vitro assay. After this correlation is established, the company could use the Standard References for qualifying, monitoring and requalifying company Master References without the use of animals. Such a program would eliminate the need for animals for requalification of Master References and the need for each company to develop and validate a battery of Master Reference Monitoring assays. It would also provide advantages in terms of reduced costs and reduced time for requalification testing. As such it would provide a strong incentive for companies to develop and use in vitro assays for potency testing.
The Quantitative Science of Evaluating Imaging Evidence.

PubMed

Genders, Tessa S S; Ferket, Bart S; Hunink, M G Myriam

2017-03-01

Cardiovascular diagnostic imaging tests are increasingly used in everyday clinical practice, but are often imperfect, just like any other diagnostic test. The performance of a cardiovascular diagnostic imaging test is usually expressed in terms of sensitivity and specificity compared with the reference standard (gold standard) for diagnosing the disease. However, evidence-based application of a diagnostic test also requires knowledge about the pre-test probability of disease, the benefit of making a correct diagnosis, the harm caused by false-positive imaging test results, and potential adverse effects of performing the test itself. To assist in clinical decision making regarding appropriate use of cardiovascular diagnostic imaging tests, we reviewed quantitative concepts related to diagnostic performance (e.g., sensitivity, specificity, predictive values, likelihood ratios), as well as possible biases and solutions in diagnostic performance studies, Bayesian principles, and the threshold approach to decision making. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Clinical data interoperability based on archetype transformation.

PubMed

Costa, Catalina Martínez; Menárguez-Tortosa, Marcos; Fernández-Breis, Jesualdo Tomás

2011-10-01

The semantic interoperability between health information systems is a major challenge to improve the quality of clinical practice and patient safety. In recent years many projects have faced this problem and provided solutions based on specific standards and technologies in order to satisfy the needs of a particular scenario. Most of such solutions cannot be easily adapted to new scenarios, thus more global solutions are needed. In this work, we have focused on the semantic interoperability of electronic healthcare records standards based on the dual model architecture and we have developed a solution that has been applied to ISO 13606 and openEHR. The technological infrastructure combines reference models, archetypes and ontologies, with the support of Model-driven Engineering techniques. For this purpose, the interoperability infrastructure developed in previous work by our group has been reused and extended to cover the requirements of data transformation. Copyright © 2011 Elsevier Inc. All rights reserved.
Goya: 'in sickness and in health'.

PubMed

Casey, Laura L

2006-01-01

The following paper serves primarily to discuss the nature and cause of the multiple, documented illnesses suffered by the 18th Century Spanish artist Francisco Goya y Lucientes. In doing so it explores the artist's defiance of contemporary social mores, religious doctrines and the rigid standards of artistic romanticism. Furthermore, it examines the impact of illness upon artistic expression and the apparent correlation between heightened artistic proficiency and clinical depression with particular reference to the aforementioned artist. In addition, it provides a brief insight into the complexion of medical practice in Spain during the period of the Inquisition contrasted with those standards of conduct encompassed within the newly emerging movement of Enlightenment.
Pressure ulcer risk assessment and prevention: a systematic comparative effectiveness review.

PubMed

Chou, Roger; Dana, Tracy; Bougatsos, Christina; Blazina, Ian; Starmer, Amy J; Reitel, Katie; Buckley, David I

2013-07-02

Pressure ulcers are associated with substantial health burdens but may be preventable. To review the clinical utility of pressure ulcer risk assessment instruments and the comparative effectiveness of preventive interventions in persons at higher risk. MEDLINE (1946 through November 2012), CINAHL, the Cochrane Library, grant databases, clinical trial registries, and reference lists. Randomized trials and observational studies on effects of using risk assessment on clinical outcomes and randomized trials of preventive interventions on clinical outcomes. Multiple investigators abstracted and checked study details and quality using predefined criteria. One good-quality trial found no evidence that use of a pressure ulcer risk assessment instrument, with or without a protocolized intervention strategy based on assessed risk, reduces risk for incident pressure ulcers compared with less standardized risk assessment based on nurses' clinical judgment. In higher-risk populations, 1 good-quality and 4 fair-quality randomized trials found that more advanced static support surfaces were associated with lower risk for pressure ulcers compared with standard mattresses (relative risk range, 0.20 to 0.60). Evidence on the effectiveness of low-air-loss and alternating-air mattresses was limited, with some trials showing no clear differences from advanced static support surfaces. Evidence on the effectiveness of nutritional supplementation, repositioning, and skin care interventions versus usual care was limited and had methodological shortcomings, precluding strong conclusions. Only English-language articles were included, publication bias could not be formally assessed, and most studies had methodological shortcomings. More advanced static support surfaces are more effective than standard mattresses for preventing ulcers in higher-risk populations. The effectiveness of formal risk assessment instruments and associated intervention protocols compared with less standardized assessment methods and the effectiveness of other preventive interventions compared with usual care have not been clearly established.
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.
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
Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

PubMed

Heinzerling, L; Frew, A J; Bindslev-Jensen, C; Bonini, S; Bousquet, J; Bresciani, M; Carlsen, K-H; van Cauwenberge, P; Darsow, U; Fokkens, W J; Haahtela, T; van Hoecke, H; Jessberger, B; Kowalski, M L; Kopp, T; Lahoz, C N; Lodrup Carlsen, K C; Papadopoulos, N G; Ring, J; Schmid-Grendelmeier, P; Vignola, A M; Wöhrl, S; Zuberbier, T

2005-10-01

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.
DICOM for quantitative imaging biomarker development: a standards based approach to sharing clinical data and structured PET/CT analysis results in head and neck cancer research.

PubMed

Fedorov, Andriy; Clunie, David; Ulrich, Ethan; Bauer, Christian; Wahle, Andreas; Brown, Bartley; Onken, Michael; Riesmeier, Jörg; Pieper, Steve; Kikinis, Ron; Buatti, John; Beichel, Reinhard R

2016-01-01

Background. Imaging biomarkers hold tremendous promise for precision medicine clinical applications. Development of such biomarkers relies heavily on image post-processing tools for automated image quantitation. Their deployment in the context of clinical research necessitates interoperability with the clinical systems. Comparison with the established outcomes and evaluation tasks motivate integration of the clinical and imaging data, and the use of standardized approaches to support annotation and sharing of the analysis results and semantics. We developed the methodology and tools to support these tasks in Positron Emission Tomography and Computed Tomography (PET/CT) quantitative imaging (QI) biomarker development applied to head and neck cancer (HNC) treatment response assessment, using the Digital Imaging and Communications in Medicine (DICOM(®)) international standard and free open-source software. Methods. Quantitative analysis of PET/CT imaging data collected on patients undergoing treatment for HNC was conducted. Processing steps included Standardized Uptake Value (SUV) normalization of the images, segmentation of the tumor using manual and semi-automatic approaches, automatic segmentation of the reference regions, and extraction of the volumetric segmentation-based measurements. Suitable components of the DICOM standard were identified to model the various types of data produced by the analysis. A developer toolkit of conversion routines and an Application Programming Interface (API) were contributed and applied to create a standards-based representation of the data. Results. DICOM Real World Value Mapping, Segmentation and Structured Reporting objects were utilized for standards-compliant representation of the PET/CT QI analysis results and relevant clinical data. A number of correction proposals to the standard were developed. The open-source DICOM toolkit (DCMTK) was improved to simplify the task of DICOM encoding by introducing new API abstractions. Conversion and visualization tools utilizing this toolkit were developed. The encoded objects were validated for consistency and interoperability. The resulting dataset was deposited in the QIN-HEADNECK collection of The Cancer Imaging Archive (TCIA). Supporting tools for data analysis and DICOM conversion were made available as free open-source software. Discussion. We presented a detailed investigation of the development and application of the DICOM model, as well as the supporting open-source tools and toolkits, to accommodate representation of the research data in QI biomarker development. We demonstrated that the DICOM standard can be used to represent the types of data relevant in HNC QI biomarker development, and encode their complex relationships. The resulting annotated objects are amenable to data mining applications, and are interoperable with a variety of systems that support the DICOM standard.
Metrology in Medicine: From Measurements to Decision, with Specific Reference to Anesthesia and Intensive Care

PubMed Central

Imhoff, Michael; Cecconi, Maurizio

2015-01-01

Metrology is the science of measurements. Although of critical importance in medicine and especially in critical care, frequent confusion in terms and definitions impact either interphysician communications or understanding of manufacturers’ and engineers’ instructions and limitations when using devices. In this review, we first list the terms defined by the International Bureau of Weights and Measures regarding quantities and units, measurements, devices for measurement, properties of measuring devices, and measurement standards. The traditional tools for assessing the most important measurement quality criteria are also reviewed with clinical examples for diagnosis, alarm, and titration purposes, as well as for assessing the uncertainty of reference methods. PMID:25625255
Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin.

PubMed

Sun, Hsin-Yun; Liao, Hsiao-Wei; Sheng, Meng-Huei; Tai, Hui-Min; Kuo, Ching-Hua; Sheng, Wang-Huei

2016-07-01

Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. Copyright © 2016 Elsevier Inc. All rights reserved.
A Framework for Establishing Standard Reference Scale of Texture by Multivariate Statistical Analysis Based on Instrumental Measurement and Sensory Evaluation.

PubMed

Zhi, Ruicong; Zhao, Lei; Xie, Nan; Wang, Houyin; Shi, Bolin; Shi, Jingye

2016-01-13

A framework of establishing standard reference scale (texture) is proposed by multivariate statistical analysis according to instrumental measurement and sensory evaluation. Multivariate statistical analysis is conducted to rapidly select typical reference samples with characteristics of universality, representativeness, stability, substitutability, and traceability. The reasonableness of the framework method is verified by establishing standard reference scale of texture attribute (hardness) with Chinese well-known food. More than 100 food products in 16 categories were tested using instrumental measurement (TPA test), and the result was analyzed with clustering analysis, principal component analysis, relative standard deviation, and analysis of variance. As a result, nine kinds of foods were determined to construct the hardness standard reference scale. The results indicate that the regression coefficient between the estimated sensory value and the instrumentally measured value is significant (R(2) = 0.9765), which fits well with Stevens's theory. The research provides reliable a theoretical basis and practical guide for quantitative standard reference scale establishment on food texture characteristics.
Measurement standards for interdisciplinary medical rehabilitation.

