[The relationship between Ridit analysis and rank sum test for one-way ordinal contingency table in medical research].

PubMed

Wang, Ling; Xia, Jie-lai; Yu, Li-li; Li, Chan-juan; Wang, Su-zhen

2008-06-01

To explore several numerical methods of ordinal variable in one-way ordinal contingency table and their interrelationship, and to compare corresponding statistical analysis methods such as Ridit analysis and rank sum test. Formula deduction was based on five simplified grading approaches including rank_r(i), ridit_r(i), ridit_r(ci), ridit_r(mi), and table scores. Practical data set was verified by SAS8.2 in clinical practice (to test the effect of Shiwei solution in treatment for chronic tracheitis). Because of the linear relationship of rank_r(i) = N ridit_r(i) + 1/2 = N ridit_r(ci) = (N + 1) ridit_r(mi), the exact chi2 values in Ridit analysis based on ridit_r(i), ridit_r(ci), and ridit_r(mi), were completely the same, and they were equivalent to the Kruskal-Wallis H test. Traditional Ridit analysis was based on ridit_r(i), and its corresponding chi2 value calculated with an approximate variance (1/12) was conservative. The exact chi2 test of Ridit analysis should be used when comparing multiple groups in the clinical researches because of its special merits such as distribution of mean ridit value on (0,1) and clear graph expression. The exact chi2 test of Ridit analysis can be output directly by proc freq of SAS8.2 with ridit and modridit option (SCORES =). The exact chi2 test of Ridit analysis is equivalent to the Kruskal-Wallis H test, and should be used when comparing multiple groups in the clinical researches.

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

PubMed

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

Comparison of design strategies for a three-arm clinical trial with time-to-event endpoint: Power, time-to-analysis, and operational aspects.

PubMed

Asikanius, Elina; Rufibach, Kaspar; Bahlo, Jasmin; Bieska, Gabriele; Burger, Hans Ulrich

2016-11-01

To optimize resources, randomized clinical trials with multiple arms can be an attractive option to simultaneously test various treatment regimens in pharmaceutical drug development. The motivation for this work was the successful conduct and positive final outcome of a three-arm randomized clinical trial primarily assessing whether obinutuzumab plus chlorambucil in patients with chronic lympocytic lymphoma and coexisting conditions is superior to chlorambucil alone based on a time-to-event endpoint. The inference strategy of this trial was based on a closed testing procedure. We compare this strategy to three potential alternatives to run a three-arm clinical trial with a time-to-event endpoint. The primary goal is to quantify the differences between these strategies in terms of the time it takes until the first analysis and thus potential approval of a new drug, number of required events, and power. Operational aspects of implementing the various strategies are discussed. In conclusion, using a closed testing procedure results in the shortest time to the first analysis with a minimal loss in power. Therefore, closed testing procedures should be part of the statistician's standard clinical trials toolbox when planning multiarm clinical trials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparing the characteristics of users of an online service for STI self-sampling with clinic service users: a cross-sectional analysis.

PubMed

Barnard, Sharmani; Free, Caroline; Bakolis, Ioannis; Turner, Katy M E; Looker, Katharine J; Baraitser, Paula

2018-02-07

Online services for self-sampling at home could improve access to STI testing; however, little is known about those using this new modality of care. This study describes the characteristics of users of online services and compares them with users of clinic services. We conducted a cross-sectional analysis of routinely collected data on STI testing activity from online and clinic sexual health services in Lambeth and Southwark between 1January 2016 and 31March 2016. Activity was included for chlamydia, gonorrhoea, HIV and syphilis testing for residents of the boroughs aged 16 years and older. Logistic regression models were used to explore potential associations between type of service use with age group, gender, ethnic group, sexual orientation, positivity and Index of Multiple Deprivation (IMD) quintiles. We used the same methods to explore potential associations between return of complete samples for testing with age group, gender, ethnic group, sexual orientation and IMD quintiles among online users. 6456 STI tests were carried out by residents in the boroughs. Of these, 3582 (55.5%) were performed using clinic services and 2874 (44.5%) using the online service. In multivariate analysis, online users were more likely than clinic users to be aged between 20 and 30 years, female, white British, homosexual or bisexual, test negative for chlamydia or gonorrhoea and live in less deprived areas. Of the individuals that ordered a kit from the online service, 72.5% returned sufficient samples. In multivariate analysis, returners were more likely than non-returners to be aged >20 years and white British. Nearly half (44.5%) of all basic STI testing was done online, although the characteristics of users of clinic and online services differed and positivity rates for those using the online service for testing were lower. Clinics remain an important point of access for some groups. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cost analysis of a novel HIV testing strategy in community pharmacies and retail clinics.

PubMed

Lecher, Shirley Lee; Shrestha, Ram K; Botts, Linda W; Alvarez, Jorge; Moore, James H; Thomas, Vasavi; Weidle, Paul J

2015-01-01

To document the cost of implementing point-of-care (POC) human immunodeficiency virus (HIV) rapid testing in busy community pharmacies and retail clinics. Providing HIV testing services in community pharmacies and retail clinics is an innovative way to expand HIV testing. The cost of implementing POC HIV rapid testing in a busy retail environment needs to be documented to provide program and policy leaders with adequate information for planning and budgeting. Cost analysis from a pilot project that provided confidential POC HIV rapid testing services in community pharmacies and retail clinics. The pharmacy sites were operated under several different ownership structures (for-profit, nonprofit, sole proprietorship, corporation, public, and private) in urban and rural areas. We included data from the initial six sites that participated in the project. We collected the time spent by pharmacy and retail clinic staff for pretest and posttest counseling in an activity log for time-in-motion for each interaction. Pharmacists and retail clinic staff. HIV rapid testing. The total cost was calculated to include costs of test kits, control kits, shipping, test supplies, training, reporting, program administration, and advertising. The six sites trained 22 staff to implement HIV testing. A total of 939 HIV rapid tests were conducted over a median time of 12 months, of which 17 were reactive. Median pretest counseling time was 2 minutes. Median posttest counseling time was 2 minutes for clients with a nonreactive test and 10 minutes for clients with a reactive test. The average cost per person tested was an estimated $47.21. When we considered only recurrent costs, the average cost per person tested was $32.17. Providing POC HIV rapid testing services required a modest amount of staff time and costs that are comparable to other services offered in these settings. HIV testing in pharmacies and retail clinics can provide an additional alternative venue for increasing the availability and accessibility of HIV testing services in the United States.

[Diagnosis and treatment options in vertigo syndromes].

PubMed

Strupp, M; Dieterich, M; Zwergal, A; Brandt, T

2015-10-01

The key to diagnosing vertigo and balance disorders is systematic analysis of case history with clinical examination of the vestibular, oculomotor, and cerebral systems in particular. Important criteria for differentiating between the various vertigo syndromes are 1) the time course of symptoms, 2) the type of symptoms, 3) modulating factors, and 4) associated symptoms. For clinical examination of the vestibular system, six important tests are available: assessment of spontaneous nystagmus, head impulse test, dynamic visual acuity, subjective visual verticality, positioning manoeuvre, and the Romberg test/gait analysis with eyes open and closed. On the basis of five clinical signs (vertical divergence, central fixation nystagmus, gaze-evoked nystagmus, saccades, normal head impulse test), the clinical examination is able to differentiate between acute central and peripheral vestibular syndromes with a sensitivity and specificity of over 90%. The most relevant laboratory examinations are caloric irrigation and the video head-impulse test for canal function and the vestibular evoked myogenic potentials for otolith function. Finally, treatment is based upon four therapeutic principles: physiotherapy, pharmacotherapy, psychotherapy, and in rare cases, surgery.

Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.

PubMed

Canu, Letizia; Rapizzi, Elena; Zampetti, Benedetta; Fucci, Rossella; Nesi, Gabriella; Richter, Susan; Qin, Nan; Giachè, Valentino; Bergamini, Carlo; Parenti, Gabriele; Valeri, Andrea; Ercolino, Tonino; Eisenhofer, Graeme; Mannelli, Massimo

2014-07-01

About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.

Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

NASA Astrophysics Data System (ADS)

Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

2016-12-01

A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

Clinical evaluation of a novel population-based regression analysis for detecting glaucomatous visual field progression.

PubMed

Kovalska, M P; Bürki, E; Schoetzau, A; Orguel, S F; Orguel, S; Grieshaber, M C

2011-04-01

The distinction of real progression from test variability in visual field (VF) series may be based on clinical judgment, on trend analysis based on follow-up of test parameters over time, or on identification of a significant change related to the mean of baseline exams (event analysis). The aim of this study was to compare a new population-based method (Octopus field analysis, OFA) with classic regression analyses and clinical judgment for detecting glaucomatous VF changes. 240 VF series of 240 patients with at least 9 consecutive examinations available were included into this study. They were independently classified by two experienced investigators. The results of such a classification served as a reference for comparison for the following statistical tests: (a) t-test global, (b) r-test global, (c) regression analysis of 10 VF clusters and (d) point-wise linear regression analysis. 32.5 % of the VF series were classified as progressive by the investigators. The sensitivity and specificity were 89.7 % and 92.0 % for r-test, and 73.1 % and 93.8 % for the t-test, respectively. In the point-wise linear regression analysis, the specificity was comparable (89.5 % versus 92 %), but the sensitivity was clearly lower than in the r-test (22.4 % versus 89.7 %) at a significance level of p = 0.01. A regression analysis for the 10 VF clusters showed a markedly higher sensitivity for the r-test (37.7 %) than the t-test (14.1 %) at a similar specificity (88.3 % versus 93.8 %) for a significant trend (p = 0.005). In regard to the cluster distribution, the paracentral clusters and the superior nasal hemifield progressed most frequently. The population-based regression analysis seems to be superior to the trend analysis in detecting VF progression in glaucoma, and may eliminate the drawbacks of the event analysis. Further, it may assist the clinician in the evaluation of VF series and may allow better visualization of the correlation between function and structure owing to VF clusters. © Georg Thieme Verlag KG Stuttgart · New York.

[Static posturography versus clinical tests in elderly people with vestibular pathology].

PubMed

Ortuño-Cortés, Miguel A; Martín-Sanz, Eduardo; Barona-de Guzmán, Rafael

2008-01-01

Balance can be quantified by clinical tests and through instrumental studies. The objective of this paper is to determine the correlation between static posturography and 4 clinical tests of balance in elderly people with vestibular disorders and to identify its capability to discriminate the groups studied. 60 patients with vestibular disorders and 60 healthy subjects performed 4 clinical tests (one leg standing with opened eyes, Timed Up and Go, Tinetti and Berg tests) and a static posturography analysis (NedSVE/IBV system) under 4 conditions: Romberg Test, Eyes Open (REO), Romberg Test, Eyes Closed (REC), Romberg Test on Foam with Eyes Open (RFEO), and Romberg Test on Foam with Eyes Closed (RFEC). RFEO correlated best with the clinical tests and RFEC was the worst. RFEO distinguished between healthy individuals and decompensated patients. RFEO gave the best information about postural balance in the elderly. RFEC was not useful. Static posturography can be useful to distinguish vestibular compensation status.

Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.

PubMed

Simon, Richard

2008-06-01

Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for developing the diagnostic test, including their threshold of positivity, from the data used for evaluating treatment effectiveness in subsets determined by the test. Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospective definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions.

Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians.

PubMed

Qaseem, Amir; McLean, Robert M; Starkey, Melissa; Forciea, Mary Ann

2017-01-03

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the diagnosis of gout. This guideline is based on a systematic review of published studies on gout diagnosis, identified using several databases, from database inception to February 2016. Evaluated outcomes included the accuracy of the test results; intermediate outcomes (results of laboratory and radiographic tests, such as serum urate and synovial fluid crystal analysis and radiographic or ultrasonography changes); clinical decision making (additional testing and pharmacologic or dietary management); short-term clinical (patient-centered) outcomes, such as pain and joint swelling and tenderness; and adverse effects of the tests. This guideline grades the evidence and recommendations by using the ACP grading system, which is based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. The target audience for this guideline includes all clinicians, and the target patient population includes adults with joint inflammation suspected to be gout. ACP recommends that clinicians use synovial fluid analysis when clinical judgment indicates that diagnostic testing is necessary in patients with possible acute gout. (Grade: weak recommendation, low-quality evidence).

Prevalence of upper airway obstruction in patients with apparently asymptomatic euthyroid multi nodular goitre

PubMed Central

Menon, Sunil K.; Jagtap, Varsha S.; Sarathi, Vijaya; Lila, Anurag R.; Bandgar, Tushar R.; Menon, Padmavathy S; Shah, Nalini S.

2011-01-01

Aims: To study the prevalence of upper airway obstruction (UAO) in “apparently asymptomatic” patients with euthyroid multinodular goitre (MNG) and find correlation between clinical features, UAO on pulmonary function test (PFT) and tracheal narrowing on computerised tomography (CT). Materials and Methods: Consecutive patients with apparently asymptomatic euthyroid MNG attending thyroid clinic in a tertiary centre underwent clinical examination to elicit features of UAO, PFT, and CT of neck and chest. Statistical Analysis Used: Statistical analysis was done with SPSS version 11.5 using paired t-test, Chi square test, and Fisher's exact test. P value of <0.05 was considered to be significant. Results: Fifty-six patients (52 females and four males) were studied. The prevalence of UAO (PFT) and significant tracheal narrowing (CT) was 14.3%. and 9.3%, respectively. Clinical features failed to predict UAO or significant tracheal narrowing. Tracheal narrowing (CT) did not correlate with UAO (PFT). Volume of goitre significantly correlated with degree of tracheal narrowing. Conclusions: Clinical features do not predict UAO on PFT or tracheal narrowing on CT in apparently asymptomatic patients with euthyroid MNG. PMID:21966649

Summarising and validating test accuracy results across multiple studies for use in clinical practice.

PubMed

Riley, Richard D; Ahmed, Ikhlaaq; Debray, Thomas P A; Willis, Brian H; Noordzij, J Pieter; Higgins, Julian P T; Deeks, Jonathan J

2015-06-15

Following a meta-analysis of test accuracy studies, the translation of summary results into clinical practice is potentially problematic. The sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of a test may differ substantially from the average meta-analysis findings, because of heterogeneity. Clinicians thus need more guidance: given the meta-analysis, is a test likely to be useful in new populations, and if so, how should test results inform the probability of existing disease (for a diagnostic test) or future adverse outcome (for a prognostic test)? We propose ways to address this. Firstly, following a meta-analysis, we suggest deriving prediction intervals and probability statements about the potential accuracy of a test in a new population. Secondly, we suggest strategies on how clinicians should derive post-test probabilities (PPV and NPV) in a new population based on existing meta-analysis results and propose a cross-validation approach for examining and comparing their calibration performance. Application is made to two clinical examples. In the first example, the joint probability that both sensitivity and specificity will be >80% in a new population is just 0.19, because of a low sensitivity. However, the summary PPV of 0.97 is high and calibrates well in new populations, with a probability of 0.78 that the true PPV will be at least 0.95. In the second example, post-test probabilities calibrate better when tailored to the prevalence in the new population, with cross-validation revealing a probability of 0.97 that the observed NPV will be within 10% of the predicted NPV. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Old wine in new bottles: validating the clinical utility of SPECT in predicting cognitive performance in mild traumatic brain injury.

PubMed

Romero, Kristoffer; Lobaugh, Nancy J; Black, Sandra E; Ehrlich, Lisa; Feinstein, Anthony

2015-01-30

The neural underpinnings of cognitive dysfunction in mild traumatic brain injury (TBI) are not fully understood. Consequently, patient prognosis using existing clinical imaging is somewhat imprecise. Single photon emission computed tomography (SPECT) is a frequently employed investigation in this population, notwithstanding uncertainty over the clinical utility of the data obtained. In this study, subjects with mild TBI underwent (99m)Tc-ECD SPECT scanning, and were administered a brief battery of cognitive tests and self-report symptom scales of concussion and emotional distress. Testing took place 2 weeks (n=84) and 1 year (n=49) post-injury. Multivariate analysis (i.e., partial least squares analysis) revealed that frontal perfusion in right superior frontal and middle frontal gyri predicted poorer performance on the Stroop test, an index of executive function, both at initial and follow-up testing. Conversely, SPECT scans categorized as normal or abnormal by radiologists did not differentiate cognitively impaired from intact subjects. These results demonstrate the clinical utility of SPECT in mild TBI, but only when data are subjected to blood flow quantification analysis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The impact of lay counselors on HIV testing rates: Quasi-experimental evidence from lay counselor redeployment in KwaZulu-Natal, South Africa.

PubMed

Hu, Janice; Geldsetzer, Pascal; Steele, Sarah Jane; Matthews, Philippa; Ortblad, Katrina; Solomon, Tsion; Shroufi, Amir; van Cutsem, Gilles; Tanser, Frank; Wyke, Sally; Vollmer, Sebastian; Pillay, Deenan; Mcconnell, Margaret; Bärnighausen, Till

2018-06-14

This study aimed to determine the causal effect of the number of lay counselors employed at a primary care clinic in rural South Africa on the number of clinic-based HIV tests performed. Fixed effects panel analysis. We collected monthly data on the number of lay counselors employed and HIV tests performed at nine primary care clinics in rural KwaZulu-Natal from January 2014 to December 2015. Using clinic- and month-level fixed effects regressions, we exploited the fact that lay counselors were removed from clinics at two quasi-random time points by a redeployment policy. A total of 24,526 HIV tests were conducted over the study period. 21 of 27 lay counselors were removed across the nine clinics in the two redeployment waves. A ten percent reduction in the number of lay counselors was associated with a 4.9% (95% confidence interval [CI]: 2.8 - 7.0, p < 0.001) decrease in the number of HIV tests performed. In absolute terms, losing one lay counselor from a clinic was associated with a mean of 29.7 (95% CI: 21.2 - 38.2, p < 0.001) fewer HIV tests carried out at the clinic per month. This study provides evidence for the crucial role that lay counselors play in the HIV response in rural South Africa. More broadly, this analysis supports the use of lay cadres in the HIV response and by extension UNAIDS' and the African Union's goal to triple the number of community health workers in sub-Saharan Africa by 2020.

[Blood sampling using "dried blood spot": a clinical biology revolution underway?].

PubMed

Hirtz, Christophe; Lehmann, Sylvain

2015-01-01

Blood testing using the dried blood spot (DBS) is used since the 1960s in clinical analysis, mainly within the framework of the neonatal screening (Guthrie test). Since then numerous analytes such as nucleic acids, small molecules or lipids, were successfully measured on the DBS. While this pre-analytical method represents an interesting alternative to classic blood sampling, its use in routine is still limited. We review here the different clinical applications of the blood sampling on DBS and estimate its future place, supported by the new methods of analysis as the LC-MS mass spectrometry.

Use of clinical movement screening tests to predict injury in sport

PubMed Central

Chimera, Nicole J; Warren, Meghan

2016-01-01

Clinical movement screening tests are gaining popularity as a means to determine injury risk and to implement training programs to prevent sport injury. While these screens are being used readily in the clinical field, it is only recently that some of these have started to gain attention from a research perspective. This limits applicability and poses questions to the validity, and in some cases the reliability, of the clinical movement tests as they relate to injury prediction, intervention, and prevention. This editorial will review the following clinical movement screening tests: Functional Movement Screen™, Star Excursion Balance Test, Y Balance Test, Drop Jump Screening Test, Landing Error Scoring System, and the Tuck Jump Analysis in regards to test administration, reliability, validity, factors that affect test performance, intervention programs, and usefulness for injury prediction. It is important to review the aforementioned factors for each of these clinical screening tests as this may help clinicians interpret the current body of literature. While each of these screening tests were developed by clinicians based on what appears to be clinical practice, this paper brings to light that this is a need for collaboration between clinicians and researchers to ensure validity of clinically meaningful tests so that they are used appropriately in future clinical practice. Further, this editorial may help to identify where the research is lacking and, thus, drive future research questions in regards to applicability and appropriateness of clinical movement screening tools. PMID:27114928

Investigation of the association between the test day milk fat-protein ratio and clinical mastitis using a Poisson regression approach for analysis of time-to-event data.

PubMed

Zoche-Golob, V; Heuwieser, W; Krömker, V

2015-09-01

The objective of the present study was to investigate the association between the milk fat-protein ratio and the incidence rate of clinical mastitis including repeated cases of clinical mastitis to determine the usefulness of this association to monitor metabolic disorders as risk factors for udder health. Herd records from 10 dairy herds of Holstein cows in Saxony, Germany, from September 2005-2011 (36,827 lactations of 17,657 cows) were used for statistical analysis. A mixed Poisson regression model with the weekly incidence rate of clinical mastitis as outcome variable was fitted. The model included repeated events of the outcome, time-varying covariates and multilevel clustering. Because the recording of clinical mastitis might have been imperfect, a probabilistic bias analysis was conducted to assess the impact of the misclassification of clinical mastitis on the conventional results. The lactational incidence of clinical mastitis was 38.2%. In 36.2% and 34.9% of the lactations, there was at least one dairy herd test day with a fat-protein ratio of <1.0 or >1.5, respectively. Misclassification of clinical mastitis was assumed to have resulted in bias towards the null. A clinical mastitis case increased the incidence rate of following cases of the same cow. Fat-protein ratios of <1.0 and >1.5 were associated with higher incidence rates of clinical mastitis depending on week in milk. The effect of a fat-protein ratio >1.5 on the incidence rate of clinical mastitis increased considerably over the course of lactation, whereas the effect of a fat-protein ratio <1.0 decreased. Fat-protein ratios <1.0 or >1.5 on the precedent test days of all cows irrespective of their time in milk seemed to be better predictors for clinical mastitis than the first test day results per lactation. Copyright © 2015 Elsevier B.V. All rights reserved.

Body fluid analysis: clinical utility and applicability of published studies to guide interpretation of today's laboratory testing in serous fluids.

PubMed

Block, Darci R; Algeciras-Schimnich, Alicia

2013-01-01

Requests for testing various analytes in serous fluids (e.g., pleural, peritoneal, pericardial effusions) are submitted daily to clinical laboratories. Testing of these fluids deviates from assay manufacturers' specifications, as most laboratory assays are optimized for testing blood or urine specimens. These requests add a burden to clinical laboratories, which need to validate assay performance characteristics in these fluids to exclude matrix interferences (given the different composition of body fluids) while maintaining regulatory compliance. Body fluid testing for a number of analytes has been reported in the literature; however, understanding the clinical utility of these analytes is critical because laboratories must address the analytic and clinical validation requirements, while educating clinicians on proper test utilization. In this article, we review the published data to evaluate the clinical utility of testing for numerous analytes in body fluid specimens. We also highlight the pre-analytic and analytic variables that need to be considered when reviewing published studies in body fluid testing. Finally, we provide guidance on how published studies might (or might not) guide interpretation of test results in today's clinical laboratories.

Effects of structured written feedback by cards on medical students' performance at Mini Clinical Evaluation Exercise (Mini-CEX) in an outpatient clinic.

PubMed

Haghani, Fariba; Hatef Khorami, Mohammad; Fakhari, Mohammad

2016-07-01

Feedback cards are recommended as a feasible tool for structured written feedback delivery in clinical education while effectiveness of this tool on the medical students' performance is still questionable.  The purpose of this study was to compare the effects of structured written feedback by cards as well as verbal feedback versus verbal feedback alone on the clinical performance of medical students at the Mini Clinical Evaluation Exercise (Mini-CEX) test in an outpatient clinic. This is a quasi-experimental study with pre- and post-test comprising four groups in two terms of medical students' externship. The students' performance was assessed through the Mini-Clinical Evaluation Exercise (Mini-CEX) as a clinical performance evaluation tool. Structured written feedbacks were given to two experimental groups by designed feedback cards as well as verbal feedback, while in the two control groups feedback was delivered verbally as a routine approach in clinical education. By consecutive sampling method, 62 externship students were enrolled in this study and seven students were excluded from the final analysis due to their absence for three days. According to the ANOVA analysis and Post Hoc Tukey test,  no statistically significant difference was observed among the four groups at the pre-test, whereas a statistically significant difference was observed between the experimental and control groups at the post-test  (F = 4.023, p =0.012). The effect size of the structured written feedbacks on clinical performance was 0.19. Structured written feedback by cards could improve the performance of medical students in a statistical sense. Further studies must be conducted in other clinical courses with longer durations.

Impact of a Routine, Opt-Out HIV Testing Program on HIV Testing and Case Detection in North Carolina Sexually-Transmitted Disease Clinics

PubMed Central

Klein, Pamela W.; Messer, Lynne C.; Myers, Evan R.; Weber, David J.; Leone, Peter A.; Miller, William C.

2016-01-01

The impact of routine, opt-out HIV testing programs in clinical settings is inconclusive. The objective of this study was to estimate the impact of an expanded, routine HIV testing program in North Carolina sexually transmitted disease (STD) clinics on HIV testing and case detection. Adults aged 18–64 who received an HIV test in a North Carolina STD clinic July 1, 2005 through June 30, 2011 were included in this analysis, dichotomized at the date of implementation on November 1, 2007. HIV testing and case detection counts and rates were analyzed using interrupted time series analysis, and Poisson and multilevel logistic regression. Pre-intervention, 426 new HIV-infected cases were identified from 128,029 tests (0.33%), whereas 816 new HIV-infected cases were found from 274,745 tests post-intervention (0.30%). Pre-intervention, HIV testing increased by 55 tests per month (95% confidence interval [CI]: 41, 72), but only 34 tests per month (95% CI: 26, 42) post-intervention. Increases in HIV testing rates were most pronounced in females and non-Hispanic whites. A slight pre-intervention decline in case detection was mitigated by the intervention (mean difference [MD]=0.01; 95% CI: −0.02, 0.05). Increases in case detection rates were observed among females and non-Hispanic blacks. The impact of a routine HIV screening in North Carolina STD clinics was marginal, with the greatest benefit among persons not traditionally targeted for HIV testing. The use of a pre-intervention comparison period identified important temporal trends that otherwise would have been ignored. PMID:24825338

Reliability Measure of a Clinical Test: Appreciation of Music in Cochlear Implantees (AMICI)

PubMed Central

Cheng, Min-Yu; Spitzer, Jaclyn B.; Shafiro, Valeriy; Sheft, Stanley; Mancuso, Dean

2014-01-01

Purpose The goals of this study were (1) to investigate the reliability of a clinical music perception test, Appreciation of Music in Cochlear Implantees (AMICI), and (2) examine associations between the perception of music and speech. AMICI was developed as a clinical instrument for assessing music perception in persons with cochlear implants (CIs). The test consists of four subtests: (1) music versus environmental noise discrimination, (2) musical instrument identification (closed-set), (3) musical style identification (closed-set), and (4) identification of musical pieces (open-set). To be clinically useful, it is crucial for AMICI to demonstrate high test-retest reliability, so that CI users can be assessed and retested after changes in maps or programming strategies. Research Design Thirteen CI subjects were tested with AMICI for the initial visit and retested again 10–14 days later. Two speech perception tests (consonant-nucleus-consonant [CNC] and Bamford-Kowal-Bench Speech-in-Noise [BKB-SIN]) were also administered. Data Analysis Test-retest reliability and equivalence of the test’s three forms were analyzed using paired t-tests and correlation coefficients, respectively. Correlation analysis was also conducted between results from the music and speech perception tests. Results Results showed no significant difference between test and retest (p > 0.05) with adequate power (0.9) as well as high correlations between the three forms (Forms A and B, r = 0.91; Forms A and C, r = 0.91; Forms B and C, r = 0.95). Correlation analysis showed high correlation between AMICI and BKB-SIN (r = −0.71), and moderate correlation between AMICI and CNC (r = 0.4). Conclusions The study showed AMICI is highly reliable for assessing musical perception in CI users. PMID:24384082

Integrated Analysis of Pharmacologic, Clinical, and SNP Microarray Data using Projection onto the Most Interesting Statistical Evidence with Adaptive Permutation Testing

PubMed Central

Pounds, Stan; Cao, Xueyuan; Cheng, Cheng; Yang, Jun; Campana, Dario; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

2010-01-01

Powerful methods for integrated analysis of multiple biological data sets are needed to maximize interpretation capacity and acquire meaningful knowledge. We recently developed Projection Onto the Most Interesting Statistical Evidence (PROMISE). PROMISE is a statistical procedure that incorporates prior knowledge about the biological relationships among endpoint variables into an integrated analysis of microarray gene expression data with multiple biological and clinical endpoints. Here, PROMISE is adapted to the integrated analysis of pharmacologic, clinical, and genome-wide genotype data that incorporating knowledge about the biological relationships among pharmacologic and clinical response data. An efficient permutation-testing algorithm is introduced so that statistical calculations are computationally feasible in this higher-dimension setting. The new method is applied to a pediatric leukemia data set. The results clearly indicate that PROMISE is a powerful statistical tool for identifying genomic features that exhibit a biologically meaningful pattern of association with multiple endpoint variables. PMID:21516175

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

Labby, Z.

Physicists are often expected to have a solid grounding in experimental design and statistical analysis, sometimes filling in when biostatisticians or other experts are not available for consultation. Unfortunately, graduate education on these topics is seldom emphasized and few opportunities for continuing education exist. Clinical physicists incorporate new technology and methods into their practice based on published literature. A poor understanding of experimental design and analysis could Result in inappropriate use of new techniques. Clinical physicists also improve current practice through quality initiatives that require sound experimental design and analysis. Academic physicists with a poor understanding of design and analysismore » may produce ambiguous (or misleading) results. This can Result in unnecessary rewrites, publication rejection, and experimental redesign (wasting time, money, and effort). This symposium will provide a practical review of error and uncertainty, common study designs, and statistical tests. Instruction will primarily focus on practical implementation through examples and answer questions such as: where would you typically apply the test/design and where is the test/design typically misapplied (i.e., common pitfalls)? An analysis of error and uncertainty will also be explored using biological studies and associated modeling as a specific use case. Learning Objectives: Understand common experimental testing and clinical trial designs, what questions they can answer, and how to interpret the results Determine where specific statistical tests are appropriate and identify common pitfalls Understand the how uncertainty and error are addressed in biological testing and associated biological modeling.« less

Prioritization in comparative effectiveness research: the CANCERGEN Experience.

PubMed

Thariani, Rahber; Wong, William; Carlson, Josh J; Garrison, Louis; Ramsey, Scott; Deverka, Patricia A; Esmail, Laura; Rangarao, Sneha; Hoban, Carolyn J; Baker, Laurence H; Veenstra, David L

2012-05-01

Systematic approaches to stakeholder-informed research prioritization are a central focus of comparative effectiveness research. Genomic testing in cancer is an ideal area to refine such approaches given rapid innovation and potentially significant impacts on patient outcomes. To develop and pilot test a stakeholder-informed approach to prioritizing genomic tests for future study in collaboration with the cancer clinical trials consortium SWOG. We conducted a landscape analysis to identify genomic tests in oncology using a systematic search of published and unpublished studies, and expert consultation. Clinically valid tests suitable for evaluation in a comparative study were presented to an external stakeholder group. Domains to guide the prioritization process were identified with stakeholder input, and stakeholders ranked tests using multiple voting rounds. A stakeholder group was created including representatives from patient-advocacy groups, payers, test developers, regulators, policy makers, and community-based oncologists. We identified 9 domains for research prioritization with stakeholder feedback: population impact; current standard of care, strength of association; potential clinical benefits, potential clinical harms, economic impacts, evidence of need, trial feasibility, and market factors. The landscape analysis identified 635 studies; of 9 tests deemed to have sufficient clinical validity, 6 were presented to stakeholders. Two tests in lung cancer (ERCC1 and EGFR) and 1 test in breast cancer (CEA/CA15-3/CA27.29) were identified as top research priorities. Use of a diverse stakeholder group to inform research prioritization is feasible in a pragmatic and timely manner. Additional research is needed to optimize search strategies, stakeholder group composition, and integration with existing prioritization mechanisms.

Prioritization in Comparative Effectiveness Research: The CANCERGEN Experience in Cancer Genomics

PubMed Central

Thariani, Rahber; Wong, William; Carlson, Josh J; Garrison, Louis; Ramsey, Scott; Deverka, Patricia A; Esmail, Laura; Rangarao, Sneha; Hoban, Carolyn J; Baker, Laurence H; Veenstra, David L

2012-01-01

Background Systematic approaches to stakeholder-informed research prioritization are a central focus of comparative effectiveness research. Genomic testing in cancer is an ideal area to refine such approaches given rapid innovation and potentially significant impacts on patient outcomes. Objective To develop and pilot-test a stakeholder-informed approach to prioritizing genomic tests for future study in collaboration with the cancer clinical trials consortium SWOG. Methods We conducted a landscape-analysis to identify genomic tests in oncology using a systematic search of published and unpublished studies, and expert consultation. Clinically valid tests suitable for evaluation in a comparative study were presented to an external stakeholder group. Domains to guide the prioritization process were identified with stakeholder input, and stakeholders ranked tests using multiple voting rounds. Results A stakeholder group was created including representatives from patient-advocacy groups, payers, test developers, regulators, policy-makers, and community-based oncologists. We identified nine domains for research prioritization with stakeholder feedback: population impact; current standard of care, strength of association; potential clinical benefits, potential clinical harms, economic impacts, evidence of need, trial feasibility, and market factors. The landscape-analysis identified 635 studies; of 9 tests deemed to have sufficient clinical validity, 6 were presented to stakeholders. Two tests in lung cancer (ERCC1 and EGFR) and one test in breast cancer (CEA/CA15-3/CA27.29) were identified as top research priorities. Conclusions Use of a diverse stakeholder group to inform research prioritization is feasible in a pragmatic and timely manner. Additional research is needed to optimize search strategies, stakeholder group composition and integration with existing prioritization mechanisms. PMID:22274803

Comparison of the Hologic Aptima HIV-1 Quant Dx Assay to the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 Test v2.0 for the quantification of HIV-1 RNA in plasma samples.

PubMed

Schønning, Kristian; Johansen, Kim; Landt, Bodil; Benfield, Thomas; Westh, Henrik

2017-07-01

HIV-RNA is the most important parameter for monitoring antiviral treatment in individuals infected with HIV-1. Knowledge of the performance of different tests for the quantification of HIV-1 RNA is therefore important for clinical care. To compare the analytical performance of the Aptima HIV-1 Quant Dx Assay (Aptima) and the COBAS Ampliprep/COBAS TaqMan HIV-1 Test v2.0 (CAPCTMv2) for the quantification of HIV-1 RNA in plasma samples. The performance of the two tests was compared on 216 clinical plasma samples, on dilutions series in seven replicates of five clinical samples of known subtype and on ten replicates of the Acrometrix High and Low Positive Control. Bland-Altman analysis of 130 samples that quantified in both tests did not show indications of gross mis-quantification of either test. A tendency of the Aptima assay to quantify higher at high viral load compared to the CAPCTMv2 was observed in Bland-Altman analysis, by Deming regression (Slope 1.13) and in dilution series of clinical samples. Precision evaluated using the Acrometrix Positive Controls was similar for the High Control (CV: 1.2% vs. 1.3%; Aptima assay vs. CAPCTMv2 test, respectively), but differed for the Low control (CV: 17.9% vs. 7.1%; Aptima assay vs. CAPCTMv2 test, respectively). However, this did not impact clinical categorization of clinical samples at neither the 50 cp/mL nor 200 cp/mL level. The Aptima assay and the CAPCTMv2 test are highly correlated and are useful for monitoring HIV-infected individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Differentiating clinical groups using the serial color-word test (S-CWT).

PubMed

Hentschel, Uwe; Rubino, I Alex; Bijleveld, Catrien

2011-04-01

The present study attempted to differentiate 11 diagnostic groups by means of the Serial Color-Word Test (S-CWT), using multivariate discriminant analysis. Two alternative scoring systems of the S-CWT were outlined. Asample of 514 individuals who had clinical diagnoses of various types and 397 controls who had no diagnostic findings comprised the sample. The first discriminant analysis failed to differentiate the groups adequately. The groups were consequently reduced to four (schizophrenia, bipolar disorders, temporo-mandibular joint pain dysfunction syndrome, and eating disturbances), which gave better reclassification findings for a clinical application of the test. This classification gave over 55% correct assignments. The final four groups had a statistically significant discrimination on the test, which remained stable also in a bootstrap procedure. Implications for treatment indications and outcomes as well as strategies for further studies using the S-CWT are discussed.

Data Mining Techniques Applied to Hydrogen Lactose Breath Test.

PubMed

Rubio-Escudero, Cristina; Valverde-Fernández, Justo; Nepomuceno-Chamorro, Isabel; Pontes-Balanza, Beatriz; Hernández-Mendoza, Yoedusvany; Rodríguez-Herrera, Alfonso

2017-01-01

Analyze a set of data of hydrogen breath tests by use of data mining tools. Identify new patterns of H2 production. Hydrogen breath tests data sets as well as k-means clustering as the data mining technique to a dataset of 2571 patients. Six different patterns have been extracted upon analysis of the hydrogen breath test data. We have also shown the relevance of each of the samples taken throughout the test. Analysis of the hydrogen breath test data sets using data mining techniques has identified new patterns of hydrogen generation upon lactose absorption. We can see the potential of application of data mining techniques to clinical data sets. These results offer promising data for future research on the relations between gut microbiota produced hydrogen and its link to clinical symptoms.

Evaluation of RSA set-up from a clinical biplane fluoroscopy system for 3D joint kinematic analysis.

PubMed

Bonanzinga, Tommaso; Signorelli, Cecilia; Bontempi, Marco; Russo, Alessandro; Zaffagnini, Stefano; Marcacci, Maurilio; Bragonzoni, Laura

2016-01-01

dinamic roentgen stereophotogrammetric analysis (RSA), a technique currently based only on customized radiographic equipment, has been shown to be a very accurate method for detecting three-dimensional (3D) joint motion. The aim of the present work was to evaluate the applicability of an innovative RSA set-up for in vivo knee kinematic analysis, using a biplane fluoroscopic image system. To this end, the Authors describe the set-up as well as a possible protocol for clinical knee joint evaluation. The accuracy of the kinematic measurements is assessed. the Authors evaluated the accuracy of 3D kinematic analysis of the knee in a new RSA set-up, based on a commercial biplane fluoroscopy system integrated into the clinical environment. The study was organized in three main phases: an in vitro test under static conditions, an in vitro test under dynamic conditions reproducing a flexion-extension range of motion (ROM), and an in vivo analysis of the flexion-extension ROM. For each test, the following were calculated, as an indication of the tracking accuracy: mean, minimum, maximum values and standard deviation of the error of rigid body fitting. in terms of rigid body fitting, in vivo test errors were found to be 0.10±0.05 mm. Phantom tests in static and kinematic conditions showed precision levels, for translations and rotations, of below 0.1 mm/0.2° and below 0.5 mm/0.3° respectively for all directions. the results of this study suggest that kinematic RSA can be successfully performed using a standard clinical biplane fluoroscopy system for the acquisition of slow movements of the lower limb. a kinematic RSA set-up using a clinical biplane fluoroscopy system is potentially applicable and provides a useful method for obtaining better characterization of joint biomechanics.

Significance testing of clinical data using virus dynamics models with a Markov chain Monte Carlo method: application to emergence of lamivudine-resistant hepatitis B virus.

PubMed Central

Burroughs, N J; Pillay, D; Mutimer, D

1999-01-01

Bayesian analysis using a virus dynamics model is demonstrated to facilitate hypothesis testing of patterns in clinical time-series. Our Markov chain Monte Carlo implementation demonstrates that the viraemia time-series observed in two sets of hepatitis B patients on antiviral (lamivudine) therapy, chronic carriers and liver transplant patients, are significantly different, overcoming clinical trial design differences that question the validity of non-parametric tests. We show that lamivudine-resistant mutants grow faster in transplant patients than in chronic carriers, which probably explains the differences in emergence times and failure rates between these two sets of patients. Incorporation of dynamic models into Bayesian parameter analysis is of general applicability in medical statistics. PMID:10643081

A critical analysis of test-retest reliability in instrument validation studies of cancer patients under palliative care: a systematic review

PubMed Central

2014-01-01

Background Patient-reported outcome validation needs to achieve validity and reliability standards. Among reliability analysis parameters, test-retest reliability is an important psychometric property. Retested patients must be in a clinically stable condition. This is particularly problematic in palliative care (PC) settings because advanced cancer patients are prone to a faster rate of clinical deterioration. The aim of this study was to evaluate the methods by which multi-symptom and health-related qualities of life (HRQoL) based on patient-reported outcomes (PROs) have been validated in oncological PC settings with regards to test-retest reliability. Methods A systematic search of PubMed (1966 to June 2013), EMBASE (1980 to June 2013), PsychInfo (1806 to June 2013), CINAHL (1980 to June 2013), and SCIELO (1998 to June 2013), and specific PRO databases was performed. Studies were included if they described a set of validation studies. Studies were included if they described a set of validation studies for an instrument developed to measure multi-symptom or multidimensional HRQoL in advanced cancer patients under PC. The COSMIN checklist was used to rate the methodological quality of the study designs. Results We identified 89 validation studies from 746 potentially relevant articles. From those 89 articles, 31 measured test-retest reliability and were included in this review. Upon critical analysis of the overall quality of the criteria used to determine the test-retest reliability, 6 (19.4%), 17 (54.8%), and 8 (25.8%) of these articles were rated as good, fair, or poor, respectively, and no article was classified as excellent. Multi-symptom instruments were retested over a shortened interval when compared to the HRQoL instruments (median values 24 hours and 168 hours, respectively; p = 0.001). Validation studies that included objective confirmation of clinical stability in their design yielded better results for the test-retest analysis with regard to both pain and global HRQoL scores (p < 0.05). The quality of the statistical analysis and its description were of great concern. Conclusion Test-retest reliability has been infrequently and poorly evaluated. The confirmation of clinical stability was an important factor in our analysis, and we suggest that special attention be focused on clinical stability when designing a PRO validation study that includes advanced cancer patients under PC. PMID:24447633

Utility of repeat testing of critical values: a Q-probes analysis of 86 clinical laboratories.

PubMed

Lehman, Christopher M; Howanitz, Peter J; Souers, Rhona; Karcher, Donald S

2014-06-01

A common laboratory practice is to repeat critical values before reporting the test results to the clinical care provider. This may be an unnecessary step that delays the reporting of critical test results without adding value to the accuracy of the test result. To determine the proportions of repeated chemistry and hematology critical values that differ significantly from the original value as defined by the participating laboratory, to determine the threshold differences defined by the laboratory as clinically significant, and to determine the additional time required to analyze the repeat test. Participants prospectively reviewed critical test results for 4 laboratory tests: glucose, potassium, white blood cell count, and platelet count. Participants reported the following information: initial and repeated test result; time initial and repeat results were first known to laboratory staff; critical result notification time; if the repeat result was still a critical result; if the repeat result was significantly different from the initial result, as judged by the laboratory professional or policy; significant difference threshold, as defined by the laboratory; the make and model of the instrument used for primary and repeat testing. Routine, repeat analysis of critical values is a common practice. Most laboratories did not formally define a significant difference between repeat results. Repeated results were rarely considered significantly different. Median repeated times were at least 17 to 21 minutes for 10% of laboratories. Twenty percent of laboratories reported at least 1 incident in the last calendar year of delayed result reporting that clinicians indicated had adversely affected patient care. Routine repeat analysis of automated chemistry and hematology critical values is unlikely to be clinically useful and may adversely affect patient care.

HIV Antibody Test

MedlinePlus

... Free Fetal DNA Cerebrospinal Fluid (CSF) Analysis Ceruloplasmin Chemistry Panels Chickenpox and Shingles Tests Chlamydia Testing Chloride ... D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp. 487-490. Bennett, ...

Lipase Test

MedlinePlus

... Free Fetal DNA Cerebrospinal Fluid (CSF) Analysis Ceruloplasmin Chemistry Panels Chickenpox and Shingles Tests Chlamydia Testing Chloride ... D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 281-287. Wu, ...

CK-MB Test

MedlinePlus

... Free Fetal DNA Cerebrospinal Fluid (CSF) Analysis Ceruloplasmin Chemistry Panels Chickenpox and Shingles Tests Chlamydia Testing Chloride ... Missouri. Pp. 312-315. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER and ...

SacLab: A toolbox for saccade analysis to increase usability of eye tracking systems in clinical ophthalmology practice.