PubMed

Johnston, M V; Keith, R A; Hinderer, S R

1992-12-01

Rehabilitation must address problems inherent in the measurement of human function and health-related quality of life, as well as problems in diagnosis and measurement of impairment. This educational document presents an initial set of standards to be used as guidelines for development and use of measurement and evaluation procedures and instruments for interdisciplinary, health-related rehabilitation. Part I covers general measurement principles and technical standards, beginning with validity, the central consideration for use of measures. Subsequent sections focus on reliability and errors of measurement, norms and scaling, development of measures, and technical manuals and guides. Part II covers principles and standards for use of measures. General principles of application of measures in practice are discussed first, followed by standards to protect persons being measured and then by standards for administrative applications. Many explanations, examples, and references are provided to help professionals understand measurement principles. Improved measurement will ensure the basis of rehabilitation as a science and nourish its success as a clinical service.
A National Trial on Differences in Cerebral Perfusion Pressure Values by Measurement Location.

PubMed

McNett, Molly M; Bader, Mary Kay; Livesay, Sarah; Yeager, Susan; Moran, Cristina; Barnes, Arianna; Harrison, Kimberly R; Olson, DaiWai M

2018-04-01

Cerebral perfusion pressure (CPP) is a key parameter in management of brain injury with suspected impaired cerebral autoregulation. CPP is calculated by subtracting intracranial pressure (ICP) from mean arterial pressure (MAP). Despite consensus on importance of CPP monitoring, substantial variations exist on anatomical reference points used to measure arterial MAP when calculating CPP. This study aimed to identify differences in CPP values based on measurement location when using phlebostatic axis (PA) or tragus (Tg) as anatomical reference points. The secondary study aim was to determine impact of differences on patient outcomes at discharge. This was a prospective, repeated measures, multi-site national trial. Adult ICU patients with neurological injury necessitating ICP and CPP monitoring were consecutively enrolled from seven sites. Daily MAP/ICP/CPP values were gathered with the arterial transducer at the PA, followed by the Tg as anatomical reference points. A total of 136 subjects were enrolled, resulting in 324 paired observations. There were significant differences for CPP when comparing values obtained at PA and Tg reference points (p < 0.000). Differences remained significant in repeated measures model when controlling for clinical factors (mean CPP-PA = 80.77, mean CPP-Tg = 70.61, p < 0.000). When categorizing CPP as binary endpoint, 18.8% of values were identified as adequate with PA values, yet inadequate with CPP values measured at the Tg. Findings identify numerical differences for CPP based on anatomical reference location and highlight importance of a standard reference point for both clinical practice and future trials to limit practice variations and heterogeneity of findings.
Evaluating new HbA1c methods for adoption by the IFCC and NGSP reference networks using international quality targets.

PubMed

Lenters-Westra, Erna; English, Emma

2017-08-28

As a reference laboratory for HbA1c, it is essential to have accurate and precise HbA1c methods covering a range of measurement principles. We report an evaluation of the Abbott Enzymatic (Architect c4000), Roche Gen.3 HbA1c (Cobas c513) and Tosoh G11 using different quality targets. The effect of hemoglobin variants, other potential interferences and the performance in comparison to both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the National Glycohemoglobin Standardization Program (NGSP) reference systems was assessed using certified evaluation protocols. Each of the evaluated HbA1c methods had CVs <3% in SI units and <2% in NGSP units at 46 mmol/mol (6.4%) and 72 mmol/mol (8.7%) and passed the NGSP criteria when compared with six secondary reference measurement procedures (SRMPs). Sigma was 8.6 for Abbott Enzymatic, 3.3 for Roche Cobas c513 and 6.9 for Tosoh G11. No clinically significant interference was detected for the common Hb variants for the three methods. All three methods performed well and are suitable for clinical application in the analysis of HbA1c. Partly based on the result of this study, the Abbott Enzymatic method on the Architect c4000 and the Roche Gen.3 HbA1c on the Cobas c513 are now official, certified IFCC and NGSP SRMPs in the IFCC and NGSP networks. Sigma metrics quality criteria presented in a graph distinguish between good and excellent performance.
Application of Bayes' to the prediction of referral decisions made by specialist optometrists in relation to chronic open angle glaucoma.

PubMed

Gurney, J C; Ansari, E; Harle, D; O'Kane, N; Sagar, R V; Dunne, M C M

2018-02-09

To determine the accuracy of a Bayesian learning scheme (Bayes') applied to the prediction of clinical decisions made by specialist optometrists in relation to the referral refinement of chronic open angle glaucoma. This cross-sectional observational study involved collection of data from the worst affected or right eyes of a consecutive sample of cases (n = 1,006) referred into the West Kent Clinical Commissioning Group Community Ophthalmology Team (COT) by high street optometrists. Multilevel classification of each case was based on race, sex, age, family history of chronic open angle glaucoma, reason for referral, Goldmann Applanation Tonometry (intraocular pressure and interocular asymmetry), optic nerve head assessment (vertical size, cup disc ratio and interocular asymmetry), central corneal thickness and visual field analysis (Hodapp-Parrish-Anderson classification). Randomised stratified tenfold cross-validation was applied to determine the accuracy of Bayes' by comparing its output to the clinical decisions of three COT specialist optometrists; namely, the decision to discharge, follow-up or refer each case. Outcomes of cross-validation, expressed as means and standard deviations, showed that the accuracy of Bayes' was high (95%, 2.0%) but that it falsely discharged (3.4%, 1.6%) or referred (3.1%, 1.5%) some cases. The results indicate that Bayes' has the potential to augment the decisions of specialist optometrists.
18 CFR 38.2 - Incorporation by reference of North American Energy Standards Board Wholesale Electric Quadrant...

Code of Federal Regulations, 2011 CFR

2011-04-01

....13, 001-1.0, 001-9.7, 001-14.1.3, and 001-15.1.2); (2) Open Access Same-Time Information Systems... reference of North American Energy Standards Board Wholesale Electric Quadrant standards. 38.2 Section 38.2... UTILITIES § 38.2 Incorporation by reference of North American Energy Standards Board Wholesale Electric...
[Research about re-evaluation of screening of traditonal Chinese medicine symptoms item of post-marketing medicine Xuezhikang].

PubMed

He, Wei; Xie, Yanming; Wang, Yongyan

2011-10-01

The purpose of post-marketing Chinese medicine re-evaluation is to identify Chinese medicine clinical indications, while designing scientific and rational of Chinese medicine symptoms items are important to the result of symptoms re-evaluation. This study give screening of traditional Chinese medicine(TCM) symptoms item of post-marketing medicine Xuezhikang re-evaluation as example that reference to principle dyslipidemia clinical research, academic dissertations, Xuezhikang directions, clinical expert practice experience etc. while standardization those symptom names and screening 41 dyslipidemia common symptoms. Furthermore, this paper discuss about the accoerdance and announcements when screening symptoms item, so as to providing a research thread to manufacture PRO chart for post-marketing medicine re-evaluation.

Towards a Framework for Developing Semantic Relatedness Reference Standards

PubMed Central

Pakhomov, Serguei V.S.; Pedersen, Ted; McInnes, Bridget; Melton, Genevieve B.; Ruggieri, Alexander; Chute, Christopher G.

2010-01-01

Our objective is to develop a framework for creating reference standards for functional testing of computerized measures of semantic relatedness. Currently, research on computerized approaches to semantic relatedness between biomedical concepts relies on reference standards created for specific purposes using a variety of methods for their analysis. In most cases, these reference standards are not publicly available and the published information provided in manuscripts that evaluate computerized semantic relatedness measurement approaches is not sufficient to reproduce the results. Our proposed framework is based on the experiences of medical informatics and computational linguistics communities and addresses practical and theoretical issues with creating reference standards for semantic relatedness. We demonstrate the use of the framework on a pilot set of 101 medical term pairs rated for semantic relatedness by 13 medical coding experts. While the reliability of this particular reference standard is in the “moderate” range; we show that using clustering and factor analyses offers a data-driven approach to finding systematic differences among raters and identifying groups of potential outliers. We test two ontology-based measures of relatedness and provide both the reference standard containing individual ratings and the R program used to analyze the ratings as open-source. Currently, these resources are intended to be used to reproduce and compare results of studies involving computerized measures of semantic relatedness. Our framework may be extended to the development of reference standards in other research areas in medical informatics including automatic classification, information retrieval from medical records and vocabulary/ontology development. PMID:21044697
Determination of hematology and plasma chemistry reference intervals for 3 populations of captive Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus).

PubMed

Matsche, Mark A; Arnold, Jill; Jenkins, Erin; Townsend, Howard; Rosemary, Kevin

2014-09-01

The imperiled status of Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus), a large, long-lived, anadromous fish found along the Atlantic coast of North America, has prompted efforts at captive propagation for research and stock enhancement. The purpose of this study was to establish hematology and plasma chemistry reference intervals of captive Atlantic sturgeon maintained under different culture conditions. Blood specimens were collected from a total of 119 fish at 3 hatcheries: Lamar, PA (n = 36, ages 10-14 years); Chalk Point, MD (n = 40, siblings of Lamar); and Horn Point, Cambridge, MD (n = 43, mixed population from Chesapeake Bay). Reference intervals (using robust techniques), median, mean, and standard deviations were determined for WBC, RBC, thrombocytes, PCV, HGB, MCV, MCH, MCHC, and absolute counts for lymphocytes (L), neutrophils (N), monocytes, and eosinophils. Chemistry analytes included concentrations of total proteins, albumin, glucose, urea, calcium, phosphate, sodium, potassium, chloride, and globulins, AST, CK, and LDH activities, and osmolality. Mean concentrations of total proteins, albumin, and glucose were at or below the analytic range. Statistical comparisons showed significant differences among hatcheries for each remaining plasma chemistry analyte and for PCV, RBC, MCHC, MCH, eosinophil and monocyte counts, and N:L ratio throughout all 3 groups. Therefore, reference intervals were calculated separately for each population. Reference intervals for fish maintained under differing conditions should be established per population. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.
Hg0 and HgCl2 Reference Gas Standards: ?NIST Traceability ...