PubMed

Cercenelli, Laura; Tiberi, Guido; Corazza, Ivan; Giannaccare, Giuseppe; Fresina, Michela; Marcelli, Emanuela

2017-01-01

Many open source software packages have been recently developed to expand the usability of eye tracking systems to study oculomotor behavior, but none of these is specifically designed to encompass all the main functions required for creating eye tracking tests and for providing the automatic analysis of saccadic eye movements. The aim of this study is to introduce SacLab, an intuitive, freely-available MATLAB toolbox based on Graphical User Interfaces (GUIs) that we have developed to increase the usability of the ViewPoint EyeTracker (Arrington Research, Scottsdale, AZ, USA) in clinical ophthalmology practice. SacLab consists of four processing modules that enable the user to easily create visual stimuli tests (Test Designer), record saccadic eye movements (Data Recorder), analyze the recorded data to automatically extract saccadic parameters of clinical interest (Data Analyzer) and provide an aggregate analysis from multiple eye movements recordings (Saccade Analyzer), without requiring any programming effort by the user. A demo application of SacLab to carry out eye tracking tests for the analysis of horizontal saccades was reported. We tested the usability of SacLab toolbox with three ophthalmologists who had no programming experience; the ophthalmologists were briefly trained in the use of SacLab GUIs and were asked to perform the demo application. The toolbox gained an enthusiastic feedback from all the clinicians in terms of intuitiveness, ease of use and flexibility. Test creation and data processing were accomplished in 52±21s and 46±19s, respectively, using the SacLab GUIs. SacLab may represent a useful tool to ease the application of the ViewPoint EyeTracker system in clinical routine in ophthalmology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Blood Urea Nitrogen Test

MedlinePlus

... Free Fetal DNA Cerebrospinal Fluid (CSF) Analysis Ceruloplasmin Chemistry Panels Chickenpox and Shingles Tests Chlamydia Testing Chloride ... mmol/L 1 from Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns ...

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials

PubMed Central

Guydish, J.; Manser, S.T.; Jessup, M.; Tajima, B.; Sears, C.; Montini, T.

2010-01-01

The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. PMID:20890376

Diagnostic accuracy of clinical tests of the hip: a systematic review with meta-analysis.

PubMed

Reiman, Michael P; Goode, Adam P; Hegedus, Eric J; Cook, Chad E; Wright, Alexis A

2013-09-01

Hip Physical Examination (HPE) tests have long been used to diagnose a myriad of intra-and extra-articular pathologies of the hip joint. Useful clinical utility is necessary to support diagnostic imaging and subsequent surgical decision making. Summarise and evaluate the current research and utility on the diagnostic accuracy of HPE tests for the hip joint germane to sports related injuries and pathology. A computer-assisted literature search of MEDLINE, CINHAL and EMBASE databases (January 1966 to January 2012) using keywords related to diagnostic accuracy of the hip joint. This systematic review with meta-analysis utilised the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the search and reporting phases of the study. Der-Simonian and Laird random effects models were used to summarise sensitivities (SN), specificities (SP), likelihood ratios and diagnostic OR. The employed search strategy revealed 25 potential articles, with 10 demonstrating high quality. Fourteen articles qualified for meta-analysis. The meta-analysis demonstrated that most tests possess weak diagnostic properties with the exception of the patellar-pubic percussion test, which had excellent pooled SN 95 (95% CI 92 to 97%) and good specificity 86 (95% CI 78 to 92%). Several studies have investigated pathology in the hip. Few of the current studies are of substantial quality to dictate clinical decision-making. Currently, only the patellar-pubic percussion test is supported by the data as a stand-alone HPE test. Further studies involving high quality designs are needed to fully assess the value of HPE tests for patients with intra- and extra-articular hip dysfunction.

Clinical application of high throughput molecular screening techniques for pharmacogenomics

PubMed Central

Wiita, Arun P; Schrijver, Iris

2011-01-01

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

Acellular dermal matrix allograft versus free gingival graft: a histological evaluation and split-mouth randomized clinical trial.

PubMed

de Resende, Daniel Romeu Benchimol; Greghi, Sebastião Luiz Aguiar; Siqueira, Aline Franco; Benfatti, César Augusto Magalhães; Damante, Carla Andreotti; Ragghianti Zangrando, Mariana Schutzer

2018-04-30

This split-mouth controlled randomized clinical trial evaluated clinical and histological results of acellular dermal matrix allograft (ADM) compared to autogenous free gingival graft (FGG) for keratinized tissue augmentation. Twenty-five patients with the absence or deficiency of keratinized tissue (50 sites) were treated with FGG (control group) and ADM (test group). Clinical parameters included keratinized tissue width (KTW) (primary outcome), soft tissue thickness (TT), recession depth (RD), probing depth (PD), and clinical attachment level (CAL). Esthetic perception was evaluated by patients and by a calibrated periodontist using visual analog scale (VAS). Histological analysis included biopsies of five different patients from both test and control sites for each evaluation period (n = 25). The analysis included percentage of connective tissue components, epithelial luminal to basal surface ratio, tissue maturation, and presence of elastic fibers. Data were evaluated by ANOVA complemented by Tukey's tests (p < 0.05). After 6 months, PD and CAL demonstrated no differences between groups. ADM presented higher RD compared to FGG in all periods. Mean tissue shrinkage for control and test groups was 12.41 versus 55.7%. TT was inferior for ADM group compared to FGG. Esthetics perception by professional evaluation showed superior results for ADM. Histomorphometric analysis demonstrated higher percentage of cellularity, blood vessels, and epithelial luminal to basal surface ratio for FGG group. ADM group presented higher percentage of collagen fibers and inflammatory infiltrate. Both treatments resulted in improvement of clinical parameters, except for RD. ADM group presented more tissue shrinkage and delayed healing, confirmed histologically, but superior professional esthetic perception. This study added important clinical and histological data to contribute in the decision-making process between indication of FGG or ADM.

The pitfalls of hair analysis for toxicants in clinical practice: three case reports.

PubMed Central

Frisch, Melissa; Schwartz, Brian S

2002-01-01

Hair analysis is used to assess exposure to heavy metals in patients presenting with nonspecific symptoms and is a commonly used procedure in patients referred to our clinic. We are frequently called on to evaluate patients who have health-related concerns as a result of hair analysis. Three patients first presented to outside physicians with nonspecific, multisystemic symptoms. A panel of analytes was measured in hair, and one or more values were interpreted as elevated. As a result of the hair analysis and other unconventional diagnostic tests, the patients presented to us believing they suffered from metal toxicity. In this paper we review the clinical efficacy of this procedure within the context of a patient population with somatic disorders and no clear risk factors for metal intoxication. We also review limitations of hair analysis in this setting; these limitations include patient factors such as low pretest probability of disease and test factors such as the lack of validation of analytic techniques, the inability to discern between exogenous contaminants and endogenous toxicants in hair, the variability of analytic procedures, low interlaboratory reliability, and the increased likelihood of false positive test results in the measurement of panels of analytes. PMID:11940463

Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data--The Influence of Different Parameters in a Routine Clinical Microbiology Laboratory.

PubMed

Kohlmann, Rebekka; Gatermann, Sören G

2016-01-01

Many clinical microbiology laboratories report on cumulative antimicrobial susceptibility testing (cAST) data on a regular basis. Criteria for generation of cAST reports, however, are often obscure and inconsistent. Whereas the CLSI has published a guideline for analysis and presentation of cAST data, national guidelines directed at clinical microbiology laboratories are not available in Europe. Thus, we sought to describe the influence of different parameters in the process of cAST data analysis in the setting of a German routine clinical microbiology laboratory during 2 consecutive years. We developed various program scripts to assess the consequences ensuing from different algorithms for calculation of cumulative antibiograms from the data collected in our clinical microbiology laboratory in 2013 and 2014. One of the most pronounced effects was caused by exclusion of screening cultures for multi-drug resistant organisms which decreased the MRSA rate in some cases to one third. Dependent on the handling of duplicate isolates, i.e. isolates of the same species recovered from successive cultures on the same patient during the time period analyzed, we recorded differences in resistance rates of up to 5 percentage points for S. aureus, E. coli and K. pneumoniae and up to 10 percentage points for P. aeruginosa. Stratification by site of care and specimen type, testing of antimicrobials selectively on resistant isolates, change of interpretation rules and analysis at genus level instead of species level resulted in further changes of calculated antimicrobial resistance rates. The choice of parameters for cAST data analysis may have a substantial influence on calculated antimicrobial resistance rates. Consequently, comparability of cAST reports from different clinical microbiology laboratories may be limited. We suggest that laboratories communicate the strategy used for cAST data analysis as long as national guidelines for standardized cAST data analysis and reporting do not exist in Europe.

Factors associated with Chlamydia trachomatis testing in a high school based screening and previously in clinical practice: a cross-sectional study in Norway

PubMed Central

2013-01-01

Background High school based chlamydia screening has been shown to increase uptake and detect hidden infections among sexually active adolescents. Our study aimed to: i) examine the proportions of 15–20 year-olds tested in a high school based screening and previously in clinical practice, ii) determine chlamydia prevalence according to testing pattern, and iii) examine factors associated with testing in the two settings. Methods A population based cross-sectional study was conducted in 5 high schools in Norway in 2009, using web-questionnaires and Chlamydia trachomatis PCR in first-void urine (800 girls/818 boys, mean age 17.2 years). Only sexually active participants at risk for chlamydia infections were included in the analyses. Crude and multivariable logistic regression models were applied with ‘clinic based testing’ and ‘school based screening’ as outcome variables. Results 56% of girls and 21% of boys reported previous clinic based testing. In the school based screening, 93% were tested with no gender difference. 42% of girls and 74% of boys were tested for the first time at school (‘school-only test’). Both girls with clinic based testing and girls with school-only test had high chlamydia prevalence (7.3% vs 7.2%). Boys with clinic based testing had twice the prevalence of those with school-only test (6.2% vs 3.0%, p = 0.01). Half of infections were detected in participants with school-only test. One-fifth were repeat infections. In multivariable analysis of girls and boys combined, female gender, older age, early sexual debut, no condom use at first and last intercourse, steady relationship, and higher number of lifetime partners increased the odds of clinic based testing. The odds of school based screening increased with male gender, academic affiliation, later sexual debut, condom use at first intercourse, and current urogenital symptoms in multivariable analysis. Conclusions More than half the girls had been tested prior to the school based screening and had high prevalence independent of previous clinic based testing. School screening was mostly associated with factors unknown to increase chlamydia infection risk, while clinic based testing was associated with traditional risk factors. The unusually high and equal participation between genders and the detection of a large chlamydia reservoir confirms the value of school based screening suggesting this approach to be further explored in Norway. PMID:23915415

What variables can influence clinical reasoning?

PubMed

Ashoorion, Vahid; Liaghatdar, Mohammad Javad; Adibi, Peyman

2012-12-01

Clinical reasoning is one of the most important competencies that a physician should achieve. Many medical schools and licensing bodies try to predict it based on some general measures such as critical thinking, personality, and emotional intelligence. This study aimed at providing a model to design the relationship between the constructs. Sixty-nine medical students participated in this study. A battery test devised that consist four parts: Clinical reasoning measures, personality NEO inventory, Bar-On EQ inventory, and California critical thinking questionnaire. All participants completed the tests. Correlation and multiple regression analysis consumed for data analysis. There is low to moderate correlations between clinical reasoning and other variables. Emotional intelligence is the only variable that contributes clinical reasoning construct (r=0.17-0.34) (R(2) chnage = 0.46, P Value = 0.000). Although, clinical reasoning can be considered as a kind of thinking, no significant correlation detected between it and other constructs. Emotional intelligence (and its subscales) is the only variable that can be used for clinical reasoning prediction.

Organizational characteristics of HIV/syphilis testing services for men who have sex with men in South China: a social entrepreneurship analysis and implications for creating sustainable service models.

PubMed

Tucker, Joseph D; Muessig, Kathryn E; Cui, Rosa; Bien, Cedric H; Lo, Elaine J; Lee, Ramon; Wang, Kaidi; Han, Larry; Liu, Feng-Ying; Yang, Li-Gang; Yang, Bin; Larson, Heidi; Peeling, Rosanna W

2014-11-25

UNAIDS has called for greater HIV/syphilis testing worldwide just as local HIV/syphilis testing programs are cut or altered. New models are needed to make HIV/syphilis testing services sustainable while retaining their essential public health function. Social entrepreneurship, using business principles to promote a social cause, provides a framework to pilot programs that sustainably expand testing. Drawing on fieldwork in two South Chinese cities, we examined organizational and financial characteristics of current HIV/syphilis testing systems for men who have sex with men (MSM) in addition to new pilot programs focused on revenue-generation for sustainability. We undertook a qualitative study to explore organizational and financial characteristics of HIV/syphilis testing for MSM. Data were collected from men who have sex with men and policy stakeholders in Guangzhou and Hong Kong. Framework analysis was used to identify themes and then code the data. Our qualitative research study included MSM and policy stakeholders (n = 84). HIV/syphilis testing services were implemented at a wide range of organizations which we grouped broadly as independent community-based organizations (CBOs), independent clinics, and hybrid CBO-clinic sites. From an organizational perspective, hybrid CBO-clinic sites offered the inclusive environment of an MSM CBO linked to the technical capacity and trained staff of a clinic. From a financial perspective, stakeholders expressed concern about the sustainability and effectiveness of sexual health services reliant on external funding. We identified four hybrid CBO-clinic organizations that launched pilot testing programs in order to generate revenue while expanding HIV testing. Many MSM CBOs are searching for new organizational models to account for decreased external support. Hybrid CBO-clinic organizations create a strong foundation to increase HIV/syphilis testing using social entrepreneurship models in China.

Comparison of 16S rRNA sequencing with biochemical testing for species-level identification of clinical isolates of Neisseria spp.

PubMed

Mechergui, Arij; Achour, Wafa; Ben Hassen, Assia

2014-08-01

We aimed to compare accuracy of genus and species level identification of Neisseria spp. using biochemical testing and 16S rRNA sequence analysis. These methods were evaluated using 85 Neisseria spp. clinical isolates initially identified to the genus level by conventional biochemical tests and API NH system (Bio-Mérieux(®)). In 34 % (29/85), more than one possibility was given by 16S rRNA sequence analysis. In 6 % (5/85), one of the possibilities offered by 16S rRNA gene sequencing, agreed with the result given by biochemical testing. In 4 % (3/85), the same species was given by both methods. 16S rRNA gene sequencing results did not correlate well with biochemical tests.

Physical examination tests of the shoulder: a systematic review and meta-analysis of diagnostic test performance.

PubMed

Gismervik, Sigmund Ø; Drogset, Jon O; Granviken, Fredrik; Rø, Magne; Leivseth, Gunnar

2017-01-25

Physical examination tests of the shoulder (PETS) are clinical examination maneuvers designed to aid the assessment of shoulder complaints. Despite more than 180 PETS described in the literature, evidence of their validity and usefulness in diagnosing the shoulder is questioned. This meta-analysis aims to use diagnostic odds ratio (DOR) to evaluate how much PETS shift overall probability and to rank the test performance of single PETS in order to aid the clinician's choice of which tests to use. This study adheres to the principles outlined in the Cochrane guidelines and the PRISMA statement. A fixed effect model was used to assess the overall diagnostic validity of PETS by pooling DOR for different PETS with similar biomechanical rationale when possible. Single PETS were assessed and ranked by DOR. Clinical performance was assessed by sensitivity, specificity, accuracy and likelihood ratio. Six thousand nine-hundred abstracts and 202 full-text articles were assessed for eligibility; 20 articles were eligible and data from 11 articles could be included in the meta-analysis. All PETS for SLAP (superior labral anterior posterior) lesions pooled gave a DOR of 1.38 [1.13, 1.69]. The Supraspinatus test for any full thickness rotator cuff tear obtained the highest DOR of 9.24 (sensitivity was 0.74, specificity 0.77). Compression-Rotation test obtained the highest DOR (6.36) among single PETS for SLAP lesions (sensitivity 0.43, specificity 0.89) and Hawkins test obtained the highest DOR (2.86) for impingement syndrome (sensitivity 0.58, specificity 0.67). No single PETS showed superior clinical test performance. The clinical performance of single PETS is limited. However, when the different PETS for SLAP lesions were pooled, we found a statistical significant change in post-test probability indicating an overall statistical validity. We suggest that clinicians choose their PETS among those with the highest pooled DOR and to assess validity to their own specific clinical settings, review the inclusion criteria of the included primary studies. We further propose that future studies on the validity of PETS use randomized research designs rather than the accuracy design relying less on well-established gold standard reference tests and efficient treatment options.

Antibiotic therapy as an adjunct to scaling and root planing in smokers: a systematic review and meta-analysis.

PubMed

Assem, Naida Zanini; Alves, Márcio Luiz Ferro; Lopes, Alessandra Barreto; Gualberto, Erivan Clementino; Garcia, Valdir Gouveia; Theodoro, Letícia Helena

2017-07-03

The aim of this study was to perform a systematic review and meta-analysis to examine the effect of systemic antibiotics in the periodontal treatment of smokers. The selection criteria were as follows: controlled randomized clinical trials; studies published in English; studies with smoker patients diagnosed with chronic periodontitis; patients without systemic diseases; studies that used systemic antibiotic therapy associated with periodontal treatment; studies that presented results for the test and control groups and assessments of clinical periodontal parameters, such as probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL). The differences in average weights were calculated with a confidence interval (CI) of 95% for PD reduction, CAL gain and BOP. The means of the periodontal clinical parameters were compared between the baseline and post-treatment periods between the test groups and the control groups. The heterogeneity was assessed using the Cochran Q test (Q (df = 3), α = 5%). A total of 67 articles were found, and after the selection process, three randomized controlled trials were included in the meta-analysis. The results indicate that SRP associated with systemic antibiotics promoted additional benefits when compared to SRP alone, with a greater reduction of PD (p = 0.0359, CI = -0.42, -0.01) and a gain of CAL (p = 0.0161, CI = -0.39, -0.04). There was a modest PD reduction (PD, DM -0.21) and a modest CAL gain (CAL, DM -0.22). The results of our meta-analysis reveal the clinical benefits of systemic antibiotics as an adjunct to the non-surgical periodontal treatment of smokers. These clinical improvements, although statistically significant, appeared to be of little clinical relevance.

Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

PubMed

DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D

2013-10-01

Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P < 0.001) and antiretroviral (Kruskal-Wallis P < 0.001).

Use of patient flow analysis to improve patient visit efficiency by decreasing wait time in a primary care-based disease management programs for anticoagulation and chronic pain: a quality improvement study.

PubMed

Potisek, Nicholas M; Malone, Robb M; Shilliday, Betsy Bryant; Ives, Timothy J; Chelminski, Paul R; DeWalt, Darren A; Pignone, Michael P

2007-01-15

Patients with chronic conditions require frequent care visits. Problems can arise during several parts of the patient visit that decrease efficiency, making it difficult to effectively care for high volumes of patients. The purpose of the study is to test a method to improve patient visit efficiency. We used Patient Flow Analysis to identify inefficiencies in the patient visit, suggest areas for improvement, and test the effectiveness of clinic interventions. At baseline, the mean visit time for 93 anticoagulation clinic patient visits was 84 minutes (+/- 50 minutes) and the mean visit time for 25 chronic pain clinic patient visits was 65 minutes (+/- 21 minutes). Based on these data, we identified specific areas of inefficiency and developed interventions to decrease the mean time of the patient visit. After interventions, follow-up data found the mean visit time was reduced to 59 minutes (+/-25 minutes) for the anticoagulation clinic, a time decrease of 25 minutes (t-test 39%; p < 0.001). Mean visit time for the chronic pain clinic was reduced to 43 minutes (+/- 14 minutes) a time decrease of 22 minutes (t-test 34 %; p < 0.001). Patient Flow Analysis is an effective technique to identify inefficiencies in the patient visit and efficiently collect patient flow data. Once inefficiencies are identified they can be improved through brief interventions.

Decision analysis to complete diagnostic research by closing the gap between test characteristics and cost-effectiveness.

PubMed

Schaafsma, Joanna D; van der Graaf, Yolanda; Rinkel, Gabriel J E; Buskens, Erik

2009-12-01

The lack of a standard methodology in diagnostic research impedes adequate evaluation before implementation of constantly developing diagnostic techniques. We discuss the methodology of diagnostic research and underscore the relevance of decision analysis in the process of evaluation of diagnostic tests. Overview and conceptual discussion. Diagnostic research requires a stepwise approach comprising assessment of test characteristics followed by evaluation of added value, clinical outcome, and cost-effectiveness. These multiple goals are generally incompatible with a randomized design. Decision-analytic models provide an important alternative through integration of the best available evidence. Thus, critical assessment of clinical value and efficient use of resources can be achieved. Decision-analytic models should be considered part of the standard methodology in diagnostic research. They can serve as a valid alternative to diagnostic randomized clinical trials (RCTs).

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

PubMed

Hoyle, R H

1991-02-01

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

Clinical Utility of Epstein-Barr Virus DNA Testing in the Treatment of Nasopharyngeal Carcinoma Patients.

PubMed

Kim, Kelly Y; Le, Quynh-Thu; Yom, Sue S; Ng, Raymond H W; Chan, K C Allen; Bratman, Scott V; Welch, John J; Divi, Rao L; Petryshyn, Raymond A; Conley, Barbara A

2017-08-01

Epstein-Barr virus (EBV) DNA analysis has been shown to be useful for early detection, prognostication, and monitoring of treatment response of nasopharyngeal carcinoma (NPC), and the recent literature provides growing evidence of the clinical utility of EBV DNA testing, particularly to inform treatment decisions for NPC patients. Despite the fact that NPC is a rare disease, the NRG Oncology cooperative group has successfully activated a phase 2/3 randomized clinical trial for NPC with international partners and in that process has discovered that the development of a harmonized EBV DNA test is absolutely critical for integration into clinical trials and for future deployment in clinical and central laboratories. In November 2015, the National Cancer Institute (NCI) convened a workshop of international experts in the treatment of NPC and EBV testing to provide a forum for discussing the state of EBV DNA testing and its clinical utility, and to stimulate consideration of future studies and clinical practice guidelines for EBV DNA. This review provides a summary of that discussion. Published by Elsevier Inc.

Diagnostic accuracy and receiver-operating characteristics curve analysis in surgical research and decision making.

PubMed

Søreide, Kjetil; Kørner, Hartwig; Søreide, Jon Arne

2011-01-01

In surgical research, the ability to correctly classify one type of condition or specific outcome from another is of great importance for variables influencing clinical decision making. Receiver-operating characteristic (ROC) curve analysis is a useful tool in assessing the diagnostic accuracy of any variable with a continuous spectrum of results. In order to rule a disease state in or out with a given test, the test results are usually binary, with arbitrarily chosen cut-offs for defining disease versus health, or for grading of disease severity. In the postgenomic era, the translation from bench-to-bedside of biomarkers in various tissues and body fluids requires appropriate tools for analysis. In contrast to predetermining a cut-off value to define disease, the advantages of applying ROC analysis include the ability to test diagnostic accuracy across the entire range of variable scores and test outcomes. In addition, ROC analysis can easily examine visual and statistical comparisons across tests or scores. ROC is also favored because it is thought to be independent from the prevalence of the condition under investigation. ROC analysis is used in various surgical settings and across disciplines, including cancer research, biomarker assessment, imaging evaluation, and assessment of risk scores.With appropriate use, ROC curves may help identify the most appropriate cutoff value for clinical and surgical decision making and avoid confounding effects seen with subjective ratings. ROC curve results should always be put in perspective, because a good classifier does not guarantee the expected clinical outcome. In this review, we discuss the fundamental roles, suggested presentation, potential biases, and interpretation of ROC analysis in surgical research.

The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus.

PubMed

Taraborelli, M; Lazzaroni, M G; Martinazzi, N; Fredi, M; Cavazzana, I; Franceschini, F; Tincani, A

2016-12-16

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- β2Glycoprotein I IgG/IgM >99th percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher's exact test for categorical variables and Student's t or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values <0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p<0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p<0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p<0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS.

Rasch analysis on OSCE data : An illustrative example.

PubMed

Tor, E; Steketee, C

2011-01-01

The Objective Structured Clinical Examination (OSCE) is a widely used tool for the assessment of clinical competence in health professional education. The goal of the OSCE is to make reproducible decisions on pass/fail status as well as students' levels of clinical competence according to their demonstrated abilities based on the scores. This paper explores the use of the polytomous Rasch model in evaluating the psychometric properties of OSCE scores through a case study. The authors analysed an OSCE data set (comprised of 11 stations) for 80 fourth year medical students based on the polytomous Rasch model in an effort to answer two research questions: (1) Do the clinical tasks assessed in the 11 OSCE stations map on to a common underlying construct, namely clinical competence? (2) What other insights can Rasch analysis offer in terms of scaling, item analysis and instrument validation over and above the conventional analysis based on classical test theory? The OSCE data set has demonstrated a sufficient degree of fit to the Rasch model (Χ(2) = 17.060, DF=22, p=0.76) indicating that the 11 OSCE station scores have sufficient psychometric properties to form a measure for a common underlying construct, i.e. clinical competence. Individual OSCE station scores with good fit to the Rasch model (p > 0.1 for all Χ(2) statistics) further corroborated the characteristic of unidimensionality of the OSCE scale for clinical competence. A Person Separation Index (PSI) of 0.704 indicates sufficient level of reliability for the OSCE scores. Other useful findings from the Rasch analysis that provide insights, over and above the analysis based on classical test theory, are also exemplified using the data set. The polytomous Rasch model provides a useful and supplementary approach to the calibration and analysis of OSCE examination data.

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

PubMed Central

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

2015-01-01

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

BNP and NT-proBNP Test

MedlinePlus

... Free Fetal DNA Cerebrospinal Fluid (CSF) Analysis Ceruloplasmin Chemistry Panels Chickenpox and Shingles Tests Chlamydia Testing Chloride ... 488-95. William Clarke. Contemporary Practice in Clinical Chemistry, 2nd Edition Paperback – February 4, 2011. ISBN-13: ...

Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy: A cross-sectional analysis.

PubMed

Schmidt, Simone; Hafner, Patricia; Klein, Andrea; Rubino-Nacht, Daniela; Gocheva, Vanya; Schroeder, Jonas; Naduvilekoot Devasia, Arjith; Zuesli, Stephanie; Bernert, Guenther; Laugel, Vincent; Bloetzer, Clemens; Steinlin, Maja; Capone, Andrea; Gloor, Monika; Tobler, Patrick; Haas, Tanja; Bieri, Oliver; Zumbrunn, Thomas; Fischer, Dirk; Bonati, Ulrike

2018-01-01

The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative muscle MRI of thigh muscles in ambulant Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1). Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon technique, and transverse relaxation time (T2) measurements. All clinical assessments were highly significantly inter-correlated with p < 0.001. The strongest correlation with the motor function measure and its D1-subscore was shown by the 6-minute walk test. Clinical assessments showed no correlation with age. Importantly, quantitative muscle MRI values significantly correlated with all clinical assessments with the extensors showing the strongest correlation. In contrast to the clinical assessments, quantitative muscle MRI values were highly significantly correlated with age. In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Rural Health Clinics (RHCs)

MedlinePlus

... Toolkits Economic Impact Analysis Tool Community Health Gateway Sustainability Planning Tools Testing New Approaches Rural Health IT ... of the certification process is the RHC Cost Report. Once a clinic has received its Medicare Provider ...

Development of a clinically validated bulk failure test for ceramic crowns.

PubMed

Kelly, J Robert; Rungruanganunt, Patchnee; Hunter, Ben; Vailati, Francesca

2010-10-01

Traditional testing of ceramic crowns creates a stress state and damage modes that differ greatly from those seen clinically. There is a need to develop and communicate an in vitro testing protocol that is clinically valid. The purpose of this study was to develop an in vitro failure test for ceramic single-unit prostheses that duplicates the failure mechanism and stress state observed in clinically failed prostheses. This article first compares characteristics of traditional load-to-failure tests of ceramic crowns with the growing body of evidence regarding failure origins and stress states at failure from the examination of clinically failed crowns, finite element analysis (FEA), and data from clinical studies. Based on this analysis, an experimental technique was systematically developed and test materials were identified to recreate key aspects of clinical failure in vitro. One potential dentin analog material (an epoxy filled with woven glass fibers; NEMA grade G10) was evaluated for elastic modulus in blunt contact and for bond strength to resin cement as compared to hydrated dentin. Two bases with different elastic moduli (nickel chrome and resin-based composite) were tested for influence on failure loads. The influence of water during storage and loading (both monotonic and cyclic) was examined. Loading piston materials (G10, aluminum, stainless steel) and piston designs were varied to eliminate Hertzian cracking and to improve performance. Testing was extended from a monolayer ceramic (leucite-filled glass) to a bilayer ceramic system (glass-infiltrated alumina). The influence of cyclic rate on mean failure loads was examined (2 Hz, 10 Hz, 20 Hz) with the extremes compared statistically (t test; α=.05). Failure loads were highly influenced by base elastic modulus (t test; P<.001). Cyclic loading while in water significantly decreased mean failure loads (1-way ANOVA; P=.003) versus wet storage/dry cycling (350 N vs. 1270 N). G10 was not significantly different from hydrated dentin in terms of blunt contact elastic behavior or resin cement bond strength. Testing was successful with the bilayered ceramic, and the cycling rate altered mean failure loads only slightly (approximately 5%). Test methods and materials were developed to validly simulate many aspects of clinical failure. Copyright © 2010 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Comparative testing of disinfectant efficacy on planktonic bacteria and bacterial biofilms using a new assay based on kinetic analysis of metabolic activity.

PubMed

Günther, F; Scherrer, M; Kaiser, S J; DeRosa, A; Mutters, N T

2017-03-01

The aim of our study was to develop a new reproducible method for disinfectant efficacy testing on bacterial biofilms and to evaluate the efficacy of different disinfectants against biofilms. Clinical multidrug-resistant strains were chosen as test isolates to ensure practical relevance. We compared the standard qualitative suspension assay for disinfectant testing, which does not take into account biofilm formation, to the new biofilm viability assay that uses kinetic analysis of metabolic activity in biofilms after disinfectant exposure to evaluate disinfectant efficacy. In addition, the efficacy of four standard disinfectants to clinical isolates was tested using both methods. All tested disinfectants were effective against test isolates when in planktonic state using the standard qualitative suspension assay, while disinfectants were only weakly effective against bacteria in biofilms. Disinfectant efficacy testing on planktonic organisms ignores biofilms and overestimates disinfectant susceptibility of bacteria. However, biofilm forming, e.g. on medical devices or hospital surfaces, is the natural state of bacterial living and needs to be considered in disinfectant testing. Although bacterial biofilms are the predominant manner of bacterial colonization, most standard procedures for antimicrobial susceptibility testing and efficacy testing of disinfectants are adapted for application to planktonic bacteria. To our knowledge, this is the first study to use a newly developed microplate-based biofilm test system that uses kinetic analysis of the metabolic activity in biofilms, after disinfectant exposure, to evaluate disinfectant efficacy. Our study shows that findings obtained from disinfectant efficacy testing on planktonic bacteria cannot be extrapolated to predict disinfectant efficacy on bacterial biofilms of clinically relevant multidrug-resistant organisms. © 2016 The Society for Applied Microbiology.

Clinical usefulness of the clock drawing test applying rasch analysis in predicting of cognitive impairment.

PubMed

Yoo, Doo Han; Lee, Jae Shin

2016-07-01

[Purpose] This study examined the clinical usefulness of the clock drawing test applying Rasch analysis for predicting the level of cognitive impairment. [Subjects and Methods] A total of 187 stroke patients with cognitive impairment were enrolled in this study. The 187 patients were evaluated by the clock drawing test developed through Rasch analysis along with the mini-mental state examination of cognitive evaluation tool. An analysis of the variance was performed to examine the significance of the mini-mental state examination and the clock drawing test according to the general characteristics of the subjects. Receiver operating characteristic analysis was performed to determine the cutoff point for cognitive impairment and to calculate the sensitivity and specificity values. [Results] The results of comparison of the clock drawing test with the mini-mental state showed significant differences in according to gender, age, education, and affected side. A total CDT of 10.5, which was selected as the cutoff point to identify cognitive impairement, showed a sensitivity, specificity, Youden index, positive predictive, and negative predicive values of 86.4%, 91.5%, 0.8, 95%, and 88.2%. [Conclusion] The clock drawing test is believed to be useful in assessments and interventions based on its excellent ability to identify cognitive disorders.

Tetherless ergonomics workstation to assess nurses' physical workload in a clinical setting.

PubMed

Smith, Warren D; Nave, Michael E; Hreljac, Alan P

2011-01-01

Nurses are at risk of physical injury when moving immobile patients. This paper describes the development and testing of a tetherless ergonomics workstation that is suitable for studying nurses' physical workload in a clinical setting. The workstation uses wearable sensors to record multiple channels of body orientation and muscle activity and wirelessly transmits them to a base station laptop computer for display, storage, and analysis. In preparation for use in a clinical setting, the workstation was tested in a laboratory equipped for multi-camera video motion analysis. The testing included a pilot study of the effect of bed height on student nurses' physical workload while they repositioned a volunteer posing as a bedridden patient toward the head of the bed. Each nurse subject chose a preferred bed height, and data were recorded, in randomized order, with the bed at this height, at 0.1 m below this height, and at 0.1 m above this height. The testing showed that the body orientation recordings made by the wearable sensors agreed closely with those obtained from the video motion analysis system. The pilot study showed the following trends: As the bed height was raised, the nurses' trunk flexion at both thoracic and lumbar sites and lumbar muscle effort decreased, whereas trapezius and deltoid muscle effort increased. These trends will be evaluated by further studies of practicing nurses in the clinical setting.

An automated system for chromosome analysis. Volume 1: Goals, system design, and performance

NASA Technical Reports Server (NTRS)

Castleman, K. R.; Melnyk, J. H.

1975-01-01

The design, construction, and testing of a complete system to produce karyotypes and chromosome measurement data from human blood samples, and a basis for statistical analysis of quantitative chromosome measurement data is described. The prototype was assembled, tested, and evaluated on clinical material and thoroughly documented.

The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

PubMed

Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

2018-01-01

The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

Mobile phone interference with medical equipment and its clinical relevance: a systematic review.

PubMed

Lawrentschuk, Nathan; Bolton, Damien M

2004-08-02

To conduct a systematic review of studies on clinically relevant digital mobile phone electromagnetic interference with medical equipment. MEDLINE and SUMSEARCH were searched for the period 1966-2004. The Cochrane Library and Database of Abstracts of Reviews of Effects were also searched for systematic reviews. Studies were eligible if published in a peer-reviewed journal in English, and if they included testing of digital mobile phones for clinically relevant interference with medical equipment used to monitor or treat patients, but not implantable medical devices. As there was considerable heterogeneity in medical equipment studied and the conduct of testing, results were summarised rather than subjected to meta-analysis. Clinically relevant electromagnetic interference (EMI) secondary to mobile phones potentially endangering patients occurred in 45 of 479 devices tested at 900 MHz and 14 of 457 devices tested at 1800 MHz. However, in the largest studies, the prevalence of clinically relevant EMI was low. Most clinically relevant EMI occurred when mobile phones were used within 1 m of medical equipment. Although testing was not standardised between studies and equipment tested was not identical, it is of concern that at least 4% of devices tested in any study were susceptible to clinically relevant EMI. All studies recommend some type of restriction of mobile phone use in hospitals, with use greater than 1 m from equipment and restrictions in clinical areas being the most common.

Development and validation of a whole-exome sequencing test for simultaneous detection of point mutations, indels and copy-number alterations for precision cancer care

PubMed Central

Rennert, Hanna; Eng, Kenneth; Zhang, Tuo; Tan, Adrian; Xiang, Jenny; Romanel, Alessandro; Kim, Robert; Tam, Wayne; Liu, Yen-Chun; Bhinder, Bhavneet; Cyrta, Joanna; Beltran, Himisha; Robinson, Brian; Mosquera, Juan Miguel; Fernandes, Helen; Demichelis, Francesca; Sboner, Andrea; Kluk, Michael; Rubin, Mark A; Elemento, Olivier

2016-01-01

We describe Exome Cancer Test v1.0 (EXaCT-1), the first New York State-Department of Health-approved whole-exome sequencing (WES)-based test for precision cancer care. EXaCT-1 uses HaloPlex (Agilent) target enrichment followed by next-generation sequencing (Illumina) of tumour and matched constitutional control DNA. We present a detailed clinical development and validation pipeline suitable for simultaneous detection of somatic point/indel mutations and copy-number alterations (CNAs). A computational framework for data analysis, reporting and sign-out is also presented. For the validation, we tested EXaCT-1 on 57 tumours covering five distinct clinically relevant mutations. Results demonstrated elevated and uniform coverage compatible with clinical testing as well as complete concordance in variant quality metrics between formalin-fixed paraffin embedded and fresh-frozen tumours. Extensive sensitivity studies identified limits of detection threshold for point/indel mutations and CNAs. Prospective analysis of 337 cancer cases revealed mutations in clinically relevant genes in 82% of tumours, demonstrating that EXaCT-1 is an accurate and sensitive method for identifying actionable mutations, with reasonable costs and time, greatly expanding its utility for advanced cancer care. PMID:28781886

Levey-Jennings Analysis Uncovers Unsuspected Causes of Immunohistochemistry Stain Variability.

PubMed

Vani, Kodela; Sompuram, Seshi R; Naber, Stephen P; Goldsmith, Jeffrey D; Fulton, Regan; Bogen, Steven A

Almost all clinical laboratory tests use objective, quantitative measures of quality control (QC), incorporating Levey-Jennings analysis and Westgard rules. Clinical immunohistochemistry (IHC) testing, in contrast, relies on subjective, qualitative QC review. The consequences of using Levey-Jennings analysis for QC assessment in clinical IHC testing are not known. To investigate this question, we conducted a 1- to 2-month pilot test wherein the QC for either human epidermal growth factor receptor 2 (HER-2) or progesterone receptor (PR) in 3 clinical IHC laboratories was quantified and analyzed with Levey-Jennings graphs. Moreover, conventional tissue controls were supplemented with a new QC comprised of HER-2 or PR peptide antigens coupled onto 8 μm glass beads. At institution 1, this more stringent analysis identified a decrease in the HER-2 tissue control that had escaped notice by subjective evaluation. The decrement was due to heterogeneity in the tissue control itself. At institution 2, we identified a 1-day sudden drop in the PR tissue control, also undetected by subjective evaluation, due to counterstain variability. At institution 3, a QC shift was identified, but only with 1 of 2 controls mounted on each slide. The QC shift was due to use of the instrument's selective reagent drop zones dispense feature. None of these events affected patient diagnoses. These case examples illustrate that subjective QC evaluation of tissue controls can detect gross assay failure but not subtle changes. The fact that QC issues arose from each site, and in only a pilot study, suggests that immunohistochemical stain variability may be an underappreciated problem.

The development and psychometric testing of a theory-based instrument to evaluate nurses' perception of clinical reasoning competence.

PubMed

Liou, Shwu-Ru; Liu, Hsiu-Chen; Tsai, Hsiu-Min; Tsai, Ying-Huang; Lin, Yu-Ching; Chang, Chia-Hao; Cheng, Ching-Yu

2016-03-01

The purpose of the study was to develop and psychometrically test the Nurses Clinical Reasoning Scale. Clinical reasoning is an essential skill for providing safe and quality patient care. Identifying pre-graduates' and nurses' needs and designing training courses to improve their clinical reasoning competence becomes a critical task. However, there is no instrument focusing on clinical reasoning in the nursing profession. Cross-sectional design was used. This study included the development of the scale, a pilot study that preliminary tested the readability and reliability of the developed scale and a main study that implemented and tested the psychometric properties of the developed scale. The Nurses Clinical Reasoning Scale was developed based on the Clinical Reasoning Model. The scale includes 15 items using a Likert five-point scale. Data were collected from 2013-2014. Two hundred and fifty-one participants comprising clinical nurses and nursing pre-graduates completed and returned the questionnaires in the main study. The instrument was tested for internal consistency and test-retest reliability. Its validity was tested with content, construct and known-groups validity. One factor emerged from the factor analysis. The known-groups validity was confirmed. The Cronbach's alpha for the entire instrument was 0·9. The reliability and validity of the Nurses Clinical Reasoning Scale were supported. The scale is a useful tool and can be easily administered for the self-assessment of clinical reasoning competence of clinical nurses and future baccalaureate nursing graduates. Study limitations and further recommendations are discussed. © 2015 John Wiley & Sons Ltd.

Auditing the frequency and the clinical and economic impact of testing for Fabry disease in patients under the age of 70 with a stroke admitted to Saint Vincent's University Hospital over a 6-month period.

PubMed

Lambe, J; Noone, I; Lonergan, R; Tubridy, N

2018-02-01

Fabry disease is an X-linked recessive lysosomal storage disorder that provokes multi-organ morbidity, including early-onset stroke. Worldwide prevalence may be greater than previously estimated, with many experiencing first stroke prior to diagnosis of Fabry disease. The aim of this study is to screen a cohort of stroke patients under 70 years of age, evaluating the clinical and economic efficacy of such a broad screening programme for Fabry disease. All stroke patients under 70 years of age who were entered into the Saint Vincent's University Hospital stroke database over a 6-month period underwent enzyme analysis and/or genetic testing as appropriate for Fabry disease. Patients' past medical histories were analysed for clinical signs suggestive of Fabry disease. Cost-effectiveness analysis of testing was performed and compared to overall economic impact of young stroke in Ireland. Of 22 patients tested for Fabry disease, no new cases were detected. Few clinical indicators of Fabry disease were identified at the time of testing. Broad screening programmes for Fabry disease are highly unlikely to offset the cost of testing. The efficacy of future screening programmes will depend on careful selection of an appropriate patient cohort of young stroke patients with multi-organ morbidity and a positive family history.

What variables can influence clinical reasoning?

PubMed Central

Ashoorion, Vahid; Liaghatdar, Mohammad Javad; Adibi, Peyman

2012-01-01

Background: Clinical reasoning is one of the most important competencies that a physician should achieve. Many medical schools and licensing bodies try to predict it based on some general measures such as critical thinking, personality, and emotional intelligence. This study aimed at providing a model to design the relationship between the constructs. Materials and Methods: Sixty-nine medical students participated in this study. A battery test devised that consist four parts: Clinical reasoning measures, personality NEO inventory, Bar-On EQ inventory, and California critical thinking questionnaire. All participants completed the tests. Correlation and multiple regression analysis consumed for data analysis. Results: There is low to moderate correlations between clinical reasoning and other variables. Emotional intelligence is the only variable that contributes clinical reasoning construct (r=0.17-0.34) (R2 chnage = 0.46, P Value = 0.000). Conclusion: Although, clinical reasoning can be considered as a kind of thinking, no significant correlation detected between it and other constructs. Emotional intelligence (and its subscales) is the only variable that can be used for clinical reasoning prediction. PMID:23853636

Use of error grid analysis to evaluate acceptability of a point of care prothrombin time meter.

PubMed

Petersen, John R; Vonmarensdorf, Hans M; Weiss, Heidi L; Elghetany, M Tarek

2010-02-01

Statistical methods (linear regression, correlation analysis, etc.) are frequently employed in comparing methods in the central laboratory (CL). Assessing acceptability of point of care testing (POCT) equipment, however, is more difficult because statistically significant biases may not have an impact on clinical care. We showed how error grid (EG) analysis can be used to evaluate POCT PT INR with the CL. We compared results from 103 patients seen in an anti-coagulation clinic that were on Coumadin maintenance therapy using fingerstick samples for POCT (Roche CoaguChek XS and S) and citrated venous blood samples for CL (Stago STAR). To compare clinical acceptability of results we developed an EG with zones A, B, C and D. Using 2nd order polynomial equation analysis, POCT results highly correlate with the CL for CoaguChek XS (R(2)=0. 955) and CoaguChek S (R(2)=0. 93), respectively but does not indicate if POCT results are clinically interchangeable with the CL. Using EG it is readily apparent which levels can be considered clinically identical to the CL despite analytical bias. We have demonstrated the usefulness of EG in determining acceptability of POCT PT INR testing and how it can be used to determine cut-offs where differences in POCT results may impact clinical care. Copyright 2009 Elsevier B.V. All rights reserved.

A data grid for imaging-based clinical trials

NASA Astrophysics Data System (ADS)

Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

2007-03-01

Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

Chlamydia screening and prophylactic treatment in termination of pregnancy clinics in the Netherlands and Great Britain: a qualitative study.

PubMed

van den Berg, Georgina F; Picavet, Charles; Hoopman, Rianne; Lohr, Patricia A; Op de Coul, Eline L M

2016-12-01

Women having a termination of pregnancy (TOP) have higher rates of Chlamydia trachomatis (CT) than the general population. In this study, we explored CT treatment and prevention in Dutch TOP clinics in comparison to that provided in Great Britain (GB). A qualitative study including 14 semi-structured interviews with health care professionals (HCPs) in TOP clinics (the Netherlands: 9, GB: 5). Interviews were recorded, transcribed, and analysed by thematic content analysis. Prophylactic treatment with azithromycin is routinely prescribed after surgical TOP, but not after medical TOP ('abortion pill'). Sexually transmitted infections (STI) tests are offered to clients who are considered at high risk of having STI. Uptake varies according to health insurance coverage of STI testing. Some Dutch clinics are able to provide free testing for women under 25 years of age. Sexual health counselling is often limited to discussing birth control. The major difference between the Netherlands and GB is that GB TOP clinics more often offer free STI testing and prophylaxis to their clients. HCPs in Dutch TOP clinics consider STI testing an important part of their service, but financial barriers prevent testing on location. Dutch TOP clinics should offer STI tests to all women, and collaboration with public health services could improve STI testing and counselling for young people. Furthermore, clinics should treat all TOP clients with prophylactic azithromycin. This could prevent CT and other upper genital tract post-abortion infections.