EPA Pesticide Factsheets

EPA and NIST have collaborated to establish the necessary procedures for establishing the required NIST traceability of commercially-provided Hg0 and HgCl2 reference generators. This presentation will discuss the approach of a joint EPA/NIST study to accurately quantify the true concentrations of Hg0 and HgCl2 reference gases produced from high quality, NIST-traceable, commercial Hg0 and HgCl2 generators. This presentation will also discuss the availability of HCl and Hg0 compressed reference gas standards as a result of EPA's recently approved Alternative Methods 114 and 118. Gaseous elemental mercury (Hg0) and oxidized mercury (HgCl2) reference standards are integral to the use of mercury continuous emissions monitoring systems (Hg CEMS) for regulatory compliance emissions monitoring. However, a quantitative disparity of approximately 7-10% has been observed between commercial Hg0 and HgCl2 reference gases which currently limits the use of (HgCl2) reference gas standards. Resolving this disparity would enable the expanded use of (HgCl2) reference gas standards for regulatory compliance purposes.
Privacy enhanced group communication in clinical environment

NASA Astrophysics Data System (ADS)

Li, Mingyan; Narayanan, Sreeram; Poovendran, Radha

2005-04-01

Privacy protection of medical records has always been an important issue and is mandated by the recent Health Insurance Portability and Accountability Act (HIPAA) standards. In this paper, we propose security architectures for a tele-referring system that allows electronic group communication among professionals for better quality treatments, while protecting patient privacy against unauthorized access. Although DICOM defines the much-needed guidelines for confidentiality of medical data during transmission, there is no provision in the existing medical security systems to guarantee patient privacy once the data has been received. In our design, we address this issue by enabling tracing back to the recipient whose received data is disclosed to outsiders, using watermarking technique. We present security architecture design of a tele-referring system using a distributed approach and a centralized web-based approach. The resulting tele-referring system (i) provides confidentiality during the transmission and ensures integrity and authenticity of the received data, (ii) allows tracing of the recipient who has either distributed the data to outsiders or whose system has been compromised, (iii) provides proof of receipt or origin, and (iv) can be easy to use and low-cost to employ in clinical environment.
An approach for utilizing clinical statements in HL7 RIM to evaluate eligibility criteria.

PubMed

Bache, Richard; Daniel, Christel; James, Julie; Hussain, Sajjad; McGilchrist, Mark; Delaney, Brendan; Taweel, Adel

2014-01-01

The HL7 RIM (Reference Information Model) is a commonly used standard for the exchange of clinical data and can be employed for integrating the patient care and clinical research domains. Yet it is not sufficiently well specified to ensure a canonical representation of structured clinical data when used for the automated evaluation of eligibility criteria from a clinical trial protocol. We present an approach to further constrain the RIM to create a common information model to hold clinical data. In order to demonstrate our approach, we identified 132 distinct data elements from 10 rich clinical trails. We then defined a taxonomy to (i) identify the types of data elements that would need to be stored and (ii) define the types of predicate that would be used to evaluate them. This informed the definition of a pattern used to represent the data, which was shown to be sufficient for storing and evaluating the clinical statements required by the trials.
The EuroPrevall outpatient clinic study on food allergy: background and methodology.

PubMed

Fernández-Rivas, M; Barreales, L; Mackie, A R; Fritsche, P; Vázquez-Cortés, S; Jedrzejczak-Czechowicz, M; Kowalski, M L; Clausen, M; Gislason, D; Sinaniotis, A; Kompoti, E; Le, T-M; Knulst, A C; Purohit, A; de Blay, F; Kralimarkova, T; Popov, T; Asero, R; Belohlavkova, S; Seneviratne, S L; Dubakiene, R; Lidholm, J; Hoffmann-Sommergruber, K; Burney, P; Crevel, R; Brill, M; Fernández-Pérez, C; Vieths, S; Clare Mills, E N; van Ree, R; Ballmer-Weber, B K

2015-05-01

The EuroPrevall project aimed to develop effective management strategies in food allergy through a suite of interconnected studies and a multidisciplinary integrated approach. To address some of the gaps in food allergy diagnosis, allergen risk management and socio-economic impact and to complement the EuroPrevall population-based surveys, a cross-sectional study in 12 outpatient clinics across Europe was conducted. We describe the study protocol. Patients referred for immediate food adverse reactions underwent a consistent and standardized allergy work-up that comprised collection of medical history; assessment of sensitization to 24 foods, 14 inhalant allergens and 55 allergenic molecules; and confirmation of clinical reactivity and food thresholds by standardized double-blind placebo-controlled food challenges (DBPCFCs) to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple and peach. A standardized methodology for a comprehensive evaluation of food allergy was developed and implemented in 12 outpatient clinics across Europe. A total of 2121 patients (22.6% <14 years) reporting 8257 reactions to foods were studied, and 516 DBPCFCs were performed. This is the largest multicentre European case series in food allergy, in which subjects underwent a comprehensive, uniform and standardized evaluation including DBPCFC, by a methodology which is made available for further studies in food allergy. The analysis of this population will provide information on the different phenotypes of food allergy across Europe, will allow to validate novel in vitro diagnostic tests, to establish threshold values for major allergenic foods and to analyse the socio-economic impact of food allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Pulse oximetry-derived respiratory rate in general care floor patients.

PubMed

Addison, Paul S; Watson, James N; Mestek, Michael L; Ochs, James P; Uribe, Alberto A; Bergese, Sergio D

2015-02-01

Respiratory rate is recognized as a clinically important parameter for monitoring respiratory status on the general care floor (GCF). Currently, intermittent manual assessment of respiratory rate is the standard of care on the GCF. This technique has several clinically-relevant shortcomings, including the following: (1) it is not a continuous measurement, (2) it is prone to observer error, and (3) it is inefficient for the clinical staff. We report here on an algorithm designed to meet clinical needs by providing respiratory rate through a standard pulse oximeter. Finger photoplethysmograms were collected from a cohort of 63 GCF patients monitored during free breathing over a 25-min period. These were processed using a novel in-house algorithm based on continuous wavelet-transform technology within an infrastructure incorporating confidence-based averaging and logical decision-making processes. The computed oximeter respiratory rates (RRoxi) were compared to an end-tidal CO2 reference rate (RRETCO2). RRETCO2 ranged from a lowest recorded value of 4.7 breaths per minute (brpm) to a highest value of 32.0 brpm. The mean respiratory rate was 16.3 brpm with standard deviation of 4.7 brpm. Excellent agreement was found between RRoxi and RRETCO2, with a mean difference of -0.48 brpm and standard deviation of 1.77 brpm. These data demonstrate that our novel respiratory rate algorithm is a potentially viable method of monitoring respiratory rate in GCF patients. This technology provides the means to facilitate continuous monitoring of respiratory rate, coupled with arterial oxygen saturation and pulse rate, using a single non-invasive sensor in low acuity settings.
Standardization of immunotherapy adverse events in patient information leaflets and development of an interface terminology for outpatients' monitoring.

PubMed

Zini, E M; Lanzola, G; Quaglini, S; Cornet, R

2018-01-01

Immunotherapy is effective for treating cancer, but it is also associated with a wide spectrum of adverse events. In order to detect them early, the patients need to be monitored at home, between the therapy administrations, e.g., by asking them to report outcomes, usually including symptoms and quality of life measures. For the collected data to be reusable, the symptoms need to be in a standardized form. The aim of this study is to explore the standardization of the information contained in the patient information leaflets (PILs) of immunotherapy drugs, by creating an interface terminology of immunotherapy-related adverse events, which should support a consistent collection of symptoms from the patients. PILs contain a significant amount of information in free text, but they mix patient-reportable and clinically assessable events. We extracted a list of patient-reportable adverse events, mapped them to reference terminologies and compared the mapping results to choose the best-performing reference terminology. The PILs standardization led to the extraction of 151 symptoms and 424 terms, including both preferred terms and synonyms in English and Italian. Among the reference terminologies we considered, SNOMED CT allowed us to map all concepts and became, hence, the main reference terminology for the resulting interface terminology. A preliminary validation on the PIL of a new immunotherapy drug showed that our interface terminology already contained all the mentioned symptoms. PILs provide a valuable source for determining adverse events. The resulting interface terminology includes Italian and English terms for patient-reportable adverse events for five immunotherapy drugs representative of their category. Further work will be undertaken to evaluate the usability of the interface terminology and the patients' experience and satisfaction with the proposed terms, made available for example through an app, as well as its effectiveness on data quality and quality of care. Copyright © 2017 Elsevier Inc. All rights reserved.
Reference values for the muscle power sprint test in 6- to 12-year-old children.

PubMed

Douma-van Riet, Danielle; Verschuren, Olaf; Jelsma, Dorothee; Kruitwagen, Cas; Smits-Engelsman, Bouwien; Takken, Tim

2012-01-01

The aims of this study were (1) to develop centile reference values for anaerobic performance of Dutch children tested using the Muscle Power Sprint Test (MPST) and (2) to examine the test-retest reliability of the MPST. Children who were developing typically (178 boys and 201 girls) and aged 6 to 12 years (mean = 8.9 years) were recruited. The MPST was administered to 379 children, and test-retest reliability was examined in 47 children. MPST scores were transformed into centile curves, which were created using generalized additive models for location, scale, and shape. Height-related reference curves were created for both genders. Excellent (intraclass correlation coefficient = 0.98) test-retest reliability was demonstrated. The reference values for the MPST of children who are developing typically and aged 6 to 12 years can serve as a clinical standard in pediatric physical therapy practice. The MPST is a reliable and practical method for determining anaerobic performance in children.
Quality evaluation of LC-MS/MS-based E. coli H antigen typing (MS-H) through label-free quantitative data analysis in a clinical sample setup.

PubMed

Cheng, Keding; Sloan, Angela; McCorrister, Stuart; Peterson, Lorea; Chui, Huixia; Drebot, Mike; Nadon, Celine; Knox, J David; Wang, Gehua

2014-12-01

The need for rapid and accurate H typing is evident during Escherichia coli outbreak situations. This study explores the transition of MS-H, a method originally developed for rapid H antigen typing of E. coli using LC-MS/MS of flagella digest of reference strains and some clinical strains, to E. coli isolates in clinical scenario through quantitative analysis and method validation. Motile and nonmotile strains were examined in batches to simulate clinical sample scenario. Various LC-MS/MS batch run procedures and MS-H typing rules were compared and summarized through quantitative analysis of MS-H data output for a standard method development. Label-free quantitative data analysis of MS-H typing was proven very useful for examining the quality of MS-H result and the effects of some sample carryovers from motile E. coli isolates. Based on this, a refined procedure and protein identification rule specific for clinical MS-H typing was established and validated. With LC-MS/MS batch run procedure and database search parameter unique for E. coli MS-H typing, the standard procedure maintained high accuracy and specificity in clinical situations, and its potential to be used in a clinical setting was clearly established. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Diagnosis and constitutional and laboratory features of Korean girls referred for precocious puberty

PubMed Central

Kim, Doosoo; Cho, Sung-Yoon; Maeng, Se-Hyun; Yi, Eun Sang; Jung, Yu Jin; Park, Sung Won; Sohn, Young Bae

2012-01-01

Purpose Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups. Methods The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP), pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS), weight standard deviation score (WSDS), and body mass index standard deviation score (BMISDS) of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic. Results The PP groups comprised fast puberty (67%), premature thelarche (17%), true PP (15%), and pseudo PP (1%). Advanced bone age and levels of estradiol, basal luteinizing hormone (LH), and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P<0.05). Conclusion The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group. PMID:23300504
A Case for the Standardized Assessment of Testamentary Capacity

PubMed Central

Brenkel, Megan; Whaley, Kimberley; Herrmann, Nathan; Crawford, Kerri; Hazan, Elias; Cardiff, Laura; Owen, Adrian M.

2018-01-01

Background With an increasingly aged, frail population that holds a disproportionate amount of wealth, clinicians (especially those with expertise in older adults) may be asked with more frequency to offer a clinical opinion on testamentary capacity (TC), the mental capacity to make a will. Method This paper reviews the legal criteria as well as the empirical research on assessment tools for determining testamentary capacity (TC). We also review the relevance of instruments used for the assessment of other decisional capacities in order to evince the potential value of developing a standardized assessment of TC for clinician experts. Results The legal criteria, often referred to as a “test”, for determining requisite TC (Banks v. Goodfellow) have remained much the same since 1870 with minimal clinical input and, as such, there has been little development in TC assessment instruments. Decisional instruments designed to assess Consent to Treatment may have relevance for TC. Conclusion We make the case for a semi-structured interview that includes standardized criteria for the legal test for TC, supplemented by a validated brief neuropsychological assessment, which together comprise a Contemporaneous Assessment Instrument (CAI) for TC. PMID:29581818
Clinical Decision Support-based Quality Measurement (CDS-QM) Framework: Prototype Implementation, Evaluation, and Future Directions

PubMed Central

Kukhareva, Polina V; Kawamoto, Kensaku; Shields, David E; Barfuss, Darryl T; Halley, Anne M; Tippetts, Tyler J; Warner, Phillip B; Bray, Bruce E; Staes, Catherine J

2014-01-01

Electronic quality measurement (QM) and clinical decision support (CDS) are closely related but are typically implemented independently, resulting in significant duplication of effort. While it seems intuitive that technical approaches could be re-used across these two related use cases, such reuse is seldom reported in the literature, especially for standards-based approaches. Therefore, we evaluated the feasibility of using a standards-based CDS framework aligned with anticipated EHR certification criteria to implement electronic QM. The CDS-QM framework was used to automate a complex national quality measure (SCIP-VTE-2) at an academic healthcare system which had previously relied on time-consuming manual chart abstractions. Compared with 305 manually-reviewed reference cases, the recall of automated measurement was 100%. The precision was 96.3% (CI:92.6%-98.5%) for ascertaining the denominator and 96.2% (CI:92.3%-98.4%) for the numerator. We therefore validated that a standards-based CDS-QM framework can successfully enable automated QM, and we identified benefits and challenges with this approach. PMID:25954389
Antianaerobic Antimicrobials: Spectrum and Susceptibility Testing

PubMed Central

Wexler, Hannah M.; Goldstein, Ellie J. C.

2013-01-01

SUMMARY Susceptibility testing of anaerobic bacteria recovered from selected cases can influence the choice of antimicrobial therapy. The Clinical and Laboratory Standards Institute (CLSI) has standardized many laboratory procedures, including anaerobic susceptibility testing (AST), and has published documents for AST. The standardization of testing methods by the CLSI allows comparisons of resistance trends among various laboratories. Susceptibility testing should be performed on organisms recovered from sterile body sites, those that are isolated in pure culture, or those that are clinically important and have variable or unique susceptibility patterns. Organisms that should be considered for individual isolate testing include highly virulent pathogens for which susceptibility cannot be predicted, such as Bacteroides, Prevotella, Fusobacterium, and Clostridium spp.; Bilophila wadsworthia; and Sutterella wadsworthensis. This review describes the current methods for AST in research and reference laboratories. These methods include the use of agar dilution, broth microdilution, Etest, and the spiral gradient endpoint system. The antimicrobials potentially effective against anaerobic bacteria include beta-lactams, combinations of beta-lactams and beta-lactamase inhibitors, metronidazole, chloramphenicol, clindamycin, macrolides, tetracyclines, and fluoroquinolones. The spectrum of efficacy, antimicrobial resistance mechanisms, and resistance patterns against these agents are described. PMID:23824372
Accuracy of point-of-care serum creatinine devices for detecting patients at risk of contrast-induced nephropathy: a critical overview.

PubMed

Martínez Lomakin, Felipe; Tobar, Catalina

2014-12-01

Contrast-induced nephropathy (CIN) is a common event in hospitals, with reported incidences ranging from 1 to 30%. Patients with underlying kidney disease have an increased risk of developing CIN. Point-of-care (POC) creatinine devices are handheld devices capable of providing quantitative data on a patient's kidney function that could be useful in stratifying preventive measures. This overview aims to synthesize the current evidence on diagnostic accuracy and clinical utility of POC creatinine devices in detecting patients at risk of CIN. Five databases were searched for diagnostic accuracy studies or clinical trials that evaluated the usefulness of POC devices in detecting patients at risk of CIN. Selected articles were critically appraised to assess their individual risk of bias by the use of standard criteria; 13 studies were found that addressed the diagnostic accuracy or clinical utility of POC creatinine devices. Most studies incurred a moderate to high risk of bias. Overall concordance between POC devices and reference standards (clinical laboratory procedures) was found to be moderate, with 95% limits of agreement often lying between -35.4 and +35.4 µmol/L (-0.4 and +0.4 mg/dL). Concordance was shown to decrease with worsening kidney function. Data on the clinical utility of these devices were limited, but a significant reduction in time to diagnosis was reported in two studies. Overall, POC creatinine devices showed a moderate concordance with standard clinical laboratory creatinine measurements. Several biases could have induced optimism in these estimations. Results obtained from these devices may be unreliable in cases of severe kidney failure. Randomized trials are needed to address the clinical utility of these devices.
Improved Automated Detection of Diabetic Retinopathy on a Publicly Available Dataset Through Integration of Deep Learning.

PubMed

Abràmoff, Michael David; Lou, Yiyue; Erginay, Ali; Clarida, Warren; Amelon, Ryan; Folk, James C; Niemeijer, Meindert

2016-10-01

To compare performance of a deep-learning enhanced algorithm for automated detection of diabetic retinopathy (DR), to the previously published performance of that algorithm, the Iowa Detection Program (IDP)-without deep learning components-on the same publicly available set of fundus images and previously reported consensus reference standard set, by three US Board certified retinal specialists. We used the previously reported consensus reference standard of referable DR (rDR), defined as International Clinical Classification of Diabetic Retinopathy moderate, severe nonproliferative (NPDR), proliferative DR, and/or macular edema (ME). Neither Messidor-2 images, nor the three retinal specialists setting the Messidor-2 reference standard were used for training IDx-DR version X2.1. Sensitivity, specificity, negative predictive value, area under the curve (AUC), and their confidence intervals (CIs) were calculated. Sensitivity was 96.8% (95% CI: 93.3%-98.8%), specificity was 87.0% (95% CI: 84.2%-89.4%), with 6/874 false negatives, resulting in a negative predictive value of 99.0% (95% CI: 97.8%-99.6%). No cases of severe NPDR, PDR, or ME were missed. The AUC was 0.980 (95% CI: 0.968-0.992). Sensitivity was not statistically different from published IDP sensitivity, which had a CI of 94.4% to 99.3%, but specificity was significantly better than the published IDP specificity CI of 55.7% to 63.0%. A deep-learning enhanced algorithm for the automated detection of DR, achieves significantly better performance than a previously reported, otherwise essentially identical, algorithm that does not employ deep learning. Deep learning enhanced algorithms have the potential to improve the efficiency of DR screening, and thereby to prevent visual loss and blindness from this devastating disease.
Reevaluation of the NOAA/CMDL carbon monoxide reference scale and comparisons with CO reference gases at NASA-Langley and the Fraunhofer Institut

NASA Technical Reports Server (NTRS)

Novelli, P. C.; Collins, J. E., Jr.; Myers, R. C.; Sachse, G. W.; Scheel, H. E.

1994-01-01

The carbon monoxide (CO) reference scale created by the National Oceanic and Atmospheric Administration/Climate Monitoring and Diagnostics Laboratory (NOAA/CMDL) is used to quantify measurements of CO in the atmosphere, calibrate standards of other laboratories and to otherwise provide reference gases to the community measuring atmospheric CO. This reference scale was created based upon a set of primary standards prepared by gravimetric methods at CMDL and has been propagated to a set of working standards. In this paper we compare CO mixing ratios assigned to the working standards by three approaches: (1) calibration against the original gravimetric standards, (2) calibration using only working standards as the reference gas, and (3) calibration against three new gravimetric standards prepared to CMDL. The agreement between these values was typically better than 1%. The calibration histories of CMDL working standards are reviewed with respect to expected rates of CO change in the atmosphere. Using a Monte Carlo approach to simulate the effect of drifting standards on calculated mixing ratios, we conclude that the error solely associated with the maintenance of standards will limit the ability to detect small CO changes in the atmosphere. We also report results of intercalibration experiments conducted between CMDL and the Diode Laser Sensor Group (DACOM) at the NASA Langley Research Center (Hampton, Virginia), and CMDL and the Fraunhofer-Institut (Garmisch-Partenkirchen, Germany). Each laboratory calibrated several working standards for CO using their reference gases, and these results were compared to calibrations conducted by CMDL. The intercomparison of eight standards (CO concentrations between approximately 100 and approximately 165 ppb) by CMDL and NASA agreed to better than +/- 2%. The calibration of six standards (CO concentrations between approximately 50 and approximately 210 ppb) by CMDL and the Fraunhofer-Institut agreed to within +/- 2% for four standards, and to within +/- 5% for all six standards.
Echocardiography parameters of clinically normal adult captive chimpanzees (Pan troglodytes).