Development of the Clinical Teaching Effectiveness Questionnaire in the United States.

PubMed

Wormley, Michelle E; Romney, Wendy; Greer, Anna E

2017-01-01

The purpose of this study was to develop a valid measure for assessing clinical teaching effectiveness within the field of physical therapy. The Clinical Teaching Effectiveness Questionnaire (CTEQ) was developed via a 4-stage process, including (1) initial content development, (2) content analysis with 8 clinical instructors with over 5 years of clinical teaching experience, (3) pilot testing with 205 clinical instructors from 2 universities in the Northeast of the United States, and (4) psychometric evaluation, including principal component analysis. The scale development process resulted in a 30-item questionnaire with 4 sections that relate to clinical teaching: learning experiences, learning environment, communication, and evaluation. The CTEQ provides a preliminary valid measure for assessing clinical teaching effectiveness in physical therapy practice.

[Clinical Tests Testing New Therapies for Stargardt Disease].

PubMed

Kousal, B; Ďuďáková, Ľ; Hlavatá, L; Lišková, P

2016-02-01

To provide information on currently ongoing clinical trials for Stargardt disease. We have searched the clinical trial register (www.clinicaltrials.gov) for the keyword "Stargardt" and list active ongoing studies. There are currently eight registered clinical trials enrolling patients with Stargardt disease; all in phase I or II aiming at four mechanisms of action: inhibition of the production of vitamin A toxic dimers, gene therapy restoring wild type transcription of the ABCA4 gene, neuroprotection preventing retinal cells from oxidative damage, and replacement of the damaged retinal pigment epithelium using stem cell therapy. The basic prerequisite for enrolment in the vast majority of clinical trials is confirmation of the clinical diagnosis by mutational analysis. The wide variety of therapies that are registered as clinical trials for Stargardt disease significantly raises the possibility that effective treatments will be available in the near future for this currently incurable condition and that molecular genetic testing should be increasingly considered. Stargardt disease, clinical trial, ABCA4, mutation.

Time-Efficiency Analysis Comparing Digital and Conventional Workflows for Implant Crowns: A Prospective Clinical Crossover Trial.

PubMed

Joda, Tim; Brägger, Urs

2015-01-01

To compare time-efficiency in the production of implant crowns using a digital workflow versus the conventional pathway. This prospective clinical study used a crossover design that included 20 study participants receiving single-tooth replacements in posterior sites. Each patient received a customized titanium abutment plus a computer-aided design/computer-assisted manufacture (CAD/CAM) zirconia suprastructure (for those in the test group, using digital workflow) and a standardized titanium abutment plus a porcelain-fused-to-metal crown (for those in the control group, using a conventional pathway). The start of the implant prosthetic treatment was established as the baseline. Time-efficiency analysis was defined as the primary outcome, and was measured for every single clinical and laboratory work step in minutes. Statistical analysis was calculated with the Wilcoxon rank sum test. All crowns could be provided within two clinical appointments, independent of the manufacturing process. The mean total production time, as the sum of clinical plus laboratory work steps, was significantly different. The mean ± standard deviation (SD) time was 185.4 ± 17.9 minutes for the digital workflow process and 223.0 ± 26.2 minutes for the conventional pathway (P = .0001). Therefore, digital processing for overall treatment was 16% faster. Detailed analysis for the clinical treatment revealed a significantly reduced mean ± SD chair time of 27.3 ± 3.4 minutes for the test group compared with 33.2 ± 4.9 minutes for the control group (P = .0001). Similar results were found for the mean laboratory work time, with a significant decrease of 158.1 ± 17.2 minutes for the test group vs 189.8 ± 25.3 minutes for the control group (P = .0001). Only a few studies have investigated efficiency parameters of digital workflows compared with conventional pathways in implant dental medicine. This investigation shows that the digital workflow seems to be more time-efficient than the established conventional production pathway for fixed implant-supported crowns. Both clinical chair time and laboratory manufacturing steps could be effectively shortened with the digital process of intraoral scanning plus CAD/CAM technology.

Cost-benefit and cost-savings analyses of antiarrhythmic medication monitoring.

PubMed

Snider, Melissa; Carnes, Cynthia; Grover, Janel; Davis, Rich; Kalbfleisch, Steven

2012-09-15

The economic impact of pharmacist-managed antiarrhythmic drug therapy monitoring on an academic medical center's electrophysiology (EP) program was investigated. Data were collected for the initial two years of patient visits (n = 816) to a pharmacist-run clinic for antiarrhythmic drug therapy monitoring. A retrospective cost analysis was conducted to assess the direct costs associated with three appointment models: (1) a clinic office visit only, (2) a clinic visit involving electrocardiography and basic laboratory tests, and (3) a clinic visit including pulmonary function testing and chest x-rays in addition to electrocardiography and laboratory testing. A subset of patient cases (n = 18) were included in a crossover analysis comparing pharmacist clinic care and usual care in an EP physician clinic. The primary endpoints were the cost benefits and cost savings associated with pharmacy-clinic care versus usual care. A secondary endpoint was improvement of overall EP program efficiency. The payer mix was 61.6% (n = 498) Medicare, 33.2% (n = 268) managed care, and 5.2% (n = 42) other. Positive contribution margins were demonstrated for all appointment models. The pharmacist-managed clinic also yielded cost savings by reducing overall patient care charges by 21% relative to usual care. By the second year, the pharmacy clinic improved EP program efficiency by scheduling an average of 24 patients per week, in effect freeing up one day per week of EP physician time to spend on other clinical activities. Pharmacist monitoring of antiarrhythmic drug therapy in an out-patient clinic provided cost benefits, cost savings, and improved overall EP program efficiency.

Robust inference for responder analysis: Innovative clinical trial design using a minimum p-value approach.

PubMed

Lin, Yunzhi

2016-08-15

Responder analysis is in common use in clinical trials, and has been described and endorsed in regulatory guidance documents, especially in trials where "soft" clinical endpoints such as rating scales are used. The procedure is useful, because responder rates can be understood more intuitively than a difference in means of rating scales. However, two major issues arise: 1) such dichotomized outcomes are inefficient in terms of using the information available and can seriously reduce the power of the study; and 2) the results of clinical trials depend considerably on the response cutoff chosen, yet in many disease areas there is no consensus as to what is the most appropriate cutoff. This article addresses these two issues, offering a novel approach for responder analysis that could both improve the power of responder analysis and explore different responder cutoffs if an agreed-upon common cutoff is not present. Specifically, we propose a statistically rigorous clinical trial design that pre-specifies multiple tests of responder rates between treatment groups based on a range of pre-specified responder cutoffs, and uses the minimum of the p-values for formal inference. The critical value for hypothesis testing comes from permutation distributions. Simulation studies are carried out to examine the finite sample performance of the proposed method. We demonstrate that the new method substantially improves the power of responder analysis, and in certain cases, yields power that is approaching the analysis using the original continuous (or ordinal) measure.

Presymptomatic electrophysiological tests predict clinical onset and survival in SOD1(G93A) ALS mice.

PubMed

Mancuso, Renzo; Osta, Rosario; Navarro, Xavier

2014-12-01

We assessed the predictive value of electrophysiological tests as a marker of clinical disease onset and survival in superoxide-dismutase 1 (SOD1)(G93A) mice. We evaluated the accuracy of electrophysiological tests in differentiating transgenic versus wild-type mice. We made a correlation analysis of electrophysiological parameters and the onset of symptoms, survival, and number of spinal motoneurons. Presymptomatic electrophysiological tests show great accuracy in differentiating transgenic versus wild-type mice, with the most sensitive parameter being the tibialis anterior compound muscle action potential (CMAP) amplitude. The CMAP amplitude at age 10 weeks correlated significantly with clinical disease onset and survival. Electrophysiological tests increased their survival prediction accuracy when evaluated at later stages of the disease and also predicted the amount of lumbar spinal motoneuron preservation. Electrophysiological tests predict clinical disease onset, survival, and spinal motoneuron preservation in SOD1(G93A) mice. This is a methodological improvement for preclinical studies. © 2014 Wiley Periodicals, Inc.

Assessing copy number from exome sequencing and exome array CGH based on CNV spectrum in a large clinical cohort.

PubMed

Retterer, Kyle; Scuffins, Julie; Schmidt, Daniel; Lewis, Rachel; Pineda-Alvarez, Daniel; Stafford, Amanda; Schmidt, Lindsay; Warren, Stephanie; Gibellini, Federica; Kondakova, Anastasia; Blair, Amanda; Bale, Sherri; Matyakhina, Ludmila; Meck, Jeanne; Aradhya, Swaroop; Haverfield, Eden

2015-08-01

Detection of copy-number variation (CNV) is important for investigating many genetic disorders. Testing a large clinical cohort by array comparative genomic hybridization provides a deep perspective on the spectrum of pathogenic CNV. In this context, we describe a bioinformatics approach to extract CNV information from whole-exome sequencing and demonstrate its utility in clinical testing. Exon-focused arrays and whole-genome chromosomal microarray analysis were used to test 14,228 and 14,000 individuals, respectively. Based on these results, we developed an algorithm to detect deletions/duplications in whole-exome sequencing data and a novel whole-exome array. In the exon array cohort, we observed a positive detection rate of 2.4% (25 duplications, 318 deletions), of which 39% involved one or two exons. Chromosomal microarray analysis identified 3,345 CNVs affecting single genes (18%). We demonstrate that our whole-exome sequencing algorithm resolves CNVs of three or more exons. These results demonstrate the clinical utility of single-exon resolution in CNV assays. Our whole-exome sequencing algorithm approaches this resolution but is complemented by a whole-exome array to unambiguously identify intragenic CNVs and single-exon changes. These data illustrate the next advancements in CNV analysis through whole-exome sequencing and whole-exome array.Genet Med 17 8, 623-629.

[Development and equivalence evaluation of spondee lists of mandarin speech test materials].

PubMed

Zhang, Hua; Wang, Shuo; Wang, Liang; Chen, Jing; Chen, Ai-ting; Guo, Lian-sheng; Zhao, Xiao-yan; Ji, Chen

2006-06-01

To edit the spondee (disyllable) word lists as a part of mandarin speech test materials (MSTM). These will be basic speech materials for routine tests in clinics and laboratories. Two groups of professionals (audiologists, Chinese and Mandarin scientists, linguistician and statistician) were set up at first. The editing principles were established after 3 round table meetings. Ten spondee lists, each with 50 words, were edited and recorded into cassettes. All lists were phonemically balanced (3-dimensions: vowels, consonants and Chinese tones). Seventy-three normal hearing college students were tested. The speech was presented by earphone monaurally. Three statistic methods were used for equivalent analysis. Related analysis showed that all lists were much related, except List 5. Cluster analysis showed that all ten lists could be classified as two groups. But Kappa test showed that the lists' homogeneity were not well. Spondee lists are one of the most routine speech test materials. Their editing, recording and equivalent evaluation are affected by many factors. This also needs multi-discipline cooperation. All lists edited in present study need future modification in recording and testing in order to be used clinically and in research. The phonemic balance should be kept.

First external quality assurance program for bloodstream Real-Time PCR monitoring of treatment response in clinical trials of Chagas disease.

PubMed

Ramírez, Juan C; Parrado, Rudy; Sulleiro, Elena; de la Barra, Anabelle; Rodríguez, Marcelo; Villarroel, Sandro; Irazu, Lucía; Alonso-Vega, Cristina; Alves, Fabiana; Curto, María A; García, Lineth; Ortiz, Lourdes; Torrico, Faustino; Gascón, Joaquim; Flevaud, Laurence; Molina, Israel; Ribeiro, Isabela; Schijman, Alejandro G

2017-01-01

Real-Time PCR (qPCR) testing is recommended as both a diagnostic and outcome measurement of etiological treatment in clinical practice and clinical trials of Chagas disease (CD), but no external quality assurance (EQA) program provides performance assessment of the assays in use. We implemented an EQA system to evaluate the performance of molecular biology laboratories involved in qPCR based follow-up in clinical trials of CD. An EQA program was devised for three clinical trials of CD: the E1224 (NCT01489228), a pro-drug of ravuconazole; the Sampling Study (NCT01678599), that used benznidazole, both conducted in Bolivia; and the CHAGASAZOL (NCT01162967), that tested posaconazole, conducted in Spain. Four proficiency testing panels containing negative controls and seronegative blood samples spiked with 1, 10 and 100 parasite equivalents (par. eq.)/mL of four Trypanosoma cruzi stocks, were sent from the Core Lab in Argentina to the participating laboratories located in Bolivia and Spain. Panels were analyzed simultaneously, blinded to sample allocation, at 4-month intervals. In addition, 302 random blood samples from both trials carried out in Bolivia were sent to Core Lab for retesting analysis. The analysis of proficiency testing panels gave 100% of accordance (within laboratory agreement) and concordance (between laboratory agreement) for all T. cruzi stocks at 100 par. eq./mL; whereas their values ranged from 71 to 100% and from 62 to 100% at 1 and 10 par. eq./mL, respectively, depending on the T. cruzi stock. The results obtained after twelve months of preparation confirmed the stability of blood samples in guanidine-EDTA buffer. No significant differences were found between qPCR results from Bolivian laboratory and Core Lab for retested clinical samples. This EQA program for qPCR analysis of CD patient samples may significantly contribute to ensuring the quality of laboratory data generated in clinical trials and molecular diagnostics laboratories of CD.

Clinical learning environment and supervision: experiences of Norwegian nursing students - a questionnaire survey.

PubMed

Skaalvik, Mari Wolff; Normann, Hans Ketil; Henriksen, Nils

2011-08-01

To measure nursing students' experiences and satisfaction with their clinical learning environments. The primary interest was to compare the results between students with respect to clinical practice in nursing homes and hospital wards. Clinical learning environments are important for the learning processes of nursing students and for preferences for future workplaces. Working with older people is the least preferred area of practice among nursing students in Norway. A cross-sectional design. A validated questionnaire was distributed to all nursing students from five non-randomly selected university colleges in Norway. A total of 511 nursing students completed a Norwegian version of the questionnaire, Clinical Learning Environment, Supervision and Nurse Teacher (CLES+T) evaluation scale in 2009. Data including descriptive statistics were analysed using the Statistical Program for the Social Sciences. Factor structure was analysed by principal component analysis. Differences across sub-groups were tested with chi-square tests and Mann-Whitney U test for categorical variables and t-tests for continuous variables. Ordinal logistic regression analysis of perceptions of the ward as a good learning environment was performed with supervisory relationships and institutional contexts as independent variables, controlling for age, sex and study year. The participating nursing students with clinical placements in nursing homes assessed their clinical learning environment significantly more negatively than those with hospital placements on nearby all sub-dimensions. The evidence found in this study indicates that measures should be taken to strengthen nursing homes as learning environments for nursing students. To recruit more graduated nurses to work in nursing homes, actions to improve the learning environment are needed. © 2011 Blackwell Publishing Ltd.

Nondispersive infrared spectrometry for 13CO2/12CO2-measurements: a clinically feasible analyzer for stable isotope breath tests in gastroenterology.

PubMed

Braden, B; Caspary, W F; Lembcke, B

1999-06-01

13C-urea breath tests have become clinical routine for the diagnosis of Helicobacter pylori infection and other isotope breath tests have been invented e.g. for gastric emptying or quantitative liver function testing. Recently, isotope-selective nondispersive infrared spectrometers (NDIRS) have been developed for the analysis of the 13CO2/12CO2-enrichment in breath. In this study, we prospectively tested the validity of a newly developed NDIRS in comparison to isotope ratio mass spectrometry (IRMS). 142 patients with dyspeptic symptoms were tested for Helicobacter pylori infection using the 13C-urea breath test. The isotope ratio analysis of the breath samples was performed in duplicate both using IRMS and NDIRS. The results of the baseline-corrected 13CO2-exhalation values between IRMS and NDIRS were in excellent agreement. The mean difference between both methods was 0.28 +/- 1.93 delta/1000. Evaluating the qualitative urea breath test results in reference to IRMS as the reference the NDIRS had a sensitivity of 97.8% and a specificity of 98.9%. The isotope-selective nondispersive infrared spectroscopy is going to become a reliable, but low-cost and easy-to-operate alternative to expensive isotope ratio mass spectrometry in the analysis of 13C-breath tests.

Placental growth factor (alone or in combination with soluble fms-like tyrosine kinase 1) as an aid to the assessment of women with suspected pre-eclampsia: systematic review and economic analysis.

PubMed

Frampton, Geoff K; Jones, Jeremy; Rose, Micah; Payne, Liz

2016-11-01

Pre-eclampsia (PE) prediction based on blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities can result in false-positive diagnoses. This may lead to unnecessary antenatal admissions and preterm delivery. Blood tests that measure placental growth factor (PlGF) or the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to PlGF could aid prediction of PE if either were added to routine clinical assessment or used as a replacement for proteinuria testing. To evaluate the diagnostic accuracy and cost-effectiveness of PlGF-based tests for patients referred to secondary care with suspected PE in weeks 20-37 of pregnancy. Systematic reviews and an economic analysis. Bibliographic databases including MEDLINE, EMBASE, Web of Science and The Cochrane Library and Database of Abstracts of Reviews of Effects were searched up to July 2015 for English-language references. Conferences, websites, systematic reviews and confidential company submissions were also accessed. Systematic reviews of test accuracy and economic studies were conducted to inform an economic analysis. Test accuracy studies were required to include women with suspected PE and report quantitatively the accuracy of PlGF-based tests; their risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. The economic studies review had broad eligibility criteria to capture any types of economic analysis; critical appraisal employed standard checklists consistent with National Institute for Health and Care Excellence criteria. Study selection, critical appraisal and data extraction in both reviews were performed by two reviewers. An independent economic analysis was conducted based on a decision tree model, using the best evidence available. The model evaluates costs (2014, GBP) from a NHS and Personal Social Services perspective. Given the short analysis time horizon, no discounting was undertaken. Four studies were included in the systematic review of test accuracy: two on Alere's Triage ® PlGF test (Alere, Inc., San Diego, CA, USA) for predicting PE requiring delivery within a specified time and two on Roche Diagnostics' Elecsys ® sFlt-1 to PlGF ratio test (Roche Diagnostics GmbH, Mannheim, Germany) for predicting PE within a specified time. Three studies were included in the systematic review of economic studies, and two confidential company economic analyses were assessed separately. Study heterogeneity precluded meta-analyses of test accuracy or cost-analysis outcomes, so narrative syntheses were conducted to inform the independent economic model. The model predicts that, when supplementing routine clinical assessment for rule-out and rule-in of PE, the two tests would be cost-saving in weeks 20-35 of gestation, and marginally cost-saving in weeks 35-37, but with minuscule impact on quality of life. Length of neonatal intensive care unit stay was the most influential parameter in sensitivity analyses. All other sensitivity analyses had negligible effects on results. No head-to-head comparisons of the tests were identified. No studies investigated accuracy of PlGF-based tests when used as a replacement for proteinuria testing. Test accuracy studies were found to be at high risk of clinical review bias. The Triage and Elecsys tests would save money if added to routine clinical assessment for PE. The magnitude of savings is uncertain, but the tests remain cost-saving under worst-case assumptions. Further research is required to clarify how the test results would be interpreted and applied in clinical practice. This study is registered as PROSPERO CRD42015017670. The National Institute for Health Research Health Technology Assessment programme.

Exact tests using two correlated binomial variables in contemporary cancer clinical trials.

PubMed

Yu, Jihnhee; Kepner, James L; Iyer, Renuka

2009-12-01

New therapy strategies for the treatment of cancer are rapidly emerging because of recent technology advances in genetics and molecular biology. Although newer targeted therapies can improve survival without measurable changes in tumor size, clinical trial conduct has remained nearly unchanged. When potentially efficacious therapies are tested, current clinical trial design and analysis methods may not be suitable for detecting therapeutic effects. We propose an exact method with respect to testing cytostatic cancer treatment using correlated bivariate binomial random variables to simultaneously assess two primary outcomes. The method is easy to implement. It does not increase the sample size over that of the univariate exact test and in most cases reduces the sample size required. Sample size calculations are provided for selected designs.

Factors associated with the decision of the rheumatologist to order sacroiliac joints magnetic resonance imaging (SI-MRI) or HLA-B27 testing in the diagnostic work-up of patients with spondyloarthritis in clinical practice.

PubMed

Bautista-Molano, Wilson; Landewé, Robert B M; Serna, Cesar; Valle-Oñate, Rafael; van der Heijde, Désirée

2017-01-01

To evaluate the patients' characteristics associated with the clinical decision to request SI-MRI and/or HLA-B27 in patients with SpA in daily practice. Patients referred to a rheumatology outpatient-clinic in a national referral-centre were selected. Patients with a clinical diagnosis of SpA according to the rheumatologist were included. SI-MRI and HLA-B27 was available for patients in whom the rheumatologists had ordered these tests. Characteristics associated with ordering SI-MRI or HLA-B27 were identified with univariable analyses. Variables with p-value <0.05 and >80% completeness were selected for further analysis. A multivariable logistic regression analysis was used to evaluate the determinants related with the decision to perform SI-MRI and/or HLA-B27 and odds ratios with 95% confidence intervals were calculated. In total, 581 patients with SpA were included in the cohort, 72% were men, mean age 34.6±12.1 and disease duration 7.3±9.7 years. Of these patients, 24% (n=137) had SI-MRI and 77% (n=441) had HLA-B27 tests ordered. Independently predictive factors for ordering a SI-MRI were the presence of IBP (OR=1.81), enthesitis (OR=1.57) and the number of initial-symptoms at presentation (OR=1.27 per additional symptom present). Independently predictive factors of HLA-B27 testing were the number of initial-symptoms (OR=1.45 per symptom) and uveitis (OR=3.19). This study strongly suggests that rheumatologists use certain clinical clues to decide if they order expensive and scarce tests in the diagnostic work-up of SpA patients. These manifestations may increase the efficiency of these tests in clinical practice and suggest that clinical reasoning follows principles of Bayesian theory.

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

PubMed Central

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

2014-01-01

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

A concise evidence-based physical examination for diagnosis of acromioclavicular joint pathology: a systematic review.

PubMed

Krill, Michael K; Rosas, Samuel; Kwon, KiHyun; Dakkak, Andrew; Nwachukwu, Benedict U; McCormick, Frank

2018-02-01

The clinical examination of the shoulder joint is an undervalued diagnostic tool for evaluating acromioclavicular (AC) joint pathology. Applying evidence-based clinical tests enables providers to make an accurate diagnosis and minimize costly imaging procedures and potential delays in care. The purpose of this study was to create a decision tree analysis enabling simple and accurate diagnosis of AC joint pathology. A systematic review of the Medline, Ovid and Cochrane Review databases was performed to identify level one and two diagnostic studies evaluating clinical tests for AC joint pathology. Individual test characteristics were combined in series and in parallel to improve sensitivities and specificities. A secondary analysis utilized subjective pre-test probabilities to create a clinical decision tree algorithm with post-test probabilities. The optimal special test combination to screen and confirm AC joint pathology combined Paxinos sign and O'Brien's Test, with a specificity of 95.8% when performed in series; whereas, Paxinos sign and Hawkins-Kennedy Test demonstrated a sensitivity of 93.7% when performed in parallel. Paxinos sign and O'Brien's Test demonstrated the greatest positive likelihood ratio (2.71); whereas, Paxinos sign and Hawkins-Kennedy Test reported the lowest negative likelihood ratio (0.35). No combination of special tests performed in series or in parallel creates more than a small impact on post-test probabilities to screen or confirm AC joint pathology. Paxinos sign and O'Brien's Test is the only special test combination that has a small and sometimes important impact when used both in series and in parallel. Physical examination testing is not beneficial for diagnosis of AC joint pathology when pretest probability is unequivocal. In these instances, it is of benefit to proceed with procedural tests to evaluate AC joint pathology. Ultrasound-guided corticosteroid injections are diagnostic and therapeutic. An ultrasound-guided AC joint corticosteroid injection may be an appropriate new standard for treatment and surgical decision-making. II - Systematic Review.

Knowledge and skills of cancer clinical trials nurses in Australia.

PubMed

Scott, Kathleen; White, Kate; Johnson, Catherine; Roydhouse, Jessica K

2012-05-01

  This paper is a report of the development and testing of a questionnaire measuring knowledge and skills of cancer clinical trials nurse in Australia.   The role of cancer clinical trials nurse, widely acknowledged as an integral member of the clinical research team, has evolved in recent years. Elements of the clinical trials nurse role in cancer have previously been described. To evaluate specific cancer clinical trials nurse educational and training needs, the development of a valid and reliable tool is required.   In 2009, a study was conducted in three stages. Stage I: questionnaire development and pilot testing; stage II: focus group; stage III: national survey. Internal consistency reliability testing and multi-trait analysis of item convergent/divergent validity were employed. Regression analysis was used to identify predictors of clinical trials nurse knowledge and skills.   The national survey was a 48-item questionnaire, measuring six clinical trial knowledge and seven skills sub-scales. Of 61 respondents, 90% were women, with mean age 43 years, 19 years as a Registered Nurse and 5 years as a cancer clinical trials nurse. Self-reported knowledge and skills were satisfactory to good. Internal consistency reliability was high (Cronbach's alpha: knowledge = 0·98; skills = 0·90). Criteria for item convergent/divergent validity were met. Number of years as cancer clinical trials nurse was positively related to self-reported knowledge and skills.   Preliminary data suggest that the national survey is reliable and valid. Data have contributed to better understanding the knowledge and skills of cancer clinical trials nurse in Australia and development of a postgraduate course in clinical trials. © 2011 Blackwell Publishing Ltd.

Big data in sleep medicine: prospects and pitfalls in phenotyping

PubMed Central

Bianchi, Matt T; Russo, Kathryn; Gabbidon, Harriett; Smith, Tiaundra; Goparaju, Balaji; Westover, M Brandon

2017-01-01

Clinical polysomnography (PSG) databases are a rich resource in the era of “big data” analytics. We explore the uses and potential pitfalls of clinical data mining of PSG using statistical principles and analysis of clinical data from our sleep center. We performed retrospective analysis of self-reported and objective PSG data from adults who underwent overnight PSG (diagnostic tests, n=1835). Self-reported symptoms overlapped markedly between the two most common categories, insomnia and sleep apnea, with the majority reporting symptoms of both disorders. Standard clinical metrics routinely reported on objective data were analyzed for basic properties (missing values, distributions), pairwise correlations, and descriptive phenotyping. Of 41 continuous variables, including clinical and PSG derived, none passed testing for normality. Objective findings of sleep apnea and periodic limb movements were common, with 51% having an apnea–hypopnea index (AHI) >5 per hour and 25% having a leg movement index >15 per hour. Different visualization methods are shown for common variables to explore population distributions. Phenotyping methods based on clinical databases are discussed for sleep architecture, sleep apnea, and insomnia. Inferential pitfalls are discussed using the current dataset and case examples from the literature. The increasing availability of clinical databases for large-scale analytics holds important promise in sleep medicine, especially as it becomes increasingly important to demonstrate the utility of clinical testing methods in management of sleep disorders. Awareness of the strengths, as well as caution regarding the limitations, will maximize the productive use of big data analytics in sleep medicine. PMID:28243157

An Alternative Study of Transfer of Learning in Clinical Evaluation.

ERIC Educational Resources Information Center

Patel, Vimla; Cranton, Patricia A.

The use of an alternative methodology to study transfer of learning in clinical instruction during medical school was investigated. The environment in which clinical instruction takes place was examined, after which hypotheses were proposed and tested in a quasi-experimental design. The first phase of the study, an ethnographic analysis of the…

Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys.

PubMed

Lee, David C; Varela, Aurore; Kostenuik, Paul J; Ominsky, Michael S; Keaveny, Tony M

2016-08-01

Finite element analysis has not yet been validated for measuring changes in whole-bone strength at the hip or spine in people after treatment with an osteoporosis agent. Toward that end, we assessed the ability of a clinically approved implementation of finite element analysis to correctly quantify treatment effects on vertebral strength, comparing against direct mechanical testing, in cynomolgus monkeys randomly assigned to one of three 16-month-long treatments: sham surgery with vehicle (Sham-Vehicle), ovariectomy with vehicle (OVX-Vehicle), or ovariectomy with denosumab (OVX-DMAb). After treatment, T12 vertebrae were retrieved, scanned with micro-CT, and mechanically tested to measure compressive strength. Blinded to the strength data and treatment codes, the micro-CT images were coarsened and homogenized to create continuum-type finite element models, without explicit porosity. With clinical translation in mind, these models were then analyzed for strength using the U.S. Food and Drug Administration (FDA)-cleared VirtuOst software application (O.N. Diagnostics, Berkeley, CA, USA), developed for analysis of human bones. We found that vertebral strength by finite element analysis was highly correlated (R(2)  = 0.97; n = 52) with mechanical testing, independent of treatment (p = 0.12). Further, the size of the treatment effect on strength (ratio of mean OVX-DMAb to mean OVX-Vehicle, as a percentage) was large and did not differ (p = 0.79) between mechanical testing (+57%; 95% CI [26%, 95%]) and finite element analysis (+51% [20%, 88%]). The micro-CT analysis revealed increases in cortical thickness (+45% [19%, 73%]) and trabecular bone volume fraction (+24% [8%, 42%]). These results show that a preestablished clinical finite element analysis implementation-developed for human bone and clinically validated in fracture-outcome studies-correctly quantified the observed treatment effects of denosumab on vertebral strength in cynomolgus monkeys. One implication is that the treatment effects in this study are well explained by the features contained within these finite element models, namely, the bone geometry and mass and the spatial distribution of bone mass. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Deciphering Sources of Variability in Clinical Pathology.

PubMed

Tripathi, Niraj K; Everds, Nancy E; Schultze, A Eric; Irizarry, Armando R; Hall, Robert L; Provencher, Anne; Aulbach, Adam

2017-01-01

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled "Deciphering Sources of Variability in Clinical Pathology-It's Not Just about the Numbers" that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

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

PubMed

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

2015-04-01

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

Socio-demographic and structural barriers to being tested for chlamydia in general practice.

PubMed

Lau, Andrew; Spark, Simone; Tomnay, Jane; Smith, Meredith T; Fairley, Christopher K; Guy, Rebecca J; Donovan, Basil; Hocking, Jane S

2016-02-15

To investigate socio-demographic and structural factors associated with not providing a specimen for chlamydia testing following a request by a general practitioner. Cross-sectional analysis of chlamydia testing data for men and women aged 16-29 years attending general practice clinics participating in a cluster randomised controlled trial evaluating the effectiveness of a chlamydia testing intervention. The study period was the 2013 calendar year. The proportion of chlamydia test requests for which the patient did not provide a specimen for testing. During the study period, there were 13 225 chlamydia test requests, for which a chlamydia test was not performed in 2545 instances (19.2%; 95% CI, 16.5-22.3%). Multivariate analysis indicated that the odds for not undertaking a requested test were higher for men (adjusted odds ratio [aOR], 1.4; 95% CI, 1.3-1.6), those aged 16-19 years (aOR, 1.3; 95% CI, 1.1-1.4), those living in areas of greater socio-economic disadvantage (aOR, 1.2; 95% CI, 1.1-1.4 for each additional quintile of Index of Relative Socio-economic Disadvantage), and those attending clinics without on-site pathology collection (aOR, 1.4; 95% CI, 1.0-1.9). One in five young people did not submit a specimen for chlamydia testing despite their GP requesting it. This highlights the need for clinics to establish systems which ensure that men and those aged 16-19 years undertake chlamydia tests requested by a GP.

Diagnostic accuracy of HLA-B*57:01 screening for the prediction of abacavir hypersensitivity and clinical utility of the test: a meta-analytic review.

PubMed

Cargnin, Sarah; Jommi, Claudio; Canonico, Pier Luigi; Genazzani, Armando A; Terrazzino, Salvatore

2014-05-01

To determine diagnostic accuracy of HLA-B*57:01 testing for prediction of abacavir-induced hypersensitivity and to quantify the clinical benefit of pretreatment screening through a meta-analytic review of published studies. A comprehensive search was performed up to June 2013. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. The pooled diagnostic estimates were calculated using a random effect model. Despite the presence of heterogeneity in sensitivity or specificity estimates, the pooled diagnostic odds ratio to detect abacavir-induced hypersensitivity on the basis of clinical criteria was 33.07 (95% CI: 22.33-48.97, I(2): 13.9%), while diagnostic odds ratio for detection of immunologically confirmed abacavir hypersensitivity was 1141 (95% CI: 409-3181, I(2): 0%). Pooled analysis of risk ratio showed that prospective HLA-B*57:01 testing significantly reduced the incidence of abacavir-induced hypersensitivity. This meta-analysis demonstrates an excellent diagnostic accuracy of HLA-B*57:01 testing to detect immunologically confirmed abacavir hypersensitivity and corroborates existing recommendations.

An automated smartphone-based diagnostic assay for point-of-care semen analysis

PubMed Central

Kanakasabapathy, Manoj Kumar; Sadasivam, Magesh; Singh, Anupriya; Preston, Collin; Thirumalaraju, Prudhvi; Venkataraman, Maanasa; Bormann, Charles L.; Draz, Mohamed Shehata; Petrozza, John C.; Shafiee, Hadi

2017-01-01

Male infertility affects up to 12% of the world’s male population and is linked to various environmental and medical conditions. Manual microscope-based testing and computer-assisted semen analysis (CASA) are the current standard methods to diagnose male infertility; however, these methods are labor-intensive, expensive, and laboratory-based. Cultural and socially dominated stigma against male infertility testing hinders a large number of men from getting tested for infertility, especially in resource-limited African countries. We describe the development and clinical testing of an automated smartphone-based semen analyzer designed for quantitative measurement of sperm concentration and motility for point-of-care male infertility screening. Using a total of 350 clinical semen specimens at a fertility clinic, we have shown that our assay can analyze an unwashed, unprocessed liquefied semen sample with <5-s mean processing time and provide the user a semen quality evaluation based on the World Health Organization (WHO) guidelines with ~98% accuracy. The work suggests that the integration of microfluidics, optical sensing accessories, and advances in consumer electronics, particularly smartphone capabilities, can make remote semen quality testing accessible to people in both developed and developing countries who have access to smartphones. PMID:28330865

HER2 testing of gastro-oesophageal adenocarcinoma: a commentary and guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee.

PubMed

Wong, Newton A C S; Amary, Fernanda; Butler, Rachel; Byers, Richard; Gonzalez, David; Haynes, Harry R; Ilyas, Mohammad; Salto-Tellez, Manuel; Taniere, Philippe

2018-05-01

The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Adequate application of quantitative and qualitative statistic analytic methods in acupuncture clinical trials].

PubMed

Tan, Ming T; Liu, Jian-ping; Lao, Lixing

2012-08-01

Recently, proper use of the statistical methods in traditional Chinese medicine (TCM) randomized controlled trials (RCTs) has received increased attention. Statistical inference based on hypothesis testing is the foundation of clinical trials and evidence-based medicine. In this article, the authors described the methodological differences between literature published in Chinese and Western journals in the design and analysis of acupuncture RCTs and the application of basic statistical principles. In China, qualitative analysis method has been widely used in acupuncture and TCM clinical trials, while the between-group quantitative analysis methods on clinical symptom scores are commonly used in the West. The evidence for and against these analytical differences were discussed based on the data of RCTs assessing acupuncture for pain relief. The authors concluded that although both methods have their unique advantages, quantitative analysis should be used as the primary analysis while qualitative analysis can be a secondary criterion for analysis. The purpose of this paper is to inspire further discussion of such special issues in clinical research design and thus contribute to the increased scientific rigor of TCM research.

Budget impact analysis of gene expression tests to aid therapy decisions for breast cancer patients in Germany.

PubMed

Lux, M P; Nabieva, N; Hildebrandt, T; Rebscher, H; Kümmel, S; Blohmer, J-U; Schrauder, M G

2018-02-01

Many women with early-stage, hormone receptor-positive breast cancer may not benefit from adjuvant chemotherapy. Gene expression tests can reduce chemotherapy over- and undertreatment by providing prognostic information on the likelihood of recurrence and, with Oncotype DX, predictive information on chemotherapy benefit. These tests are currently not reimbursed by German healthcare payers. An analysis was conducted to evaluate the budget impact of gene expression tests in Germany. Costs of gene expression tests and medical and non-medical costs associated with treatment were assessed from healthcare payer and societal perspectives. Costs were estimated from data collected at a university hospital and were combined with decision impact data for Oncotype DX, MammaPrint, Prosigna and EndoPredict (EPclin). Changes in chemotherapy use and budget impact were evaluated over 1 year for 20,000 women. Chemotherapy was associated with substantial annual costs of EUR 19,003 and EUR 84,412 per therapy from the healthcare payer and societal perspective, respectively. Compared with standard care, only Oncotype DX was associated with cost savings to healthcare payers and society (EUR 5.9 million and EUR 253 million, respectively). Scenario analysis showed that both women at high clinical but low genomic risk and low clinical but high genomic risk were important contributors to costs. Oncotype DX was the only gene expression test that was estimated to reduce costs versus standard care in Germany. The reimbursement of Oncotype DX testing in standard clinical practice in Germany should be considered. Copyright © 2017 Elsevier Ltd. All rights reserved.

A proposal for clinical genetics (genetics in medicine) education for medical technologists and other health professionals in Japan.

PubMed

Kohzaki, Hidetsugu

2014-01-01

Since the completion of the Human Genome Project, technology has developed markedly in fields such as medical genetics and genetic counseling in the medical arena. In particular, this technology has advanced the discovery of and ways of understanding various genes responsible for genetic diseases, and genetic polymorphisms thought to be associated with disease. Some have been implicated as factors in common lifestyle diseases and have increased the significance of genetic testing. In Japan, doctors and other health professionals, such as nurse and medical technologists have been engaged in genetic testing and genetic disease treatment. Chromosomal and gene aberrations were detected mainly by medical technologists. However, due to the nature of medical technologists who have to provide various clinical tests, such as blood test, pre-medical technology students are required to cover tremendous knowledge of different academic fields to pass the national exam. Therefore, the time allowed for such students to study chromosomal and gene analysis is quite limited. Moreover, they are forced to enter the medical setting without receiving sufficient training. Among them, only few medical technologists specialize in chromosomal and gene analysis. However, with the advancement of clinical genetics and development of chromosomal and gene analysis, conducting clinical practice is becoming more and more difficult for medical technologists who just passed the national exam. Also, doctors and other health professionals have not been able to keep up with service demands either. This paper attempts to address knowledge and skills gaps (especially clinical genetics, English, and ICT literacy) of medical technologists and we propose educational methods to prepare medical genetics professionals in Japan to meet these gaps.

Risk prediction for chronic kidney disease progression using heterogeneous electronic health record data and time series analysis.

PubMed

Perotte, Adler; Ranganath, Rajesh; Hirsch, Jamie S; Blei, David; Elhadad, Noémie

2015-07-01

As adoption of electronic health records continues to increase, there is an opportunity to incorporate clinical documentation as well as laboratory values and demographics into risk prediction modeling. The authors develop a risk prediction model for chronic kidney disease (CKD) progression from stage III to stage IV that includes longitudinal data and features drawn from clinical documentation. The study cohort consisted of 2908 primary-care clinic patients who had at least three visits prior to January 1, 2013 and developed CKD stage III during their documented history. Development and validation cohorts were randomly selected from this cohort and the study datasets included longitudinal inpatient and outpatient data from these populations. Time series analysis (Kalman filter) and survival analysis (Cox proportional hazards) were combined to produce a range of risk models. These models were evaluated using concordance, a discriminatory statistic. A risk model incorporating longitudinal data on clinical documentation and laboratory test results (concordance 0.849) predicts progression from state III CKD to stage IV CKD more accurately when compared to a similar model without laboratory test results (concordance 0.733, P<.001), a model that only considers the most recent laboratory test results (concordance 0.819, P < .031) and a model based on estimated glomerular filtration rate (concordance 0.779, P < .001). A risk prediction model that takes longitudinal laboratory test results and clinical documentation into consideration can predict CKD progression from stage III to stage IV more accurately than three models that do not take all of these variables into consideration. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Effect of slice thickness on brain magnetic resonance image texture analysis

PubMed Central

2010-01-01

Background The accuracy of texture analysis in clinical evaluation of magnetic resonance images depends considerably on imaging arrangements and various image quality parameters. In this paper, we study the effect of slice thickness on brain tissue texture analysis using a statistical approach and classification of T1-weighted images of clinically confirmed multiple sclerosis patients. Methods We averaged the intensities of three consecutive 1-mm slices to simulate 3-mm slices. Two hundred sixty-four texture parameters were calculated for both the original and the averaged slices. Wilcoxon's signed ranks test was used to find differences between the regions of interest representing white matter and multiple sclerosis plaques. Linear and nonlinear discriminant analyses were applied with several separate training and test sets to determine the actual classification accuracy. Results Only moderate differences in distributions of the texture parameter value for 1-mm and simulated 3-mm-thick slices were found. Our study also showed that white matter areas are well separable from multiple sclerosis plaques even if the slice thickness differs between training and test sets. Conclusions Three-millimeter-thick magnetic resonance image slices acquired with a 1.5 T clinical magnetic resonance scanner seem to be sufficient for texture analysis of multiple sclerosis plaques and white matter tissue. PMID:20955567

A psychometric analysis of the reading the mind in the eyes test: toward a brief form for research and applied settings

PubMed Central

Olderbak, Sally; Wilhelm, Oliver; Olaru, Gabriel; Geiger, Mattis; Brenneman, Meghan W.; Roberts, Richard D.

2015-01-01

The Reading the Mind in the Eyes Test is a popular measure of individual differences in Theory of Mind that is often applied in the assessment of particular clinical populations (primarily, individuals on the autism spectrum). However, little is known about the test's psychometric properties, including factor structure, internal consistency, and convergent validity evidence. We present a psychometric analysis of the test followed by an evaluation of other empirically proposed and statistically identified structures. We identified, and cross-validated in a second sample, an adequate short-form solution that is homogeneous with adequate internal consistency, and is moderately related to Cognitive Empathy, Emotion Perception, and strongly related to Vocabulary. We recommend the use of this short-form solution in normal adults as a more precise measure over the original version. Future revisions of the test should seek to reduce the test's reliance on one's vocabulary and evaluate the short-form structure in clinical populations. PMID:26500578

Using Multigroup Confirmatory Factor Analysis to Test Measurement Invariance in Raters: A Clinical Skills Examination Application

ERIC Educational Resources Information Center

Kahraman, Nilufer; Brown, Crystal B.

2015-01-01

Psychometric models based on structural equation modeling framework are commonly used in many multiple-choice test settings to assess measurement invariance of test items across examinee subpopulations. The premise of the current article is that they may also be useful in the context of performance assessment tests to test measurement invariance…

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation.

PubMed

Fleeman, N; McLeod, C; Bagust, A; Beale, S; Boland, A; Dundar, Y; Jorgensen, A; Payne, K; Pirmohamed, M; Pushpakom, S; Walley, T; de Warren-Penny, P; Dickson, R

2010-01-01

To determine whether testing for cytochrome P450 (CYP) polymorphisms in adults entering antipsychotic treatment for schizophrenia leads to improvement in outcomes, is useful in medical, personal or public health decision-making, and is a cost-effective use of health-care resources. The following electronic databases were searched for relevant published literature: Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA) Registry and the Centre for Health Economics website. In addition, publicly available information on various genotyping tests was sought from the internet and advisory panel members. A systematic review of analytical validity, clinical validity and clinical utility of CYP testing was undertaken. Data were extracted into structured tables and narratively discussed, and meta-analysis was undertaken when possible. A review of economic evaluations of CYP testing in psychiatry and a review of economic models related to schizophrenia were also carried out. For analytical validity, 46 studies of a range of different genotyping tests for 11 different CYP polymorphisms (most commonly CYP2D6) were included. Sensitivity and specificity were high (99-100%). For clinical validity, 51 studies were found. In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found. The only other significant finding linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the inclusion criteria for clinical utility. One economic evaluation assessing the costs and benefits of CYP testing for prescribing antidepressants and 28 economic models of schizophrenia were identified; none was suitable for developing a model to examine the cost-effectiveness of CYP testing. Tests for determining genotypes appear to be accurate although not all aspects of analytical validity were reported. Given the absence of convincing evidence from clinical validity studies, the lack of clinical utility and economic studies, and the unsuitability of published schizophrenia models, no model was developed; instead key features and data requirements for economic modelling are presented. Recommendations for future research cover both aspects of research quality and data that will be required to inform the development of future economic models.