PubMed

Sleeper, Meg M; Drobatz, Ken; Lee, D Richard; Lammey, Michael L

2014-04-15

To generate reference ranges for echocardiographic variables in clinically normal adult chimpanzees (Pan troglodytes). Retrospective cohort study. 88 clinically normal adult chimpanzees. Echocardiographic data obtained between 2002 and 2011 from chimpanzees at the Alamogordo Primate Facility were reviewed (263 echocardiograms obtained from 158 individuals). Data from clinically normal individuals (33 females and 55 males) were analyzed. Basic cardiac parameters measured in all individuals included aortic root diameter and left atrial diameter in the short and long axis during diastole. Left ventricular measurements included left ventricular internal diameter in systole and diastole and diastolic septal and posterior wall thickness. The E point to septal separation was also measured. Spectral Doppler measurements included the peak flow velocity of the pulmonary artery and aorta and diastolic transmitral flow. The presence of arrhythmias was also noted. Standard echocardiographic findings for a large group of adult female and male chimpanzees were obtained. Female and male chimpanzees were grouped by age in 10-year blocks, and echocardiographic findings were analyzed statistically by 10-year block. In male chimpanzees, cardiac arrhythmias were noted to increase with age. Cardiovascular disease is an important cause of morbidity and death in captive chimpanzees; however, basic echocardiographic measurements from a large cohort of clinically normal animals have not previously been reported. The number of animals in the present study was insufficient to generate reference ranges; however, data from a large cohort of clinically normal animals are presented. This information will be useful for veterinarians working in clinical and research settings with this species.
Assessment of statistical significance and clinical relevance.

PubMed

Kieser, Meinhard; Friede, Tim; Gondan, Matthias

2013-05-10

In drug development, it is well accepted that a successful study will demonstrate not only a statistically significant result but also a clinically relevant effect size. Whereas standard hypothesis tests are used to demonstrate the former, it is less clear how the latter should be established. In the first part of this paper, we consider the responder analysis approach and study the performance of locally optimal rank tests when the outcome distribution is a mixture of responder and non-responder distributions. We find that these tests are quite sensitive to their planning assumptions and have therefore not really any advantage over standard tests such as the t-test and the Wilcoxon-Mann-Whitney test, which perform overall well and can be recommended for applications. In the second part, we present a new approach to the assessment of clinical relevance based on the so-called relative effect (or probabilistic index) and derive appropriate sample size formulae for the design of studies aiming at demonstrating both a statistically significant and clinically relevant effect. Referring to recent studies in multiple sclerosis, we discuss potential issues in the application of this approach. Copyright © 2012 John Wiley & Sons, Ltd.
22 CFR 705.101 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Cross-reference to employee ethical conduct... INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS EMPLOYEE ETHICAL CONDUCT STANDARDS AND FINANCIAL DISCLOSURE REGULATIONS § 705.101 Cross-reference to employee ethical conduct standards and financial disclosure...

Certification of elements in and use of standard reference material 3280 multivitamin/multielement tablets

USDA-ARS?s Scientific Manuscript database

Standard Reference Material (SRM) 3280 Multivitamin/Multielement Tablets was issued by the National Institute of Standards and Technology (NIST) in 2009 and has certified and reference mass fraction values for 13 vitamins, 26 elements, and 2 carotenoids. Elements were measured using two or more ana...
22 CFR 705.101 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Cross-reference to employee ethical conduct... INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS EMPLOYEE ETHICAL CONDUCT STANDARDS AND FINANCIAL DISCLOSURE REGULATIONS § 705.101 Cross-reference to employee ethical conduct standards and financial disclosure...
22 CFR 705.101 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Cross-reference to employee ethical conduct... INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS EMPLOYEE ETHICAL CONDUCT STANDARDS AND FINANCIAL DISCLOSURE REGULATIONS § 705.101 Cross-reference to employee ethical conduct standards and financial disclosure...
22 CFR 705.101 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Cross-reference to employee ethical conduct... INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS EMPLOYEE ETHICAL CONDUCT STANDARDS AND FINANCIAL DISCLOSURE REGULATIONS § 705.101 Cross-reference to employee ethical conduct standards and financial disclosure...
22 CFR 705.101 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Cross-reference to employee ethical conduct... INVESTMENT CORPORATION ADMINISTRATIVE PROVISIONS EMPLOYEE ETHICAL CONDUCT STANDARDS AND FINANCIAL DISCLOSURE REGULATIONS § 705.101 Cross-reference to employee ethical conduct standards and financial disclosure...
In vitro susceptibility of filamentous fungi to itraconazole, voriconazole and posaconazole by Clinical and Laboratory Standards Institute reference method and E-test.

PubMed

Kondori, N; Svensson, E; Mattsby-Baltzer, I

2011-09-01

The use of anti-fungal agents has increased dramatically in recent years and new drugs have been developed. Several methods are available for determinations of their specific biological activities, i.e. the standard method for minimum inhibitory concentration-determination is described in M-38 [Clinical and Laboratory Standards Institute document M-38 (CLSI M-38)]. However, alternative methods, such as the E-test, are currently available in Mycology laboratories. The susceptibilities of clinical isolates of Aspergillus spp. (n = 29), Fusarium spp. (n = 5), zygomycetes (n = 21) and Schizophyllum (n = 1) were determined for itraconazole, voriconazole and posaconazole, using the CLSI M-38-A broth dilution method and also by the E-test. A good overall agreement (83.7%) between the two methods for all drugs and organisms was observed. Analyses of voriconazole showed a better agreement (93%) between the methods than posaconazole and itraconazole (85% and 74% respectively). Aspergillus spp. were the most susceptible fungi to the anti-fungal agents tested in this study. Posaconazole was the most active drug against filamentous fungi in vitro, followed by itraconazole and voriconazole. The latter (voriconazole) demonstrated no significant in vitro activity against zygomycetes. © 2010 Blackwell Verlag GmbH.
Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and accurate identification of Pseudallescheria/Scedosporium species.

PubMed

Sitterlé, E; Giraud, S; Leto, J; Bouchara, J P; Rougeron, A; Morio, F; Dauphin, B; Angebault, C; Quesne, G; Beretti, J L; Hassouni, N; Nassif, X; Bougnoux, M E

2014-09-01

An increasing number of infections due to Pseudallescheria/Scedosporium species has been reported during the past decades, both in immunocompromised and immunocompetent patients. Additionally, these fungi are now recognized worldwide as common agents of fungal colonization of the airways in cystic fibrosis patients, which represents a risk factor for disseminated infections after lung transplantation. Currently six species are described within the Pseudallescheria/Scedosporium genus, including Scedosporium prolificans and species of the Pseudallescheria/Scedosporium apiospermum complex (i.e. S. apiospermum sensu stricto, Pseudallescheria boydii, Scedosporium aurantiacum, Pseudallescheria minutispora and Scedosporium dehoogii). Precise identification of clinical isolates at the species level is required because these species differ in their antifungal drug susceptibility patterns. Matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF)/mass spectrometry (MS) is a powerful tool to rapidly identify moulds at the species level. We investigated the potential of this technology to discriminate Pseudallescheria/Scedosporium species. Forty-seven reference strains were used to build a reference database library. Profiles from 3-, 5- and 7-day-old cultures of each reference strain were analysed to identify species-specific discriminating profiles. The database was tested for accuracy using a set of 64 clinical or environmental isolates previously identified by multilocus sequencing. All isolates were unequivocally identified at the species level by MALDI-TOF/MS. Our results, obtained using a simple protocol, without prior protein extraction or standardization of the culture, demonstrate that MALDI-TOF/MS is a powerful tool for rapid identification of Pseudallescheria/Scedosporium species that cannot be currently identified by morphological examination in the clinical setting. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.
Psychological Intervention in Primary Care After Earthquakes in Lorca, Spain

PubMed Central

Garriga, Ascensión; Egea, Carmen

2015-01-01

Objective: After the earthquakes that occurred in Lorca, Spain, on May 11, 2011, the regional mental health management employed 2 clinical psychologists for 6 months to provide care to people referred by primary care physicians. The objective was to address the expected increased demand for treatment of mental disorders, notably posttraumatic stress disorder (PTSD) and adjustment disorders. Method: Referred individuals were evaluated and treated according to a clinical protocol designed ad hoc from June 12, 2011, to November 30, 2011. The protocol provided a stepped intervention guided by clinical and psychometric assessment using “normalization” for those with no psychiatric diagnosis, brief group treatment for mild to moderate PTSD or adjustment disorders, individual treatment for more severe PTSD, and referral to the local mental health center for other mental health disorders. Standard adult and child scales to assess posttraumatic, depression, and anxiety symptoms and resilience were used at initial assessment to guide treatment allocation and repeated to assess outcome status. Psychologists also provided a clinical assessment of symptom resolution at the end of the study. Results: Rates of symptom resolution and improvements on all scales (PTSD, depression, anxiety, and resilience) demonstrated clinically and statistically significant improvement in all treatment groups (P = .000). Dropout was low. Medications were prescribed frequently to adults; no child received medication as a result of the earthquakes. No case of mental disorder related to the earthquakes was referred to the local mental health center during the 6 months of psychologist intervention. Conclusion:The structured intervention resulted in a high resolution of cases and low dropout, allowing treatment of a larger number of people with optimal frequency (weekly), devoting more time to the most severe cases and less to those moderately or mildly affected. PMID:26137356
Alternative mass reference standards for direct analysis in real time mass spectrometry.

PubMed

Cody, Robert B; Dane, A John

2016-05-30

Mass spectra were acquired with the Direct Analysis in Real Time (DART®) ion source for an amine-terminated polyether used as positive-ion mass reference standards and for several fluorinated materials commonly used as negative-ion reference standards for mass spectrometry. A commercial time-of-flight mass spectrometer equipped with a DART ion source was used for all measurements. Mass reference standards deposited onto the sealed end of a glass melting point tube were suspended in the DART gas stream for analysis. A polyetheramine (Jeffamine® M-600) produced intense peaks corresponding to protonated molecules. Perfluorotributylamine (PFTBA), and perfluorotripentylamine, gave useful reference spectra for different m/z ranges. DART mass spectra of Ultramark 1621® resembled those previously reported for Fast Atom Bombardment (FAB) and Electrospray Ionization (ESI). Fomblin®Y, a fluorinated ether, was the most useful negative-ion reference standard of the materials tested. The material is commercially available, inexpensive, and provides reference peaks covering the m/z range 85 to >3000. Jeffamine-M600 was found to be a convenient alternative to polyethers such as polyethylene glycol (PEG) for DART positive-ion mass calibration. Fomblin Y was suitable for use as a negative-ion reference standard. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Updating OSHA standards based on national consensus standards. Direct final rule.