Correlation between Histological Status of the Pulp and Its Response to Sensibility Tests

PubMed Central

Naseri, Mandana; Khayat, Akbar; Zamaheni, Sara; Shojaeian, Shiva

2017-01-01

Introduction: The purpose of this study was to assess the accuracy of sensibility tests by correlating it with histologic pulp condition. Methods and Materials: Assessment of clinical signs and symptoms were performed on 65 permanent teeth that were scheduled to be extracted for periodontal, prosthodontic or orthodontic reasons. The normal pulp and reversible pulpitis were considered as treatable tooth conditions while irreversible pulpitis and necrosis were considered as untreatable conditions. The teeth were then extracted and sectioned for histological analysis of dental pulp. Histologic status and classification corresponded to the treatable or untreatable pulp condition. Comparisons between histological treatable and untreatable pulp condition were performed with chi-square analysis for sensibility test responses. The positive predictive value (PPV), negative predictive value (NPV) and accuracy to detect untreatable from treatable pulp condition were calculated for each test. Results: A significant difference was detected in the normal and a sharp lingered response to heat and cold tests. There was significant difference in the negative response to EPT between histological groups. The kappa agreement coefficient between clinical and histological diagnosis of pulp condition was about 0.843 (P<0.001). The accuracy of cold and heat tests and EPT to detect treatable pulp or untreatable pulp states were 78, 74 and 62%, respectively. The sensibility tests diagnosed untreatable pulpitis with a higher probability (NPV=63%-67% -54%, PPV=83%-91% -95% for heat, cold and EPT, respectively). Conclusion: Sensibility test results were more likely to diagnose pulpal disease or untreatable pulp conditions. However, to increase the diagnostic accuracy patient history, clinical signs and symptoms and also radiographic findings in conjunction with sensibility tests must be used. The result of this small study demonstrated a good agreement between clinical and histological pulp diagnosis. PMID:28179918

Systematic Review and Meta-Analysis of Studies Evaluating Diagnostic Test Accuracy: A Practical Review for Clinical Researchers-Part II. Statistical Methods of Meta-Analysis

PubMed Central

Lee, Juneyoung; Kim, Kyung Won; Choi, Sang Hyun; Huh, Jimi

2015-01-01

Meta-analysis of diagnostic test accuracy studies differs from the usual meta-analysis of therapeutic/interventional studies in that, it is required to simultaneously analyze a pair of two outcome measures such as sensitivity and specificity, instead of a single outcome. Since sensitivity and specificity are generally inversely correlated and could be affected by a threshold effect, more sophisticated statistical methods are required for the meta-analysis of diagnostic test accuracy. Hierarchical models including the bivariate model and the hierarchical summary receiver operating characteristic model are increasingly being accepted as standard methods for meta-analysis of diagnostic test accuracy studies. We provide a conceptual review of statistical methods currently used and recommended for meta-analysis of diagnostic test accuracy studies. This article could serve as a methodological reference for those who perform systematic review and meta-analysis of diagnostic test accuracy studies. PMID:26576107

Two-sample statistics for testing the equality of survival functions against improper semi-parametric accelerated failure time alternatives: an application to the analysis of a breast cancer clinical trial.

PubMed

Broët, Philippe; Tsodikov, Alexander; De Rycke, Yann; Moreau, Thierry

2004-06-01

This paper presents two-sample statistics suited for testing equality of survival functions against improper semi-parametric accelerated failure time alternatives. These tests are designed for comparing either the short- or the long-term effect of a prognostic factor, or both. These statistics are obtained as partial likelihood score statistics from a time-dependent Cox model. As a consequence, the proposed tests can be very easily implemented using widely available software. A breast cancer clinical trial is presented as an example to demonstrate the utility of the proposed tests.

[Generalization of the results of clinical studies through the analysis of subgroups].

PubMed

Costa, João; Fareleira, Filipa; Ascensão, Raquel; Vaz Carneiro, António

2012-01-01

Subgroup analysis in clinical trials are usually performed to define the potential heterogeneity of treatment effect in relation with the baseline risk, physiopathology, practical application of therapy or the under-utilization in clinical practice of effective interventions due to uncertainties of its benefit/risk ratio. When appropriately planned, subgroup analysis are a valid methodology the define benefits in subgroups of patients, thus providing good quality evidence to support clinical decision making. However, in order to be correct, subgroup analysis should be defined a priori, done in small numbers, should be fully reported and, most important, must endure statistical tests for interaction. In this paper we present an example of the treatment of post-menopausal osteoporosis, in which the benefits of an intervention (the higher the fracture risk is, the better the benefit is) with a specific agent (bazedoxifene) was only disclosed after a post-hoc analysis of the initial global trial sample.

Introduction to Clinical Microbiology for the General Dentist.

PubMed

Rams, Thomas E; van Winkelhoff, Arie J

2017-04-01

Clinical oral microbiology may help dental professionals identify infecting pathogenic species and evaluate their in vitro antimicrobial susceptibility. Saliva, dental plaque biofilms, mucosal smears, abscess aspirates, and soft tissue biopsies are sources of microorganisms for laboratory testing. Microbial-based treatment end points may help clinicians better identify patients in need of additional or altered dental therapies before the onset of clinical treatment failure, and help improve patient oral health outcomes. Microbiological testing appears particularly helpful in periodontal disease treatment planning. Further research and technological advances are likely to increase the availability and clinical utility of microbiological analysis in modern dental practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Periodic limb movements of sleep: empirical and theoretical evidence supporting objective at-home monitoring

PubMed Central

Moro, Marilyn; Goparaju, Balaji; Castillo, Jelina; Alameddine, Yvonne; Bianchi, Matt T

2016-01-01

Introduction Periodic limb movements of sleep (PLMS) may increase cardiovascular and cerebrovascular morbidity. However, most people with PLMS are either asymptomatic or have nonspecific symptoms. Therefore, predicting elevated PLMS in the absence of restless legs syndrome remains an important clinical challenge. Methods We undertook a retrospective analysis of demographic data, subjective symptoms, and objective polysomnography (PSG) findings in a clinical cohort with or without obstructive sleep apnea (OSA) from our laboratory (n=443 with OSA, n=209 without OSA). Correlation analysis and regression modeling were performed to determine predictors of periodic limb movement index (PLMI). Markov decision analysis with TreeAge software compared strategies to detect PLMS: in-laboratory PSG, at-home testing, and a clinical prediction tool based on the regression analysis. Results Elevated PLMI values (>15 per hour) were observed in >25% of patients. PLMI values in No-OSA patients correlated with age, sex, self-reported nocturnal leg jerks, restless legs syndrome symptoms, and hypertension. In OSA patients, PLMI correlated only with age and self-reported psychiatric medications. Regression models indicated only a modest predictive value of demographics, symptoms, and clinical history. Decision modeling suggests that at-home testing is favored as the pretest probability of PLMS increases, given plausible assumptions regarding PLMS morbidity, costs, and assumed benefits of pharmacological therapy. Conclusion Although elevated PLMI values were commonly observed, routinely acquired clinical information had only weak predictive utility. As the clinical importance of elevated PLMI continues to evolve, it is likely that objective measures such as PSG or at-home PLMS monitors will prove increasingly important for clinical and research endeavors. PMID:27540316

Optimal management of adults with pharyngitis – a multi-criteria decision analysis

PubMed Central

Singh, Sonal; Dolan, James G; Centor, Robert M

2006-01-01

Background Current practice guidelines offer different management recommendations for adults presenting with a sore throat. The key issue is the extent to which the clinical likelihood of a Group A streptococcal infection should affect patient management decisions. To help resolve this issue, we conducted a multi-criteria decision analysis using the Analytic Hierarchy Process. Methods We defined optimal patient management using four criteria: 1) reduce symptom duration; 2) prevent infectious complications, local and systemic; 3) minimize antibiotic side effects, minor and anaphylaxis; and 4) achieve prudent use of antibiotics, avoiding both over-use and under-use. In our baseline analysis we assumed that all criteria and sub-criteria were equally important except minimizing anaphylactic side effects, which was judged very strongly more important than minimizing minor side effects. Management strategies included: a) No test, No treatment; b) Perform a rapid strep test and treat if positive; c) Perform a throat culture and treat if positive; d) Perform a rapid strep test and treat if positive; if negative obtain a throat culture and treat if positive; and e) treat without further tests. We defined four scenarios based on the likelihood of group A streptococcal infection using the Centor score, a well-validated clinical index. Published data were used to estimate the likelihoods of clinical outcomes and the test operating characteristics of the rapid strep test and throat culture for identifying group A streptococcal infections. Results Using the baseline assumptions, no testing and no treatment is preferred for patients with Centor scores of 1; two strategies – culture and treat if positive and rapid strep with culture of negative results – are equally preferable for patients with Centor scores of 2; and rapid strep with culture of negative results is the best management strategy for patients with Centor scores 3 or 4. These results are sensitive to the priorities assigned to the decision criteria, especially avoiding over-use versus under-use of antibiotics, and the population prevalence of Group A streptococcal pharyngitis. Conclusion The optimal clinical management of adults with sore throat depends on both the clinical probability of a group A streptococcal infection and clinical judgments that incorporate individual patient and practice circumstances. PMID:16533386

Influence networks among substance abuse treatment clinics: implications for the dissemination of innovations.

PubMed

Johnson, Kimberly; Quanbeck, Andrew; Maus, Adam; Gustafson, David H; Dearing, James W

2015-09-01

Understanding influence networks among substance abuse treatment clinics may speed the diffusion of innovations. The purpose of this study was to describe influence networks in Massachusetts, Michigan, New York, Oregon, and Washington and test two expectations, using social network analysis: (1) Social network measures can identify influential clinics; and (2) Within a network, some weakly connected clinics access out-of-network sources of innovative evidence-based practices and can spread these innovations through the network. A survey of 201 clinics in a parent study on quality improvement provided the data. Network measures and sociograms were obtained from adjacency matrixes created by UCINet. We used regression analysis to determine whether network status relates to clinics' adopting innovations. Findings suggest that influential clinics can be identified and that loosely linked clinics were likely to join the study sooner than more influential clinics but were not more likely to have improved outcomes than other organizations. Findings identify the structure of influence networks for SUD treatment organizations and have mixed results on how those structures impacted diffusion of the intervention under study. Further study is necessary to test whether use of knowledge of the network structure will have an effect on the pace and breadth of dissemination of innovations.

Responsiveness of clinical tests for people with neck pain.

PubMed

Jørgensen, René; Ris, Inge; Juhl, Carsten; Falla, Deborah; Juul-Kristensen, Birgit

2017-12-28

Responsiveness of a clinical test is highly relevant in order to evaluate the effect of a given intervention. However, the responsiveness of clinical tests for people with neck pain has not been adequately evaluated. The objective of the present study was to examine the responsiveness of four clinical tests which are low cost and easy to perform in a clinical setting, including the craniocervical flexion test, cervical active range of movement, test for the cervical extensors and pressure pain threshold testing. This study is a secondary analysis of data collected in a previously published randomised controlled trial. Participants were randomized to either physical training, exercises and pain education combined or pain education only. Participants were tested on the clinical tests at baseline and at 4-month follow-up. An anchor-based approach using Receiver Operator Characteristics (ROC) curves was used to evaluate responsiveness of the clinical tests. The Neck Disability Index was used to discriminate between those who had improved and those who were unchanged at the 4-month follow-up. Minimum Clinically Important Difference (MCID), together with sensitivity, specificity, positive and negative predictive values, in addition to positive and negative likelihood ratios were calculated. In total, 164 participants completed the 4 month follow up. One-hundred forty four participants were classified as unchanged whereas 20 patients were considered to be improved. Twenty-six participants didn't complete all of the clinical tests, leaving a total of 138 to be included for analyses. Area Under Curve (AUC) ranged from 0.50-0.62 for the clinical tests, and were all below an acceptable level. MCID was generally large, and the corresponding sensitivity and specificity was low with sensitivity ranging from 20 to 60%, and specificity from 54 to 86%. LR+ (0.8-2.07) and LR- (0.7-1.1) showed low diagnostic value for all variables, with PPV ranging from 12.1 to 26.1 and NPV ranging from 84.7 to 89.2. Responsiveness of the included clinical tests was generally low when using change in NDI score as the anchor from baseline to the 4-month follow up. Further investigations of responsiveness are warranted, possibly using other anchors, which to a higher degree resemble similar dimensions as the clinical tests.

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

PubMed Central

Peto, R.; Pike, M. C.; Armitage, P.; Breslow, N. E.; Cox, D. R.; Howard, S. V.; Mantel, N.; McPherson, K.; Peto, J.; Smith, P. G.

1977-01-01

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses. PMID:831755

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

PubMed

Kumar, Amal; Chakraborty, Bhaswat S

2016-01-01

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

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

PubMed

Mandelker, Diana; Zhang, Liying; Kemel, Yelena; Stadler, Zsofia K; Joseph, Vijai; Zehir, Ahmet; Pradhan, Nisha; Arnold, Angela; Walsh, Michael F; Li, Yirong; Balakrishnan, Anoop R; Syed, Aijazuddin; Prasad, Meera; Nafa, Khedoudja; Carlo, Maria I; Cadoo, Karen A; Sheehan, Meg; Fleischut, Megan H; Salo-Mullen, Erin; Trottier, Magan; Lipkin, Steven M; Lincoln, Anne; Mukherjee, Semanti; Ravichandran, Vignesh; Cambria, Roy; Galle, Jesse; Abida, Wassim; Arcila, Marcia E; Benayed, Ryma; Shah, Ronak; Yu, Kenneth; Bajorin, Dean F; Coleman, Jonathan A; Leach, Steven D; Lowery, Maeve A; Garcia-Aguilar, Julio; Kantoff, Philip W; Sawyers, Charles L; Dickler, Maura N; Saltz, Leonard; Motzer, Robert J; O'Reilly, Eileen M; Scher, Howard I; Baselga, Jose; Klimstra, David S; Solit, David B; Hyman, David M; Berger, Michael F; Ladanyi, Marc; Robson, Mark E; Offit, Kenneth

2017-09-05

Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing. Since May 2015, 1040 of these patients with advanced cancer were referred by their oncologists for germline analysis of 76 cancer predisposition genes. Patients with clinically actionable inherited mutations whose genetic test results would not have been predicted by published decision rules were identified. Follow-up for potential clinical implications of mutation detection was through May 2017. Tumor and germline sequencing compared with the predicted yield of targeted germline sequencing based on clinical guidelines. Proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing that would not have been detected by guideline-directed testing. Of 1040 patients, the median age was 58 years (interquartile range, 50.5-66 years), 65.3% were male, and 81.3% had stage IV disease at the time of genomic analysis, with prostate, renal, pancreatic, breast, and colon cancer as the most common diagnoses. Of the 1040 patients, 182 (17.5%; 95% CI, 15.3%-19.9%) had clinically actionable mutations conferring cancer susceptibility, including 149 with moderate- to high-penetrance mutations; 101 patients tested (9.7%; 95% CI, 8.1%-11.7%) would not have had these mutations detected using clinical guidelines, including 65 with moderate- to high-penetrance mutations. Frequency of inherited mutations was related to case mix, stage, and founder mutations. Germline findings led to discussion or initiation of change to targeted therapy in 38 patients tested (3.7%) and predictive testing in the families of 13 individuals (1.3%), including 6 for whom genetic evaluation would not have been initiated by guideline-based testing. In this referral population with selected advanced cancers, universal sequencing of a broad panel of cancer-related genes in paired germline and tumor DNA samples was associated with increased detection of individuals with potentially clinically significant heritable mutations over the predicted yield of targeted germline testing based on current clinical guidelines. Knowledge of these additional mutations can help guide therapeutic and preventive interventions, but whether all of these interventions would improve outcomes for patients with cancer or their family members requires further study. clinicaltrials.gov Identifier: NCT01775072.

Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis

PubMed Central

Biswas, Hope H.; Ortega, Oscar; Gordon, Aubree; Standish, Katherine; Balmaseda, Angel; Kuan, Guillermina; Harris, Eva

2012-01-01

Background Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. Methods Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. Results One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. Conclusions Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management. PMID:22413033

Clinical implementation of RNA signatures for pharmacogenomic decision-making

PubMed Central

Tang, Weihua; Hu, Zhiyuan; Muallem, Hind; Gulley, Margaret L

2011-01-01

RNA profiling is increasingly used to predict drug response, dose, or toxicity based on analysis of drug pharmacokinetic or pharmacodynamic pathways. Before implementing multiplexed RNA arrays in clinical practice, validation studies are carried out to demonstrate sufficient evidence of analytic and clinical performance, and to establish an assay protocol with quality assurance measures. Pathologists assure quality by selecting input tissue and by interpreting results in the context of the input tissue as well as the technologies that were used and the clinical setting in which the test was ordered. A strength of RNA profiling is the array-based measurement of tens to thousands of RNAs at once, including redundant tests for critical analytes or pathways to promote confidence in test results. Instrument and reagent manufacturers are crucial for supplying reliable components of the test system. Strategies for quality assurance include careful attention to RNA preservation and quality checks at pertinent steps in the assay protocol, beginning with specimen collection and proceeding through the various phases of transport, processing, storage, analysis, interpretation, and reporting. Specimen quality is checked by probing housekeeping transcripts, while spiked and exogenous controls serve as a check on analytic performance of the test system. Software is required to manipulate abundant array data and present it for interpretation by a laboratory physician who reports results in a manner facilitating therapeutic decision-making. Maintenance of the assay requires periodic documentation of personnel competency and laboratory proficiency. These strategies are shepherding genomic arrays into clinical settings to provide added value to patients and to the larger health care system. PMID:23226056

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents.

PubMed

Leigh, Margaret W; Ferkol, Thomas W; Davis, Stephanie D; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D; Sagel, Scott D; Milla, Carlos; Olivier, Kenneth N; Sullivan, Kelli M; Zariwala, Maimoona A; Pittman, Jessica E; Shapiro, Adam J; Carson, Johnny L; Krischer, Jeffrey; Hazucha, Milan J; Knowles, Michael R

2016-08-01

Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0-18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as "definite PCD" (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), "probable/possible PCD" (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and "other diagnosis or undefined." Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. From 534 participants 18 years of age and younger, 205 were identified as having "definite PCD" (including 164 with two mutations in a PCD-associated gene), 187 were categorized as "other diagnosis or undefined," and 142 were defined as having "probable/possible PCD." Participants with "definite PCD" were compared with the "other diagnosis or undefined" group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167).

Development and initial evaluation of the Clinical Information Systems Success Model (CISSM).

PubMed

Garcia-Smith, Dianna; Effken, Judith A

2013-06-01

Most clinical information systems (CIS) today are technically sound, but the number of successful implementations of these systems is low. The purpose of this study was to develop and test a theoretically based integrated CIS Success Model (CISSM) from the nurse perspective. Model predictors of CIS success were taken from existing research on information systems acceptance, user satisfaction, use intention, user behavior and perceptions, as well as clinical research. Data collected online from 234 registered nurses in four hospitals were used to test the model. Each nurse had used the Cerner Power Chart Admission Health Profile for at least 3 months. Psychometric testing and factor analysis of the 23-item CISSM instrument established its construct validity and reliability. Initial analysis showed nurses' satisfaction with and dependency on CIS use predicted their perceived CIS use Net Benefit. Further analysis identified Social Influence and Facilitating Conditions as other predictors of CIS user Net Benefit. The level of hospital CIS integration may account for the role of CIS Use Dependency in the success of CIS. Based on our experience, CISSM provides a formative as well as summative tool for evaluating CIS success from the nurse's perspective. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

PubMed Central

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-01-01

Purpose Genetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. Methods We prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing. Results WGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A. Conclusion WGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort. PMID:28771251

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.

PubMed

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-04-01

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

Rapid phenotypic antimicrobial susceptibility testing using nanoliter arrays.

PubMed

Avesar, Jonathan; Rosenfeld, Dekel; Truman-Rosentsvit, Marianna; Ben-Arye, Tom; Geffen, Yuval; Bercovici, Moran; Levenberg, Shulamit

2017-07-18

Antibiotic resistance is a major global health concern that requires action across all sectors of society. In particular, to allow conservative and effective use of antibiotics clinical settings require better diagnostic tools that provide rapid determination of antimicrobial susceptibility. We present a method for rapid and scalable antimicrobial susceptibility testing using stationary nanoliter droplet arrays that is capable of delivering results in approximately half the time of conventional methods, allowing its results to be used the same working day. In addition, we present an algorithm for automated data analysis and a multiplexing system promoting practicality and translatability for clinical settings. We test the efficacy of our approach on numerous clinical isolates and demonstrate a 2-d reduction in diagnostic time when testing bacteria isolated directly from urine samples.

Development of Amplified 16S Ribosomal DNA Restriction Analysis for Identification of Actinomyces Species and Comparison with Pyrolysis-Mass Spectrometry and Conventional Biochemical Tests

PubMed Central

Hall, Val; O’Neill, G. L.; Magee, J. T.; Duerden, B. I.

1999-01-01

Identification of Actinomyces spp. by conventional phenotypic methods is notoriously difficult and unreliable. Recently, the application of chemotaxonomic and molecular methods has clarified the taxonomy of the group and has led to the recognition of several new species. A practical and discriminatory identification method is now needed for routine identification of clinical isolates. Amplified 16S ribosomal DNA restriction analysis (ARDRA) was applied to reference strains (n = 27) and clinical isolates (n = 36) of Actinomyces spp. and other gram-positive rods. Clinical strains were identified initially to the species level by conventional biochemical tests. However, given the low degree of confidence in conventional methods, the findings obtained by ARDRA were also compared with those obtained by pyrolysis-mass spectrometry. The ARDRA profiles generated by the combination of HaeIII and HpaII endonuclease digestion differentiated all reference strains to the species or subspecies level. The profiles correlated well with the findings obtained by pyrolysis-mass spectrometry and by conventional tests and enabled the identification of 31 of 36 clinical isolates to the species level. ARDRA was shown to be a simple, rapid, cost-effective, and highly discriminatory method for routine identification of Actinomyces spp. of clinical origin. PMID:10364594

The UK Clinical Aptitude Test and clinical course performance at Nottingham: a prospective cohort study.

PubMed

Yates, Janet; James, David

2013-02-26

The UK Clinical Aptitude Test (UKCAT) was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Verbal Reasoning, Quantitative Reasoning, Abstract Reasoning, and Decision Analysis), and the results are available to students and admission panels in advance of the selection process. Our first study showed little evidence of any predictive validity for performance in the first two years of the Nottingham undergraduate course.The study objective was to determine whether the UKCAT scores had any predictive value for the later parts of the course, largely delivered via clinical placements. Students entering the course in 2007 and who had taken the UKCAT were asked for permission to use their anonymised data in research. The UKCAT scores were incorporated into a database with routine pre-admission socio-demographics and subsequent course performance data. Correlation analysis was followed by hierarchical multivariate linear regression. The original study group comprised 204/254 (80%) of the full entry cohort. With attrition over the five years of the course this fell to 185 (73%) by Year 5. The Verbal Reasoning score and the UKCAT Total score both demonstrated some univariate correlations with clinical knowledge marks, and slightly less with clinical skills. No parts of the UKCAT proved to be an independent predictor of clinical course marks, whereas prior attainment was a highly significant predictor (p <0.001). This study of one cohort of Nottingham medical students showed that UKCAT scores at admission did not independently predict subsequent performance on the course. Whilst the test adds another dimension to the selection process, its fairness and validity in selecting promising students remains unproven, and requires wider investigation and debate by other schools.

Advanced Techniques in Pulmonary Function Test Analysis Interpretation and Diagnosis

PubMed Central

Gildea, T.J.; Bell, C. William

1980-01-01

The Pulmonary Functions Analysis and Diagnostic System is an advanced clinical processing system developed for use at the Pulmonary Division, Department of Medicine at the University of Nebraska Medical Center. The system generates comparative results and diagnostic impressions for a variety of routine and specialized pulmonary functions test data. Routine evaluation deals with static lung volumes, breathing mechanics, diffusing capacity, and blood gases while specialized tests include lung compliance studies, small airways dysfunction studies and dead space to tidal volume ratios. Output includes tabular results of normal vs. observed values, clinical impressions and commentary and, where indicated, a diagnostic impression. A number of pulmonary physiological and state variables are entered or sampled (A to D) with periodic status reports generated for the test supervisor. Among the various physiological variables sampled are respiratory frequency, minute ventilation, oxygen consumption, carbon dioxide production, and arterial oxygen saturation.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Reliability of physical functioning tests in patients with low back pain: a systematic review.

PubMed

Denteneer, Lenie; Van Daele, Ulrike; Truijen, Steven; De Hertogh, Willem; Meirte, Jill; Stassijns, Gaetane

2018-01-01

The aim of this study was to provide a comprehensive overview of physical functioning tests in patients with low back pain (LBP) and to investigate their reliability. A systematic computerized search was finalized in four different databases on June 24, 2017: PubMed, Web of Science, Embase, and MEDLINE. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed during all stages of this review. Clinical studies that investigate the reliability of physical functioning tests in patients with LBP were eligible. The methodological quality of the included studies was assessed with the use of the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. To come to final conclusions on the reliability of the identified clinical tests, the current review assessed three factors, namely, outcome assessment, methodological quality, and consistency of description. A total of 20 studies were found eligible and 38 clinical tests were identified. Good overall test-retest reliability was concluded for the extensor endurance test (intraclass correlation coefficient [ICC]=0.93-0.97), the flexor endurance test (ICC=0.90-0.97), the 5-minute walking test (ICC=0.89-0.99), the 50-ft walking test (ICC=0.76-0.96), the shuttle walk test (ICC=0.92-0.99), the sit-to-stand test (ICC=0.91-0.99), and the loaded forward reach test (ICC=0.74-0.98). For inter-rater reliability, only one test, namely, the Biering-Sörensen test (ICC=0.88-0.99), could be concluded to have an overall good inter-rater reliability. None of the identified clinical tests could be concluded to have a good intrarater reliability. Further investigation should focus on a better overall study methodology and the use of identical protocols for the description of clinical tests. The assessment of reliability is only a first step in the recommendation process for the use of clinical tests. In future research, the identified clinical tests in the current review should be further investigated for validity. Only when these clinimetric properties of a clinical test have been thoroughly investigated can a final conclusion regarding the clinical and scientific use of the identified tests be made. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression profiling and expanded immunohistochemistry tests to guide the use of adjuvant chemotherapy in breast cancer management: a systematic review and cost-effectiveness analysis.

PubMed

Ward, S; Scope, A; Rafia, R; Pandor, A; Harnan, S; Evans, P; Wyld, L

2013-10-01

Gene expression profiling (GEP) and expanded immunohistochemistry (IHC) tests aim to improve decision-making relating to adjuvant chemotherapy for women with early breast cancer. The aim of this report is to assess the clinical effectiveness and cost-effectiveness of nine GEP and expanded IHC tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer in England and Wales. The nine tests are BluePrint, Breast Cancer Index (BCI), IHC4, MammaPrint, Mammostrat, NPI plus (NPI+), OncotypeDX, PAM50 and Randox Breast Cancer Array. Databases searched included MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. Databases were searched from January 2009 to May 2011 for the OncotypeDX and MammaPrint tests and from January 2002 to May 2011 for the other tests. A systematic review of the evidence on clinical effectiveness (analytical validity, clinical validity and clinical utility) and cost-effectiveness was conducted. An economic model was developed to evaluate the cost-effectiveness of adjuvant chemotherapy treatment guided by four of the nine test (OncotypeDX, IHC4, MammaPrint and Mammostrat) compared with current clinical practice in England and Wales, using clinicopathological parameters, in women with oestrogen receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early breast cancer. The literature searches for clinical effectiveness identified 5993 citations, of which 32 full-text papers or abstracts (30 studies) satisfied the criteria for the effectiveness review. A narrative synthesis was performed. Evidence for OncotypeDX supported the prognostic capability of the test. There was some evidence on the impact of the test on decision-making and to support the case that OncotypeDX predicts chemotherapy benefit; however, few studies were UK based and limitations in relation to study design were identified. Evidence for MammaPrint demonstrated that the test score was a strong independent prognostic factor, but the evidence is non-UK based and is based on small sample sizes. Evidence on the Mammostrat test showed that the test was an independent prognostic tool for women with ER+, tamoxifen-treated breast cancer. The three studies appeared to be of reasonable quality and provided data from a UK setting (one study). One large study reported on clinical validity of the IHC4 test, with IHC4 score a highly significant predictor of distant recurrence. This study included data from a UK setting and appeared to be of reasonable quality. Evidence for the remaining five tests (PAM50, NPI+, BCI, BluePrint and Randox) was limited. The economic analysis suggests that treatment guided using IHC4 has the greatest potential to be cost-effective at a £20,000 threshold, given the low cost of the test; however, further research is needed on the analytical validity and clinical utility of IHC4, and the exact cost of the test needs to be confirmed. Current limitations in the evidence base produce significant uncertainty in the results. OncotypeDX has a more robust evidence base, but further evidence on its impact on decision-making in the UK and the predictive ability of the test in an ER+, LN-, HER- population receiving current drug regimens is needed. For MammaPrint and Mammostrat there were significant gaps in the available evidence and the estimates of cost-effectiveness produced were not considered to be robust by the External Assessment Group. Methodological weaknesses in the clinical evidence base relate to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence. Further evidence is required on the clinical utility of all of the tests and on UK-based populations. A key area of uncertainty relates to whether the tests provide prognostic or predictive ability. The clinical evidence base for OncotypeDX is considered to be the most robust. The economic analysis suggested that treatment guided using IHC4 has the most potential to be cost-effective at a threshold of £20,000; however, the evidence base to support IHC4 needs significant further research. PROSPERO 2011:CRD42011001361, available from www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42011001361.

Measuring continuous baseline covariate imbalances in clinical trial data

PubMed Central

Ciolino, Jody D.; Martin, Renee’ H.; Zhao, Wenle; Hill, Michael D.; Jauch, Edward C.; Palesch, Yuko Y.

2014-01-01

This paper presents and compares several methods of measuring continuous baseline covariate imbalance in clinical trial data. Simulations illustrate that though the t-test is an inappropriate method of assessing continuous baseline covariate imbalance, the test statistic itself is a robust measure in capturing imbalance in continuous covariate distributions. Guidelines to assess effects of imbalance on bias, type I error rate, and power for hypothesis test for treatment effect on continuous outcomes are presented, and the benefit of covariate-adjusted analysis (ANCOVA) is also illustrated. PMID:21865270

[Analysis of breath hydrogen (H2) in diagnosis of gastrointestinal function: validation of a pocket breath H2 test analyzer].

PubMed

Braden, B; Braden, C P; Klutz, M; Lembcke, B

1993-04-01

Breath hydrogen (H2) analysis, as used in gastroenterologic function tests, requires a stationary analysis system equipped with a gaschromatograph or an electrochemical sensor cell. Now a portable breath H2-analyzer has been miniaturized to pocket size (104 mm x 62 mm x 29 mm). The application of this device in clinical practice has been assessed in comparison to the standard GMI-exhaled monitor. The pocket analyzer showed a linear response to standards with H2-concentrations ranging from 0-100 ppm (n = 7), which was not different from the GMI-apparatus. The correlation of both methods during clinical application (lactose tolerance tests, mouth-to-coecum transit time determined with lactulose) was excellent (Y = 1.08 X + 0.96; r = 0.959). Using the new device, both, analysis (3 s vs. 90 s) and the reset-time (43 s vs. 140 s) were shorter whereas calibration was more feasible with the GMI-apparatus. It is concluded, that the considerably cheaper pocket-sized breath H2-analyzer is as precise and sensitive as the GMI-exhaled monitor, and thus presents a valid alternative for H2-breath tests.

The characterisation of next generation ceramic bearings for orthopaedic hip applications

NASA Astrophysics Data System (ADS)

Insley, Gerard M.

Two zirconia toughened alumina ceramic materials were characterised for application as bearing surfaces for hip joint arthroplasty. Both ceramics were supplied by orthopaedic ceramic suppliers in the form of flat discs, flexural strength bars and finished ball heads and cups. Analysis techniques involved standard and novel test methods in order to gauge the suitability of the ZTA for this application. These included mechanical strength testing, phase composition analysis by x-ray diffraction, accelerated and real time stability testing, friction testing and hip simulator testing under standard and nonstandard conditions. Alumina was used as a control in all testing. The results show the ZTA materials to be 50 to 75% stronger and up to 25% tougher than the alumina. Both materials differ in terms of their processing, microstructure and crystalline phase composition, however both showed no tetragonal to monoclinic degradation after both accelerated and real time ageing. The friction and wear tests show the ZTA to be performing as well as the alumina in normal test conditions. However, when microseparation is introduced into the hip simulator testing the ZTA ceramics wear significantly less than the alumina. Clinical analysis of a series of explanted heads showed that microseparation definitely occurs in the clinical situation with wear scars observed in eleven out of sixteen components. Zirconia toughened alumina is suitable as a fourth generation bearing surface for hip joint arthroplasty.

qPCR-High resolution melt analysis for drug susceptibility testing of Mycobacterium leprae directly from clinical specimens of leprosy patients.

PubMed

Araujo, Sergio; Goulart, Luiz Ricardo; Truman, Richard W; Goulart, Isabela Maria B; Vissa, Varalakshmi; Li, Wei; Matsuoka, Masanori; Suffys, Philip; Fontes, Amanda B; Rosa, Patricia S; Scollard, David M; Williams, Diana L

2017-06-01

Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite's stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite's stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing. Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy.

What's to Be Done About Laboratory Quality? Process Indicators, Laboratory Stewardship, the Outcomes Problem, Risk Assessment, and Economic Value: Responding to Contemporary Global Challenges.

PubMed

Meier, Frederick A; Badrick, Tony C; Sikaris, Kenneth A

2018-02-17

For 50 years, structure, process, and outcomes measures have assessed health care quality. For clinical laboratories, structural quality has generally been assessed by inspection. For assessing process, quality indicators (QIs), statistical monitors of steps in the clinical laboratory total testing, have proliferated across the globe. Connections between structural and process laboratory measures and patient outcomes, however, have rarely been demonstrated. To inform further development of clinical laboratory quality systems, we conducted a selective but worldwide review of publications on clinical laboratory quality assessment. Some QIs, like seven generic College of American Pathologists Q-Tracks monitors, have demonstrated significant process improvement; other measures have uncovered critical opportunities to improve test selection and result management. The College of Pathologists of Australasia Key Indicator Monitoring and Management System has deployed risk calculations, introduced from failure mode effects analysis, as surrogate measures for outcomes. Showing economic value from clinical laboratory testing quality is a challenge. Clinical laboratories should converge on fewer (7-14) rather than more (21-35) process monitors; monitors should cover all steps of the testing process under laboratory control and include especially high-risk specimen-quality QIs. Clinical laboratory stewardship, the combination of education interventions among clinician test orderers and report consumers with revision of test order formats and result reporting schemes, improves test ordering, but improving result reception is more difficult. Risk calculation reorders the importance of quality monitors by balancing three probabilities: defect frequency, weight of potential harm, and detection difficulty. The triple approach of (1) a more focused suite of generic consensus quality indicators, (2) more active clinical laboratory testing stewardship, and (3) integration of formal risk assessment, rather than competing with economic value, enhances it.

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

PubMed

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

2017-06-01

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

Regression-based statistical mediation and moderation analysis in clinical research: Observations, recommendations, and implementation.

PubMed

Hayes, Andrew F; Rockwood, Nicholas J

2017-11-01

There have been numerous treatments in the clinical research literature about various design, analysis, and interpretation considerations when testing hypotheses about mechanisms and contingencies of effects, popularly known as mediation and moderation analysis. In this paper we address the practice of mediation and moderation analysis using linear regression in the pages of Behaviour Research and Therapy and offer some observations and recommendations, debunk some popular myths, describe some new advances, and provide an example of mediation, moderation, and their integration as conditional process analysis using the PROCESS macro for SPSS and SAS. Our goal is to nudge clinical researchers away from historically significant but increasingly old school approaches toward modifications, revisions, and extensions that characterize more modern thinking about the analysis of the mechanisms and contingencies of effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factitious diarrhea induced by stimulant laxatives: accuracy of diagnosis by a clinical reference laboratory using thin layer chromatography.

PubMed

Shelton, Joseph H; Santa Ana, Carol A; Thompson, Donald R; Emmett, Michael; Fordtran, John S

2007-01-01

Surreptitious ingestion of laxatives can lead to serious factitious diseases that are difficult to diagnose. Most cases involve ingestion of bisacodyl or senna. Thin layer chromatography (TLC) of urine or stool is the only commercially available test for these laxatives. Such testing is considered highly reliable, but its accuracy in clinical practice is unknown. Our aim was to evaluate the reliability of TLC laxative testing by a clinical reference laboratory in the United States. Diarrhea was induced in healthy volunteers by ingestion of bisacodyl, senna, or a control laxative (n = 11 for each laxative group). Samples of urine and diarrheal stool were sent in blinded fashion to the clinical reference laboratory for bisacodyl and senna analysis. TLC testing for bisacodyl-induced diarrhea revealed a sensitivity of 73% and specificity of 91% when urine was tested and sensitivity and specificity of 91% and 96%, respectively, when stool was analyzed. When diarrhea was induced by senna, the TLC assay for senna failed to identify even a single urine or stool specimen as positive (zero% sensitivity). Considering the expected prevalence of surreptitious laxative abuse in patients with chronic idiopathic diarrhea (2.4%-25%, depending on the clinical setting), TLC of urine or stool for bisacodyl by this reference laboratory would often produce misleading results, and testing for senna would have no clinical value. The major problems are false-positive tests for bisacodyl and false-negative tests for senna.

Clinical Tests Have Limited Predictive Value for Chronic Ankle Instability When Conducted in the Acute Phase of a First-Time Lateral Ankle Sprain Injury.

PubMed

Doherty, Cailbhe; Bleakley, Chris; Hertel, Jay; Caulfield, Brian; Ryan, John; Delahunt, Eamonn

2018-04-01

To evaluate whether a battery of clinical assessments for acute lateral ankle sprain (LAS) can be used to predict long-term recovery. Cohort study. University biomechanics laboratory. Individuals (N=82) were assessed using a clinical test battery within 2 weeks of incurring a first-time LAS. Not applicable. The clinical test battery included scores on the talar glide test (degrees), the anterior drawer, talar tilt, figure of 8 for swelling (millimeters) and knee to wall (millimeters) tests, and handheld goniometric range of motion (inversion, eversion, and plantarflexion [in degrees]). Scores on the Cumberland Ankle Instability Tool taken 12 months after the clinical test battery were used to classify participants as having chronic ankle instability (CAI) or as being LAS copers. Forty percent of participants were designated as having CAI, with 60% being designated as LAS copers. A logistic regression analysis revealed that a combined model using scores from the talar glide, talar tilt, and anterior drawer tests in addition to plantarflexion range of motion was statistically significant (P<.01) and correctly classified cases with moderate accuracy (68.8%). The final model had moderate sensitivity (64%) and good specificity (72%). The clinical tests used in this investigation have limited predictive value for CAI when conducted in the acute phase of a first-time LAS injury. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

TU-B-304-01: The Aftermath of TG-142

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

Klein, E.

2015-06-15

Although published in 2009, the AAPM TG-142 report on accelerator quality assurance still proves a challenge for full clinical implementation. The choice of methodologies to satisfy TG-142 requirements is critical to a successful application. Understanding the philosophy of TG-142 can help in creating an institution-specific QA practice that is both efficient and effective. The concept of maintaining commissioned beam profiles is still found confusing. The physicist must also consider technologies not covered by TG-142 (i.e. arc therapy techniques). On the horizon is TG-198 report on implementing TG-142. Although the community still lacks a final TG-100 report, performing a failure-mode -and-effectsmore » analysis and statistical process control analysis to determine the institution-specific clinical impact of each TG-142 test may be useful for identifying trends for pro-active surveillance. Learning Objectives: To better understand the confusing and controversial aspects of TG-142. To understand what is still missing from TG-142 and how to account for these tests in clinical practice To describe which QA tests in TG-142 yield the largest potential clinical result if not discovered.« less

TU-B-304-02: Quantitative FMEA of TG-142

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

O’Daniel, J.

2015-06-15

Although published in 2009, the AAPM TG-142 report on accelerator quality assurance still proves a challenge for full clinical implementation. The choice of methodologies to satisfy TG-142 requirements is critical to a successful application. Understanding the philosophy of TG-142 can help in creating an institution-specific QA practice that is both efficient and effective. The concept of maintaining commissioned beam profiles is still found confusing. The physicist must also consider technologies not covered by TG-142 (i.e. arc therapy techniques). On the horizon is TG-198 report on implementing TG-142. Although the community still lacks a final TG-100 report, performing a failure-mode -and-effectsmore » analysis and statistical process control analysis to determine the institution-specific clinical impact of each TG-142 test may be useful for identifying trends for pro-active surveillance. Learning Objectives: To better understand the confusing and controversial aspects of TG-142. To understand what is still missing from TG-142 and how to account for these tests in clinical practice To describe which QA tests in TG-142 yield the largest potential clinical result if not discovered.« less

TU-B-304-00: The Aftermath of TG-142

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

NONE

2015-06-15

Although published in 2009, the AAPM TG-142 report on accelerator quality assurance still proves a challenge for full clinical implementation. The choice of methodologies to satisfy TG-142 requirements is critical to a successful application. Understanding the philosophy of TG-142 can help in creating an institution-specific QA practice that is both efficient and effective. The concept of maintaining commissioned beam profiles is still found confusing. The physicist must also consider technologies not covered by TG-142 (i.e. arc therapy techniques). On the horizon is TG-198 report on implementing TG-142. Although the community still lacks a final TG-100 report, performing a failure-mode -and-effectsmore » analysis and statistical process control analysis to determine the institution-specific clinical impact of each TG-142 test may be useful for identifying trends for pro-active surveillance. Learning Objectives: To better understand the confusing and controversial aspects of TG-142. To understand what is still missing from TG-142 and how to account for these tests in clinical practice To describe which QA tests in TG-142 yield the largest potential clinical result if not discovered.« less

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

2016-05-01

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

The role of technology in the clinical laboratory of the future.

PubMed

Wilkinson, D S

1997-01-01

Advances in automation and informatics will drive the implementation of new technology as we enter the 21st century. Five technologies which will have the greatest impact on the practice of laboratory medicine during the next decade include molecular diagnostics, near patient testing, image analysis, robotics, and information management. The list of molecular pathology tests with potential clinical utility expands daily. Some, such as tests for human immune deficiency virus (HIV) and hepatitis C virus, already are available as commercial kits. Quality assessment and proficiency testing programs still are evolving. DNA tests in oncology, such as T- and B-cell gene rearrangements and t(9;22) translocation, have proven useful in detecting small numbers of tumor cells and have demonstrated clinical utility in some circumstances. Tests for monogenetic diseases, such as sickle cell disease, are useful in planning antenatal management of mothers at risk. Screening tests for the genetic predisposition for certain forms of colon and breast cancer and Alzheimer's Disease are now possible. This suggests the potential for large scale screening of populations at risk. Continued improvements in biosensor technology and miniaturization will increase the ability to test for many analytes at or near the patient. The generally increased cost per test must be reconciled with the potential to decrease the overall cost of care by improved turnaround time. Computerized image analysis will radically change, and in some cases eliminate, manual clinical microscopy in urinalysis, hematology, immunohistochemistry, and cytology. Robotics will greatly decrease personnel requirements for repetitive tasks, such as specimen transport, processing, and aliquoting. We will process many specimens from start to finish without human intervention. Image management systems will allow archiving of diagnostic gross and microscopic images along with the traditional text descriptions and diagnosis. Telepathology will link smaller centers with expert consultants in tertiary centers. Voice recognition systems will obviate the need for transcriptionists. Modern database architectures will allow the clinical laboratory to measure performance effectiveness and clinical outcomes and will place laboratorians at the forefront of outcomes research. Hand-held devices will allow physicians to conveniently order laboratory tests and retrieve results, further decreasing the functional turnaround time for laboratory testing. All of these technologies will be expensive to implement, but well-planned deployment will both decrease cost and improve the quality of medical care.

A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology

PubMed Central

Hess, Erik P; Wells, George A; Jaffe, Allan; Stiell, Ian G

2008-01-01

Background Chest pain is the second most common chief complaint in North American emergency departments. Data from the U.S. suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed, with slightly higher rates reported in a recent Canadian study (4.6% and 6.4%, respectively). Information obtained from the history, 12-lead ECG, and a single set of cardiac enzymes is unable to identify patients who are safe for early discharge with sufficient sensitivity. The 2007 ACC/AHA guidelines for UA/NSTEMI do not identify patients at low risk for adverse cardiac events who can be safely discharged without provocative testing. As a result large numbers of low risk patients are triaged to chest pain observation units and undergo provocative testing, at significant cost to the healthcare system. Clinical decision rules use clinical findings (history, physical exam, test results) to suggest a diagnostic or therapeutic course of action. Currently no methodologically robust clinical decision rule identifies patients safe for early discharge. Methods/design The goal of this study is to derive a clinical decision rule which will allow emergency physicians to accurately identify patients with chest pain who are safe for early discharge. The study will utilize a prospective cohort design. Standardized clinical variables will be collected on all patients at least 25 years of age complaining of chest pain prior to provocative testing. Variables strongly associated with the composite outcome acute myocardial infarction, revascularization, or death will be further analyzed with multivariable analysis to derive the clinical rule. Specific aims are to: i) apply standardized clinical assessments to patients with chest pain, incorporating results of early cardiac testing; ii) determine the inter-observer reliability of the clinical information; iii) determine the statistical association between the clinical findings and the composite outcome; and iv) use multivariable analysis to derive a highly sensitive clinical decision rule to guide triage decisions. Discussion The study will derive a highly sensitive clinical decision rule to identify low risk patients safe for early discharge. This will improve patient care, lower healthcare costs, and enhance flow in our busy and overcrowded emergency departments. PMID:18254973

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Public health and clinical impact of increasing emergency department-based HIV testing: perspectives from the 2007 conference of the National Emergency Department HIV Testing Consortium.