PubMed

2007-12-14

In this direct final rule, the Agency is removing several references to consensus standards that have requirements that duplicate, or are comparable to, other OSHA rules; this action includes correcting a paragraph citation in one of these OSHA rules. The Agency also is removing a reference to American Welding Society standard A3.0-1969 ("Terms and Definitions") in its general-industry welding standards. This rulemaking is a continuation of OSHA's ongoing effort to update references to consensus and industry standards used throughout its rules.
Optical-Fiber Power Meter Comparison between NIST and KRISS.

PubMed

Vayshenker, I; Kim, S K; Hong, K; Lee, D-H; Livigni, D J; Li, X; Lehman, J H

2012-01-01

We describe the results of a comparison of reference standards between the National Institute of Standards and Technology (NIST-USA) and Korea Research Institute of Standards and Science (KRISS-R.O. Korea) for optical fiber-based power measurements at wavelengths of 1302 nm and 1546 nm. We compare the laboratories' reference standards by means of a temperature-controlled optical trap detector. Measurement results showed the largest difference of less than 2.5 parts in 10(3), which is within the combined standard (k=1) uncertainty for the two laboratories' reference standards.
Evaluation of Xpert MTB/RIF assay in children with presumed pulmonary tuberculosis in Papua New Guinea.

PubMed

Kasa Tom, Sharon; Welch, Henry; Kilalang, Cornelia; Tefuarani, Nakapi; Vince, John; Lavu, Evelyn; Johnson, Karen; Magaye, Ruth; Duke, Trevor

2018-05-01

The Gene Xpert MTB/ RIF assay (Xpert) is used for rapid, simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin resistance. This study examined the accuracy of Xpert in children with suspected pulmonary tuberculosis (PTB). Children admitted to Port Moresby General Hospital with suspected PTB were prospectively enrolled between September 2014 and March 2015. They were classified into probable, possible and TB-unlikely groups. Sputum or gastric aspirates were tested by Xpert and smear microscopy; mycobacterial culture was undertaken on a subset. Children were diagnosed with TB on the basis of standard criteria which were used as the primary reference standard. Xpert, smear for acid-fast bacilli (AFB) and the Edwards TB score were compared with the primary reference standard. A total of 93 children ≤14 years with suspected PTB were enrolled; 67 (72%) were classified as probable, 21 (22%) possible and 5 (5.4%) TB-unlikely. Eighty were treated for TB based on the primary reference standard. Xpert was positive in 26/93 (28%) MTB cases overall, including 22/67 (33%) with probable TB and 4/21 (19%) with possible TB. Three (13%) samples identified rifampicin resistance. Xpert confirmed more cases of TB than AFB smear (26 vs 13, p = 0.019). The sensitivity of Xpert, AFB smear and an Edwards TB score of ≥7 was 31% (25/80), 16% (13/80) and 90% (72/80), respectively, and the specificity was 92% (12/13), 100% (13/13) and 31% (4/13), respectively, when compared with the primary reference standard. Xpert sensitivity is sub-optimal and cannot be relied upon for diagnosing TB, although a positive result is confirmatory. A detailed history and examination, standardised clinical criteria, radiographs and available tests remain the most appropriate way of diagnosing TB in children in resource-limited countries. Xpert helps confirm PTB better than AFB smear, and identifies rifampicin resistance. Practical guidelines should be used to identify children who will benefit from an Xpert assay.
Report on the Project for Establishment of the Standardized Korean Laboratory Terminology Database, 2015.

PubMed

Jung, Bo Kyeung; Kim, Jeeyong; Cho, Chi Hyun; Kim, Ju Yeon; Nam, Myung Hyun; Shin, Bong Kyung; Rho, Eun Youn; Kim, Sollip; Sung, Heungsup; Kim, Shinyoung; Ki, Chang Seok; Park, Min Jung; Lee, Kap No; Yoon, Soo Young

2017-04-01

The National Health Information Standards Committee was established in 2004 in Korea. The practical subcommittee for laboratory test terminology was placed in charge of standardizing laboratory medicine terminology in Korean. We aimed to establish a standardized Korean laboratory terminology database, Korea-Logical Observation Identifier Names and Codes (K-LOINC) based on former products sponsored by this committee. The primary product was revised based on the opinions of specialists. Next, we mapped the electronic data interchange (EDI) codes that were revised in 2014, to the corresponding K-LOINC. We established a database of synonyms, including the laboratory codes of three reference laboratories and four tertiary hospitals in Korea. Furthermore, we supplemented the clinical microbiology section of K-LOINC using an alternative mapping strategy. We investigated other systems that utilize laboratory codes in order to investigate the compatibility of K-LOINC with statistical standards for a number of tests. A total of 48,990 laboratory codes were adopted (21,539 new and 16,330 revised). All of the LOINC synonyms were translated into Korean, and 39,347 Korean synonyms were added. Moreover, 21,773 synonyms were added from reference laboratories and tertiary hospitals. Alternative strategies were established for mapping within the microbiology domain. When we applied these to a smaller hospital, the mapping rate was successfully increased. Finally, we confirmed K-LOINC compatibility with other statistical standards, including a newly proposed EDI code system. This project successfully established an up-to-date standardized Korean laboratory terminology database, as well as an updated EDI mapping to facilitate the introduction of standard terminology into institutions. © 2017 The Korean Academy of Medical Sciences.
Standardization of automated 25-hydroxyvitamin D assays: How successful is it?

PubMed

Elsenberg, E H A M; Ten Boekel, E; Huijgen, H; Heijboer, A C

2017-12-01

Multiple 25(OH)D assays have recently been aligned to improve comparibility. In this study we investigated the performance of these assays using both native single-donor sera with target values certified by a reference method as well as single donor sera from a heterogeneous patient population. 25(OH)D levels were measured in twenty reference samples (Ref!25OHD; Labquality, Finland) using five automated methods (Lumipulse, Liaison, Cobas, iSYS and Access) and one aligned ID-XLC-MS/MS method (slope: 1,00; intercept: 0,00; R=0,996). Furthermore, 25(OH)D concentrations measured in 50 pregnant women and 52 random patients using the 5 automated assays were compared to the ID-XLC-MS/MS. In addition, Vitamin D binding protein (DBP) was measured. Most automated assays showed significant differences in 25(OH)D levels measured in reference samples. Slopes varied from 1,00 to 1,33, intercepts from -5.48 to -15,81nmol/L and the R from 0,971 to 0,997. This inaccuracy was even more prominent in a heterogeneous patient population. Slopes varied from 0,75 to 1,35, intercepts from -9.02 to 11,51nmol/L and the R from 0,840 to 0,949. For most assays the deviation in 25(OH)D concentration increased with elevating DBP concentrations suggesting that DBP might be one of the factors contributing to the inaccuracy in currently used automated 25(OH)D methods. Despite the use of standardized assays, we observed significant differences in 25(OH)D concentrations in some automated methods using reference material obtained from healthy single donor sera. In sera of a patient population this inaccuracy was even worse which is highly concerning as patient samples are being investigated in clinical laboratories. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
PFGE standard operating procedures for Listeria monocytogenes: harmonizing the typing of food and clinical strains in Europe.

PubMed

Michelon, Damien; Félix, Benjamin; Vingadassalon, Noemie; Mariet, Jean-François; Larsson, Jonas T; Møller-Nielsen, Eva; Roussel, Sophie

2015-03-01

Listeria monocytogenes is a foodborne pathogen responsible for a severe disease known as listeriosis. The European Centre for Disease Prevention and Control (ECDC) coordinates a network of national public health laboratories (NPHLs) in charge of typing clinical strains. In food, it is the European Union Reference Laboratory for L. monocytogenes (EURL Lm), which manages a network of National Reference Laboratories (NRLs). A pulsed-field gel electrophoresis (PFGE) standard operating procedure (EURL SOP) has been used routinely at the EURL Lm since 2007. The EURL Lm has recommended that NRLs use the EURL SOP, whereas the Statens Serum Institut (SSI), under contract for ECDC, requested that NPHLs use Halpins' SOP (HSOP) published in 2010 for the PulseNet USA network. An update of Halpins' SOP (uHSOP) was published in 2013. To facilitate the exchange of profiles among human and food European reference laboratories, it is crucial to ensure that the PFGE profiles obtained with these different SOPs are comparable. The aim here was to compare the EURL SOP with HSOP and uHSOP. The panel comprised 114 well-characterized SSI/EURL strains. All were characterized at the EURL using both the EURL SOP and uHSOP. Seventy of the 114 strains were also characterized at the SSI using HSOP. The EURL SOP and uHSOP produced indistinguishable combined (ApaI/AscI) profiles for the 114 strains tested. The EURL SOP and HSOP produced indistinguishable combined profiles for 69 of the 70 strains tested. One strain displayed for the AscI profile an additional low-intensity band at 184 kbp with HSOP. For this strain, SSI and EUR Lm had already observed the same profile from NPHLs and NRLs. However, this deviation is minor as it accounted for about 1% of all the 114 combined profiles. This study should facilitate the exchange of reproducible PFGE profiles among human and food reference laboratories.
Medico-legal issues in radiological consultation.

PubMed

Mozumdar, Biswita C; Jones, Gary

2003-01-01

Providers increasingly use radiological services for diagnosis and treatment. Both the referring physician and the radiological consultant can contribute to efficient and effective consultation, and direct interaction may facilitate the process further. Furthermore, inadequate communication can influence poor patient outcome. We examine the roles and responsibilities of referring physicians and consultant radiologists, and present a malpractice case, Townsend v. Turk 218 Cal. App. 3d 278 (1990), to identify medico-legal issues in radiological consultation. Important issues are implied by the Townsend case. First, it is the clinician's responsibility to include clinical information that is appropriate and adequate. Further, the radiologist is a valuable resource in the selection of the optimal procedure, provided that he or she is aware of the patient's history. The second issue discussed by the court represents a possibly more pervasive problem. The interaction between a consulting radiologist--indeed any specialist--and a treating physician is subject to difficulties caused by different conceptions of professional boundaries. The position taken by the court in the Townsend case is consistent with the traditional view that a consulting radiologist has an attenuated duty to the patient. It also would seem to receive at least some support from the language contained in the current revision of the ACR Standard for Communication: Diagnostic Radiology, effective Jan. 1, 2002: ...The referring physician or healthcare provider also shares in the responsibility of obtaining results of imaging studies they have ordered. Despite the result of the Townsend case and the current formulation of the ACR Standards, however, radiologists face risks of litigation. Indeed, the emerging trend in radiological consultation is the direct communication of results to the patient. It is clear that improved communication between radiologists and referring physicians is both desirable and imperative. Clinico-radiological encounters yield additional clinical information and guide the decision-making process. In the Townsend case, direct interaction would have resolved ambiguity.
Comparative analysis of four commercial on-farm culture methods to identify bacteria associated with clinical mastitis in dairy cattle.