PubMed

Kecojevic, Aleksandar; Lindsell, Christopher J; Lyons, Michael S; Holtgrave, David; Torres, Gretchen; Heffelfinger, James; Brown, Jeremy; Couture, Eileen; Jung, Julianna; Connell, Samantha; Rothman, Richard E

2011-07-01

Understanding perceived benefits and disadvantages of HIV testing in emergency departments (EDs) is imperative to overcoming barriers to implementation. We codify those domains of public health and clinical care most affected by implementing HIV testing in EDs, as determined by expert opinion. Opinions were systematically collected from attendees of the 2007 National ED HIV Testing Consortium meeting. Structured evaluation of strengths, weaknesses, opportunities, and threats analysis was conducted to assess the impact of ED-based HIV testing on public health. A modified Delphi method was used to assess the impact of ED-based HIV testing on clinical care from both individual patient and individual provider perspectives. Opinions were provided by 98 experts representing 42 academic and nonacademic institutions. Factors most frequently perceived to affect public health were (strengths) high volume of ED visits and high prevalence of HIV, (weaknesses) undue burden on EDs, (opportunities) reduction of HIV stigma, and (threats) lack of resources in EDs. Diagnostic testing and screening for HIV were considered to have a favorable impact on ED clinical care from both individual patient and individual provider perspectives; however, negative test results were not perceived to have any benefit from the provider's perspective. The need for HIV counseling in the ED was considered to have a negative impact on clinical care from the provider's perspective. Experts in ED-based HIV testing perceived expanded ED HIV testing to have beneficial impacts for both the public health and individual clinical care; however, limited resources were frequently cited as a possible impediment. Many issues must be resolved through further study, education, and policy changes if the full potential of HIV testing in EDs is to be realized. Copyright © 2011. Published by Mosby, Inc.

Clinical Pharmacology Quality Assurance (CPQA) Program: Models for Longitudinal Analysis of Antiretroviral (ARV) Proficiency Testing for International Laboratories

PubMed Central

DiFrancesco, Robin; Rosenkranz, Susan L.; Taylor, Charlene R.; Pande, Poonam G.; Siminski, Suzanne M.; Jenny, Richard W.; Morse, Gene D.

2013-01-01

Among National Institutes of Health (NIH) HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals (ARV). Drug assay data are, in turn, entered into study-specific datasets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semi-annual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance (CPQA) program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1)assess the precision and accuracy of concentrations reported by individual CPLs; (2)determine factors associated with round-specific and long-term assay accuracy, precision and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21)drug concentration results reported for clinical trial samples by multiple CPLs).Using the CLIA acceptance of meeting criteria for ≥2/3 consecutive rounds, all ten laboratories that participated in three or more rounds per analyte maintained CLIA proficiency. Significant associations were present between magnitude of error and CPL (Kruskal Wallis [KW]p<0.001), and ARV (KW p<0.001). PMID:24052065

Two-Sample Statistics for Testing the Equality of Survival Functions Against Improper Semi-parametric Accelerated Failure Time Alternatives: An Application to the Analysis of a Breast Cancer Clinical Trial

PubMed Central

BROËT, PHILIPPE; TSODIKOV, ALEXANDER; DE RYCKE, YANN; MOREAU, THIERRY

2010-01-01

This paper presents two-sample statistics suited for testing equality of survival functions against improper semi-parametric accelerated failure time alternatives. These tests are designed for comparing either the short- or the long-term effect of a prognostic factor, or both. These statistics are obtained as partial likelihood score statistics from a time-dependent Cox model. As a consequence, the proposed tests can be very easily implemented using widely available software. A breast cancer clinical trial is presented as an example to demonstrate the utility of the proposed tests. PMID:15293627

Agreement between clinical and laboratory methods assessing tonic and cross-link components of accommodation and vergence.

PubMed

Neveu, Pascaline; Priot, Anne-Emmanuelle; Philippe, Matthieu; Fuchs, Philippe; Roumes, Corinne

2015-09-01

Several tests are available to optometrists for investigating accommodation and vergence. This study sought to investigate the agreement between clinical and laboratory methods and to clarify which components are actually measured when tonic and cross-link of accommodation and vergence are assessed. Tonic vergence, tonic accommodation, accommodative vergence (AC/A) and vergence accommodation (CA/C) were measured using several tests. Clinical tests were compared to the laboratory assessment, the latter being regarded as an absolute reference. The repeatability of each test and the degree of agreement between the tests were quantified using Bland-Altman analysis. The values obtained for each test were found to be stable across repetitions; however, in most cases, significant differences were observed between tests supposed to measure the same oculomotor component. Tonic and cross-link components cannot be easily assessed because proximal and instrumental responses interfere with the assessment. Other components interfere with oculomotor assessment. Specifically, accommodative divergence interferes with tonic vergence estimation and the type of accommodation considered in the AC/A ratio affects its magnitude. Results on clinical tonic accommodation and clinical CA/C show that further investigation is needed to clarify the limitations associated with the use of difference of Gaussian as visual targets to open the accommodative loop. Although different optometric tests of accommodation and vergence rely on the same basic principles, the results of this study indicate that clinical and laboratory methods actually involve distinct components. These differences, which are induced by methodological choices, must be taken into account, when comparing studies or when selecting a test to investigate a particular oculomotor component. © 2015 The Authors. Clinical and Experimental Optometry © 2015 Optometry Australia.

A pilot evaluation of a computer-based psychometric test battery designed to detect impairment in patients with cirrhosis.

PubMed

Cook, Nicola A; Kim, Jin Un; Pasha, Yasmin; Crossey, Mary Me; Schembri, Adrian J; Harel, Brian T; Kimhofer, Torben; Taylor-Robinson, Simon D

2017-01-01

Psychometric testing is used to identify patients with cirrhosis who have developed hepatic encephalopathy (HE). Most batteries consist of a series of paper-and-pencil tests, which are cumbersome for most clinicians. A modern, easy-to-use, computer-based battery would be a helpful clinical tool, given that in its minimal form, HE has an impact on both patients' quality of life and the ability to drive and operate machinery (with societal consequences). We compared the Cogstate™ computer battery testing with the Psychometric Hepatic Encephalopathy Score (PHES) tests, with a view to simplify the diagnosis. This was a prospective study of 27 patients with histologically proven cirrhosis. An analysis of psychometric testing was performed using accuracy of task performance and speed of completion as primary variables to create a correlation matrix. A stepwise linear regression analysis was performed with backward elimination, using analysis of variance. Strong correlations were found between the international shopping list, international shopping list delayed recall of Cogstate and the PHES digit symbol test. The Shopping List Tasks were the only tasks that consistently had P values of <0.05 in the linear regression analysis. Subtests of the Cogstate battery correlated very strongly with the digit symbol component of PHES in discriminating severity of HE. These findings would indicate that components of the current PHES battery with the international shopping list tasks of Cogstate would be discriminant and have the potential to be used easily in clinical practice.

Clinically relevant diagnostic research in primary care: the example of B-type natriuretic peptides in the detection of heart failure.

PubMed

Kelder, Johannes C; Rutten, Frans H; Hoes, Arno W

2009-02-01

With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart failure, we will discuss the major methodological issues crucial in diagnostic research; most notably the choice of the study population and the data analysis with a multivariable approach. BNP have been studied extensively in the emergency care setting, and also several studies in the primary care are available. The usefulness of this test when applied in combination with other readily available tests is still not adequately addressed in the relevant patient domain, i.e. those who are clinically suspected of heart failure by their GP. Future diagnostic research in primary care should be targeted much more at answering the clinically relevant question 'Is it useful to add this (new) test to the other tests I usually perform, including history taking and physical examination, in patients I suspect of having a certain disease'.

Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation.

PubMed

Verbruggen, Krijn T; Knijff, Wilma A; Soorani-Lunsing, Roelineke J; Sijens, Paul E; Verhoeven, Nanda M; Salomons, Gajja S; Goorhuis-Brouwer, Siena M; van Spronsen, Francjan J

2007-09-01

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the biosynthesis of creatine (Cr). So far, reports have not focused on the description of developmental abilities in this disorder. Here, we present the result of formal testing of developmental abilities in a GAMT-deficient patient. Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a severe language production delay and nearly normal nonverbal development. Treatment with oral Cr supplementation led to partial restoration of the cerebral Cr concentration and a clinically remarkable acceleration of language production development. In contrast to clinical observation, formal testing showed a rather harmonic developmental delay before therapy and a general improvement, but no specific acceleration of language development after therapy. From our case, we conclude that in GAMT deficiency language delay is not always more prominent than delays in other developmental areas. The discrepancy between the clinical impression and formal testing underscores the importance of applying standardized tests in children with developmental delays. Screening for Cr deficiency by metabolite analysis of body fluids or proton magnetic resonance spectroscopy of the brain deficiency should be considered in any child with global developmental delay/mental retardation lacking clues for an alternative etiology.

Quantitative methods in assessment of neurologic function.

PubMed

Potvin, A R; Tourtellotte, W W; Syndulko, K; Potvin, J

1981-01-01

Traditionally, neurologists have emphasized qualitative techniques for assessing results of clinical trials. However, in recent years qualitative evaluations have been increasingly augmented by quantitative tests for measuring neurologic functions pertaining to mental state, strength, steadiness, reactions, speed, coordination, sensation, fatigue, gait, station, and simulated activities of daily living. Quantitative tests have long been used by psychologists for evaluating asymptomatic function, assessing human information processing, and predicting proficiency in skilled tasks; however, their methodology has never been directly assessed for validity in a clinical environment. In this report, relevant contributions from the literature on asymptomatic human performance and that on clinical quantitative neurologic function are reviewed and assessed. While emphasis is focused on tests appropriate for evaluating clinical neurologic trials, evaluations of tests for reproducibility, reliability, validity, and examiner training procedures, and for effects of motivation, learning, handedness, age, and sex are also reported and interpreted. Examples of statistical strategies for data analysis, scoring systems, data reduction methods, and data display concepts are presented. Although investigative work still remains to be done, it appears that carefully selected and evaluated tests of sensory and motor function should be an essential factor for evaluating clinical trials in an objective manner.

Screening for important unwarranted variation in clinical practice: a triple-test of processes of care, costs and patient outcomes.

PubMed

Partington, Andrew; Chew, Derek P; Ben-Tovim, David; Horsfall, Matthew; Hakendorf, Paul; Karnon, Jonathan

2017-03-01

Objective Unwarranted variation in clinical practice is a target for quality improvement in health care, but there is no consensus on how to identify such variation or to assess the potential value of initiatives to improve quality in these areas. This study illustrates the use of a triple test, namely the comparative analysis of processes of care, costs and outcomes, to identify and assess the burden of unwarranted variation in clinical practice. Methods Routinely collected hospital and mortality data were linked for patients presenting with symptoms suggestive of acute coronary syndromes at the emergency departments of four public hospitals in South Australia. Multiple regression models analysed variation in re-admissions and mortality at 30 days and 12 months, patient costs and multiple process indicators. Results After casemix adjustment, an outlier hospital with statistically significantly poorer outcomes and higher costs was identified. Key process indicators included admission patterns, use of invasive diagnostic procedures and length of stay. Performance varied according to patients' presenting characteristics and time of presentation. Conclusions The joint analysis of processes, outcomes and costs as alternative measures of performance inform the importance of reducing variation in clinical practice, as well as identifying specific targets for quality improvement along clinical pathways. Such analyses could be undertaken across a wide range of clinical areas to inform the potential value and prioritisation of quality improvement initiatives. What is known about the topic? Variation in clinical practice is a long-standing issue that has been analysed from many different perspectives. It is neither possible nor desirable to address all forms of variation in clinical practice: the focus should be on identifying important unwarranted variation to inform actions to reduce variation and improve quality. What does this paper add? This paper proposes the comparative analysis of processes of care, costs and outcomes for patients with similar diagnoses presenting at alternative hospitals, using linked, routinely collected data. This triple test of performance indicators extracts maximum value from routine data to identify priority areas for quality improvement to reduce important and unwarranted variations in clinical practice. What are the implications for practitioners? The proposed analyses need to be applied to other clinical areas to demonstrate the general application of the methods. The outputs can then be validated through the application of quality improvement initiatives in clinical areas with identified important and unwarranted variation. Validated frameworks for the comparative analysis of clinical practice provide an efficient approach to valuing and prioritising actions to improve health service quality.

L-DOPA therapy interferes with urine catecholamine analysis in children with suspected neuroblastoma: a case series.

PubMed

Kelly, Alison U; Srivastava, Rajeev; Dow, Ellie; Davidson, D Fraser

2017-09-01

Neuroblastoma is the most common solid extracranial malignancy diagnosed in childhood. Clinical presentation is variable, and metastatic disease is common at diagnosis. Analyses of urinary catecholamines and their metabolites are commonly requested as a first-line investigation when clinical suspicion exists. Levodopa (L-Dopa) therapy is utilized as a treatment for a number of disorders in childhood, including Dopa-responsive dystonia. Neuroblastoma may mimic some of the clinical features of this disorder. L-Dopa can interfere with analysis of urinary catecholamines and their metabolites and complicate the interpretation of results. We present the cases of three children who were prescribed L-dopa at the time of analysis of urinary catecholamines and metabolites as a screen for neuroblastoma, but who did not have the disease. Comparison of their results with those from cases with true neuroblastoma reveal that it is impossible to reliably distinguish true neuroblastoma from L-Dopa therapy using these tests. We recommend that patients should be off L-dopa therapy, if possible when these tests are performed. These cases illustrate the importance of providing clinical details and drug history to the laboratory in order to avoid diagnostic confusion.

Analysis of on-line clinical laboratory manuals and practical recommendations.

PubMed

Beckwith, Bruce; Schwartz, Robert; Pantanowitz, Liron

2004-04-01

On-line clinical laboratory manuals are a valuable resource for medical professionals. To our knowledge, no recommendations currently exist for their content or design. To analyze publicly accessible on-line clinical laboratory manuals and to propose guidelines for their content. We conducted an Internet search for clinical laboratory manuals written in English with individual test listings. Four individual test listings in each manual were evaluated for 16 data elements, including sample requirements, test methodology, units of measure, reference range, and critical values. Web sites were also evaluated for supplementary information and search functions. We identified 48 on-line laboratory manuals, including 24 academic or community hospital laboratories and 24 commercial or reference laboratories. All manuals had search engines and/or test indices. No single manual contained all 16 data elements evaluated. An average of 8.9 (56%) elements were present (range, 4-14). Basic sample requirements (specimen and volume needed) were the elements most commonly present (98% of manuals). The frequency of the remaining data elements varied from 10% to 90%. On-line clinical laboratory manuals originate from both hospital and commercial laboratories. While most manuals were user-friendly and contained adequate specimen-collection information, other important elements, such as reference ranges, were frequently absent. To ensure that clinical laboratory manuals are of maximal utility, we propose the following 13 data elements be included in individual test listings: test name, synonyms, test description, test methodology, sample requirements, volume requirements, collection guidelines, transport guidelines, units of measure, reference range, critical values, test availability, and date of latest revision.

Prior HIV testing among STD patients in Guangdong Province, China: opportunities for expanding detection of sexually transmitted HIV infection.

PubMed

Tucker, Joseph D; Yang, Li-Gang; Yang, Bin; Young, Darwin; Henderson, Gail E; Huang, Shu-Jie; Lu, He-Kun; Chen, Xiang-Sheng; Cohen, Myron S

2012-03-01

Expanding HIV testing is important among individuals at increased risk for sexual HIV transmission in China, but little is known about prior HIV testing experiences among sexually transmitted disease (STD) patients. This cross-sectional study of 1792 outpatients from 6 public STD clinics in Guangdong Province recorded detailed information about ever having been tested for HIV infection in addition to sociodemographic variables, health seeking, clinical STD history, and HIV stigma using a validated survey instrument. A total of 456 (25.4%) of the STD patients in this sample had ever been tested for HIV infection. STD patients who were male, had higher income, more education, were at City A and City C, received STD services at public facilities, had used intravenous drugs, and had a history of an STD were more likely to ever receive an HIV test in multivariate analysis. Low perceived HIV risk was the most common reason for not receiving an HIV test. Only 7.7% of the sample reported fear of discrimination or loss of face as influencing their lack of HIV testing. Incomplete prior HIV screening among STD patients in China suggests the need for broadening HIV testing opportunities at STD clinics and similar clinical settings attended by those with increased sexual risk.

An automated smartphone-based diagnostic assay for point-of-care semen analysis.

PubMed

Kanakasabapathy, Manoj Kumar; Sadasivam, Magesh; Singh, Anupriya; Preston, Collin; Thirumalaraju, Prudhvi; Venkataraman, Maanasa; Bormann, Charles L; Draz, Mohamed Shehata; Petrozza, John C; Shafiee, Hadi

2017-03-22

Male infertility affects up to 12% of the world's male population and is linked to various environmental and medical conditions. Manual microscope-based testing and computer-assisted semen analysis (CASA) are the current standard methods to diagnose male infertility; however, these methods are labor-intensive, expensive, and laboratory-based. Cultural and socially dominated stigma against male infertility testing hinders a large number of men from getting tested for infertility, especially in resource-limited African countries. We describe the development and clinical testing of an automated smartphone-based semen analyzer designed for quantitative measurement of sperm concentration and motility for point-of-care male infertility screening. Using a total of 350 clinical semen specimens at a fertility clinic, we have shown that our assay can analyze an unwashed, unprocessed liquefied semen sample with <5-s mean processing time and provide the user a semen quality evaluation based on the World Health Organization (WHO) guidelines with ~98% accuracy. The work suggests that the integration of microfluidics, optical sensing accessories, and advances in consumer electronics, particularly smartphone capabilities, can make remote semen quality testing accessible to people in both developed and developing countries who have access to smartphones. Copyright © 2017, American Association for the Advancement of Science.

The Italian pilot external quality assessment program for cystic fibrosis sweat test.

PubMed

Salvatore, Marco; Floridia, Giovanna; Amato, Annalisa; Censi, Federica; Carta, Claudio; de Stefano, Maria Chiara; Ferrari, Gianluca; Tosto, Fabrizio; Capoluongo, Ettore; Caruso, Ubaldo; Castaldo, Giuseppe; Cirilli, Natalia; Corbetta, Carlo; Padoan, Rita; Raia, Valeria; Taruscio, Domenica

2016-05-01

Sweat chloride test is the gold standard test for cystic fibrosis (CF) diagnosis. In 2014 the Istituto Superiore di Sanità established the Italian pilot external quality assessment program for CF sweat test (IEQA-ST). Ten laboratories, included among the 33 Italian CF Referral Centers, were selected and enrolled on the basis of their attitude to perform sweat test (ST) analysis by using methods recommended by the Italian Guidelines. They received three different sweat-like samples (normal, borderline and pathologic chloride concentration), with mock clinical indications, for analysis according to routine procedures. Assessment, performed by a panel of experts, covered analytical performance, interpretation and reporting of results; categories of "poor" and "satisfactory" performance were not defined. All data were managed through a web utility. The program identified important areas of interest and, in some case, of concern. It is important to underline that results are referred to a small proportion, i.e. about 30%, of Italian laboratories performing CF ST in the context of the Referral Centers. Data collected highlight the importance of participation in EQA programs as it may improve laboratory/clinical performance; our study represents a model for the setting up of a large-scale EQA scheme for ST. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Feline focus: Diagnostic testing for feline thyroid disease: hyperthyroidism.

PubMed

Peterson, Mark E

2013-08-01

In older cats presenting with clinical features of hyperthyroidism, confirming the diagnosis of thyroid disease is usually straightforward. However, the potential for false-negative and false-positive results exists with all thyroid function tests, especially when used for routine screening of large numbers of asymptomatic cats. Therefore, all thyroid function test results must be interpreted in light of the cat's history, clinical signs, and other laboratory findings. If a high serum thyroxine (T4) value is found in a cat that lacks clinical signs of hyperthyroidism, or if hyperthyroidism is suspected in a cat with normal total T4 concentrations, repeating the total T4 analysis, determining the free T4 concentration, or performing thyroid scintigraphy may be needed to confirm the diagnosis.

Diagnostic and therapeutic update on diabetic foot osteomyelitis.

PubMed

Lázaro-Martínez, José Luis; Tardáguila-García, Aroa; García-Klepzig, José Luis

2017-02-01

Diabetic foot osteomyelitis (DFO) is the most common infection associated to diabetic foot ulcers (DFU). This review is designed to provide an update on the diagnosis and treatment of DFO based on an analysis of MEDLINE through PubMed using as search criterion "Diabetic Foot Osteomyelitis". Authors have included in this review the most relevant manuscripts regarding diagnosis and treatment of DFO. After review and critical analysis of publications, it may be concluded that diagnosis of DFO is not simple because of its heterogeneous presentation. Clinical inflammatory signs, probe-to-bone test, and plain X-rays are postulated as the basic tests for clinical diagnosis when DFO is suspected. Diagnosis should be supported by laboratory tests, of which ESR (>70mm/h) has been shown to be most precise. MRI is the most accurate imaging test, especially for differential diagnosis with Charcot foot. Pathogen isolation by bone culture is essential when the patient is treated with ATB only. Medical or surgical treatment should be based on the clinical characteristics of the patient and the lesion. Surgery should always be an option if medical treatment fails. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical history as a predictor of penicillin skin test outcome.

PubMed

Wong, Benjamin B L; Keith, Paul K; Waserman, Susan

2006-08-01

Up to 10% of the population reports an "allergy" to penicillin, whereas approximately 1.1% has positive penicillin skin test results. Where penicillin skin tests are unavailable, some have advocated using history to decide whether to use a penicillin-related antibiotic. To determine if clinical history predicts penicillin skin test results. Retrospective medical record review of 94 consecutive patients who had previously taken penicillin referred for penicillin allergy. Case histories were taken, penicillin skin tests performed, and an oral challenge recommended if skin test results were negative. Of 91 cases studied, the average patient age was 27 years (range, 6 months to 82 years; 36% female). Fifty-two (57%) experienced hives as their main adverse reaction. Sixteen (18%) had at least 1 positive test result. Of this group, 9 had hives as their main symptom, whereas 1 had respiratory problems and 1 had angioedema. Most patients with positive skin test results had experienced their reaction at least 3 years ago. Regression analysis showed that age, sex, and clinical history, including type of reaction, time of reaction after penicillin ingestion, or time since the last reaction, were not associated with skin test positivity. Seventy-two (96%) of the 75 patients who had negative skin test results underwent oral challenge. Seventy had negative challenge results. The negative predictive value of a negative penicillin skin test result was 97%. Clinical history was not predictive of subsequent penicillin skin test results.

Clinical applications of preimplantation genetic testing.

PubMed

Brezina, Paul R; Kutteh, William H

2015-02-19

Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most. © BMJ Publishing Group Ltd 2015.

Nursing students' viewpoints toward two methods of clinical conference and clinical nursing round.

PubMed

Gheidanzadeh, Maryam; Baghersad, Zahra; Abazari, Parvaneh

2017-01-01

Clinical education provides a chance to combine theoretical knowledge and clinical skills. Students are the key elements in the evaluation of clinical education efficacy. The present study was aimed to define nursing students' viewpoints concerning conformity to the characteristics of clinical conference and clinical round. This descriptive analytical study was conducted on the bachelor's students of the 4 th -6 th semester of nursing. Sampling was conducted using census sampling method during the 2 nd semester of 2014-2015 school year. Data collection tool was a three-section researcher-made questionnaire containing demographic, nursing round, and clinical conference characteristics. Descriptive and inferential statistical tests (independent t -test, ANOVA, and Spearman and Pearson correlation coefficients) were used for data analysis. Participants were 134 bachelor's students of the 4 th -6 th semester of nursing. According to half of the participants, conformity to the characteristics of clinical conference (45.5%, 53%) and clinical round (44%, 51.5%) were poor and medium, respectively. Paired t -test showed a significant difference between students' viewpoints toward the planning of clinical conference and clinical nursing round ( P = 0.006, t = 2.77). According to the results of the present study on students' viewpoints, clinical education faces a serious challenge with regard to clinical education methods. Considering the necessity and importance of clinical education, more investigation should be conducted to detect its relevant factors and plan for its improvement.

From Usability Testing to Clinical Simulations: Bringing Context into the Design and Evaluation of Usable and Safe Health Information Technologies. Contribution of the IMIA Human Factors Engineering for Healthcare Informatics Working Group.

PubMed

Kushniruk, A; Nohr, C; Jensen, S; Borycki, E M

2013-01-01

The objective of this paper is to explore human factors approaches to understanding the use of health information technology (HIT) by extending usability engineering approaches to include analysis of the impact of clinical context through use of clinical simulations. Methods discussed are considered on a continuum from traditional laboratory-based usability testing to clinical simulations. Clinical simulations can be conducted in a simulation laboratory and they can also be conducted in real-world settings. The clinical simulation approach attempts to bring the dimension of clinical context into stronger focus. This involves testing of systems with representative users doing representative tasks, in representative settings/environments. Application of methods where realistic clinical scenarios are used to drive the study of users interacting with systems under realistic conditions and settings can lead to identification of problems and issues with systems that may not be detected using traditional usability engineering methods. In conducting such studies, careful consideration is needed in creating ecologically valid test scenarios. The evidence obtained from such evaluation can be used to improve both the usability and safety of HIT. In addition, recent work has shown that clinical simulations, in particular those conducted in-situ, can lead to considerable benefits when compared to the costs of running such studies. In order to bring context of use into the testing of HIT, clinical simulation, involving observing representative users carrying out tasks in representative settings, holds considerable promise.

Resistance monitoring of human pathogenic bacteria in Germany, SWOT analysis and examples.

PubMed

Witte, Wolfgang

2006-06-01

Determination of antibiotic resistance has two main goals in clinical-microbiological diagnosis. One aspect is preservation of antibacterial chemotherapy. Furthermore, trends in resistance development should be monitored and should serve as an early warning-system for occurrence and spread of new and clinically important antibiotic resistances. Plenty of data on antibiotic resistance is gathered on a routine basis in medical-microbiological diagnosis and often it is stored in electronic databases that could be interlinked. The main reason that the available data is not being used for resistance monitoring in Germany is the widely used methodology of the agar diffusion test. It is the cheapest and by far the most inaccurate method of determining resistance. The test results are not always comparable with tests for all substance groups from national standards (also limited international comparability). Trend analysis of the resistance situation in Germany can therefore only be determined through individual studies. These studies are discussed according to a SWOT analysis (SWOT = Strengths, Weaknesses, Opportunities, Threats).

[Survey results of medical insurance reimbursement system for independent medical laboratories in Korea].

PubMed

Bae, Sook Young; Kwon, Jung Ah; Kim, Jang Su; Yoon, Soo Young; Lee, Chang Kyu; Lee, Kap No; Kim, Dae Won; Min, Won Ki; Cha, Young Joo; Chae, Seok Lae; Hwang, Yoo Sung

2007-04-01

A questionnaire survey was performed to perceive the problem of the current medical insurance reimbursement system for laboratory tests referred to independent medical laboratories; then, we intended to find a way to improve the reimbursement system. Questionnaires were distributed to 220 independent medical laboratories and 700 laboratory physicians from July through October 2005. Frequency analysis was used to analyse the replies from 109 respondents to 25 questionnaire items regarding the current medical insurance reimbursement system for referral tests, problems with the system, and suggestions for the improvement of the system. Among the 109 respondents to this survey, 49 (45.8%) considered the current reimbursement system to be unsatisfactory, while only 16 (15.0%) answered satisfactory. The problem was that the referral clinics-not the laboratories that performed the tests--would first receive their reimbursement for the laboratory tests from Health Insurance Review Agency (HIRA) and then give a portion of the laboratory test fees to the independent medical laboratories after the deduction of administrative fees. They (62.5% of the respondents) would prefer a separated reimbursement system by which the referral clinic-as well as the independent medical laboratory-would receive their reimbursement directly from HIRA through an Electronic Data Interchange (EDI) system. In this new system, 34% of the respondents expected the quality of the laboratory tests to be improved; however, 41.6% answered that the income of the referral clinic is expected to decrease. For the improvement of the medical insurance reimbursement system, the administrative fee for the referral clinic and the test fee for the independent medical laboratory should be reimbursed directly to the respective organizations. These changes could be made possible with the proper analysis of medical costs and the development of an effective EDI reimbursement system.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

VEGF-A clinical significance in gastric cancers: immunohistochemical analysis of a wide Italian cohort.

PubMed

Lastraioli, E; Boni, L; Romoli, M R; Crescioli, S; Taddei, A; Beghelli, S; Tomezzoli, A; Vindigni, C; Saragoni, L; Messerini, L; Bernini, M; Bencini, L; Giommoni, E; Freschi, G; Di Costanzo, F; Scarpa, A; Morgagni, P; Farsi, M; Roviello, F; De Manzoni, G; Bechi, P; Arcangeli, A

2014-10-01

The clinical significance of VEGF-A expression in gastric cancer (GC) has been reported with contradicting results. We analyzed the expression and clinical significance of VEGF-A in a wide Italian cohort of GC specimens. VEGF-A expression was tested by immunohistochemistry in 507 patients with GC of all clinical stages. The impact of VEGF-A on overall survival (OS) was evaluated in conjunction with clinical and pathological parameters. In the Italian cohort we studied VEGF-A was not an independent prognostic factor neither at the univariate nor at multivariate analysis. Although frequently expressed, in our study VEGF-A was not able to discriminate between groups of patients with different risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diagnostic value of history and physical examination in patients suspected of lumbosacral nerve root compression

PubMed Central

Vroomen, P; de Krom, M C T F M; Wilmink, J; Kester, A; Knottnerus, J

2002-01-01

Objective: To evaluate patient characteristics, symptoms, and examination findings in the clinical diagnosis of lumbosacral nerve root compression causing sciatica. Methods: The study involved 274 patients with pain radiating into the leg. All had a standardised clinical assessment and magnetic resonance (MR) imaging. The associations between patient characteristics, clinical findings, and lumbosacral nerve root compression on MR imaging were analysed. Results: Nerve root compression was associated with three patient characteristics, three symptoms, and four physical examination findings (paresis, absence of tendon reflexes, a positive straight leg raising test, and increased finger-floor distance). Multivariate analysis, analysing the independent diagnostic value of the tests, showed that nerve root compression was predicted by two patient characteristics, four symptoms, and two signs (increased finger-floor distance and paresis). The straight leg raise test was not predictive. The area under the curve of the receiver-operating characteristic was 0.80 for the history items. It increased to 0.83 when the physical examination items were added. Conclusions: Various clinical findings were found to be associated with nerve root compression on MR imaging. While this set of findings agrees well with those commonly used in daily practice, the tests tended to have lower sensitivity and specificity than previously reported. Stepwise multivariate analysis showed that most of the diagnostic information revealed by physical examination findings had already been revealed by the history items. PMID:11971050

CUSUM-Logistic Regression analysis for the rapid detection of errors in clinical laboratory test results.

PubMed

Sampson, Maureen L; Gounden, Verena; van Deventer, Hendrik E; Remaley, Alan T

2016-02-01

The main drawback of the periodic analysis of quality control (QC) material is that test performance is not monitored in time periods between QC analyses, potentially leading to the reporting of faulty test results. The objective of this study was to develop a patient based QC procedure for the more timely detection of test errors. Results from a Chem-14 panel measured on the Beckman LX20 analyzer were used to develop the model. Each test result was predicted from the other 13 members of the panel by multiple regression, which resulted in correlation coefficients between the predicted and measured result of >0.7 for 8 of the 14 tests. A logistic regression model, which utilized the measured test result, the predicted test result, the day of the week and time of day, was then developed for predicting test errors. The output of the logistic regression was tallied by a daily CUSUM approach and used to predict test errors, with a fixed specificity of 90%. The mean average run length (ARL) before error detection by CUSUM-Logistic Regression (CSLR) was 20 with a mean sensitivity of 97%, which was considerably shorter than the mean ARL of 53 (sensitivity 87.5%) for a simple prediction model that only used the measured result for error detection. A CUSUM-Logistic Regression analysis of patient laboratory data can be an effective approach for the rapid and sensitive detection of clinical laboratory errors. Published by Elsevier Inc.

In Vivo Measurement of Drug Efficacy in Breast Cancer

DTIC Science & Technology

2016-10-01

analysis. At the clinical level, this study will result in pertinent data regarding several agents currently in clinical trials. At the basic science ...clinical level, this study will result in pertinent data regarding several agents currently in clinical trials. At the basic science level, we will...mg/kg BLZ-945 or encapsulated drug were tested in BALB/C mice expressing tumors in mammary fat pads, showing limited additional efficacy as seen

Acute bacterial and viral meningitis.

PubMed

Bartt, Russell

2012-12-01

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

The clinical relevance of birch pollen profilin cross-reactivity in sensitized patients.

PubMed

Wölbing, F; Kunz, J; Kempf, W E; Grimmel, C; Fischer, J; Biedermann, T

2017-04-01

Overlapping seasons and cross-reactivity, especially to grass pollen profilin, can hamper the diagnosis of birch pollen allergy. To identify the primary sensitizing allergen and the clinical relevance of cross-sensitization, we correlated sensitization profiles with in vitro and in vivo tests, symptom scores, and pollen counts. A total of 433 patients with positive skin prick test (SPT) to birch pollen were analyzed regarding IgE to major birch and grass pollen allergens Bet v 1 and Phl p 1/p 5 and the profilins Bet v 2 and Phl p 12. Subgroups were analyzed by basophil activation test (BAT) and CAP-FEIA-based cross- and self-inhibition tests. A total of 349 patients were sensitized to Bet v 1, 44 patients to both Bet v 1 and Bet v 2, and 15 patients to Bet v 2 only. From Bet v 2-sensitized patients, 40 were also sensitized to Phl p 12. Ex vivo, Bet v 2 and Phl p 12 induced dose-dependent activation in basophils of these patients. Cross- and self-inhibition tests with both allergens confirmed cross-reactivity. However, semiquantitative analysis of SPTs demonstrated markedly increased reactivity to grass compared to birch pollen extract in Bet v 2 only sensitized patients. Accordingly, in most of those patients, clinical symptoms precisely correlated with grass pollen counts. Identification of the clinically relevant and sensitizing allergen needs correlation of actual pollen counts with clinical symptoms and sensitization status to major allergens. Semiquantitative analysis of SPT or BAT and determining profilin-specific IgE can contribute to making the diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implications for HIV testing policy derived from combining data on voluntary confidential testing with viral sequences and serological analyses.

PubMed

Brown, A E; Murphy, G; Rinck, G; Clewley, J P; Hill, C; Parry, J V; Johnson, A M; Pillay, D; Gill, O N

2009-02-01

Laboratory, clinical and sequence-based data were combined to assess the differential uptake of voluntary confidential HIV testing (VCT) according to risk and explore the occurrence of HIV transmission from individuals with recently acquired HIV infection, before the diagnostic opportunity. Between 1999 and 2002, nearly 30,000 anonymous tests for previously undiagnosed HIV infection were conducted among men who have sex with men (MSM) attending 15 sentinel sexually transmitted infection (STI) clinics in England, Wales and Northern Ireland. Using a serological testing algorithm, undiagnosed HIV-infected men were categorised into those with recent and non-recent infection. VCT uptake was compared between HIV-negative, recently HIV-infected and non-recently HIV-infected men. A phylogenetic analysis of HIV pol sequences from 127 recently HIV-infected MSM was conducted to identify instances in which transmission may have occurred before the diagnostic opportunity. HIV-negative MSM were more likely to receive VCT at clinic visits compared with undiagnosed HIV-infected MSM (56% (14,020/24,938) vs 31% (335/1072); p<0.001). Recently HIV-infected MSM were more likely to receive VCT compared with those with non-recent infections (42% (97/229) vs 28% (238/844); p<0.001). 22% (95/425) of undiagnosed HIV-infected MSM with STI received VCT. Phylogenetic analysis revealed at least seven transmissions may have been generated by recently HIV-infected MSM: a group that attended STI clinics soon after seroconversion. The integration of clinical, laboratory and sequence-based data reveals the need for specific targeting of the recently HIV exposed, and those with STI, for VCT. VCT promotion alone may be limited in its ability to prevent HIV transmission.

Obesity and worsening of chronic venous disease and joint mobility.

PubMed

Belczak, Cleusa Ema Quilici; de Godoy, José Maria Pereira; Belzack, Sergio Quilici; Ramos, Rubiana Neves; Caffaro, Roberto Augusto

2014-09-01

The aim of this study was to investigate a possible relationship between obesity and decreased mobility of the talocrural joint and in turn chronic venous disease. One hundred obese patients recruited at Hospital Santa Casa de Maringa, Parana were enrolled by order of arrival at the hospital in a randomized quantitative cross-sectional study. Inclusion criteria were patients with a body mass index above 30 kg/m(2) and the exclusion criteria were infectious conditions that would interfere with the assessment. Patients were graded according to the clinical, etiological, anatomical and pathophysiological classification. Talocrural goniometry was performed to assess the degree of mobility of the legs. The Kolmogorov-Smirnov normality test, Kruskal-Wallis test, Dunn's Multiple comparison test and analysis of variance were used for statistical analysis tests with an alpha error of 5% being considered acceptable. The increase in body mass index is correlated to the reduction in joint mobility (Kruskal-Wallis test: p-value <0.0001) and increase in clinical, etiological, anatomical and pathophysiological classification is correlated to a decrease in joint mobility and the increase in age is associated with an increase in clinical, etiological, anatomical and pathophysiological classification (Kruskal-Wallis test: p-value <0.0001). Obesity is associated with deterioration in joint mobility and worsening of chronic venous disease. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

PubMed

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

2006-10-01

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

An Economic Evaluation of Preclinical Testing Strategies Compared to the Compulsory Scrapie Flock Scheme in the Control of Classical Scrapie

PubMed Central

Hawkins, Neil; Houston, Fiona; Fryer, Helen; Kao, Rowland

2012-01-01

Cost-benefit is rarely combined with nonlinear dynamic models when evaluating control options for infectious diseases. The current strategy for scrapie in Great Britain requires that all genetically susceptible livestock in affected flocks be culled (Compulsory Scrapie Flock Scheme or CSFS). However, this results in the removal of many healthy sheep, and a recently developed pre-clinical test for scrapie now offers a strategy based on disease detection. We explore the flock level cost-effectiveness of scrapie control using a deterministic transmission model and industry estimates of costs associated with genotype testing, pre-clinical tests and the value of a sheep culled. Benefit was measured in terms of the reduction in the number of infected sheep sold on, compared to a baseline strategy of doing nothing, using Incremental Cost Effectiveness analysis to compare across strategies. As market data was not available for pre-clinical testing, a threshold analysis was used to set a unit-cost giving equal costs for CSFS and multiple pre-clinical testing (MT, one test each year for three consecutive years). Assuming a 40% within-flock proportion of susceptible genotypes and a test sensitivity of 90%, a single test (ST) was cheaper but less effective than either the CSFS or MT strategies (30 infected-sales-averted over the lifetime of the average epidemic). The MT strategy was slightly less effective than the CSFS and would be a dominated strategy unless preclinical testing was cheaper than the threshold price of £6.28, but may be appropriate for flocks with particularly valuable livestock. Though the ST is not currently recommended, the proportion of susceptible genotypes in the national flock is likely to continue to decrease; this may eventually make it a cost-effective alternative to the MT or CSFS. PMID:22412943

Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary.

PubMed

Hannouf, M B; Winquist, E; Mahmud, S M; Brackstone, M; Sarma, S; Rodrigues, G; Rogan, P; Hoch, J S; Zaric, G S

2017-06-01

We aimed to investigate the cost-effectiveness of a 2000-gene-expression profiling (GEP) test to help identify the primary tumor site when clinicopathological diagnostic evaluation was inconclusive in patients with cancer of unknown primary (CUP). We built a decision-analytic-model to project the lifetime clinical and economic consequences of different clinical management strategies for CUP. The model was parameterized using follow-up data from the Manitoba Cancer Registry, cost data from Manitoba Health administrative databases and secondary sources. The 2000-GEP-based strategy compared to current clinical practice resulted in an incremental cost-effectiveness ratio (ICER) of $44,151 per quality-adjusted life years (QALY) gained. The total annual-budget impact was $36.2 million per year. A value-of-information analysis revealed that the expected value of perfect information about the test's clinical impact was $4.2 million per year. The 2000-GEP test should be considered for adoption in CUP. Field evaluations of the test are associated with a large societal benefit.

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

PubMed Central

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

2015-01-01

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

Hair Mineral Analysis and Disruptive Behavior in Clinically Normal Young Men.

ERIC Educational Resources Information Center

Struempler, Richard E.; And Others

1985-01-01

Forty young navy recruits were selected for hair mineral analysis on the basis of three criteria: mental test scores, demerits during training, and premature discharge from the navy. Statistical analysis revealed several significant relationships between behavioral criteria and mineral measures. Findings confirmed, in a nonclinical sample, hair…

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

PubMed

Kim, Chong H; Simmons, Sierra C; Williams, Lance A; Staley, Elizabeth M; Zheng, X Long; Pham, Huy P

2017-11-01

The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center. © 2017 AABB.

Molecular allergy diagnostics using multiplex assays: methodological and practical considerations for use in research and clinical routine: Part 21 of the Series Molecular Allergology.

PubMed

Jakob, Thilo; Forstenlechner, Peter; Matricardi, Paolo; Kleine-Tebbe, Jörg

The availability of single allergens and their use in microarray technology enables the simultaneous determination of specific IgE (sIgE) to a multitude of different allergens (> 100) in a multiplex procedure requiring only minute amounts of serum. This allows extensive individual sensitization profiles to be determined from a single analysis. Combined with a patient's medical history, these profiles simplify identification of cross-reactivity; permit a more accurate estimation of the risk of severe reactions; and enable the indication for specific immunotherapy to be more precisely established, particularly in cases of polysensitization. Strictly speaking, a multiplex assay is not a single test, but instead more than 100 simultaneous tests. This places considerable demands on the production, quality assurance, and interpretation of data. The following chapter describes the multiplex test systems currently available and discusses their characteristics. Performance data are presented and the sIgE values obtained from multiplex and singleplex assays are compared. Finally, the advantages and limitations of molecular allergy diagnostics using multiplex assays in clinical routine are discussed, and innovative possibilities for clinical research are described. The multiplex diagnostic tests available for clinical routine have now become well established. The interpretation of test results is demanding, particularly since all individual results need to be checked for their plausibility and clinical relevance on the basis of previous history (patient history, clinical symptoms, challenge test results). There is still room for improvement in certain areas, for example with respect to the overall test sensitivity of the method, as well as the availability and quality of particular allergens. The current test systems are just the beginning of a continuous development that will influence and most likely change clinical allergology in the coming years.

Clinical trials transparency and the Trial and Experimental Studies Transparency (TEST) act.

PubMed

Logvinov, Ilana

2014-03-01

Clinical trial research is the cornerstone for successful advancement of medicine that provides hope for millions of people in the future. Full transparency in clinical trials may allow independent investigators to evaluate study designs, perform additional analysis of data, and potentially eliminate duplicate studies. Current regulatory system and publishers rely on investigators and pharmaceutical industries for complete and accurate reporting of results from completed clinical trials. Legislation seems to be the only way to enforce mandatory disclosure of results. The Trial and Experimental Studies Transparency (TEST) Act of 2012 was introduced to the legislators in the United States to promote greater transparency in research industry. Public safety and advancement of science are the driving forces for the proposed policy change. The TEST Act may benefit the society and researchers; however, there are major concerns with participants' privacy and intellectual property protection. Copyright © 2014 Elsevier Inc. All rights reserved.

Rat electropharmacograms of the flavonoids rutin and quercetin in comparison to those of moclobemide and clinically used reference drugs suggest antidepressive and/or neuroprotective action.

PubMed

Dimpfel, Wilfried

2009-04-01

In order to be able to test single constituents of herbal plant extracts with respect to possible clinical usefulness, the model of local field potential analysis leading to the so-called electropharmacogram has been successfully used in rats to classify the effects of theanine and theogallin in the past. The present investigation aims at the prediction of efficacy and possible mechanisms of action of rutin and quercetin. Adult rats (day-night converted) were instrumented with four bipolar concentric electrodes into the frontal cortex, hippocampus, striatum and reticular formation. Field potentials were recorded during a pre-drug reference period of 45 min followed by oral administration of the particular test compound and 4h recording thereafter. Data were transmitted wirelessly to the computer for spectral frequency analysis. Rutin (5-80 mg/kg) as well as quercetin (5-40 mg/kg orally) produced similar electropharmacograms with dose dependent decreases of spectral alpha2 and beta1 frequencies within all brain areas. Peak effects were reached 4h after administration. The pattern of changes approached that obtained after 2.5mg/kg of moclobemide during the first hour as revealed by discriminant analysis in comparison to a large matrix of other drugs with known clinical indications. Data suggest antidepressant capabilities for rutin and quercetin with inhibition of monoamino oxidase at least as part of the mechanism of action. Both compounds should be tested clinically in patients with symptoms of depression.

Comprehensive analysis of cochlear implant failure: usefulness of clinical symptom-based algorithm combined with in situ integrity testing.

PubMed

Yamazaki, Hiroshi; O'Leary, Stephen; Moran, Michelle; Briggs, Robert

2014-04-01

Accurate diagnosis of cochlear implant failures is important for management; however, appropriate strategies to assess possible device failures are not always clear. The purpose of this study is to understand correlation between causes of device failure and the presenting clinical symptoms as well as results of in situ integrity testing and to propose effective strategies for diagnosis of device failure. Retrospective case review. Cochlear implant center at a tertiary referral hospital. Twenty-seven cases with suspected device failure of Cochlear Nucleus systems (excluding CI512 failures) on the basis of deterioration in auditory perception from January 2000 to September 2012 in the Melbourne cochlear implant clinic. Clinical presentations and types of abnormalities on in situ integrity testing were compared with modes of device failure detected by returned device analysis. Sudden deterioration in auditory perception was always observed in cases with "critical damage": either fracture of the integrated circuit or most or all of the electrode wires. Subacute or gradually progressive deterioration in auditory perception was significantly associated with a more limited number of broken electrode wires. Cochlear implant mediated auditory and nonauditory symptoms were significantly associated with an insulation problem. An algorithm based on the time course of deterioration in auditory perception and cochlear implant-mediated auditory and nonauditory symptoms was developed on the basis of these retrospective analyses, to help predict the mode of device failure. In situ integrity testing, which included close monitoring of device function in routine programming sessions as well as repeating the manufacturer's integrity test battery, was sensitive enough to detect malfunction in all suspected device failures, and each mode of device failure showed a characteristic abnormality on in situ integrity testing. Our clinical manifestation-based algorithm combined with in situ integrity testing may be useful for accurate diagnosis and appropriate management of device failure. Close monitoring of device function in routine programming sessions as well as repeating the manufacturer's integrity test battery is important if the initial in situ integrity testing is inconclusive because objective evidence of failure in the implanted device is essential to recommend explantation/reimplantation.

Analysis and design of randomised clinical trials involving competing risks endpoints.

PubMed

Tai, Bee-Choo; Wee, Joseph; Machin, David

2011-05-19

In randomised clinical trials involving time-to-event outcomes, the failures concerned may be events of an entirely different nature and as such define a classical competing risks framework. In designing and analysing clinical trials involving such endpoints, it is important to account for the competing events, and evaluate how each contributes to the overall failure. An appropriate choice of statistical model is important for adequate determination of sample size. We describe how competing events may be summarised in such trials using cumulative incidence functions and Gray's test. The statistical modelling of competing events using proportional cause-specific and subdistribution hazard functions, and the corresponding procedures for sample size estimation are outlined. These are illustrated using data from a randomised clinical trial (SQNP01) of patients with advanced (non-metastatic) nasopharyngeal cancer. In this trial, treatment has no effect on the competing event of loco-regional recurrence. Thus the effects of treatment on the hazard of distant metastasis were similar via both the cause-specific (unadjusted csHR = 0.43, 95% CI 0.25 - 0.72) and subdistribution (unadjusted subHR 0.43; 95% CI 0.25 - 0.76) hazard analyses, in favour of concurrent chemo-radiotherapy followed by adjuvant chemotherapy. Adjusting for nodal status and tumour size did not alter the results. The results of the logrank test (p = 0.002) comparing the cause-specific hazards and the Gray's test (p = 0.003) comparing the cumulative incidences also led to the same conclusion. However, the subdistribution hazard analysis requires many more subjects than the cause-specific hazard analysis to detect the same magnitude of effect. The cause-specific hazard analysis is appropriate for analysing competing risks outcomes when treatment has no effect on the cause-specific hazard of the competing event. It requires fewer subjects than the subdistribution hazard analysis for a similar effect size. However, if the main and competing events are influenced in opposing directions by an intervention, a subdistribution hazard analysis may be warranted.

Practical considerations for volumetric wear analysis of explanted hip arthroplasties.

PubMed

Langton, D J; Sidaginamale, R P; Holland, J P; Deehan, D; Joyce, T J; Nargol, A V F; Meek, R D; Lord, J K

2014-01-01

Wear debris released from bearing surfaces has been shown to provoke negative immune responses in the recipient. Excessive wear has been linked to early failure of prostheses. Analysis using coordinate measuring machines (CMMs) can provide estimates of total volumetric material loss of explanted prostheses and can help to understand device failure. The accuracy of volumetric testing has been debated, with some investigators stating that only protocols involving hundreds of thousands of measurement points are sufficient. We looked to examine this assumption and to apply the findings to the clinical arena. We examined the effects on the calculated material loss from a ceramic femoral head when different CMM scanning parameters were used. Calculated wear volumes were compared with gold standard gravimetric tests in a blinded study. Various scanning parameters including point pitch, maximum point to point distance, the number of scanning contours or the total number of points had no clinically relevant effect on volumetric wear calculations. Gravimetric testing showed that material loss can be calculated to provide clinically relevant degrees of accuracy. Prosthetic surfaces can be analysed accurately and rapidly with currently available technologies. Given these results, we believe that routine analysis of explanted hip components would be a feasible and logical extension to National Joint Registries. Cite this article: Bone Joint Res 2014;3:60-8.

The "four quadrants" approach to clinical ethics case analysis; an application and review.

PubMed

Sokol, D K

2008-07-01

In 1982, Jonsen, Siegler and Winslade published Clinical Ethics, in which they described the "four quadrants" approach, a new method of analysing clinical ethics cases. Although the book is now in its 6th edition, a literature search has revealed only one academic paper demonstrating the method at work. This paper is an attempt to start filling this gap. As a way of describing and testing the approach, I apply the four quadrants method to a detailed clinical ethics case. The analysis is interspersed with reflections on the method itself. It is hoped that this experiment will encourage ethicists and clinicians to devote more attention to this neglected approach.

Investigation of potential cognitive tests for use with older adults in audiology clinics.

PubMed

Vaughan, Nancy; Storzbach, Daniel; Furukawa, Izumi

2008-01-01

Cognitive declines in working memory and processing speed are hallmarks of aging. Deficits in speech understanding also are seen in aging individuals. A clinical test to determine whether the cognitive aging changes contribute to aging speech understanding difficulties would be helpful for determining rehabilitation strategies in audiology clinics. To identify a clinical neurocognitive test or battery of tests that could be used in audiology clinics to help explain deficits in speech recognition in some older listeners. A correlational study examining the association between certain cognitive test scores and speech recognition performance. Speeded (time-compressed) speech was used to increase the cognitive processing load. Two hundred twenty-five adults aged 50 through 75 years were participants in this study. Both batteries of tests were administered to all participants in two separate sessions. A selected battery of neurocognitive tests and a time-compressed speech recognition test battery using various rates of speech were administered. Principal component analysis was used to extract the important component factors from each set of tests, and regression models were constructed to examine the association between tests and to identify the neurocognitive test most strongly associated with speech recognition performance. A sequencing working memory test (Letter-Number Sequencing [LNS]) was most strongly associated with rapid speech understanding. The association between the LNS test results and the compressed sentence recognition scores (CSRS) was strong even when age and hearing loss were controlled. The LNS is a sequencing test that provides information about temporal processing at the cognitive level and may prove useful in diagnosis of speech understanding problems, and in the development of aural rehabilitation and training strategies.

Job Satisfaction of Dietitians in the Army Medical Specialists Corps

DTIC Science & Technology

1981-01-01

in the clinical branches while only 3.&% were assigned as staff administrative dietitians in the production and service branches. Distribution of the...Leavenworth, Kansas and the U.S. Amy-Baylor University Program in Health Care Administration , Fort Sam Houston, Texas. Test of analysis of variance of mean...Chief, Food Service Division; Chief, Production and Service Branch; Chief, Clinical Dietetic Branch; Staff Administrative Dietitian; Staff Clinical

TU-FG-201-01: 18-Month Clinical Experience of a Linac Daily Quality Assurance (QA) Solution Using Only EPID and OBI

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

Cai, B; Sun, B; Yaddanapudi, S

Purpose: To describe the clinical use of a Linear Accelerator (Linac) DailyQA system with only EPID and OBI. To assess the reliability over an 18-month period and improve the robustness of this system based on QA failure analysis. Methods: A DailyQA solution utilizing an in-house designed phantom, combined EPID and OBI image acquisitions, and a web-based data analysis and reporting system was commissioned and used in our clinic to measure geometric, dosimetry and imaging components of a Varian Truebeam Linac. During an 18-month period (335 working days), the Daily QA results, including the output constancy, beam flatness and symmetry, uniformity,more » TPR20/10, MV and KV imaging quality, were collected and analyzed. For output constancy measurement, an independent monthly QA system with an ionization chamber (IC) and annual/incidental TG51 measurements with ADCL IC were performed and cross-compared to Daily QA system. Thorough analyses were performed on the recorded QA failures to evaluate the machine performance, optimize the data analysis algorithm, adjust the tolerance setting and improve the training procedure to prevent future failures. Results: A clinical workflow including beam delivery, data analysis, QA report generation and physics approval was established and optimized to suit daily clinical operation. The output tests over the 335 working day period cross-correlated with the monthly QA system within 1.3% and TG51 results within 1%. QA passed with one attempt on 236 days out of 335 days. Based on the QA failures analysis, the Gamma criteria is revised from (1%, 1mm) to (2%, 1mm) considering both QA accuracy and efficiency. Data analysis algorithm is improved to handle multiple entries for a repeating test. Conclusion: We described our 18-month clinical experience on a novel DailyQA system using only EPID and OBI. The long term data presented demonstrated the system is suitable and reliable for Linac daily QA.« less

Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.

PubMed

Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R; Plassman, Brenda L; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A

2014-11-01

Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. To evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. The National Alzheimer Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 National Institute on Aging-funded Alzheimer Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (N = 3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; comparable results, however, can be achieved with very sensitive tests and contrast scores. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Upgrading from VVI to DDD pacing Mode during elective replacement of pulse generator: a comparative clinical-functional analysis.

PubMed

Teno, Luiz Antonio Castilho; Costa, Roberto; Martinelli Filho, Martino; Castilho, Fabian Cecchi Teno; Ruiz, Ivan

2007-02-01

Evaluate the clinical and functional behavior of the ventricular and atrioventricular stimulation modes in the elective replacement of pulse generator in patients with chagasic cardiopathy and atrioventricular block. Twenty-seven patients under ventricular and atrioventricular stimulation were comparatively evaluated at the beginning of the study, and alternately in ventricular and atrioventricular modes in two 90-day phases, with regard to: the clinical behavior evaluated according to quality of life and functional class, and the functional behavior evaluated by transthoracic echocardiography and the six-minute walk test. The statistical analysis was performed with patients at baseline, and under ventricular and atrioventricular modes, using the chi-square test and the repeated measures analysis of variance, and taking into consideration a 0.05 level of significance. The mean quality-of-life scores were: functional capacity (VVI 71.3+/-18.2 , DDD 69.3+/-20.4); overall health status (VVI 68.1+/-21.8, DDD 69.4+/-19.4) and vitality (VVI 64.8+/-24.6 , DDD 67.6+/-25.5); on echocardiography: LVEF (VVI 52.5+/-12.8 , DDD 51.8+/-14.9), LVDD (VVI 53.0+/-7.7 , DDD 42.4+/-7.8), LA (VVI 38.6+/-5.4 DDD 38.5+/-5.1), and in the six-minute walk test: distance walked (VVI 463.4+/-84.7, DDD 462.6+/-63.4). There were four cases of complications, three of them associated with the change in stimulation mode. This study showed no differences between the two stimulation modes in the clinical behavior assessed by quality of life and functional class, and in the functional behavior, evaluated according to the ecochardiographic findings and the six-minute walk test.

Current nonclinical testing paradigm enables safe entry to First-In-Human clinical trials: The IQ consortium nonclinical to clinical translational database.

PubMed

Monticello, Thomas M; Jones, Thomas W; Dambach, Donna M; Potter, David M; Bolt, Michael W; Liu, Maggie; Keller, Douglas A; Hart, Timothy K; Kadambi, Vivek J

2017-11-01

The contribution of animal testing in drug development has been widely debated and challenged. An industry-wide nonclinical to clinical translational database was created to determine how safety assessments in animal models translate to First-In-Human clinical risk. The blinded database was composed of 182 molecules and contained animal toxicology data coupled with clinical observations from phase I human studies. Animal and clinical data were categorized by organ system and correlations determined. The 2×2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis. Sensitivity was 48% with a 43% positive predictive value (PPV). The nonhuman primate had the strongest performance in predicting adverse effects, especially for gastrointestinal and nervous system categories. When the same target organ was identified in both the rodent and nonrodent, the PPV increased. Specificity was 84% with an 86% negative predictive value (NPV). The beagle dog had the strongest performance in predicting an absence of clinical adverse effects. If no target organ toxicity was observed in either test species, the NPV increased. While nonclinical studies can demonstrate great value in the PPV for certain species and organ categories, the NPV was the stronger predictive performance measure across test species and target organs indicating that an absence of toxicity in animal studies strongly predicts a similar outcome in the clinic. These results support the current regulatory paradigm of animal testing in supporting safe entry to clinical trials and provide context for emerging alternate models. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents

PubMed Central

Ferkol, Thomas W.; Davis, Stephanie D.; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D.; Sagel, Scott D.; Milla, Carlos; Olivier, Kenneth N.; Sullivan, Kelli M.; Zariwala, Maimoona A.; Pittman, Jessica E.; Shapiro, Adam J.; Carson, Johnny L.; Krischer, Jeffrey; Hazucha, Milan J.

2016-01-01

Rationale: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. Objectives: To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Methods: Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0–18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as “definite PCD” (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), “probable/possible PCD” (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and “other diagnosis or undefined.” Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. Measurements and Main Results: From 534 participants 18 years of age and younger, 205 were identified as having “definite PCD” (including 164 with two mutations in a PCD-associated gene), 187 were categorized as “other diagnosis or undefined,” and 142 were defined as having “probable/possible PCD.” Participants with “definite PCD” were compared with the “other diagnosis or undefined” group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Conclusions: Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167). PMID:27070726

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.

Factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus: decision-curve analysis.

PubMed

Kondo, M; Nagao, Y; Mahbub, M H; Tanabe, T; Tanizawa, Y

2018-04-29

To identify factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus, using decision-curve analysis. A retrospective cohort study was performed. The participants were 123 Japanese women with gestational diabetes who underwent 75-g oral glucose tolerance tests at 8-12 weeks after delivery. They were divided into a glucose intolerance and a normal glucose tolerance group based on postpartum oral glucose tolerance test results. Analysis of the pregnancy oral glucose tolerance test results showed predictive factors for postpartum glucose intolerance. We also evaluated the clinical usefulness of the prediction model based on decision-curve analysis. Of 123 women, 78 (63.4%) had normoglycaemia and 45 (36.6%) had glucose intolerance. Multivariable logistic regression analysis showed insulinogenic index/fasting immunoreactive insulin and summation of glucose levels, assessed during pregnancy oral glucose tolerance tests (total glucose), to be independent risk factors for postpartum glucose intolerance. Evaluating the regression models, the best discrimination (area under the curve 0.725) was obtained using the basic model (i.e. age, family history of diabetes, BMI ≥25 kg/m 2 and use of insulin during pregnancy) plus insulinogenic index/fasting immunoreactive insulin <1.1. Decision-curve analysis showed that combining insulinogenic index/fasting immunoreactive insulin <1.1 with basic clinical information resulted in superior net benefits for prediction of postpartum glucose intolerance. Insulinogenic index/fasting immunoreactive insulin calculated using oral glucose tolerance test results during pregnancy is potentially useful for predicting early postpartum glucose intolerance in Japanese women with gestational diabetes. © 2018 Diabetes UK.

Learning the facts in medical school is not enough: which factors predict successful application of procedural knowledge in a laboratory setting?

PubMed

Schmidmaier, Ralf; Eiber, Stephan; Ebersbach, Rene; Schiller, Miriam; Hege, Inga; Holzer, Matthias; Fischer, Martin R

2013-02-22

Medical knowledge encompasses both conceptual (facts or "what" information) and procedural knowledge ("how" and "why" information). Conceptual knowledge is known to be an essential prerequisite for clinical problem solving. Primarily, medical students learn from textbooks and often struggle with the process of applying their conceptual knowledge to clinical problems. Recent studies address the question of how to foster the acquisition of procedural knowledge and its application in medical education. However, little is known about the factors which predict performance in procedural knowledge tasks. Which additional factors of the learner predict performance in procedural knowledge? Domain specific conceptual knowledge (facts) in clinical nephrology was provided to 80 medical students (3rd to 5th year) using electronic flashcards in a laboratory setting. Learner characteristics were obtained by questionnaires. Procedural knowledge in clinical nephrology was assessed by key feature problems (KFP) and problem solving tasks (PST) reflecting strategic and conditional knowledge, respectively. Results in procedural knowledge tests (KFP and PST) correlated significantly with each other. In univariate analysis, performance in procedural knowledge (sum of KFP+PST) was significantly correlated with the results in (1) the conceptual knowledge test (CKT), (2) the intended future career as hospital based doctor, (3) the duration of clinical clerkships, and (4) the results in the written German National Medical Examination Part I on preclinical subjects (NME-I). After multiple regression analysis only clinical clerkship experience and NME-I performance remained independent influencing factors. Performance in procedural knowledge tests seems independent from the degree of domain specific conceptual knowledge above a certain level. Procedural knowledge may be fostered by clinical experience. More attention should be paid to the interplay of individual clinical clerkship experiences and structured teaching of procedural knowledge and its assessment in medical education curricula.

The development and validation of the Clinical Teaching Behavior Inventory (CTBI-23): Nurse preceptors' and new graduate nurses' perceptions of precepting.

PubMed

Lee-Hsieh, Jane; O'Brien, Anthony; Liu, Chieh-Yu; Cheng, Su-Fen; Lee, Yea-Wen; Kao, Yu-Hsiu

2016-03-01

Few studies have examined the perceptions of clinical teaching behaviors among both nurse preceptors and preceptees. To develop a Clinical Teaching Behavior Inventory (CTBI) for nurse preceptors' self-evaluation, and for new graduate nurse preceptee evaluation of preceptor clinical teaching behaviors and to test the validity and reliability of the CTBI. This study used mixed research techniques in five phases. Phase I: based on a literature review, the researchers developed an instrument to measure clinical teaching behaviors. Phase II: 17 focus group interviews were conducted with 63 preceptors and 24 new graduate nurses from five hospitals across Taiwan. Clinical teaching behavior themes were extracted from the focus group data and integrated into the domains and items of the CTBI. Phase III: two rounds of an expert Delphi study were conducted to determine the content validity of the instrument. Phase IV: a total of 290 nurse preceptors and 260 new graduate nurses were recruited voluntarily in the same five hospitals in Taiwan. Of these, 521 completed questionnaires to test the construct validity of CTBI by using confirmatory factory analysis. Phase V: the internal consistency and reliability of the instrument were tested. CTBI consists of 23 items in six domains: (1) 'Committing to Teaching'; (2) 'Building a Learning Atmosphere'; (3) 'Using Appropriate Teaching Strategies'; (4) 'Guiding Inter-professional Communication'; (5) 'Providing Feedback and Evaluation'; and (6) 'Showing Concern and Support'. The confirmatory factor analysis yielded a good fit and reliable scores for the CTBI-23 model. The CTBI-23 is a valid and reliable instrument for identifying the clinical teaching behaviors of a preceptor as perceived by preceptors and new graduate preceptees. The CTBI-23 depicts clinical teaching behaviors of nurse preceptors in Taiwan. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Optimization of cluster analysis based on drug resistance profiles of MRSA isolates].

PubMed

Tani, Hiroya; Kishi, Takahiko; Gotoh, Minehiro; Yamagishi, Yuka; Mikamo, Hiroshige

2015-12-01

We examined 402 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from clinical specimens in our hospital between November 19, 2010 and December 27, 2011 to evaluate the similarity between cluster analysis of drug susceptibility tests and pulsed-field gel electrophoresis (PFGE). The results showed that the 402 strains tested were classified into 27 PFGE patterns (151 subtypes of patterns). Cluster analyses of drug susceptibility tests with the cut-off distance yielding a similar classification capability showed favorable results--when the MIC method was used, and minimum inhibitory concentration (MIC) values were used directly in the method, the level of agreement with PFGE was 74.2% when 15 drugs were tested. The Unweighted Pair Group Method with Arithmetic mean (UPGMA) method was effective when the cut-off distance was 16. Using the SIR method in which susceptible (S), intermediate (I), and resistant (R) were coded as 0, 2, and 3, respectively, according to the Clinical and Laboratory Standards Institute (CLSI) criteria, the level of agreement with PFGE was 75.9% when the number of drugs tested was 17, the method used for clustering was the UPGMA, and the cut-off distance was 3.6. In addition, to assess the reproducibility of the results, 10 strains were randomly sampled from the overall test and subjected to cluster analysis. This was repeated 100 times under the same conditions. The results indicated good reproducibility of the results, with the level of agreement with PFGE showing a mean of 82.0%, standard deviation of 12.1%, and mode of 90.0% for the MIC method and a mean of 80.0%, standard deviation of 13.4%, and mode of 90.0% for the SIR method. In summary, cluster analysis for drug susceptibility tests is useful for the epidemiological analysis of MRSA.

KRAS and BRAF mutation analysis in metastatic colorectal cancer: a cost-effectiveness analysis from a Swiss perspective.

PubMed

Blank, Patricia R; Moch, Holger; Szucs, Thomas D; Schwenkglenks, Matthias

2011-10-01

Monoclonal antibodies against the epidermal growth factor receptor (EGFR), such as cetuximab, have led to significant clinical benefits for metastatic colorectal cancer (mCRC) patients but have also increased treatment costs considerably. Recent evidence associates KRAS and BRAF mutations with resistance to EGFR antibodies. We assessed the cost-effectiveness of predictive testing for KRAS and BRAF mutations, prior to cetuximab treatment of chemorefractory mCRC patients. A life-long Markov simulation model was used to estimate direct medical costs (€) and clinical effectiveness [quality-adjusted life-years (QALY)] of the following strategies: KRAS testing, KRAS testing with subsequent BRAF testing of KRAS wild-types (KRAS/BRAF), cetuximab treatment without testing. Comparison was against no cetuximab treatment (reference strategy). In the testing strategies, cetuximab treatment was initiated if no mutations were detected. Best supportive care was given to all patients. Survival times/utilities were derived from published randomized clinical trials. Costs were assessed from the perspective of the Swiss health system. Average remaining lifetime costs ranged from €3,983 (no cetuximab) to €38,662 (no testing). Cetuximab treatment guided by KRAS/BRAF achieved gains of 0.491 QALYs compared with the reference strategy. The KRAS testing strategy achieved an additional gain of 0.002 QALYs compared with KRAS/BRAF. KRAS/BRAF testing was the most cost-effective approach when compared with the reference strategy (incremental cost-effectiveness ratio: €62,653/QALY). New predictive tests for KRAS and BRAF status are currently being introduced in pathology. Despite substantial costs of predictive testing, it is economically favorable to identify patients with KRAS and BRAF wild-type status. ©2011 AACR

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

PubMed

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

2017-08-01

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

Comprehensive analysis of MGMT promoter methylation: correlation with MGMT expression and clinical response in GBM.

PubMed

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-07

O⁶-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089-13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301-7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting.

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

PubMed Central

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-01

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting. PMID:21249131

An application of actuarial methods in psychiatric diagnosis.

PubMed

Overall, J E; Higgins, C W

1977-10-01

An actuarial program for psychiatric diagnosis is evaluated for agreement with final clinical diagnosis in a series of 288 patients. The acturial program provides a probability differential diagnosis based on an analysis of history and background data, symptom rating profiles, and MMPI clinical scale profiles. The observed agreement with final clinical diagnosis is approximately 50% higher than previously reported for psychological testing in this same setting. The results emphasize the importance for psychologists of clinical interview and observation skills.

Development of Standardized Material Testing Protocols for Prosthetic Liners

PubMed Central

Cagle, John C.; Reinhall, Per G.; Hafner, Brian J.; Sanders, Joan E.

2017-01-01

A set of protocols was created to characterize prosthetic liners across six clinically relevant material properties. Properties included compressive elasticity, shear elasticity, tensile elasticity, volumetric elasticity, coefficient of friction (CoF), and thermal conductivity. Eighteen prosthetic liners representing the diverse range of commercial products were evaluated to create test procedures that maximized repeatability, minimized error, and provided clinically meaningful results. Shear and tensile elasticity test designs were augmented with finite element analysis (FEA) to optimize specimen geometries. Results showed that because of the wide range of available liner products, the compressive elasticity and tensile elasticity tests required two test maxima; samples were tested until they met either a strain-based or a stress-based maximum, whichever was reached first. The shear and tensile elasticity tests required that no cyclic conditioning be conducted because of limited endurance of the mounting adhesive with some liner materials. The coefficient of friction test was based on dynamic coefficient of friction, as it proved to be a more reliable measurement than static coefficient of friction. The volumetric elasticity test required that air be released beneath samples in the test chamber before testing. The thermal conductivity test best reflected the clinical environment when thermal grease was omitted and when liner samples were placed under pressure consistent with load bearing conditions. The developed procedures provide a standardized approach for evaluating liner products in the prosthetics industry. Test results can be used to improve clinical selection of liners for individual patients and guide development of new liner products. PMID:28233885

HIV testing of pregnant women: an ethical analysis.

PubMed

Johansson, Kjell Arne; Pedersen, Kirsten Bjerkreim; Andersson, Anna-Karin

2011-12-01

Recent global advances in available technology to prevent mother-to-child HIV transmission necessitate a rethinking of contemporary and previous ethical debates on HIV testing as a means to preventing vertical transmission. In this paper, we will provide an ethical analysis of HIV-testing strategies of pregnant women. First, we argue that provider-initiated opt-out HIV testing seems to be the most effective HIV test strategy. The flip-side of an opt-out strategy is that it may end up as involuntary testing in a clinical setting. We analyse this ethical puzzle from a novel perspective, taking into account the moral importance of certain hypothetical preferences of the child, as well as the moral importance of certain actual preferences of the mother. Finally, we balance the conflicting concerns and try to arrive at an ethically sound solution to this dilemma. Our aim is to introduce a novel perspective from which to analyse testing strategies, and to explore the implications and possible benefits of our proposal. The conclusion from our analysis is that policies that recommend provider-initiated opt-out HIV testing of pregnant mothers, with a risk of becoming involuntary testing in a clinical setting, are acceptable. The rationale behind this is that the increased availability of very effective and inexpensive life-saving drugs makes the ethical problems raised by the possible intrusiveness of HIV testing less important than the child's hypothetical preferences to be born healthy. Health care providers, therefore, have a duty to offer both opt-out HIV testing and available PMTCT (preventing mother-to-child transmission) interventions. © 2011 Blackwell Publishing Ltd.

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.

Web-based training and interrater reliability testing for scoring the Hamilton Depression Rating Scale.

PubMed

Rosen, Jules; Mulsant, Benoit H; Marino, Patricia; Groening, Christopher; Young, Robert C; Fox, Debra

2008-10-30

Despite the importance of establishing shared scoring conventions and assessing interrater reliability in clinical trials in psychiatry, these elements are often overlooked. Obstacles to rater training and reliability testing include logistic difficulties in providing live training sessions, or mailing videotapes of patients to multiple sites and collecting the data for analysis. To address some of these obstacles, a web-based interactive video system was developed. It uses actors of diverse ages, gender and race to train raters how to score the Hamilton Depression Rating Scale and to assess interrater reliability. This system was tested with a group of experienced and novice raters within a single site. It was subsequently used to train raters of a federally funded multi-center clinical trial on scoring conventions and to test their interrater reliability. The advantages and limitations of using interactive video technology to improve the quality of clinical trials are discussed.

Evaluation of effect of low-level laser therapy on adolescents with temporomandibular disorder: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background A number of problems involving the temporomandibular joint (TMJ) and associated structures can lead to temporomandibular disorder (TMD). The aim of the proposed study is to assess the effect of low-level laser therapy on occlusal contacts, mandibular movements, electromyography activity in the muscles of mastication and pain in adolescents with TMD. Methods/Design A randomized, controlled, double-blind, clinical trial will be carried out involving 85 male and female adolescents between 15 and 18 years of age. The research diagnostic criteria for TMD will be used to assess all individuals who agree to participate. All participants will be submitted to a clinical examination and electromyographic analysis of the masseter muscles and anterior bundle of the temporal muscles bilaterally, to determine TMD. Based on the clinical findings, the participants will be classified as having or not having TMD. Those with TMD will be divided into four groups, three of which will receive low-level laser therapy and one of which will receive a placebo treatment. The treatments will involve the TMJ region alone, the masseter and temporal muscles alone, or both these regions together. The data will be submitted to descriptive statistical analysis. The chi-square test and Fisher’s exact test will be used to determine associations among the categorical variables. The Student’s t test and analysis of variance will be used for the comparison of mean electromyographic signals. Pearson’s correlation coefficients will be calculated for the analysis of correlations among the continuous variables. Trial registration The protocol for this study has been submitted to Clinical Trials – registration number (NCT01846000). PMID:23876095

Assessing Willingness to Test for HIV among Men who have Sex with Men Using Conjoint Analysis, Evidence for Uptake of the FDA-approved at-Home HIV Test

PubMed Central

Lee, Sung-Jae; Brooks, Ronald; Bolan, Robert K.; Flynn, Risa

2013-01-01

Men who have sex with men (MSM) in the United States represent a vulnerable population with lower rates of HIV testing. There are various specific attributes of HIV testing that may impact willingness to test (WTT) for HIV. Identifying specific attributes influencing patients’ decisions around WTT for HIV is critical to ensure improved HIV testing uptake. This study examined WTT for HIV by using conjoint analysis, an innovative method for systematically estimating consumer preferences across discrete attributes. WTT for HIV was assessed across eight hypothetical HIV testing scenarios varying across seven dichotomous attributes: location (home vs. clinic), price (free vs. $50), sample collection (finger prick vs. blood), timeliness of results (immediate vs. 1–2 weeks), privacy (anonymous vs. confidential), results given (by phone vs. in-person), and type of counseling (brochure vs. in-person). Seventy-five MSM were recruited from a community based organization providing HIV testing services in Los Angeles to participate in conjoint analysis. WTT for HIV score was based on a 100-point scale. Scores ranged from 32.2 to 80.3 for eight hypothetical HIV testing scenarios. Price of HIV testing (free vs. $50) had the highest impact on WTT (impact score=31.4, SD=29.2, p<.0001), followed by timeliness of results (immediate vs. 1–2 weeks) (impact score=13.9, SD=19.9, p=<.0001) and testing location (home vs. clinic) (impact score=10.3, SD=22.8, p=.0002). Impacts of other HIV testing attributes were not significant. Conjoint analysis method enabled direct assessment of HIV testing preferences and identified specific attributes that significantly impact WTT for HIV among MSM. This method provided empirical evidence to support the potential uptake of the newly FDA-approved over-the-counter HIV home-test kit with immediate results, with cautionary note on the cost of the kit. PMID:23651439

One-dimensional model for the intracranial pulse morphological analysis during hyperventilation and CO2 inhalation tests

NASA Astrophysics Data System (ADS)

Ryu, Jaiyoung; Hu, Xiao; Shadden, Shawn C.

2015-11-01

The brain's CO2 reactivity mechanism is coupled with cerebral autoregulation and other unique features of cerebral hemodynamics. We developed a one-dimensional nonlinear model of blood flow in the cerebral arteries coupled to lumped parameter (LP) networks. The LP networks incorporate cerebral autoregulation, CO2 reactivity, intracranial pressure, cerebrospinal fluid, and cortical collateral blood flow models. The model was used to evaluate hemodynamic variables (arterial deformation, blood velocity and pressure) in the cerebral vasculature during hyperventilation and CO2 inhalation test. Tests were performed for various arterial blood pressure (ABP) representing normal and hypotensive conditions. The increase of the cerebral blood flow rates agreed well with the published measurements for various ABP measurements taken during clinical CO2 reactivity tests. The changes in distal vasculature affected the reflected pulse wave energy, which caused the waveform morphological changes at the middle cerebral, common and internal carotid arteries. The pulse morphological analysis demonstrated agreement with previous clinical measurements for cerebral vasoconstriction and vasodilation.

Progress and prospects in pharmacogenetics of antidepressant drugs.

PubMed

Fabbri, Chiara; Crisafulli, Concetta; Calabrò, Marco; Spina, Edoardo; Serretti, Alessandro

2016-10-01

Depression is responsible for the most part of the personal and socio-economic burden due to psychiatric disorders. Since antidepressant response clusters in families, pharmacogenetics represents a meaningful tool to provide tailored treatments and improve the prognosis of depression. This review aims to summarize and discuss the pharmacogenetics of antidepressant drugs in major depressive disorder, with a focus on the most replicated genes, genome-wide association studies (GWAS), but also on the findings provided by new and promising analysis methods. In particular, multimarker tests such as pathway analysis and polygenic risk scores increase the power of detecting associations compared to the analysis of individual polymorphisms. Since genetic variants are not necessarily associated with a change in protein level, gene expression studies may provide complementary information to genetic studies. Finally, the pharmacogenetic tests that have been investigated for clinical application are discussed. Despite the lack of widespread clinical applications, preliminary results suggest that pharmacogenetics may be useful to guide antidepressant treatment. The US Food and Drug Administration included pharmacogenetic indications in the labeling of several antidepressants. This represented an important official recognition of the clinical relevance of genetic polymorphisms in antidepressant treatment.

Testing a model of research intention among U.K. clinical psychologists: a logistic regression analysis.

PubMed

Eke, Gemma; Holttum, Sue; Hayward, Mark

2012-03-01

Previous research highlights barriers to clinical psychologists conducting research, but has rarely examined U.K. clinical psychologists. The study investigated U.K. clinical psychologists' self-reported research output and tested part of a theoretical model of factors influencing their intention to conduct research. Questionnaires were mailed to 1,300 U.K. clinical psychologists. Three hundred and seventy-four questionnaires were returned (29% response-rate). This study replicated in a U.K. sample the finding that the modal number of publications was zero, highlighted in a number of U.K. and U.S. studies. Research intention was bimodally distributed, and logistic regression classified 78% of cases successfully. Outcome expectations, perceived behavioral control and normative beliefs mediated between research training environment and intention. Further research should explore how research is negotiated in clinical roles, and this issue should be incorporated into prequalification training. © 2012 Wiley Periodicals, Inc.

Expert Systems In Medical Studies - A New Twist

NASA Astrophysics Data System (ADS)

Slagle, James R.; Long, John M.; Wick, Michael R.; Matts, John P.; Leon, Arthur S.

1986-03-01

The use of experts to evaluate large amounts of trial data results in increasingly expensive and time consuming research. We are investigating the role expert systems can play in reducing the time and expense of research projects. Current methods in large clinical studies for evaluating data are often crude and superficial. We have developed, for a large clinical trial, an expert system for analysis of treadmill exercise ECG test results. In the cases we are studying, a patient is given a treadmill exercise ECG test once a year for five years. Pairs of these exercise tests are then evaluated by cardiologists to determine the condition of the patient's heart. The results of our system show great promise for the use of expert systems in reducing the time and expense of large clinical trials.

The value of the UK Clinical Aptitude Test in predicting pre-clinical performance: a prospective cohort study at Nottingham Medical School.

PubMed

Yates, Janet; James, David

2010-07-28

The UK Clinical Aptitude Test (UKCAT) was introduced in 2006 as an additional tool for the selection of medical students. It tests mental ability in four distinct domains (Quantitative Reasoning, Verbal Reasoning, Abstract Reasoning, and Decision Analysis), and the results are available to students and admissions panels in advance of the selection process. As yet the predictive validity of the test against course performance is largely unknown.The study objective was to determine whether UKCAT scores predict performance during the first two years of the 5-year undergraduate medical course at Nottingham. We studied a single cohort of students, who entered Nottingham Medical School in October 2007 and had taken the UKCAT. We used linear regression analysis to identify independent predictors of marks for different parts of the 2-year preclinical course. Data were available for 204/260 (78%) of the entry cohort. The UKCAT total score had little predictive value. Quantitative Reasoning was a significant independent predictor of course marks in Theme A ('The Cell'), (p = 0.005), and Verbal Reasoning predicted Theme C ('The Community') (p < 0.001), but otherwise the effects were slight or non-existent. This limited study from a single entry cohort at one medical school suggests that the predictive value of the UKCAT, particularly the total score, is low. Section scores may predict success in specific types of course assessment.The ultimate test of validity will not be available for some years, when current cohorts of students graduate. However, if this test of mental ability does not predict preclinical performance, it is arguably less likely to predict the outcome in the clinical years. Further research from medical schools with different types of curriculum and assessment is needed, with longitudinal studies throughout the course.

A pilot evaluation of a computer-based psychometric test battery designed to detect impairment in patients with cirrhosis

PubMed Central

Cook, Nicola A; Kim, Jin Un; Pasha, Yasmin; Crossey, Mary ME; Schembri, Adrian J; Harel, Brian T; Kimhofer, Torben; Taylor-Robinson, Simon D

2017-01-01

Background Psychometric testing is used to identify patients with cirrhosis who have developed hepatic encephalopathy (HE). Most batteries consist of a series of paper-and-pencil tests, which are cumbersome for most clinicians. A modern, easy-to-use, computer-based battery would be a helpful clinical tool, given that in its minimal form, HE has an impact on both patients’ quality of life and the ability to drive and operate machinery (with societal consequences). Aim We compared the Cogstate™ computer battery testing with the Psychometric Hepatic Encephalopathy Score (PHES) tests, with a view to simplify the diagnosis. Methods This was a prospective study of 27 patients with histologically proven cirrhosis. An analysis of psychometric testing was performed using accuracy of task performance and speed of completion as primary variables to create a correlation matrix. A stepwise linear regression analysis was performed with backward elimination, using analysis of variance. Results Strong correlations were found between the international shopping list, international shopping list delayed recall of Cogstate and the PHES digit symbol test. The Shopping List Tasks were the only tasks that consistently had P values of <0.05 in the linear regression analysis. Conclusion Subtests of the Cogstate battery correlated very strongly with the digit symbol component of PHES in discriminating severity of HE. These findings would indicate that components of the current PHES battery with the international shopping list tasks of Cogstate would be discriminant and have the potential to be used easily in clinical practice. PMID:28919805

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

PubMed

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

Bridging barriers to clinic-based HIV testing with new technology: translating self-implemented testing for African American youth.

PubMed

Catania, J A; Dolcini, M M; Harper, G W; Dowhower, D P; Dolcini-Catania, L G; Towner, S L; Timmons, A; Motley, D N; Tyler, D H

2015-12-01

Numerous barriers to clinic-based HIV testing exist (e.g., stigmatization) for African American youth. These barriers may be addressed by new technology, specifically HIV self-implemented testing (SIT). We conducted a series of formative phase 3 translation studies (49 face-to-face interviews, 9 focus groups, 1 advisory panel review) among low-income African American youth (15-19 years) and providers of adolescent services in two US cities to identify potential translation difficulties of the OraQuick SIT. Based on content analysis, we found that providers and African American youth viewed SITs positively compared to clinic-based testing. Data suggest that SITs may reduce social stigma and privacy concerns and increase convenience and normalization of HIV testing. Challenges with SIT implementation include difficulties accessing confirmatory testing, coping with adverse outcomes, and instructional materials that may be inappropriate for low socioeconomic status (SES) persons. Study results underscore the need for translation studies to identify specific comprehension and implementation problems African American youth may have with oral SITs.

Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes.

PubMed

Tomlins, Scott A; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B; Dicker, Adam P; Trock, Bruce J; DeMarzo, Angelo M; Ross, Ashley E; Schaeffer, Edward M; Klein, Eric A; Magi-Galluzzi, Cristina; Karnes, R Jeffrey; Jenkins, Robert B; Feng, Felix Y

2015-10-01

Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves. The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p<0.001). m-ETS(+) tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1(+)/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different among subtypes. A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathologic differences were found among subtypes based on global expression patterns. Molecular subtyping of prostate cancer can be achieved using extra data generated from a clinical-grade, genome-wide expression-profiling prognostic assay (Decipher). Transcriptomic and clinical analysis support three distinct molecular subtypes: (1) m-ERG(+), (2) m-ETS(+), and (3) m-SPINK1(+)/triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Incorporation of subtyping into a clinically available assay may facilitate additional applications beyond routine prognosis. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

qPCR-High resolution melt analysis for drug susceptibility testing of Mycobacterium leprae directly from clinical specimens of leprosy patients

PubMed Central

Goulart, Luiz Ricardo; Truman, Richard W.; Goulart, Isabela Maria B.; Vissa, Varalakshmi; Li, Wei; Matsuoka, Masanori; Suffys, Philip; Fontes, Amanda B.; Rosa, Patricia S.; Scollard, David M.; Williams, Diana L.

2017-01-01

Background Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. Methodology/Principal findings The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite’s stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite’s stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing. Conclusion/Significance Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy. PMID:28570560

Multiplex tests to identify gastrointestinal bacteria, viruses and parasites in people with suspected infectious gastroenteritis: a systematic review and economic analysis.

PubMed

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

2017-04-01

Gastroenteritis is a common, transient disorder usually caused by infection and characterised by the acute onset of diarrhoea. Multiplex gastrointestinal pathogen panel (GPP) tests simultaneously identify common bacterial, viral and parasitic pathogens using molecular testing. By providing test results more rapidly than conventional testing methods, GPP tests might positively influence the treatment and management of patients presenting in hospital or in the community. To systematically review the evidence for GPP tests [xTAG ® (Luminex, Toronto, ON, Canada), FilmArray (BioFire Diagnostics, Salt Lake City, UT, USA) and Faecal Pathogens B (AusDiagnostics, Beaconsfield, NSW, Australia)] and to develop a de novo economic model to compare the cost-effectiveness of GPP tests with conventional testing in England and Wales. Multiple electronic databases including MEDLINE, EMBASE, Web of Science and the Cochrane Database were searched from inception to January 2016 (with supplementary searches of other online resources). Eligible studies included patients with acute diarrhoea; comparing GPP tests with standard microbiology techniques; and patient, management, test accuracy or cost-effectiveness outcomes. Quality assessment of eligible studies used tailored Quality Assessment of Diagnostic Accuracy Studies-2, Consolidated Health Economic Evaluation Reporting Standards and Philips checklists. The meta-analysis included positive and negative agreement estimated for each pathogen. A de novo decision tree model compared patients managed with GPP testing or comparable coverage with patients managed using conventional tests, within the Public Health England pathway. Economic models included hospital and community management of patients with suspected gastroenteritis. The model estimated costs (in 2014/15 prices) and quality-adjusted life-year losses from a NHS and Personal Social Services perspective. Twenty-three studies informed the review of clinical evidence (17 xTAG, four FilmArray, two xTAG and FilmArray, 0 Faecal Pathogens B). No study provided an adequate reference standard with which to compare the test accuracy of GPP with conventional tests. A meta-analysis (of 10 studies) found considerable heterogeneity; however, GPP testing produces a greater number of pathogen-positive findings than conventional testing. It is unclear whether or not these additional 'positives' are clinically important. The review identified no robust evidence to inform consequent clinical management of patients. There is considerable uncertainty about the cost-effectiveness of GPP panels used to test for suspected infectious gastroenteritis in hospital and community settings. Uncertainties in the model include length of stay, assumptions about false-positive findings and the costs of tests. Although there is potential for cost-effectiveness in both settings, key modelling assumptions need to be verified and model findings remain tentative. No test-treat trials were retrieved. The economic model reflects one pattern of care, which will vary across the NHS. The systematic review and cost-effectiveness model identify uncertainties about the adoption of GPP tests within the NHS. GPP testing will generally correctly identify pathogens identified by conventional testing; however, these tests also generate considerable additional positive results of uncertain clinical importance. An independent reference standard may not exist to evaluate alternative approaches to testing. A test-treat trial might ascertain whether or not additional GPP 'positives' are clinically important or result in overdiagnoses, whether or not earlier diagnosis leads to earlier discharge in patients and what the health consequences of earlier intervention are. Future work might also consider the public health impact of different testing treatments, as test results form the basis for public health surveillance. This study is registered as PROSPERO CRD2016033320. The National Institute for Health Research Health Technology Assessment programme.

Pediatric Allergic Contact Dermatitis: Clinical and Epidemiological Study in a Tertiary Hospital.