PubMed

Ferreira, Jair C; Gomes, Marilia S; Bonsaglia, Erika C R; Canisso, Igor F; Garrett, Edgar F; Stewart, Jamie L; Zhou, Ziyao; Lima, Fabio S

2018-01-01

Several multiple-media culture systems have become commercially available for on-farm identification of mastitis-associated pathogens. However, the accuracy of these systems has not been thoroughly and independently validated against microbiological evaluations performed by referral laboratories. Therefore, the purpose of the present study was to evaluate the performance of commercially available culture plates (Accumast, Minnesota Easy System, SSGN and SSGNC Quad plates) to identify pathogens associated with clinical mastitis in dairy cows. Milk samples from the affected quarter with clinical mastitis were aerobically cultured with the on-farm culture systems and by two additional reference laboratories. Agreeing results from both standard laboratories were denoted as the reference standard (RS). Accuracy (Ac), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and Cohen's kappa coefficient (k) of on-farm plates were determined based on the RS culture of 211 milk samples. All four plate-systems correctly identified ≥ 84.9% of milk samples with no bacterial growth. Accumast had greater values for all overall predictive factors (Ac, Se, Sp, PPV and NPV) and a substantial agreement (k = 0.79) with RS. The inter-rater agreements of Minnesota, SSGN, and SSGNC with RS were moderate (0.45 ≤ k ≤ 0.55). The effectiveness to categorize bacterial colonies at the genus and species was numerically different amongst the commercial plates. Our findings suggest that Accumast was the most accurate on-farm culture system for identification of mastitis-associated pathogens of the four systems included in the analysis.
Comparative analysis of four commercial on-farm culture methods to identify bacteria associated with clinical mastitis in dairy cattle

PubMed Central

Ferreira, Jair C.; Gomes, Marilia S.; Bonsaglia, Erika C. R.; Canisso, Igor F.; Garrett, Edgar F.; Stewart, Jamie L.; Zhou, Ziyao

2018-01-01

Several multiple-media culture systems have become commercially available for on-farm identification of mastitis-associated pathogens. However, the accuracy of these systems has not been thoroughly and independently validated against microbiological evaluations performed by referral laboratories. Therefore, the purpose of the present study was to evaluate the performance of commercially available culture plates (Accumast, Minnesota Easy System, SSGN and SSGNC Quad plates) to identify pathogens associated with clinical mastitis in dairy cows. Milk samples from the affected quarter with clinical mastitis were aerobically cultured with the on-farm culture systems and by two additional reference laboratories. Agreeing results from both standard laboratories were denoted as the reference standard (RS). Accuracy (Ac), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively) and Cohen’s kappa coefficient (k) of on-farm plates were determined based on the RS culture of 211 milk samples. All four plate-systems correctly identified ≥ 84.9% of milk samples with no bacterial growth. Accumast had greater values for all overall predictive factors (Ac, Se, Sp, PPV and NPV) and a substantial agreement (k = 0.79) with RS. The inter-rater agreements of Minnesota, SSGN, and SSGNC with RS were moderate (0.45 ≤ k ≤ 0.55). The effectiveness to categorize bacterial colonies at the genus and species was numerically different amongst the commercial plates. Our findings suggest that Accumast was the most accurate on-farm culture system for identification of mastitis-associated pathogens of the four systems included in the analysis. PMID:29543852
Integrating Genomic Resources with Electronic Health Records using the HL7 Infobutton Standard

PubMed Central

Overby, Casey Lynnette; Del Fiol, Guilherme; Rubinstein, Wendy S.; Maglott, Donna R.; Nelson, Tristan H.; Milosavljevic, Aleksandar; Martin, Christa L.; Goehringer, Scott R.; Freimuth, Robert R.; Williams, Marc S.

2016-01-01

Summary Background The Clinical Genome Resource (ClinGen) Electronic Health Record (EHR) Workgroup aims to integrate ClinGen resources with EHRs. A promising option to enable this integration is through the Health Level Seven (HL7) Infobutton Standard. EHR systems that are certified according to the US Meaningful Use program provide HL7-compliant infobutton capabilities, which can be leveraged to support clinical decision-making in genomics. Objectives To integrate genomic knowledge resources using the HL7 infobutton standard. Two tactics to achieve this objective were: (1) creating an HL7-compliant search interface for ClinGen, and (2) proposing guidance for genomic resources on achieving HL7 Infobutton standard accessibility and compliance. Methods We built a search interface utilizing OpenInfobutton, an open source reference implementation of the HL7 Infobutton standard. ClinGen resources were assessed for readiness towards HL7 compliance. Finally, based upon our experiences we provide recommendations for publishers seeking to achieve HL7 compliance. Results Eight genomic resources and two sub-resources were integrated with the ClinGen search engine via OpenInfobutton and the HL7 infobutton standard. Resources we assessed have varying levels of readiness towards HL7-compliance. Furthermore, we found that adoption of standard terminologies used by EHR systems is the main gap to achieve compliance. Conclusion Genomic resources can be integrated with EHR systems via the HL7 Infobutton standard using OpenInfobutton. Full compliance of genomic resources with the Infobutton standard would further enhance interoperability with EHR systems. PMID:27579472
Promoting clinical and laboratory interaction by harmonization.

PubMed

Plebani, Mario; Panteghini, Mauro

2014-05-15

The lack of interchangeable results in current practice among clinical laboratories has underpinned greater attention to standardization and harmonization projects. Although the focus was mainly on the standardization and harmonization of measurement procedures and their results, the scope of harmonization goes beyond method and analytical results: it includes all other aspects of laboratory testing, including terminology and units, report formats, reference limits and decision thresholds, as well as test profiles and criteria for the interpretation of results. In particular, as evidence collected in last decades demonstrates that pre-pre- and post-post-analytical steps are more vulnerable to errors, harmonization initiatives should be performed to improve procedures and processes at the laboratory-clinical interface. Managing upstream demand, down-stream interpretation of laboratory results, and subsequent appropriate action through close relationships between laboratorians and clinicians remains a crucial issue of the laboratory testing process. Therefore, initiatives to improve test demand management from one hand and to harmonize procedures to improve physicians' acknowledgment of laboratory data and their interpretation from the other hand are needed in order to assure quality and safety in the total testing process. © 2013.

Designing Reliable Cohorts of Cardiac Patients across MIMIC and eICU

PubMed Central

Chronaki, Catherine; Shahin, Abdullah; Mark, Roger

2016-01-01

The design of the patient cohort is an essential and fundamental part of any clinical patient study. Knowledge of the Electronic Health Records, underlying Database Management System, and the relevant clinical workflows are central to an effective cohort design. However, with technical, semantic, and organizational interoperability limitations, the database queries associated with a patient cohort may need to be reconfigured in every participating site. i2b2 and SHRINE advance the notion of patient cohorts as first class objects to be shared, aggregated, and recruited for research purposes across clinical sites. This paper reports on initial efforts to assess the integration of Medical Information Mart for Intensive Care (MIMIC) and Philips eICU, two large-scale anonymized intensive care unit (ICU) databases, using standard terminologies, i.e. LOINC, ICD9-CM and SNOMED-CT. Focus of this work is lab and microbiology observations and key demographics for patients with a primary cardiovascular ICD9-CM diagnosis. Results and discussion reflecting on reference core terminology standards, offer insights on efforts to combine detailed intensive care data from multiple ICUs worldwide. PMID:27774488
Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia.

PubMed

Pfau, Doreen B; Krumova, Elena K; Treede, Rolf-Detlef; Baron, Ralf; Toelle, Thomas; Birklein, Frank; Eich, Wolfgang; Geber, Christian; Gerhardt, Andreas; Weiss, Thomas; Magerl, Walter; Maier, Christoph

2014-05-01

Age- and gender-matched reference values are essential for the clinical use of quantitative sensory testing (QST). To extend the standard test sites for QST-according to the German Research Network on Neuropathic Pain-to the trunk, we collected QST profiles on the back in 162 healthy subjects. Sensory profiles for standard test sites were within normal interlaboratory differences. QST revealed lower sensitivity on the upper back than the hand, and higher sensitivity on the lower back than the foot, but no systematic differences between these trunk sites. Age effects were significant for most parameters. Females exhibited lower pressure pain thresholds (PPT) than males, which was the only significant gender difference. Values outside the 95% confidence interval of healthy subjects (considered abnormal) required temperature changes of >3.3-8.2 °C for thermal detection. For cold pain thresholds, confidence intervals extended mostly beyond safety cutoffs, hence only relative reference data (left-right differences, hand-trunk differences) were sufficiently sensitive. For mechanical detection and pain thresholds, left-right differences were 1.5-2.3 times more sensitive than absolute reference data. The most sensitive parameter was PPT, where already side-to-side differences >35% were abnormal. Compared to trunk reference data, patients with postherpetic neuralgia exhibited thermal and tactile deficits and dynamic mechanical allodynia, mostly without reduced mechanical pain thresholds. This pattern deviates from other types of neuropathic pain. QST reference data for the trunk will also be useful for patients with postthoracotomy pain or chronic back pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
77 FR 181 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-55; Introduction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

... System. VI Updated Financial 2010-005 Chambers. Accounting Standards Board Accounting References. VII... Financial Accounting Standards Board Accounting References (FAR Case 2010-005) This final rule amends the... authoritative accounting standards owing to the Financial Accounting Standards Board's Accounting Standards...
10 CFR 50.150 - Aircraft impact assessment.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13, 2009; (B) Renewal of standard design certifications in effect on July 13, 2009 which have not..., standard design approval, or manufactured reactor; or (B) Reference a standard design certification issued... certification or standard design approval; or (B) Reference a standard design certification issued before July...
10 CFR 50.150 - Aircraft impact assessment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13, 2009; (B) Renewal of standard design certifications in effect on July 13, 2009 which have not..., standard design approval, or manufactured reactor; or (B) Reference a standard design certification issued... certification or standard design approval; or (B) Reference a standard design certification issued before July...
10 CFR 50.150 - Aircraft impact assessment.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13, 2009; (B) Renewal of standard design certifications in effect on July 13, 2009 which have not..., standard design approval, or manufactured reactor; or (B) Reference a standard design certification issued... certification or standard design approval; or (B) Reference a standard design certification issued before July...
10 CFR 50.150 - Aircraft impact assessment.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13, 2009; (B) Renewal of standard design certifications in effect on July 13, 2009 which have not..., standard design approval, or manufactured reactor; or (B) Reference a standard design certification issued... certification or standard design approval; or (B) Reference a standard design certification issued before July...
Rapid Antimicrobial Susceptibility Testing Using Forward Laser Light Scatter Technology.