PubMed

Ortiz Salvador, J M; Esteve Martínez, A; Subiabre Ferrer, D; Victoria Martínez, A M; de la Cuadra Oyanguren, J; Zaragoza Ninet, V

Few epidemiological studies have investigated the incidence of allergic contact dermatitis in children. Underdiagnosis has been observed in some studies, with many cases in which the condition is not suspected clinically and patch tests are not performed. However, the prevalence of pediatric sensitization to allergens has been reported to be as high as 20%, and the diagnosis should therefore be contemplated as a possibility in this age group. We performed a retrospective analysis of the skin allergy database of the Dermatology Department of Consorcio Hospital General Universitario de Valencia. Children between 0 and 16 years of age diagnosed with allergic contact dermatitis in the previous 15 years (between 2000 and 2015) were included in the analysis. Epidemiological (age, sex, history of atopy) and clinical (site of the lesions, allergen series applied, positive reactions, and their relevance) variables were gathered. Patch tests had been performed on 4,593 patients during the study period. Of these, 265 (6%) were children aged between 0 and 16 years. A positive reaction to at least one of the allergens tested was observed in 144 (54.3%) patients in that group. The allergens most frequently identified were the following (in decreasing order of frequency): thiomersal, cobalt chloride, colophony, paraphenylenediamine, potassium dichromate, mercury, and nickel. The sensitization was considered relevant in 177 (61.3%) cases. More than half of the children studied showed sensitization to 1 or more allergens, with a high percentage of relevant sensitizations. All children with a clinical suspicion of allergic contact dermatitis should be referred for patch testing. As no standardized test series have been developed for this age group, a high level of clinical suspicion and knowledge of the allergens most commonly involved are required when selecting the allergens to be tested. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT).

PubMed

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

2018-01-01

The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2-4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods-pertussis culture as the "gold standard," composite reference standard analysis (CRS), and latent class analysis (LCA). Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

Development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis

PubMed Central

Boston, Raymond C.; Coyne, James C.; Farrar, John T.

2010-01-01

Objective To develop and psychometrically test an owner self-administered questionnaire designed to assess severity and impact of chronic pain in dogs with osteoarthritis. Sample Population 70 owners of dogs with osteoarthritis and 50 owners of clinically normal dogs. Procedures Standard methods for the stepwise development and testing of instruments designed to assess subjective states were used. Items were generated through focus groups and an expert panel. Items were tested for readability and ambiguity, and poorly performing items were removed. The reduced set of items was subjected to factor analysis, reliability testing, and validity testing. Results Severity of pain and interference with function were 2 factors identified and named on the basis of the items contained in them. Cronbach’s α was 0.93 and 0.89, respectively, suggesting that the items in each factor could be assessed as a group to compute factor scores (ie, severity score and interference score). The test-retest analysis revealed κ values of 0.75 for the severity score and 0.81 for the interference score. Scores correlated moderately well (r = 0.51 and 0.50, respectively) with the overall quality-of-life (QOL) question, such that as severity and interference scores increased, QOL decreased. Clinically normal dogs had significantly lower severity and interference scores than dogs with osteoarthritis. Conclusions and Clinical Relevance A psychometrically sound instrument was developed. Responsiveness testing must be conducted to determine whether the questionnaire will be useful in reliably obtaining quantifiable assessments from owners regarding the severity and impact of chronic pain and its treatment on dogs with osteoarthritis. PMID:17542696

Clinical assessment of effusion in knee osteoarthritis—A systematic review

PubMed Central

Maricar, Nasimah; Callaghan, Michael J.; Parkes, Matthew J.; Felson, David T.; O׳Neill, Terence W.

2016-01-01

Objective The aim of this systematic review was to determine the validity and inter- and intra-observer reliability of the assessment of knee joint effusion in osteoarthritis (OA) of the knee. Methods MEDLINE, Web of Knowledge, CINAHL, EMBASE, and AMED were searched from their inception to February 2015. Articles were included according to a priori defined criteria: samples containing participants with knee OA; prospective evaluation of clinical tests and assessments of knee effusion that included reliability, sensitivity, and specificity of these tests. Results A total of 10 publications were reviewed. Eight of these considered reliability and four on validity of clinical assessments against ultrasound effusion. It was not possible to undertake a meta-analysis of reliability or validity because of differences in study designs and the clinical tests. Intra-observer kappa agreement for visible swelling ranged from 0.37 (suprapatellar) to 1.0 (prepatellar); for bulge sign 0.47 and balloon sign 0.37. Inter-observer kappa agreement for visible swelling ranged from −0.02 (prepatellar) to 0.65 (infrapatellar), the balloon sign −0.11 to 0.82, patellar tap −0.02 to 0.75 and bulge sign kappa −0.04 to 0.14 or reliability coefficient 0.97. Reliability and diagnostic accuracy tended to be better in experienced observers. Very few data looked at performance of individual clinical tests with sensitivity ranging 18.2–85.7% and specificity 35.3–93.3%, both higher with larger effusions. Conclusion The majority of unstandardized clinical tests to assess joint effusion in knee OA had relatively low intra- and inter-observer reliability. There is some evidence experience improved reliability and diagnostic accuracy of tests. Currently there is insufficient evidence to recommend any particular test in clinical practice. PMID:26581486

Clinical assessment of effusion in knee osteoarthritis-A systematic review.

PubMed

Maricar, Nasimah; Callaghan, Michael J; Parkes, Matthew J; Felson, David T; O'Neill, Terence W

2016-04-01

The aim of this systematic review was to determine the validity and inter- and intra-observer reliability of the assessment of knee joint effusion in osteoarthritis (OA) of the knee. MEDLINE, Web of Knowledge, CINAHL, EMBASE, and AMED were searched from their inception to February 2015. Articles were included according to a priori defined criteria: samples containing participants with knee OA; prospective evaluation of clinical tests and assessments of knee effusion that included reliability, sensitivity, and specificity of these tests. A total of 10 publications were reviewed. Eight of these considered reliability and four on validity of clinical assessments against ultrasound effusion. It was not possible to undertake a meta-analysis of reliability or validity because of differences in study designs and the clinical tests. Intra-observer kappa agreement for visible swelling ranged from 0.37 (suprapatellar) to 1.0 (prepatellar); for bulge sign 0.47 and balloon sign 0.37. Inter-observer kappa agreement for visible swelling ranged from -0.02 (prepatellar) to 0.65 (infrapatellar), the balloon sign -0.11 to 0.82, patellar tap -0.02 to 0.75 and bulge sign kappa -0.04 to 0.14 or reliability coefficient 0.97. Reliability and diagnostic accuracy tended to be better in experienced observers. Very few data looked at performance of individual clinical tests with sensitivity ranging 18.2-85.7% and specificity 35.3-93.3%, both higher with larger effusions. The majority of unstandardized clinical tests to assess joint effusion in knee OA had relatively low intra- and inter-observer reliability. There is some evidence experience improved reliability and diagnostic accuracy of tests. Currently there is insufficient evidence to recommend any particular test in clinical practice. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Antimicrobial activity of ProRoot MTA in contact with blood

PubMed Central

Farrugia, C.; Baca, P.; Camilleri, J.; Arias Moliz, M. T.

2017-01-01

Dental materials based on Portland cement, which is used in the construction industry have gained popularity for clinical use due to their hydraulic properties, the interaction with tooth tissue and their antimicrobial properties. The antimicrobial properties are optimal in vitro. However in clinical use contact with blood may affect the antimicrobial properties. This study aims to assess whether antimicrobial properties of the Portland cement-based dental cements such as mineral trioxide aggregate (MTA) are also affected by contact with blood present in clinical situations. ProRoot MTA, a Portland cement-based dental cement was characterized following contact with water, or heparinized blood after 1 day and 7 days aging. The antimicrobial activity under the mentioned conditions was assessed using 3 antimicrobial tests: agar diffusion test, direct contact test and intratubular infection test. MTA in contact with blood was severely discoloured, exhibited an additional phosphorus peak in elemental analysis, no calcium hydroxide peaks and no areas of bacterial inhibition growth in the agar diffusion test were demonstrated. ProRoot MTA showed limited antimicrobial activity, in both the direct contact test and intratubular infection test. When aged in water ProRoot MTA showed higher antimicrobial activity than when aged in blood. Antimicrobial activity reduced significantly after 7 days. Further assessment is required to investigate behaviour in clinical situations. PMID:28128328

Assessing commercial feasibility: a practical and ethical prerequisite for human clinical testing.

PubMed

Kirk, Dwayne D; Robert, Jason Scott

2005-01-01

This article proposes that an assessment of commercial feasibility should be integrated as a prerequisite for human clinical testing to improve the quality and relevance of materials being investigated, as an ethical aspect for human subject protection, and as a means of improving accountability where clinical development is funded on promises of successful translational research. A commercial feasibility analysis is not currently required to justify human clinical testing, but is assumed to have been conducted by industry participants, and use of public funds for clinical trials should be defensible in the same manner. Plant-made vaccines (PMVs) are offered in this discussion as a model for evaluating the relevance of commercial feasibility before human clinical testing. PMVs have been proposed as a potential solution for global health, based on a vision of immunizing the world against many infectious diseases. Such a vision depends on translating current knowledge in plant science and immunology into a potent vaccine that can be readily manufactured and distributed to those in need. But new biologics such as PMVs may fail to be manufactured due to financial or logistical reasons--particularly for orphan diseases without sufficient revenue incentive for industry investment--regardless of the effectiveness which might be demonstrated in human clinical testing. Moreover, all potential instruments of global health depend on translational agents well beyond the lab in order to reach those in need. A model compromising five criteria for commercial feasibility is suggested for inclusion by regulators and ethics review boards as part of the review process prior to approval of human clinical testing. Use of this model may help to facilitate safe and appropriate translational research and bring more immediate benefits to those in need.

Genetic Diagnosis and Testing in Clinical Practice

PubMed Central

McPherson, Elizabeth

2006-01-01

Genetic testing is defined as “the analysis of human DNA, RNA, chromosomes, proteins and certain metabolites in order to detect heritable disease-related genotypes, mutations, phenotypes or karyotypes for clinical purposes.” This article focuses on diagnostic and predictive genetic testing. The latter includes presymptomatic testing, which identifies individuals who are expected to become ill in the future and predisposition testing, which identifies those who are at increased risk of becoming ill. Decisions regarding genetic testing must be based not only on the analytic accuracy, availability and cost of the test, but on the clinical utility as well, including the sensitivity, specificity and interpretability of results. Clinical information, including the medical and family history and the findings of the physical examination, is vital for the selection of appropriate diagnostic tests, as well as the interpretation of the results. Presymptomatic genetic testing is a very personal choice that should only be made after the patient has had sufficient counseling to develop an understanding of the risks and benefits of the test and is able to make an informed decision. The same principle applies to predisposition testing; however, additional factors, such as the probability of a positive result, the likelihood that the disease will actually develop in those with positive results, the effect on the management of the index patient, the effects on family members, the risk of false reassurance if the result is negative or the potential for loss of hope if it is positive, all contribute to the assessment of risk versus benefit. Clinical evaluation and counseling of the patient who is at risk for a genetic disorder are labor intensive but essential for the selection and interpretation of genetic tests. PMID:16809405

Prior HIV Testing among STD Patients in Guangdong Province, China: Opportunities for Expanding Detection of Sexually Transmitted HIV Infection

PubMed Central

Tucker, Joseph D; Yang, Li-Gang; Yang, Bin; Young, Darwin; Henderson, Gail E; Huang, Shu-Jie; Lu, He-Kun; Chen, Xiang-Sheng; Cohen, Myron S

2011-01-01

Background Expanding HIV testing is important among individuals at increased risk for sexual HIV transmission in China, but little is known about prior HIV testing experiences among sexually transmitted disease (STD) patients. Methods This cross-sectional study of 1792 outpatients from six public sexually transmitted disease (STD) clinics in Guangdong Province recorded detailed information about ever having been tested for HIV infection in addition to socio-demographic variables, health seeking, clinical STD history, and HIV stigma using a validated survey instrument. Results 456 (25.4%) of the STD patients in this sample had ever been tested for HIV infection. STD patients who were male, had higher income, more education, were at City A and City C, received STD services at public facilities, had used intravenous drugs, and had a history of an STD were more likely to ever receive an HIV test in multivariate analysis. Low perceived HIV risk was the most common reason for not receiving an HIV test. Only 7.7% of the sample reported fear of discrimination or loss of face as influencing their lack of HIV testing. Conclusion Incomplete prior HIV screening among STD patients in China suggests the need for broadening HIV testing opportunities at STD clinics and similar clinical settings attended by those with increased sexual risk. PMID:22337103

Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting.

PubMed

Arroz, Maria; Came, Neil; Lin, Pei; Chen, Weina; Yuan, Constance; Lagoo, Anand; Monreal, Mariela; de Tute, Ruth; Vergilio, Jo-Anne; Rawstron, Andy C; Paiva, Bruno

2016-01-01

Major heterogeneity between laboratories in flow cytometry (FC) minimal residual disease (MRD) testing in multiple myeloma (MM) must be overcome. Cytometry societies such as the International Clinical Cytometry Society and the European Society for Clinical Cell Analysis recognize a strong need to establish minimally acceptable requirements and recommendations to perform such complex testing. A group of 11 flow cytometrists currently performing FC testing in MM using different instrumentation, panel designs (≥ 6-color) and analysis software compared the procedures between their respective laboratories and reviewed the literature to propose a consensus guideline on flow-MRD analysis and reporting in MM. Consensus guidelines support i) the use of minimum of five initial gating parameters (CD38, CD138, CD45, forward, and sideward light scatter) within the same aliquot for accurate identification of the total plasma cell compartment; ii) the analysis of potentially aberrant phenotypic markers and to report the antigen expression pattern on neoplastic plasma cells as being reduced, normal or increased, when compared to a normal reference plasma cell immunophenotype (obtained using the same instrument and parameters); and iii) the percentage of total bone marrow plasma cells plus the percentages of both normal and neoplastic plasma cells within the total bone marrow plasma cell compartment, and over total bone marrow cells. Consensus guidelines on minimal current and future MRD analyses should target a lower limit of detection of 0.001%, and ideally a limit of quantification of 0.001%, which requires at least 3 × 10(6) and 5 × 10(6) bone marrow cells to be measured, respectively. © 2015 International Clinical Cytometry Society.

[Quality of genetic services--analysis of medical genetic expert opinions solicited by private health insurance companies].

PubMed

Nippert, Reinhardt Peter; Schmidtke, Jörg

2012-01-01

Service quality for patients with genetic conditions can be assessed through the analysis of clinical genetic data sets, as was the case in this study. It represents a secondary analysis of a compilation of a single genetic expert's medical opinions covering the years 2000 to 2009, solicited by private health insurance companies with the intention of probing into medical necessity and adequacy of genetic testing ordered by physicians. Genetic testing has become an increasingly important part of clinical diagnostic services. Controlling these services does not only reduce costs but also saves patients from unwarranted over-utilisation. Therefore, the reasons given by doctors when ordering genetic tests are part of the quality of service delivery. The study revealed that more than 30% of the molecular genetic tests ordered lack sound medical reasoning and 30% of the cases studied show violation or neglect of guidelines and recommendations for diagnostic procedures with respect to genetic testing. In essence, the findings indicate a need for human genetic information among physicians. Their professional organisations are called upon to design and offer CME/CPD programmes in medical genetics to maintain and continually improve the quality of medical genetic care for patients with genetic conditions. Copyright © 2012. Published by Elsevier GmbH.

Effect of Three Clinical Curing Treatments on Fluoride Release and Surface Hardness of Glass-Ionomer Cements.

PubMed

Dionysopoulos, Dimitrios; Tolidis, Kosmas; Gerasimou, Paris; Sfeikos, Thrasyvoulos

The purpose of this study was to investigate the effect of radiant heat, ultrasonic treatment, and 42.7 wt% CaCl₂ solution on fluoride release and surface hardness in three conventional glass-ionomer cements (GICs). The fluoride release patterns of each GIC were evaluated during a 28-day period using a fluoride ion-selective electrode. The surface hardness of the tested GICs was evaluated 24 hours after preparation of the specimens using Vickers hardness test. Statistical analysis of the data was made using analysis of variance and Bonferroni post hoc test (α = .05). Radiant heat, ultrasonic, and CaCl₂ solution treatments reduced fluoride release and increased the surface hardness of the tested GICs (P < .05). Among the tested GICs, differences in fluoride release and surface hardness were observed (P < .05). The clinical treatments investigated may be effective methods for improving the setting reaction of GICs and may achieve sufficient initial mechanical properties earlier. Although a reduction in fluoride release occurs after the treatments, anticariogenic properties of the GICs may not be significantly affected.

Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research.

PubMed

Phillips, Kathryn A; Deverka, Patricia A; Sox, Harold C; Khoury, Muin J; Sandy, Lewis G; Ginsburg, Geoffrey S; Tunis, Sean R; Orlando, Lori A; Douglas, Michael P

2017-10-01

Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address.Genet Med advance online publication 13 April 2017.

Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research

PubMed Central

Phillips, Kathryn A.; Deverka, Patricia A.; Sox, Harold C.; Khoury, Muin J.; Sandy, Lewis G.; Ginsburg, Geoffrey S.; Tunis, Sean R.; Orlando, Lori A.; Douglas, Michael P.

2017-01-01

Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address. Genet Med advance online publication 13 April 2017 PMID:28406488

Evaluation of clinical methods for peroneal muscle testing.

PubMed

Sarig-Bahat, Hilla; Krasovsky, Andrei; Sprecher, Elliot

2013-03-01

Manual muscle testing of the peroneal muscles is well accepted as a testing method in musculoskeletal physiotherapy for the assessment of the foot and ankle. The peroneus longus and brevis are primary evertors and secondary plantar flexors of the ankle joint. However, some international textbooks describe them as dorsi flexors, when instructing peroneal muscle testing. The identified variability raised a question whether these educational texts are reflected in the clinical field. The purposes of this study were to investigate what are the methods commonly used in the clinical field for peroneal muscle testing and to evaluate their compatibility with functional anatomy. A cross-sectional study was conducted, using an electronic questionnaire sent to 143 Israeli physiotherapists in the musculoskeletal field. The survey questioned on the anatomical location of manual resistance and the combination of motions resisted. Ninety-seven responses were received. The majority (69%) of respondents related correctly to the peronei as evertors, but asserted that resistance should be located over the dorsal aspect of the fifth metatarsus, thereby disregarding the peroneus longus. Moreover, 38% of the respondents described the peronei as dorsi flexors, rather than plantar flexors. Only 2% selected the correct method of resisting plantarflexion and eversion at the base of the first metatarsus. We consider this technique to be the most compatible with the anatomy of the peroneus longus and brevis. The Fisher-Freeman-Halton test indicated that there was a significant relationship between responses on the questions (P = 0.0253, 95% CI 0.0249-0.0257), thus justifying further correspondence analysis. The correspondence analysis found no clustering of the answers that were compatible with anatomical evidence and were applied in the correct technique, but did demonstrate a common error, resisting dorsiflexion rather than plantarflexion, which was in agreement with the described frequencies. Inconsistencies were identified between the instruction method commonly provided for peroneal muscle testing in textbook and the functional anatomy of these muscles. Results reflect the lack of accuracy in applying functional anatomy to peroneal testing. This may be due to limited use of peroneal muscle testing or to inadequate investigation of the existing evaluation methods and their validity. Accordingly, teaching materials and clinical methods used for this test should be re-evaluated. Further research should investigate the value of peroneal muscle testing in clinical ankle evaluation. Copyright © 2012 John Wiley & Sons, Ltd.

Clinical effectiveness and cost-effectiveness of use of therapeutic monitoring of tumour necrosis factor alpha (TNF-α) inhibitors [LISA-TRACKER® enzyme-linked immunosorbent assay (ELISA) kits, TNF-α-Blocker ELISA kits and Promonitor® ELISA kits] versus standard care in patients with Crohn's disease: systematic reviews and economic modelling.

PubMed

Freeman, Karoline; Connock, Martin; Auguste, Peter; Taylor-Phillips, Sian; Mistry, Hema; Shyangdan, Deepson; Court, Rachel; Arasaradnam, Ramesh; Sutcliffe, Paul; Clarke, Aileen

2016-11-01

Systematic reviews and economic modelling of clinical effectiveness and cost-effectiveness of therapeutic monitoring of tumour necrosis factor alpha (TNF-α) inhibitors [using LISA-TRACKER ® enzyme-linked immunosorbent assay (ELISA) kits (Theradiag, Marne La Vallee, France, or Alpha Laboratories, Heriot, UK), TNF-α-Blocker ELISA kits (Immundiagnostik AG, Bensheim, Germany) and Promonitor ® ELISA kits (Proteomika, Progenika Biopharma, Bizkaia, Spain)] versus standard care for Crohn's disease (CD). Multiple electronic databases were searched from inception to December 2014 in order to identify primary studies and meta-analyses. Patients with moderate to severe active CD treated with infliximab (IFX) (Remicade ® , Merck Sharp & Dohme Ltd, Kenilworth, NJ, USA) or adalimumab (ADA) (Humira ® , AbbVie Inc., North Chicago, IL, USA). Monitoring of serum anti-TNF-α (IFX or ADA) and/or of anti-drug antibody levels using test assays with a test-treatment algorithm. Standard care. Any patient-related outcome, test agreement and cost-effectiveness estimates. The quality assessments used recognised checklists (Quality Assessment of Diagnostic Accuracy Studies-2, Cochrane, Philips and Consolidated Health Economic Evaluation Reporting Standards). Evidence was synthesised using narrative review and meta-analysis. A Markov model was built in TreeAge Pro 2013 (TreeAge Software, Inc., Williamstown, MA, USA). The model had a 4-week cycle and a 10-year time horizon, adopted a NHS and Personal Social Services perspective and used a linked evidence approach. Costs were adjusted to 2013/14 prices and discounted at 3.5%. We included 68 out of 2434 and 4 out of 2466 studies for the clinical effectiveness and cost-effectiveness reviews, respectively. Twenty-three studies comparing test methods were identified. Evidence on test concordance was sparse and contradictory, offering scant data for a linked evidence approach. Three studies [two randomised controlled trials (RCTs) and one retrospective observational study] investigated outcomes following implementation of a test algorithm. None used the specified commercial ELISA immunoassay test kits. Neither of the two RCTs demonstrated clinical benefit of a test-treatment regimen. A meta-analysis of 31 studies to estimate test accuracy for predicting clinical status indicated that 20-30% of test results are likely to be inaccurate. The four cost-effectiveness studies suggested that testing results in small cost reductions. In the economic analysis the base-case analysis showed that standard practice (no testing/therapeutic monitoring with the intervention tests) was more costly and more effective than testing for IFX. Sensitivity and scenario analyses gave similar results. The probabilistic sensitivity analysis indicated a 92% likelihood that the 'no-testing' strategy was cost-effective at a willingness to pay of £20,000 per quality-adjusted life-year. Rigorous systematic reviews were undertaken; however, the underlying evidence base was poor or lacking. There was uncertainty about a linked evidence approach and a lack of gold standard for assay comparison. The only comparative evidence available for economic evaluation was for assays other than the intervention assays. Our finding that testing is not cost-effective for IFX should be viewed cautiously in view of the limited evidence. Clinicians should be mindful of variation in performance of different assays and of the absence of standardised approaches to patient assessment and treatment algorithms. There is substantial variation in the underlying treatment pathways and uncertainty in the relative effectiveness of assay- and test-based treatment algorithms, which requires further investigation. There is very little research evidence on ADA or on drug monitoring in children with CD, and conclusions on cost-effectiveness could not be reached for these. This study is registered as PROSPERO CRD42014015278. The National Institute for Health Research Health Technology Assessment programme.

[What's the point of cost management in clinical laboratories?].

PubMed

Setoyama, Tomokazu; Yamauchi, Kazuyoshi; Katsuyama, Tsutomu

2006-11-01

Clinical laboratories need to know and manage the costs of laboratory tests, because they need financial data (1) to estimate costs per patient, (2) to request a budget to buy equipment, and (3) to improve their work; however, less than 40% laboratories practice cost management. In 2002, Shinshu University Hospital began to assess the costs of laboratory tests, but it was difficult to evaluate the quality of our cost management because there are few data and papers about the costs of laboratory tests in Japan. In this article, we practiced cost analysis using Shinshu University Hospital's data for 3 years (2002-2004), and studied the features of laboratory test costs and the problems of laboratory cost management. As a result, we listed 7 points to check cost management in clinical laboratories. This check list was established using only one data from our hospital. So, we suggest the benchmarking laboratory test costs between laboratories of the same type of hospitals or various laboratories.

[The MMPI-2 test in the evaluation of the mobbing syndrome].

PubMed

Pappone, P; Santalucia, L; Del Castello, E; De Maino, V; Garofalo, E; Cappelluccio, R; Feola, D; Ruberto, M; Liotti, F

2007-01-01

MMPI-2 test is widely used in psychodiagnostic evaluation as well as in the evaluation of psychic pathologies related to psychosocial adversative events in working activities. A more efficacious use of MMPI-2 test in the working context can be achieved by the individuation of indexes able to facilitate the evaluation of mobbing syndrome. This work is based on the analysis of 150 cases (39.7% women and 60.7% men, 30 to 60 years of age), evaluated through an accurate examination of working history and a series of clinic conversations, followed by psychodiagnostic evaluation. The average of T-scores on the clinical scale, the content scale, the PK addition scale and the validation scale were calculated from tests. Pathologic high T-scores on the scales Hs, D. Hy e Pa were found in subjects having positive mobbing anamnesis. These results strongly indicate the presence of clinical specificities in workers exposed to working harassments, and that these specificities can be efficaciously evidenced by the MMPI-2 test.

Odour Identification in Frontotemporal Lobar Degeneration

PubMed Central

Rami, Lorena; Loy, Clement T.; Hailstone, Julia; Warren, Jason D.

2008-01-01

Little information is available concerning olfactory processing in frontotemporal lobar degeneration (FTLD). We undertook a case-control study of olfactory processing in three male patients fulfilling clinical criteria for FTLD. Odour identification (semantic analysis) and odour discrimination (perceptual analysis) were investigated using tests adapted from the University of Pennsylvania Smell Identification Test. General neuropsychometry and structural volumetric brain magnetic resonance imaging (MRI) were also performed. The three patients with FTLD exhibited a disorder of olfactory processing with the characteristics of a predominantly semantic (odour identification) deficit. This olfactory deficit was more prominent in patients with greater involvement of the temporal lobes on MRI. Central deficits of odour identification may be more common in FTLD than previously recognised, and these deficits may assist in clinical characterisation. PMID:17380245

Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis.

PubMed

Rambaud-Althaus, Clotilde; Althaus, Fabrice; Genton, Blaise; D'Acremont, Valérie

2015-04-01

Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia. We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged <5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis. We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26-0·89; specificity 0·59, 0·29-0·84) and lower chest wall indrawing (four studies; 0·48, 0·16-0·82; 0·72, 0·47-0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45-2·48), grunting (1·78, 1·10-2·88), chest indrawing (1·76, 0·86-3·58), and nasal flaring (1·75, 1·20-2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09-0·96), history of fever (0·53, 0·41-0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23-0·83). Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy. Swiss National Science Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Direct-to-consumer genetic testing: an assessment of genetic counselors' knowledge and beliefs

PubMed Central

Hock, Kathryn T.; Christensen, Kurt D.; Yashar, Beverly M.; Roberts, J. Scott; Gollust, Sarah E.; Uhlmann, Wendy R.

2013-01-01

Purpose Direct-to-consumer genetic testing is a new means of obtaining genetic testing outside of a traditional clinical setting. This study assesses genetic counselors’ experience, knowledge, and beliefs regarding direct-to-consumer genetic testing for tests that would currently be offered in genetics clinics. Methods Members of the National Society of Genetic Counselors completed a web-administered survey in February 2008. Results Response rate was 36%; the final data analysis included 312 respondents. Eighty-three percent of respondents had two or fewer inquiries about direct-to-consumer genetic testing, and 14% had received requests for test interpretation or discussion. Respondents believed that genetic counselors have a professional obligation to be knowledgeable about direct-to-consumer genetic testing (55%) and interpret results (48%). Fifty-one percent of respondents thought genetic testing should be limited to a clinical setting; 56% agreed direct-to-consumer genetic testing is acceptable if genetic counseling is provided. More than 70% of respondents would definitely or possibly consider direct-to-consumer testing for patients who (1) have concerns about genetic discrimination, (2) want anonymous testing, or (3) have geographic constraints. Conclusions Results indicate that genetic counselors have limited patient experiences with direct-to-consumer genetic testing and are cautiously considering if and under what circumstances this approach should be used PMID:21233722

Biometric Analysis – A Reliable Indicator for Diagnosing Taurodontism using Panoramic Radiographs

PubMed Central

Hegde, Veda; Anegundi, Rajesh Trayambhak; Pravinchandra, K.R.

2013-01-01

Background: Taurodontism is a clinical entity with a morpho–anatomical change in the shape of the tooth, which was thought to be absent in modern man. Taurodontism is mostly observed as an isolated trait or a component of a syndrome. Various techniques have been devised to diagnose taurodontism. Aim: The aim of this study was to analyze whether a biometric analysis was useful in diagnosing taurodontism, in radiographs which appeared to be normal on cursory observations. Setting and Design: This study was carried out in our institution by using radiographs which were taken for routine procedures. Material and Methods: In this retrospective study, panoramic radiographs were obtained from dental records of children who were aged between 9–14 years, who did not have any abnormality on cursory observations. Biometric analyses were carried out on permanent mandibular first molar(s) by using a novel biometric method. The values were tabulated and analysed. Statistics: Fischer exact probability test, Chi square test and Chi-square test with Yates correction were used for statistical analysis of the data. Results: Cursory observation did not yield us any case of taurodontism. In contrast, the biometric analysis yielded us a statistically significant number of cases of taurodontism. However, there was no statistically significant difference in the number of cases with taurodontism, which was obtained between the genders and the age group which was considered. Conclusion: Thus, taurodontism was diagnosed on a biometric analysis, which was otherwise missed on a cursory observation. It is therefore necessary from the clinical point of view, to diagnose even the mildest form of taurodontism by using metric analysis rather than just relying on a visual radiographic assessment, as its occurrence has many clinical implications and a diagnostic importance. PMID:24086912

Biometric Analysis - A Reliable Indicator for Diagnosing Taurodontism using Panoramic Radiographs.

PubMed

Hegde, Veda; Anegundi, Rajesh Trayambhak; Pravinchandra, K R

2013-08-01

Taurodontism is a clinical entity with a morpho-anatomical change in the shape of the tooth, which was thought to be absent in modern man. Taurodontism is mostly observed as an isolated trait or a component of a syndrome. Various techniques have been devised to diagnose taurodontism. The aim of this study was to analyze whether a biometric analysis was useful in diagnosing taurodontism, in radiographs which appeared to be normal on cursory observations. This study was carried out in our institution by using radiographs which were taken for routine procedures. In this retrospective study, panoramic radiographs were obtained from dental records of children who were aged between 9-14 years, who did not have any abnormality on cursory observations. Biometric analyses were carried out on permanent mandibular first molar(s) by using a novel biometric method. The values were tabulated and analysed. Fischer exact probability test, Chi square test and Chi-square test with Yates correction were used for statistical analysis of the data. Cursory observation did not yield us any case of taurodontism. In contrast, the biometric analysis yielded us a statistically significant number of cases of taurodontism. However, there was no statistically significant difference in the number of cases with taurodontism, which was obtained between the genders and the age group which was considered. Thus, taurodontism was diagnosed on a biometric analysis, which was otherwise missed on a cursory observation. It is therefore necessary from the clinical point of view, to diagnose even the mildest form of taurodontism by using metric analysis rather than just relying on a visual radiographic assessment, as its occurrence has many clinical implications and a diagnostic importance.

[Analysis of on-call consultations with clinical pathologists--identification of customer's satisfaction].

PubMed

Yanai, M

2000-09-01

One aspect whereby effectiveness of clinical pathologists can be measured is customer service and satisfaction. Clinical pathologist should identify their customers, their processes and procedures to meet these needs to the customer's satisfaction. To identify customer's satisfaction, the records of on-call consultations with clinical pathologists were analyzed. Between January 1996 and December 1998, 1327 consultations were recorded, 40% of which were consultations from physicians, 50% from medical technologists. Physicians requested interpretation of laboratory data obtained, and clinical knowledge mainly concerning the microbiology and hematology during office hours. On holidays, physicians needed help performing emergency tests such as Gram stain and Wright-Giemsa stain. During office hours, medical technologists requested clinical information concerning patients in whom unreasonable data would be reported and the contact to the clinical side. Furthermore, technologists inquired about the methodology of laboratory tests during day duty on holidays. These results indicated that the clinical pathologist in our hospital could satisfy the customer(physicians and medical technologists), by providing 1) a wide range of clinical knowledge concerning not only the laboratory medicine but clinical medicine including therapeutics, 2) capability of performing emergency tests such as Gram stain and Wright-Giemsa stain, and 3) capability of interpreting the results obtained. Although these would not be adopted in every hospital, every clinical pathologist should examine his role in the hospital.

Breath Analysis in Disease Diagnosis: Methodological Considerations and Applications

PubMed Central

Lourenço, Célia; Turner, Claire

2014-01-01

Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. “Breath fingerprinting”, indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles. PMID:24957037

Breath analysis in disease diagnosis: methodological considerations and applications.

PubMed

Lourenço, Célia; Turner, Claire

2014-06-20

Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. "Breath fingerprinting", indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles.

[Implementation of quality standard UNE-EN ISO/IEC 17043 in the External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology].

PubMed

Poveda Gabaldón, Marta; Ovies, María Rosario; Orta Mira, Nieves; Serrano, M del Remedio Guna; Avila, Javier; Giménez, Alicia; Cardona, Concepción Gimeno

2011-12-01

The quality standard "UNE-EN-ISO 17043: 2010. Conformity assessment. General requirements for proficiency testing" applies to centers that organize intercomparisons in all areas. In the case of clinical microbiology laboratories, these intercomparisons must meet the management and technical standards required to achieve maximum quality in the performance of microbiological analysis and the preparation of test items (sample, product, data or other information used in the proficiency test) to enable them to be accredited. Once accredited, these laboratories can operate as a tool for quality control laboratories and competency assessment. In Spain, accreditation is granted by the Spanish Accreditation Body [Entidad Nacional de Acreditación (ENAC)]. The objective of this review is to explain how to apply the requirements of the standard to laboratories providing intercomparisons in the field of clinical microbiology (the organization responsible for all the tasks related to the development and operation of a proficiency testing program). This requires defining the scope and specifying the technical requirements (personnel management, control of equipment, facilities and environment, the design of the proficiency testing and data analysis for performance evaluation, communication with participants and confidentiality) and management requirements (document control, purchasing control, monitoring of complaints / claims, non-compliance, internal audits and management reviews). Copyright © 2011 Elsevier España S.L. All rights reserved.

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

PubMed

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

2015-10-01

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

Personality in general and clinical samples: Measurement invariance of the Multidimensional Personality Questionnaire.

PubMed

Eigenhuis, Annemarie; Kamphuis, Jan H; Noordhof, Arjen

2017-09-01

A growing body of research suggests that the same general dimensions can describe normal and pathological personality, but most of the supporting evidence is exploratory. We aim to determine in a confirmatory framework the extent to which responses on the Multidimensional Personality Questionnaire (MPQ) are identical across general and clinical samples. We tested the Dutch brief form of the MPQ (MPQ-BF-NL) for measurement invariance across a general population subsample (N = 365) and a clinical sample (N = 365), using Multiple Group Confirmatory Factor Analysis (MGCFA) and Multiple Group Exploratory Structural Equation Modeling (MGESEM). As an omnibus personality test, the MPQ-BF-NL revealed strict invariance, indicating absence of bias. Unidimensional per scale tests for measurement invariance revealed that 10% of items appeared to contain bias across samples. Item bias only affected the scale interpretation of Achievement, with individuals from the clinical sample more readily admitting to put high demands on themselves than individuals from the general sample, regardless of trait level. This formal test of equivalence provides strong evidence for the common structure of normal and pathological personality and lends further support to the clinical utility of the MPQ. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions.

PubMed

Mamiya, Yasuyuki; Nishio, Yoshiyuki; Watanabe, Hiroyuki; Yokoi, Kayoko; Uchiyama, Makoto; Baba, Toru; Iizuka, Osamu; Kanno, Shigenori; Kamimura, Naoto; Kazui, Hiroaki; Hashimoto, Mamoru; Ikeda, Manabu; Takeshita, Chieko; Shimomura, Tatsuo; Mori, Etsuro

2016-01-01

Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test. The pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer's disease (AD) and 20 healthy controls (HCs). We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC) and the concurrent validity using the Neuropsychiatric Inventory (NPI) hallucinations score as a reference. A receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs. The pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82), and moderately correlated with the NPI hallucinations score (rs = 0.42). Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%. Our study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB.

Indirect zirconia-reinforced lithium silicate ceramic CAD/CAM restorations: Preliminary clinical results after 12 months.

PubMed

Zimmermann, Moritz; Koller, Christina; Mehl, Albert; Hickel, Reinhard

2017-01-01

No clinical data are available for the new computer-aided design/computer-assisted manufacture (CAD/CAM) material zirconia-reinforced lithium silicate (ZLS) ceramic. This study describes preliminary clinical results for indirect ZLS CAD/CAM restorations after 12 months. Indirect restorations were fabricated, using the CEREC method and intraoral scanning (CEREC Omnicam, CEREC MCXL). Sixty-seven restorations were seated adhesively (baseline). Sixty restorations were evaluated after 12 months (follow-up), using modified FDI criteria. Two groups were established, according to ZLS restorations' post-processing procedure prior to adhesive seating: group I (three-step polishing, n = 32) and group II (fire glazing, n = 28). Statistical analysis was performed with Mann-Whitney U test and Wilcoxon test (P < .05). The success rate of indirect ZLS CAD/CAM restorations after 12 months was 96.7%. Two restorations clinically failed as a result of bulk fracture (failure rate 3.3%). No statistically significant differences were found for baseline and follow-up criteria (Wilcoxon test, P > .05). Statistically significant differences were found for criteria surface gloss for group I and group II (Mann-Whitney U test, P < .05). This study demonstrates ZLS CAD/CAM restorations have a high clinical success rate after 12 months. A longer clinical evaluation period is necessary to draw further conclusions.

Examining the postural awareness and flexibility changes in physical therapy students who took clinical Pilates class.

PubMed

Atilgan, Esra; Tarakci, Devrim; Mutluay, Fatma

2017-01-01

This study aimed to evaluate postural awareness and changes in posture and flexibility of students who took Clinical Pilates class as an elective course at the undergraduate level. The study conducted from 2013-2016 included 98 students who took Clinical Pilates class at the Department of Physical Therapy and Rehabilitation, School of Health Sciences, Istanbul Medipol University, Turkey. The flexibility levels of the study participants were measured before and after the Clinical Pilates education using finger-to-floor test and modified Schober's test. Observational posture analysis and postural awareness were recorded using the scale prepared by the researchers. The post-education evaluations showed that postural distortions were fixed, and a significant increase in the postural awareness of the students was observed compared with the pre-education period. The results of both modified Schober's test and finger-to-floor test, which were used to measure the flexibility levels, showed a statistically significant increase in post-education scores compared with those of the pre-education period. This study showed that the Clinical Pilates course increased postural awareness and flexibility of physical therapy students and fixed postural distortions. Thus, the inclusion of Clinical Pilates class in the undergraduate education is considered to be important.

Examining the postural awareness and flexibility changes in physical therapy students who took clinical Pilates class

PubMed Central

Atilgan, Esra; Tarakci, Devrim; Mutluay, Fatma

2017-01-01

Objective: This study aimed to evaluate postural awareness and changes in posture and flexibility of students who took Clinical Pilates class as an elective course at the undergraduate level. Methods: The study conducted from 2013-2016 included 98 students who took Clinical Pilates class at the Department of Physical Therapy and Rehabilitation, School of Health Sciences, Istanbul Medipol University, Turkey. The flexibility levels of the study participants were measured before and after the Clinical Pilates education using finger-to-floor test and modified Schober’s test. Observational posture analysis and postural awareness were recorded using the scale prepared by the researchers. Results: The post-education evaluations showed that postural distortions were fixed, and a significant increase in the postural awareness of the students was observed compared with the pre-education period. The results of both modified Schober’s test and finger-to-floor test, which were used to measure the flexibility levels, showed a statistically significant increase in post-education scores compared with those of the pre-education period. Conclusion: This study showed that the Clinical Pilates course increased postural awareness and flexibility of physical therapy students and fixed postural distortions. Thus, the inclusion of Clinical Pilates class in the undergraduate education is considered to be important. PMID:28811786

Bilateral Symmetry of Visual Function Loss in Cone-Rod Dystrophies.

PubMed

Galli-Resta, Lucia; Falsini, Benedetto; Rossi, Giuseppe; Piccardi, Marco; Ziccardi, Lucia; Fadda, Antonello; Minnella, Angelo; Marangoni, Dario; Placidi, Giorgio; Campagna, Francesca; Abed, Edoardo; Bertelli, Matteo; Zuntini, Monia; Resta, Giovanni

2016-07-01

To investigate bilateral symmetry of visual impairment in cone-rod dystrophy (CRD) patients and understand the feasibility of clinical trial designs treating one eye and using the untreated eye as an internal control. This was a retrospective study of visual function loss measures in 436 CRD patients followed at the Ophthalmology Department of the Catholic University in Rome. Clinical measures considered were best-corrected visual acuity, focal macular cone electroretinogram (fERG), and Ganzfeld cone-mediated and rod-mediated electroretinograms. Interocular agreement in each of these clinical indexes was assessed by t- and Wilcoxon tests for paired samples, structural (Deming) regression analysis, and intraclass correlation. Baseline and follow-up measures were analyzed. A separate analysis was performed on the subset of 61 CRD patients carrying likely disease-causing mutations in the ABCA4 gene. Statistical tests show a very high degree of bilateral symmetry in the extent and progression of visual impairment in the fellow eyes of CRD patients. These data contribute to a better understanding of CRDs and support the feasibility of clinical trial designs involving unilateral eye treatment with the use of fellow eye as internal control.

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

PubMed

Hamblin, Angela; Wordsworth, Sarah; Fermont, Jilles M; Page, Suzanne; Kaur, Kulvinder; Camps, Carme; Kaisaki, Pamela; Gupta, Avinash; Talbot, Denis; Middleton, Mark; Henderson, Shirley; Cutts, Anthony; Vavoulis, Dimitrios V; Housby, Nick; Tomlinson, Ian; Taylor, Jenny C; Schuh, Anna

2017-02-01

Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing. We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of "real world" data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds. This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers.

Utilization of arterial blood gas measurements in a large tertiary care hospital.

PubMed

Melanson, Stacy E F; Szymanski, Trevor; Rogers, Selwyn O; Jarolim, Petr; Frendl, Gyorgy; Rawn, James D; Cooper, Zara; Ferrigno, Massimo

2007-04-01

We describe the patterns of utilization of arterial blood gas (ABG) tests in a large tertiary care hospital. To our knowledge, no hospital-wide analysis of ABG test utilization has been published. We analyzed 491 ABG tests performed during 24 two-hour intervals, representative of different staff shifts throughout the 7-day week. The clinician ordering each ABG test was asked to fill out a utilization survey. The most common reasons for requesting an ABG test were changes in ventilator settings (27.6%), respiratory events (26.4%), and routine (25.7%). Of the results, approximately 79% were expected, and a change in patient management (eg, a change in ventilator settings) occurred in 42% of cases. Many ABG tests were ordered as part of a clinical routine or to monitor parameters that can be assessed clinically or through less invasive testing. Implementation of practice guidelines may prove useful in controlling test utilization and in decreasing costs.

[Cerebral vasospasm after subarachnoid hemorrhage].

PubMed

Milojević, T M; Baljozović, B V; Rakić, M Lj; Nestorović, B D; Dostanić, M M; Milaković, B D; Kojić, Z Z; Repac, N R; Cvrkota, I S

2008-01-01

Cerebral vasospasm causes permanent neurolological deficit or death occurance in 13% of clinical cases. Peak frequency is from 8-10th day after SAH. The purpose of this study is factor analysis that may have influence on vasospasm development , as well as predictor determination. The study is prospective and analysis 192 patients treated in Institute of Neurosurgery, Clinical Centre of Serbia, Belgrade. The majority of patients were admitted in hospital in first four days after SAH, and 184 had GCS over 7. Univariate methods of factor analysis were used, and for significance of predictors influence testing multivariante regression analysis was used. Vasospasm occurred in 22,40% of all cases. No relationships have been found between sex, age, previous hypertension, timing of surgery, appearance of hydrocephalus and intracerebral hematoma, hypertermia or mean arterial blood pressure, with occurrence of cerebral vasospasm. Factors with significantly associated with the occurance of vasospasm were: hearth disease, hypernatriemia, Hct, clinical grade on admission as well as preoperative clinical grade and Fisher CT scan grade. In the first four days after SAH, Fisher scan grade, preoperative clinical grade and Hct, appeared as predictors. After four days, clinical grade on admission and hypernatiemia, showed as poredictors.