PubMed

Hayden, Randall T; Clinton, Lani K; Hewitt, Carolyn; Koyamatsu, Terri; Sun, Yilun; Jamison, Ginger; Perkins, Rosalie; Tang, Li; Pounds, Stanley; Bankowski, Matthew J

2016-11-01

The delayed reporting of antimicrobial susceptibility testing remains a limiting factor in clinical decision-making in the treatment of bacterial infection. This study evaluates the use of forward laser light scatter (FLLS) to measure bacterial growth for the early determination of antimicrobial susceptibility. Three isolates each (two clinical isolates and one reference strain) of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were tested in triplicate using two commercial antimicrobial testing systems, the Vitek2 and the MicroScan MIC panel, to challenge the BacterioScan FLLS. The BacterioScan FLLS showed a high degree of categorical concordance with the commercial methods. Pairwise comparison with each commercial system serving as a reference standard showed 88.9% agreement with MicroScan (two minor errors) and 72.2% agreement with Vitek (five minor errors). FLLS using the BacterioScan system shows promise as a novel method for the rapid and accurate determination of antimicrobial susceptibility. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Optical Fiber Power Meter Comparison Between NIST and NIM.

PubMed

Vayshenker, I; Livigni, D J; Li, X; Lehman, J H; Li, J; Xiong, L M; Zhang, Z X

2010-01-01

We describe the results of a comparison of reference standards between the National Institute of Standards and Technology (NIST-USA) and National Institute of Metrology (NIM-China). We report optical fiber-based power measurements at nominal wavelengths of 1310 nm and 1550 nm. We compare the laboratories' reference standards by means of a commercial optical power meter. Measurement results showed the largest difference of less than 2.6 parts in 10(3), which is within the combined standard (k = 1) uncertainty for the laboratories' reference standards.
Baseline Morbidity in 2,990 Adult African Volunteers Recruited to Characterize Laboratory Reference Intervals for Future HIV Vaccine Clinical Trials

PubMed Central

Stevens, Wendy; Kamali, Anatoli; Karita, Etienne; Anzala, Omu; Sanders, Eduard J.; Jaoko, Walter; Kaleebu, Pontiano; Mulenga, Joseph; Dally, Len; Fast, Pat; Gilmour, Jill; Farah, Bashir; Birungi, Josephine; Hughes, Peter; Manigart, Olivier; Stevens, Gwynn; Yates, Sarah; Thomson, Helen; von Lieven, Andrea; Krebs, Marietta; Price, Matt A.; Stoll-Johnson, Lisa; Ketter, Nzeera

2008-01-01

Background An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. Methods Asymptomatic persons, aged 18–60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). Results and Conclusions Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons. PMID:18446196
Towards a framework for developing semantic relatedness reference standards.

PubMed

Pakhomov, Serguei V S; Pedersen, Ted; McInnes, Bridget; Melton, Genevieve B; Ruggieri, Alexander; Chute, Christopher G

2011-04-01

Our objective is to develop a framework for creating reference standards for functional testing of computerized measures of semantic relatedness. Currently, research on computerized approaches to semantic relatedness between biomedical concepts relies on reference standards created for specific purposes using a variety of methods for their analysis. In most cases, these reference standards are not publicly available and the published information provided in manuscripts that evaluate computerized semantic relatedness measurement approaches is not sufficient to reproduce the results. Our proposed framework is based on the experiences of medical informatics and computational linguistics communities and addresses practical and theoretical issues with creating reference standards for semantic relatedness. We demonstrate the use of the framework on a pilot set of 101 medical term pairs rated for semantic relatedness by 13 medical coding experts. While the reliability of this particular reference standard is in the "moderate" range; we show that using clustering and factor analyses offers a data-driven approach to finding systematic differences among raters and identifying groups of potential outliers. We test two ontology-based measures of relatedness and provide both the reference standard containing individual ratings and the R program used to analyze the ratings as open-source. Currently, these resources are intended to be used to reproduce and compare results of studies involving computerized measures of semantic relatedness. Our framework may be extended to the development of reference standards in other research areas in medical informatics including automatic classification, information retrieval from medical records and vocabulary/ontology development. Copyright © 2010 Elsevier Inc. All rights reserved.
Identification of clinical isolates of Aspergillus, including cryptic species, by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).

PubMed

Vidal-Acuña, M Reyes; Ruiz-Pérez de Pipaón, Maite; Torres-Sánchez, María José; Aznar, Javier

2017-12-08

An expanded library of matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been constructed using the spectra generated from 42 clinical isolates and 11 reference strains, including 23 different species from 8 sections (16 cryptic plus 7 noncryptic species). Out of a total of 379 strains of Aspergillus isolated from clinical samples, 179 strains were selected to be identified by sequencing of beta-tubulin or calmodulin genes. Protein spectra of 53 strains, cultured in liquid medium, were used to construct an in-house reference database in the MALDI-TOF MS. One hundred ninety strains (179 clinical isolates previously identified by sequencing and the 11 reference strains), cultured on solid medium, were blindy analyzed by the MALDI-TOF MS technology to validate the generated in-house reference database. A 100% correlation was obtained with both identification methods, gene sequencing and MALDI-TOF MS, and no discordant identification was obtained. The HUVR database provided species level (score of ≥2.0) identification in 165 isolates (86.84%) and for the remaining 25 (13.16%) a genus level identification (score between 1.7 and 2.0) was obtained. The routine MALDI-TOF MS analysis with the new database, was then challenged with 200 Aspergillus clinical isolates grown on solid medium in a prospective evaluation. A species identification was obtained in 191 strains (95.5%), and only nine strains (4.5%) could not be identified at the species level. Among the 200 strains, A. tubingensis was the only cryptic species identified. We demonstrated the feasibility and usefulness of the new HUVR database in MALDI-TOF MS by the use of a standardized procedure for the identification of Aspergillus clinical isolates, including cryptic species, grown either on solid or liquid media. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Establishing pan-European clinical trials: regulatory compliance and other practical considerations.

PubMed

Grienenberger, Aurelie

2004-01-01

There are currently many concerns in the pharmaceutical and scientific community working in or around clinical research on the EU Directive 2001/20/EC or Clinical Trials Directive. The Directive introduces regulatory requirements for all phases of study in human subjects, drawing no distinction between commercially funded drug trials and non-commercial/academic research. The Directive makes Good Clinical Practice (GCP) a legal requirement in Europe and all clinical research will be subjected to the same rigorous standards including GCP and Good Manufacturing Practice (GMP) application even at the early clinical phases as well as exhaustive pharmacovigilance and protection of trial subjects. Some of these requirements may be seen as additional burden and a brake to clinical research in Europe. However, the application of the directive should provide a single and highly regulated market of 25 European countries for investigational medicinal products. This article reviews the main aspects and areas of concern of the Directive and provide US sponsor with useful references.
Change in self-reported emotional distress and parenting among parents referred to inpatient child psychiatric family treatment

PubMed Central

Rimehaug, Tormod; Berg-Nielsen, Turid Suzanne; Wallander, Jan

2012-01-01

Rimehaug T, Berg-Nielsen TS, Wallander J. Change in self-reported emotional distress and parenting among parents referred to inpatient child psychiatric family treatment. Nord J Psychiatry 2011;64:1–8. Aims: Our aim was to examine changes in distress symptoms and parenting dimensions among parents in child psychiatry services (clinic parents) (n= 102). Parents were followed from referral and admission to 3-month and 12-month follow-ups of “treatment-as-usual” at inpatient family clinics. These measurements were compared with a sample of community parent (n = 439) standards. Methods: Standardized questionnaires measuring the child's problems, parental anxiety and depression symptoms (distress), and warmth protectiveness and authoritarianism (parenting dimensions), were distributed to parents four times (T0–T1–T2–T3). The family clinics received families whose children had long-term problems and unsatisfactory previous treatment outcomes. Results: Clinic mothers, but not fathers, showed an improvement in distress symptoms at the 3-month (T2) and 12-month (T3) follow-ups relative to at admission (T1). Nevertheless, clinic mothers displayed distress symptoms at all measurement points compared with community parents. Parents of children with learning/developmental problems and attention disorders showed significantly higher warmth scores at the 3-month and 12-month follow-up compared with at admission, although the levels remained lower than those of community parents. In contrast, parents of children with emotional problems showed the same level of warmth as community parents and lower levels of protectiveness, but no change in these parenting dimensions T1–T2. Implications: Parental emotional distress symptoms and parenting characteristics should be addressed systematically in child psychiatry to inform evaluations of the context of the child's problems and the family's treatment needs. Systematic and effective treatment components related to parenting should be implemented. PMID:22087555
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.
29 CFR 2703.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Cross-reference to employee ethical conduct standards and...-reference to employee ethical conduct standards and financial disclosure regulations. Members and employees... of Ethical Conduct at 5 CFR part 2635; the Commission's regulations at 5 CFR part 8401, which...
45 CFR 706.1 - Cross-references to employee ethical conduct standards, financial disclosure and financial...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Cross-references to employee ethical conduct... EMPLOYEE RESPONSIBILITIES AND CONDUCT § 706.1 Cross-references to employee ethical conduct standards... States Commission on Civil Rights are subject to the executive branch standards of ethical conduct...
45 CFR 1105.1 - Cross-reference to employee ethical conduct standards and financial disclosure and financial...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Cross-reference to employee ethical conduct... STANDARDS OF CONDUCT FOR EMPLOYEES § 1105.1 Cross-reference to employee ethical conduct standards and... ethical conduct at 5 CFR part 2635; the executive branch employees responsibilities and conduct...
49 CFR 99.735-1 - Cross-reference to ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Cross-reference to ethical conduct standards and... Transportation EMPLOYEE RESPONSIBILITIES AND CONDUCT General § 99.735-1 Cross-reference to ethical conduct... the executive branch-wide Standards of Ethical Conduct at 5 CFR part 2635, the Department of...
39 CFR 3000.735-101 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 39 Postal Service 1 2011-07-01 2011-07-01 false Cross-reference to employee ethical conduct... employee ethical conduct standards and financial disclosure regulations. Employees of the Postal Regulatory Commission (Commission) are subject and should refer to the executive branch-wide Standards of Ethical...

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