Effects of Direct-to-Consumer Advertising and Clinical Guidelines on Appropriate Use of Human Papillomavirus DNA Tests

PubMed Central

2011-01-01

Background Both clinical guidelines and direct-to-consumer (DTC) advertising influence use of new health care technologies, but little is known about their relative effects. The introduction of a cervical cancer screening test in 2000 offered a unique opportunity to assess the two strategies. Objective To evaluate the effects of clinical guidelines and a targeted DTC advertising campaign on overall and appropriate use of human papillomavirus (HPV) DNA tests. Research Design Quasi-experimental study using difference-in-differences analysis. Data were MarketScan private insurance claims for 500,000 women ages 21 to 64 enrolled at least 12 consecutive months from January 2001 through December 2005. Results Both clinical guidelines and DTC advertising were associated with increases in overall HPV DNA test use. DTC advertising was associated with a statistically significant increase in HPV DNA test use in two groups of DTC cities (+5.57 percent, p<0.0001; +2.54 percent, p<0.0001). DTC advertising was associated with comparable increases in the probability of appropriate and inappropriate use of the HPV DNA test in primary screening. Clinical guideline releases from the American College of Obstetricians and Gynecologists, and by a co-sponsored panel, were associated with greater increases in HPV DNA tests for appropriate primary screening than for inappropriate primary screening (β=0.3347, p<0.05 and β=0.4175, p<0.01). Conclusions DTC advertising was associated with increased overall use of a cervical cancer screening test, while clinical guidelines were differentially associated with increased appropriate use. These findings suggest distinct influences of consumer marketing and professional guidelines on the use of health care products and services. PMID:21150798

Effects of direct-to-consumer advertising and clinical guidelines on appropriate use of human papillomavirus DNA tests.

PubMed

Price, Rebecca Anhang; Frank, Richard G; Cleary, Paul D; Goldie, Sue J

2011-02-01

Both clinical guidelines and direct-to-consumer (DTC) advertising influence the use of new health care technologies, but little is known about their relative effects. The introduction of a cervical cancer screening test in 2000 offered a unique opportunity to assess the 2 strategies. To evaluate the effects of clinical guidelines and a targeted DTC advertising campaign on overall and appropriate use of human papillomavirus (HPV) DNA tests. Quasi-experimental study using difference-in-differences analysis. Data were MarketScan private insurance claims for 500,000 women aged 21 to 64 enrolled at least 12 consecutive months from January 2001 through December 2005. Both clinical guidelines and DTC advertising were associated with increases in overall HPV DNA test use. DTC advertising was associated with a statistically significant increase in HPV DNA test use in 2 groups of DTC cities (+5.57%, P < 0.0001; +2.54%, P < 0.0001). DTC advertising was associated with comparable increases in the probability of appropriate and inappropriate use of the HPV DNA test in primary screening. Clinical guideline releases from the American College of Obstetricians and Gynecologists, and by a cosponsored panel, were associated with greater increases in HPV DNA tests for appropriate primary screening than for inappropriate primary screening (β = 0.3347, P < 0.05 and β = 0.4175, P < 0.01). DTC advertising was associated with increased overall use of a cervical cancer screening test, whereas clinical guidelines were differentially associated with increased appropriate use. These findings suggest distinct influences of consumer marketing and professional guidelines on the use of health care products and services.

Shiny FHIR: An Integrated Framework Leveraging Shiny R and HL7 FHIR to Empower Standards-Based Clinical Data Applications.

PubMed

Hong, Na; Prodduturi, Naresh; Wang, Chen; Jiang, Guoqian

2017-01-01

In this study, we describe our efforts in building a clinical statistics and analysis application platform using an emerging clinical data standard, HL7 FHIR, and an open source web application framework, Shiny. We designed two primary workflows that integrate a series of R packages to enable both patient-centered and cohort-based interactive analyses. We leveraged Shiny with R to develop interactive interfaces on FHIR-based data and used ovarian cancer study datasets as a use case to implement a prototype. Specifically, we implemented patient index, patient-centered data report and analysis, and cohort analysis. The evaluation of our study was performed by testing the adaptability of the framework on two public FHIR servers. We identify common research requirements and current outstanding issues, and discuss future enhancement work of the current studies. Overall, our study demonstrated that it is feasible to use Shiny for implementing interactive analysis on FHIR-based standardized clinical data.

Analysis of the antibacterial activity and plaque control benefit of colgate total dentifrice via clinical evaluation and real-time polymerase chain reaction.

PubMed

Xu, Tao; Deshmukh, Meenal; Barnes, Virginia Monsul; Trivedi, Harsh M; Du-Thumm, Laurence; Richter, Rose; Cummins, Diane

2005-01-01

This study analyzed, from a combined clinical and molecular biologic perspective, the antibacterial and antiplaque efficacy of Colgate Total dentifrice (CTD). A single-blind crossover study design utilized 11 healthy human subjects. After a one-week washout period, subjects donated dental plaque, received a dental prophylaxis, and subsequently brushed with a test product. Twenty-four hours postbrushing, dental plaque was collected and a clinical plaque score determined. Dental plaque was submitted for Real-time Polymerase Chain Reaction (Real-time PCR) analysis. The same procedure was repeated in accordance with a crossover design for the use of the second test product. Following a one-week washout, a plaque donation, prophylaxis, and brushing with the test product ensued for each subject. Twenty-four hours post-brushing, the subjects returned for a plaque score and plaque donation. Twenty-four hours after brushing, dental plaque coverage increased 17.88% +/- 8.27% with CTD, compared to 30.42% +/- 9.97% with Colgate Cavity Protection (CCP; p = 0.005). Real-time PCR found plaque collected 24 hours after brushing with CTD exhibited, on average, fewer representative periodontal pathogens (Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, and Porphyromonas gingivalis) and fewer early colonizers (Actinomyces naeslundii) than plaque collected before brushing, whereas CCP showed a moderate effect on oral bacteria. The study provides clinical and molecular biological evidence to substantiate the antibacterial and plaque control benefits of Colgate Total, and suggests the value of combining a molecular biological method with clinical research to corroborate clinical benefits.

Comparative effectiveness and acceptability of home-based and clinic-based sampling methods for sexually transmissible infections screening in females aged 14-50 years: a systematic review and meta-analysis.

PubMed

Odesanmi, Tolulope Y; Wasti, Sharada P; Odesanmi, Omolola S; Adegbola, Omololu; Oguntuase, Olubukola O; Mahmood, Sajid

2013-12-01

Home-based sampling is a strategy to enhance uptake of sexually transmissible infection (STI) screening. This review aimed to compare the screening uptake levels of home-based self-sampling and clinic-based specimen collection for STIs (chlamydia (Chlamydia trachomatis), gonorrhoea (Neisseria gonorrhoeae) and trichomoniasis) in females aged 14-50 years. Acceptability and effect on specimen quality were determined. Sixteen electronic databases were searched from inception to September 2012. Randomised controlled trials (RCTs) comparing the uptake levels of home-based self-sampling and clinic-based sampling for chlamydia, gonorrhoea and trichomoniasis in females aged 14-50 years were eligible for inclusion. The risk of bias in the trials was assessed. Risk ratios (RRs) for dichotomous outcomes were meta-analysed. Of 3065 papers, six studies with seven RCTs contributed to the final review. Compared with clinic-based methods, home-based screening increased uptake significantly (P=0.001-0.05) in five trials and was substantiated in a meta-analysis (RR: 1.55; 95% confidence interval: 1.30-1.85; P=0.00001) of two trials. In three trials, a significant preference for home-based testing (P=0.001-0.05) was expressed. No significant difference was observed in specimen quality. Sampling was rated as easy by a significantly higher number of women (P=0.01) in the clinic group in one trial. The review provides evidence that home-based testing results in greater uptake of STI screening in females (14-50 years) than clinic-based testing without compromising quality in the developed world. Home collection strategies should be added to clinic-based screening programs to enhance uptake.

Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Lee, Hane; Deignan, Joshua L.; Strom, Samuel P.; Kantarci, Sibel; Wang, Xizhe; Quintero-Rivera, Fabiola; Vilain, Eric; Grody, Wayne W.; Perlman, Susan; Geschwind, Daniel H.; Nelson, Stanley F.

2015-01-01

IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia. PMID:25133958

Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis.

PubMed

MacKenzie-Graham, Allan; Kurth, Florian; Itoh, Yuichiro; Wang, He-Jing; Montag, Michael J; Elashoff, Robert; Voskuhl, Rhonda R

2016-08-01

Multiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown. To understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS. In this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014. Voxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores). Among the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations. These biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

The effect of telehealth systems and satisfaction with health expenditure among patients with metabolic syndrome.

PubMed

Uei, Shu-Lin; Tsai, Chung-Hung; Kuo, Yu-Ming

2016-04-29

Telehealth cost analysis has become a crucial issue for governments in recent years. In this study, we examined cases of metabolic syndrome in Hualien County, Taiwan. This research adopted the framework proposed by Marchand to establish a study process. In addition, descriptive statistics, a t test, analysis of variance, and regression analysis were employed to analyze 100 questionnaires. The results of the t$ test revealed significant differences in medical health expenditure, number of clinical visits for medical treatment, average amount of time spent commuting to clinics, amount of time spent undergoing medical treatment, and average number of people accompanying patients to medical care facilities or assisting with other tasks in the past one month, indicating that offering telehealth care services can reduce health expenditure. The statistical analysis results revealed that customer satisfaction has a positive effect on reducing health expenditure. Therefore, this study proves that telehealth care systems can effectively reduce health expenditure and directly improve customer satisfaction with medical treatment.

Is Bjerkandera adusta Important to fungus-associated chronic cough as an allergen? Eight cases' reports.

PubMed

Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

2009-10-01

Recently, we have reported a new clinical disease concept called fungus-associated chronic cough (FACC), which entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. To clarify the relationship between the exposure to environmental fungi and the development of cough attacks, we reviewed the clinical records of patients with FACC and performed a molecular biological analysis of the BM fungi. We successfully selected 8 patients with chronic cough, wherein a sputum culture yielded B. adusta beforehand; moreover, we conducted allergological tests such as the immediate-type skin test, a serological test, bronchoprovocation test, and lymphocyte stimulation test (LST), using the antigenic solution of B. adusta. The efficacy of individualized therapy and the clinical manifestations in the eight patients were examined. All the eight patients were diagnosed with FACC. Although three patients who did not show a positive reaction to the bronchoprovocation test or LST showed excellent clinical response to anti-fungal drugs; other 5 patients who showed a positive reaction to the bronchoprovocation test and/or LST seemed to be more intractable because of taking a longer time for complete remission and more frequent recurrence of cough. It was suggested that so-called allergic fungal cough (AFC), which is characterized by sensitization to B. adusta, may be included in a part of chronic intractable cough.

Phase II cancer clinical trials for biomarker-guided treatments.

PubMed

Jung, Sin-Ho

2018-01-01

The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

Post-test probability for neonatal hyperbilirubinemia based on umbilical cord blood bilirubin, direct antiglobulin test, and ABO compatibility results.

PubMed

Peeters, Bart; Geerts, Inge; Van Mullem, Mia; Micalessi, Isabel; Saegeman, Veroniek; Moerman, Jan

2016-05-01

Many hospitals opt for early postnatal discharge of newborns with a potential risk of readmission for neonatal hyperbilirubinemia. Assays/algorithms with the possibility to improve prediction of significant neonatal hyperbilirubinemia are needed to optimize screening protocols and safe discharge of neonates. This study investigated the predictive value of umbilical cord blood (UCB) testing for significant hyperbilirubinemia. Neonatal UCB bilirubin, UCB direct antiglobulin test (DAT), and blood group were determined, as well as the maternal blood group and the red blood cell antibody status. Moreover, in newborns with clinically apparent jaundice after visual assessment, plasma total bilirubin (TB) was measured. Clinical factors positively associated with UCB bilirubin were ABO incompatibility, positive DAT, presence of maternal red cell antibodies, alarming visual assessment and significant hyperbilirubinemia in the first 6 days of life. UCB bilirubin performed clinically well with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95 % CI 0.80-0.84). The combined UCB bilirubin, DAT, and blood group analysis outperformed results of these parameters considered separately to detect significant hyperbilirubinemia and correlated exponentially with hyperbilirubinemia post-test probability. Post-test probabilities for neonatal hyperbilirubinemia can be calculated using exponential functions defined by UCB bilirubin, DAT, and ABO compatibility results. • The diagnostic value of the triad umbilical cord blood bilirubin measurement, direct antiglobulin testing and blood group analysis for neonatal hyperbilirubinemia remains unclear in literature. • Currently no guideline recommends screening for hyperbilirubinemia using umbilical cord blood. What is New: • Post-test probability for hyperbilirubinemia correlated exponentially with umbilical cord blood bilirubin in different risk groups defined by direct antiglobulin test and ABO blood group compatibility results. • Exponential functions can be used to calculate hyperbilirubinemia probability.

Bayesian multivariate hierarchical transformation models for ROC analysis.

PubMed

O'Malley, A James; Zou, Kelly H

2006-02-15

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

Bayesian multivariate hierarchical transformation models for ROC analysis

PubMed Central

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

2006-01-01

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

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

PubMed

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

2018-01-01

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

Unraveling the thrombophilia paradox: from hypercoagulability to the prothrombotic state.

PubMed

Baglin, T

2010-02-01

The thrombophilia paradox whereby thrombophilia testing identifies defects associated with an increased risk of a first venous thrombosis but not of a particularly high risk of recurrence is likely the result of limitations imposed by a limited dichotomous testing strategy compounded by test inaccuracy and imprecision. Consequently, the observed intermediate phenotype (defined by limited laboratory test results) is not fully concordant with the heritable genotype. The next generation of thrombophilia tests, which utilize either individual genomic analysis or global measurement of the composite plasma intermediate phenotype, may more accurately quantify the thrombophilic risk. In conjunction with clinical risk assessment a more quantitative measurement of hypercoagulability and definition of the prothrombotic state should facilitate transition of clinical management from a disease-focused to a more patient-focused strategy.

A cluster randomized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers

PubMed Central

MacIntyre, Chandini Raina; Wang, Quanyi; Cauchemez, Simon; Seale, Holly; Dwyer, Dominic E.; Yang, Peng; Shi, Weixian; Gao, Zhanhai; Pang, Xinghuo; Zhang, Yi; Wang, Xiaoli; Duan, Wei; Rahman, Bayzidur; Ferguson, Neil

2011-01-01

Please cite this paper as: MacIntyre et al. (2011) A cluster randomized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2010.00198.x. Background  We compared the efficacy of medical masks, N95 respirators (fit tested and non fit tested), in health care workers (HCWs). Methods  A cluster randomized clinical trial (RCT) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter. Participants wore masks or respirators during the entire work shift for 4 weeks. Outcomes included clinical respiratory illness (CRI), influenza‐like illness (ILI), laboratory‐confirmed respiratory virus infection and influenza. A convenience no‐mask/respirator group of 481 health workers from nine hospitals was compared. Findings  The rates of CRI (3·9% versus 6·7%), ILI (0·3% versus 0·6%), laboratory‐confirmed respiratory virus (1·4% versus 2·6%) and influenza (0·3% versus 1%) infection were consistently lower for the N95 group compared to medical masks. By intention‐to‐treat analysis, when P values were adjusted for clustering, non‐fit‐tested N95 respirators were significantly more protective than medical masks against CRI, but no other outcomes were significant. The rates of all outcomes were higher in the convenience no‐mask group compared to the intervention arms. There was no significant difference in outcomes between the N95 arms with and without fit testing. Rates of fit test failure were low. In a post hoc analysis adjusted for potential confounders, N95 masks and hospital level were significant, but medical masks, vaccination, handwashing and high‐risk procedures were not. Interpretation  Rates of infection in the medical mask group were double that in the N95 group. A benefit of respirators is suggested but would need to be confirmed by a larger trial, as this study may have been underpowered. The finding on fit testing is specific to the type of respirator used in the study and cannot be generalized to other respirators. Trial registration  Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: ACTRN12609000257268 (http://www.anzctr.org.au). PMID:21477136

Development and psychometric testing of the clinical networks engagement tool

PubMed Central

Hecker, Kent G.; Rabatach, Leora; Noseworthy, Tom W.; White, Deborah E.

2017-01-01

Background Clinical networks are being used widely to facilitate large system transformation in healthcare, by engagement of stakeholders throughout the health system. However, there are no available instruments that measure engagement in these networks. Methods The study purpose was to develop and assess the measurement properties of a multiprofessional tool to measure engagement in clinical network initiatives. Based on components of the International Association of Public Participation Spectrum and expert panel review, we developed 40 items for testing. The draft instrument was distributed to 1,668 network stakeholders across different governance levels (leaders, members, support, frontline stakeholders) in 9 strategic clinical networks in Alberta (January to July 2014). With data from 424 completed surveys (25.4% response rate), descriptive statistics, exploratory and confirmatory factor analysis, Pearson correlations, linear regression, multivariate analysis, and Cronbach alpha were conducted to assess reliability and validity of the scores. Results Sixteen items were retained in the instrument. Exploratory factor analysis indicated a four-factor solution and accounted for 85.7% of the total variance in engagement with clinical network initiatives: global engagement, inform (provided with information), involve (worked together to address concerns), and empower (given final decision-making authority). All subscales demonstrated acceptable reliability (Cronbach alpha 0.87 to 0.99). Both the confirmatory factor analysis and regression analysis confirmed that inform, involve, and empower were all significant predictors of global engagement, with involve as the strongest predictor. Leaders had higher mean scores than frontline stakeholders, while members and support staff did not differ in mean scores. Conclusions This study provided foundational evidence for the use of this tool for assessing engagement in clinical networks. Further work is necessary to evaluate engagement in broader network functions and activities; to assess barriers and facilitators of engagement; and, to elucidate how the maturity of networks and other factors influence engagement. PMID:28350834

Cost effectiveness of population based BRCA1 founder mutation testing in Sephardi Jewish women.

PubMed

Patel, Shreeya; Legood, Rosa; Evans, D Gareth; Turnbull, Clare; Antoniou, Antonis C; Menon, Usha; Jacobs, Ian; Manchanda, Ranjit

2018-04-01

Population-based BRCA1/BRCA2 founder-mutation testing has been demonstrated as cost effective compared with family history based testing in Ashkenazi Jewish women. However, only 1 of the 3 Ashkenazi Jewish BRCA1/BRCA2 founder mutations (185delAG[c.68_69delAG]), 5382insC[c.5266dupC]), and 6174delT[c.5946delT]) is found in the Sephardi Jewish population (185delAG[c.68_69delAG]), and the overall prevalence of BRCA mutations in the Sephardi Jewish population is accordingly lower (0.7% compared with 2.5% in the Ashkenazi Jewish population). Cost-effectiveness analyses of BRCA testing have not previously been performed at these lower BRCA prevalence levels seen in the Sephardi Jewish population. Here we present a cost-effectiveness analysis for UK and US populations comparing population testing with clinical criteria/family history-based testing in Sephardi Jewish women. A Markov model was built comparing the lifetime costs and effects of population-based BRCA1 testing, with testing using family history-based clinical criteria in Sephardi Jewish women aged ≥30 years. BRCA1 carriers identified were offered magnetic resonance imaging/mammograms and risk-reducing surgery. Costs are reported at 2015 prices. Outcomes include breast cancer, ovarian cancer, and excess deaths from heart disease. All costs and outcomes are discounted at 3.5%. The time horizon is lifetime, and perspective is payer. The incremental cost-effectiveness ratio per quality-adjusted life-year was calculated. Parameter uncertainty was evaluated through 1-way and probabilistic sensitivity analysis. Population testing resulted in gain in life expectancy of 12 months (quality-adjusted life-year = 1.00). The baseline discounted incremental cost-effectiveness ratio for UK population-based testing was £67.04/quality-adjusted life-year and for US population was $308.42/quality-adjusted life-year. Results were robust in the 1-way sensitivity analysis. The probabilistic sensitivity analysis showed 100% of simulations were cost effective at £20,000/quality-adjusted life-year UK and the $100,000/quality-adjusted life-year US willingness-to-pay thresholds. Scenario analysis showed that population testing remains cost effective in UK and US populations, even if premenopausal oophorectomy does not reduce breast cancer risk or if hormone replacement therapy compliance is nil. Population-based BRCA1 testing is highly cost effective compared with clinical criteria-driven approach in Sephardi Jewish women. This supports changing the paradigm to population-based BRCA testing in the Jewish population, regardless of Ashkenazi/Sephardi ancestry. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population.

PubMed Central

Hart, D J; Spector, T D; Brown, P; Wilson, P; Doyle, D V; Silman, A J

1991-01-01

The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease. PMID:1877852

Development of Responder Definitions for Fibromyalgia Clinical Trials

PubMed Central

Arnold, Lesley M.; Williams, David A.; Hudson, James I.; Martin, Susan A.; Clauw, Daniel J.; Crofford, Leslie J.; Wang, Fujun; Emir, Birol; Lai, Chinglin; Zablocki, Rong; Mease, Philip J.

2011-01-01

Objective To develop responder definitions for fibromyalgia clinical trials using key symptom and functional domains. Methods 24 candidate responder definitions were developed by expert consensus and evaluated in 12 randomized, placebo-controlled fibromyalgia trials of 4 medications. For each definition, treatment effects of the medication compared with placebo were analyzed using the Cochran-Mantel-Haenszel test or Chi Square test. A meta-analysis of the pooled results for the 4 medications established risk ratios to determine the definitions that best favored medication over placebo. Results Two definitions performed best in the analyses. Both definitions included ≥ 30% reduction in pain and ≥ 10% improvement in physical function. They differed in that one (FM30 short version) included ≥ 30% improvement in sleep or fatigue, and the other (FM30 long version) required ≥ 30% improvement in 2 of the following symptoms: sleep, fatigue, depression, anxiety, or cognition. In the analysis of both versions, the response rate was ≥ 15% for each medication and significantly greater than placebo. The risk ratio favoring drug over placebo (95% CI) in the pooled analysis for the FM30 short version was 1.50 (1.24, 1.82), P ≤ 0.0001; the FM30 long version was 1.60 (1.31, 1.96), P ≤ 0.00001. Conclusion Among the 24 responder definitions tested, 2 were identified as most sensitive in identifying response to treatment. The identification of responder definitions for fibromyalgia clinical trials that include assessments of key symptom and functional domains may improve the sensitivity of clinical trials to identify meaningful improvements, leading to improved management of fibromyalgia. PMID:21953205

Computer interviewing in urogynaecology: concept, development and psychometric testing of an electronic pelvic floor assessment questionnaire in primary and secondary care.

PubMed

Radley, S C; Jones, G L; Tanguy, E A; Stevens, V G; Nelson, C; Mathers, N J

2006-02-01

To develop and evaluate a Web-based, electronic pelvic floor symptoms assessment questionnaire (e-PAQ)1 for women. A cross-sectional study in primary and secondary care. Two general practices, two community health clinics and a secondary care urogynaecology clinic. A total of 432 women (204 in primary care and 228 in secondary care) were recruited between June 2003 and January 2004. The e-PAQ was located on a workstation (computer, touchscreen and printer). Women completed the e-PAQ prior to their appointment. Untreated women in primary care were asked to return seven days later to complete the e-PAQ a second time (test-retest). Factor analysis, reliability, validity, patient satisfaction, completion times and system costs. In secondary care, factor analysis identified 14 domains within the four dimensions (urinary, bowel, vaginal and sexual symptoms) with internal consistency (Cronbach's alpha)>or=0.7 in 11 of these. In primary care, alpha values were all>or=0.7 and test-retest analysis found acceptable intraclass correlations of 0.50-0.95 (P<0.001) for all domains. A measure of face validity and utility was gained using a nine-item questionnaire, which yielded strongly positive patient views on relevance and acceptability. The e-PAQ offers a user-friendly clinical tool, which provides valid and reliable data. The system offers comprehensive symptoms and quality of life evaluation and may enhance the clinical episode as well as the quality of care for women with pelvic floor disorders.

Clinical color vision testing and correlation with visual function.

PubMed

Zhao, Jiawei; Davé, Sarita B; Wang, Jiangxia; Subramanian, Prem S

2015-09-01

To determine if Hardy-Rand-Rittler (H-R-R) and Ishihara testing are accurate estimates of color vision in subjects with acquired visual dysfunction. Assessment of diagnostic tools. Twenty-two subjects with optic neuropathy (aged 18-65) and 18 control subjects were recruited prospectively from an outpatient clinic. Individuals with visual acuity (VA) <20/200 or with congenital color blindness were excluded. All subjects underwent a comprehensive eye examination including VA, color vision, and contrast sensitivity testing. Color vision was assessed using H-R-R and Ishihara plates and Farnsworth D-15 (D-15) discs. D-15 is the accepted standard for detecting and classifying color vision deficits. Contrast sensitivity was measured using Pelli-Robson contrast sensitivity charts. No relationship was found between H-R-R and D-15 scores (P = .477). H-R-R score and contrast sensitivity were positively correlated (P = .003). On multivariate analysis, contrast sensitivity (β = 8.61, P < .001) and VA (β = 2.01, P = .022) both showed association with H-R-R scores. Similar to H-R-R, Ishihara score did not correlate with D-15 score (P = .973), but on multivariate analysis was related to contrast sensitivity (β = 8.69, P < .001). H-R-R and Ishihara scores had an equivalent relationship with contrast sensitivity (P = .069). Neither H-R-R nor Ishihara testing appears to assess color identification in patients with optic neuropathy. Both H-R-R and Ishihara testing are correlated with contrast sensitivity, and these tests may be useful clinical surrogates for contrast sensitivity testing. Copyright © 2015 Elsevier Inc. All rights reserved.

Meta-analysis in clinical trials revisited.

PubMed

DerSimonian, Rebecca; Laird, Nan

2015-11-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

Meta-Analysis in Clinical Trials Revisited

PubMed Central

Laird, Nan

2015-01-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effect model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the “DerSimonian and Laird method” is now often referred to as the ‘standard approach’ or a ‘popular’ method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. PMID:26343745

Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability.

PubMed

Lee, Jin Sook; Hwang, Hee; Kim, Soo Yeon; Kim, Ki Joong; Choi, Jin Sun; Woo, Mi Jung; Choi, Young Min; Jun, Jong Kwan; Lim, Byung Chan; Chae, Jong Hee

2018-09-01

Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children's Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability. © The Korean Society for Laboratory Medicine.

Novel antibacterial mouthguard material manufactured using silver-nanoparticleembedded ethylene-vinyl acetate copolymer masterbatch.

PubMed

Yoshida, Yuriko; Churei, Hiroshi; Takeuchi, Yasuo; Wada, Takahiro; Uo, Motohiro; Izumi, Yuichi; Ueno, Toshiaki

2018-01-26

The purpose of the present study was to develop an antibacterial mouthguard (MG) material using a masterbatch of silvernanoparticle-embedded ethylene-vinyl acetate (EVA) copolymers. In order to verify that the testing material was clinically applicable as an antibacterial MG material, we conducted an antibacterial test, a shock absorption test, and analysis of in vitro silver release. The colony-forming activity of Streptococcus sobrinus, Porphyromonas gingivalis, and Escherichia coli were significantly inhibited on the testing materials compared with the commercial EVA sheet (p<0.05). The shock absorption capability of the testing material was not significantly different from that of the commercial EVA sheet. Cumulative silver release (in pure water) from the testing materials were infinitesimal after soaking for 20 days, which implied that there could be no harm in wearing the MG during exercise. These results showed that this testing material could be clinically applicable as an antibacterial MG material.

Relationship between college success and employer competency ratings for graduates of a baccalaureate nursing program.

PubMed

Bolin, S E; Hogle, E L

1984-01-01

This expost facto correlational study sought to determine which measures of academic success in one class of BSN graduates predicted their competence as employees one year after graduation, as judged by their employers. The relationship between pre-entrance test scores, clinical experience grades, GPA, State Board Test Pool examination scores, and employer competency ratings were also determined. In keeping with the literature in fields other than nursing, the findings suggest that there may be little relationship between academic performance in a nursing program and subsequent job performance as a nurse, even though verbal ability may be predictive of success in school. While significant positive correlations were found between pre-entrance test data and final grade point averages, as well as pre-entrance test scores and State Board Test Pool examination scores, there was little evidence that pre-entrance test scores were predictive of nursing abilities. Isolated correlations were found between the clinical components of some nursing courses and specific nursing abilities. Using multiple regression analysis, no clinical course grade was found to be a significant predictor of the mean employer competency rating. Significant predictors were found for only four of the individual nursing abilities, with the clinical component of Leadership in Nursing being the most frequent and best predictor.

Practical considerations for volumetric wear analysis of explanted hip arthroplasties

PubMed Central

Langton, D. J.; Sidaginamale, R. P.; Holland, J. P.; Deehan, D.; Joyce, T. J.; Nargol, A. V. F.; Meek, R. D.; Lord, J. K.

2014-01-01

Objectives Wear debris released from bearing surfaces has been shown to provoke negative immune responses in the recipient. Excessive wear has been linked to early failure of prostheses. Analysis using coordinate measuring machines (CMMs) can provide estimates of total volumetric material loss of explanted prostheses and can help to understand device failure. The accuracy of volumetric testing has been debated, with some investigators stating that only protocols involving hundreds of thousands of measurement points are sufficient. We looked to examine this assumption and to apply the findings to the clinical arena. Methods We examined the effects on the calculated material loss from a ceramic femoral head when different CMM scanning parameters were used. Calculated wear volumes were compared with gold standard gravimetric tests in a blinded study. Results Various scanning parameters including point pitch, maximum point to point distance, the number of scanning contours or the total number of points had no clinically relevant effect on volumetric wear calculations. Gravimetric testing showed that material loss can be calculated to provide clinically relevant degrees of accuracy. Conclusions Prosthetic surfaces can be analysed accurately and rapidly with currently available technologies. Given these results, we believe that routine analysis of explanted hip components would be a feasible and logical extension to National Joint Registries. Cite this article: Bone Joint Res 2014;3:60–8. PMID:24627327

An introduction to multiplicity issues in clinical trials: the what, why, when and how.

PubMed

Li, Guowei; Taljaard, Monica; Van den Heuvel, Edwin R; Levine, Mitchell Ah; Cook, Deborah J; Wells, George A; Devereaux, Philip J; Thabane, Lehana

2017-04-01

In clinical trials it is not uncommon to face a multiple testing problem which can have an impact on both type I and type II error rates, leading to inappropriate interpretation of trial results. Multiplicity issues may need to be considered at the design, analysis and interpretation stages of a trial. The proportion of trial reports not adequately correcting for multiple testing remains substantial. The purpose of this article is to provide an introduction to multiple testing issues in clinical trials, and to reduce confusion around the need for multiplicity adjustments. We use a tutorial, question-and-answer approach to address the key issues of why, when and how to consider multiplicity adjustments in trials. We summarize the relevant circumstances under which multiplicity adjustments ought to be considered, as well as options for carrying out multiplicity adjustments in terms of trial design factors including Population, Intervention/Comparison, Outcome, Time frame and Analysis (PICOTA). Results are presented in an easy-to-use table and flow diagrams. Confusion about multiplicity issues can be reduced or avoided by considering the potential impact of multiplicity on type I and II errors and, if necessary pre-specifying statistical approaches to either avoid or adjust for multiplicity in the trial protocol or analysis plan. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Data Warehouse Design from HL7 Clinical Document Architecture Schema.

PubMed

Pecoraro, Fabrizio; Luzi, Daniela; Ricci, Fabrizio L

2015-01-01

This paper proposes a semi-automatic approach to extract clinical information structured in a HL7 Clinical Document Architecture (CDA) and transform it in a data warehouse dimensional model schema. It is based on a conceptual framework published in a previous work that maps the dimensional model primitives with CDA elements. Its feasibility is demonstrated providing a case study based on the analysis of vital signs gathered during laboratory tests.

Evolutions in clinical reasoning assessment: The Evolving Script Concordance Test.

PubMed

Cooke, Suzette; Lemay, Jean-François; Beran, Tanya

2017-08-01

Script concordance testing (SCT) is a method of assessment of clinical reasoning. We developed a new type of SCT case design, the evolving SCT (E-SCT), whereby the patient's clinical story is "evolving" and with thoughtful integration of new information at each stage, decisions related to clinical decision-making become increasingly clear. We aimed to: (1) determine whether an E-SCT could differentiate clinical reasoning ability among junior residents (JR), senior residents (SR), and pediatricians, (2) evaluate the reliability of an E-SCT, and (3) obtain qualitative feedback from participants to help inform the potential acceptability of the E-SCT. A 12-case E-SCT, embedded within a 24-case pediatric SCT (PaedSCT), was administered to 91 pediatric residents (JR: n = 50; SR: n = 41). A total of 21 pediatricians served on the panel of experts (POE). A one-way analysis of variance (ANOVA) was conducted across the levels of experience. Participants' feedback on the E-SCT was obtained with a post-test survey and analyzed using two methods: percentage preference and thematic analysis. Statistical differences existed across levels of training: F = 19.31 (df = 2); p < 0.001. The POE scored higher than SR (mean difference = 10.34; p < 0.001) and JR (mean difference = 16.00; p < 0.001). SR scored higher than JR (mean difference = 5.66; p < 0.001). Reliability (Cronbach's α) was 0.83. Participants found the E-SCT engaging, easy to follow and true to the daily clinical decision-making process. The E-SCT demonstrated very good reliability and was effective in distinguishing clinical reasoning ability across three levels of experience. Participants found the E-SCT engaging and representative of real-life clinical reasoning and decision-making processes. We suggest that further refinement and utilization of the evolving style case will enhance SCT as a robust, engaging, and relevant method for the assessment of clinical reasoning.

The Quality of Clinical Information in Adverse Drug Reaction Reports by Patients and Healthcare Professionals: A Retrospective Comparative Analysis.

PubMed

Rolfes, Leàn; van Hunsel, Florence; van der Linden, Laura; Taxis, Katja; van Puijenbroek, Eugène

2017-07-01

Clinical information is needed to assess the causal relationship between a drug and an adverse drug reaction (ADR) in a reliable way. Little is known about the level of relevant clinical information about the ADRs reported by patients. The aim was to determine to what extent patients report relevant clinical information about an ADR compared with their healthcare professional. A retrospective analysis of all ADR reports on the same case, i.e., cases with a report from both the patient and the patient's healthcare professional, selected from the database of the Dutch Pharmacovigilance Center Lareb, was conducted. The extent to which relevant clinical information was reported was assessed by trained pharmacovigilance assessors, using a structured tool. The following four domains were assessed: ADR, chronology, suspected drug, and patient characteristics. For each domain, the proportion of reported information in relation to information deemed relevant was calculated. An average score of all relevant domains was determined and categorized as poorly (≤45%), moderately (from 46 to 74%) or well (≥75%) reported. Data were analyzed using a paired sample t test and Wilcoxon signed rank test. A total of 197 cases were included. In 107 cases (54.3%), patients and healthcare professionals reported a similar level of clinical information. Statistical analysis demonstrated no overall differences between the groups (p = 0.126). In a unique study of cases of ADRs reported by patients and healthcare professionals, we found that patients report clinical information at a similar level as their healthcare professional. For an optimal pharmacovigilance, both healthcare professionals and patient should be encouraged to report.

Methods to increase reproducibility in differential gene expression via meta-analysis

PubMed Central

Sweeney, Timothy E.; Haynes, Winston A.; Vallania, Francesco; Ioannidis, John P.; Khatri, Purvesh

2017-01-01

Findings from clinical and biological studies are often not reproducible when tested in independent cohorts. Due to the testing of a large number of hypotheses and relatively small sample sizes, results from whole-genome expression studies in particular are often not reproducible. Compared to single-study analysis, gene expression meta-analysis can improve reproducibility by integrating data from multiple studies. However, there are multiple choices in designing and carrying out a meta-analysis. Yet, clear guidelines on best practices are scarce. Here, we hypothesized that studying subsets of very large meta-analyses would allow for systematic identification of best practices to improve reproducibility. We therefore constructed three very large gene expression meta-analyses from clinical samples, and then examined meta-analyses of subsets of the datasets (all combinations of datasets with up to N/2 samples and K/2 datasets) compared to a ‘silver standard’ of differentially expressed genes found in the entire cohort. We tested three random-effects meta-analysis models using this procedure. We showed relatively greater reproducibility with more-stringent effect size thresholds with relaxed significance thresholds; relatively lower reproducibility when imposing extraneous constraints on residual heterogeneity; and an underestimation of actual false positive rate by Benjamini–Hochberg correction. In addition, multivariate regression showed that the accuracy of a meta-analysis increased significantly with more included datasets even when controlling for sample size. PMID:27634930

Commercial test kits for detection of Lyme borreliosis: a meta-analysis of test accuracy

PubMed Central

Cook, Michael J; Puri, Basant K

2016-01-01

The clinical diagnosis of Lyme borreliosis can be supported by various test methodologies; test kits are available from many manufacturers. Literature searches were carried out to identify studies that reported characteristics of the test kits. Of 50 searched studies, 18 were included where the tests were commercially available and samples were proven to be positive using serology testing, evidence of an erythema migrans rash, and/or culture. Additional requirements were a test specificity of ≥85% and publication in the last 20 years. The weighted mean sensitivity for all tests and for all samples was 59.5%. Individual study means varied from 30.6% to 86.2%. Sensitivity for each test technology varied from 62.4% for Western blot kits, and 62.3% for enzyme-linked immunosorbent assay tests, to 53.9% for synthetic C6 peptide ELISA tests and 53.7% when the two-tier methodology was used. Test sensitivity increased as dissemination of the pathogen affected different organs; however, the absence of data on the time from infection to serological testing and the lack of standard definitions for “early” and “late” disease prevented analysis of test sensitivity versus time of infection. The lack of standardization of the definitions of disease stage and the possibility of retrospective selection bias prevented clear evaluation of test sensitivity by “stage”. The sensitivity for samples classified as acute disease was 35.4%, with a corresponding sensitivity of 64.5% for samples from patients defined as convalescent. Regression analysis demonstrated an improvement of 4% in test sensitivity over the 20-year study period. The studies did not provide data to indicate the sensitivity of tests used in a clinical setting since the effect of recent use of antibiotics or steroids or other factors affecting antibody response was not factored in. The tests were developed for only specific Borrelia species; sensitivities for other species could not be calculated. PMID:27920571

Meta-analysis of studies on biochemical marker tests for the diagnosis of premature rupture of membranes: comparison of performance indexes.

PubMed

Palacio, Montse; Kühnert, Maritta; Berger, Richard; Larios, Cindy L; Marcellin, Louis

2014-05-31

Premature rupture of the membranes (PROM) is most commonly diagnosed using physical examination; however, accurate decision making in ambiguous cases is a major challenge in current obstetric practice. As this may influence a woman's subsequent management, a number of tests designed to assist with confirming a diagnosis of PROM are commercially available. This study sought to evaluate the published data for the accuracy of two amniotic fluid-specific biomarker tests for PROM: insulin-like growth factor binding protein-1 (IGFBP-1 - Actim® PROM) and placental alpha microglobulin-1 (PAMG-1 - AmniSure®). Main analysis included all PubMed referenced studies related to Actim® PROM and AmniSure® with available data to extract performance rates. To compare accuracy, a comparison of pooled indexes of both rapid tests was performed. Studies in which both tests were used in the same clinical population were also analysed. Membrane status, whether it was known or a suspected rupture, and inclusion or not of women with bleeding, were considered. All the available studies published in PubMed up to April 2013 were reviewed. Data were retrieved from 17 studies; 10 for Actim® PROM (n = 1066), four for AmniSure® (n = 1081) and three studies in which both biomarker tests were compared directly. The pooled analysis found that the specificity and positive predictive value were significantly higher for AmniSure® compared with Actim® PROM. However, when 762 and 1385 women with known or suspected rupture of membranes, respectively, were evaluated, AmniSure® only remained significantly superior in the latter group. Furthermore, when the two tests were compared directly in the same study no statistically significant differences were observed. Remarkably, women with a history or evidence of bleeding were excluded in all four studies for AmniSure®, in two Actim® PROM studies and in two of the three studies reporting on both tests. No differences were observed in the performance of the two tests in studies where they were used under the same clinical conditions or in women with known membrane status. Although AmniSure® performed better in suspected cases of PROM, this may need further analysis as exclusion of bleeding may not be representative of the real clinical presentation of women with suspected PROM.

Evaluation of the marginal and internal gaps of three different dental prostheses: comparison of the silicone replica technique and three-dimensional superimposition analysis

PubMed Central

2017-01-01

PURPOSE The purposes of this study were to evaluate the marginal and internal gaps, and the potential clinical applications of three different methods of dental prostheses fabrication, and to compare the prostheses prepared using the silicone replica technique (SRT) and those prepared using the three-dimensional superimposition analysis (3DSA). MATERIALS AND METHODS Five Pekkton, lithium disilicate, and zirconia crowns were each manufactured and tested using both the SRT and the two-dimensional section of the 3DSA. The data were analyzed with the nonparametric version of a two-way analysis of variance using rank-transformed values and the Tukey's post-hoc test (α = .05). RESULTS Significant differences were observed between the fabrication methods in the marginal gap (P < .010), deep chamfer (P < .001), axial wall (P < .001), and occlusal area (P < .001). A significant difference in the occlusal area was found between the two measurement methods (P < .030), whereas no significant differences were found in the marginal gap (P > .350), deep chamfer (P > .719), and axial wall (P > .150). As the 3DSA method is three-dimensional, it allows for the measurement of arbitrary points. CONCLUSION All of the three fabrication methods are valid for measuring clinical objectives because they produced prostheses within the clinically acceptable range. Furthermore, a three-dimensional superimposition analysis verification method such as the silicone replica technique is also applicable in clinical settings. PMID:28680546

Northwestern University Flexible Subischial Vacuum Socket for persons with transfemoral amputation: Part 2 Description and Preliminary evaluation.

PubMed

Fatone, Stefania; Caldwell, Ryan

2017-06-01

Current transfemoral prosthetic sockets are problematic as they restrict function, lack comfort, and cause residual limb problems. Development of a subischial socket with lower proximal trim lines is an appealing way to address this problem and may contribute to improving quality of life of persons with transfemoral amputation. The purpose of this study was to illustrate the use of a new subischial socket in two subjects. Case series. Two unilateral transfemoral prosthesis users participated in preliminary socket evaluations comparing functional performance of the new subischial socket to ischial containment sockets. Testing included gait analysis, socket comfort score, and performance-based clinical outcome measures (Rapid-Sit-To-Stand, Four-Square-Step-Test, and Agility T-Test). For both subjects, comfort was better in the subischial socket, while gait and clinical outcomes were generally comparable between sockets. While these evaluations are promising regarding the ability to function in this new socket design, more definitive evaluation is needed. Clinical relevance Using gait analysis, socket comfort score and performance-based outcome measures, use of the Northwestern University Flexible Subischial Vaccum Socket was evaluated in two transfemoral prosthesis users. Socket comfort improved for both subjects with comparable function compared to ischial containment sockets.

Primary hyperoxaluria type 1: is genotyping clinically helpful?

PubMed

Leumann, Ernst; Hoppe, Bernd

2005-05-01

There is some controversy about the value of mutation analysis in the management of primary hyperoxaluria type 1 (PH1). About 50 different mutations of the AGXT gene encoding the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) are currently known. The three most common mutations in the Western population account for less than half of the mutant alleles, and no simple screening test is available. Does the genotype help in diagnosis, prognosis and therapy? Definitive diagnosis is indispensable if liver transplantation is considered and can under certain circumstances be established by mutation analysis, but a liver biopsy is still necessary to determine AGT activity in a number of cases. Prognosis is difficult to assess due to a large clinical variation, despite identical mutations. Although the homozygous 508G>A (Gly170Arg) mutation appears to be associated with a better (and 33insC with a worse) prognosis, there are too many exceptions for precise prediction. Pyridoxine responsiveness can be anticipated in some genotypes (508G>A (Gly170Arg) and 454T>A (Phe153Ile)), but it should still be tested for in all patients. Genetic testing is thus clinically helpful but has clear limitations.

Does BMI affect the clinical efficacy of proton pump inhibitor therapy in GERD? The case for rabeprazole.

PubMed

Pace, Fabio; Coudsy, Bogdana; DeLemos, Byron; Sun, Yijun; Xiang, Jim; LoCoco, John; Casalini, Stefania; Li, Honglan; Pelosini, Iva; Scarpignato, Carmelo

2011-10-01

Increased BMI is associated with a higher risk of gastroesophageal reflux disease. To investigate whether overweight/obesity (BMI≥25 kg/m(2)) affects rabeprazole clinical efficacy versus omeprazole in patients with erosive esophagitis (EE). Post-hoc analysis of EE healing rate and symptom response stratified by patient BMI was performed on data from a multicenter, double-blind, randomized, 4-to-8-week trial comparing EE healing with rabeprazole (20 mg daily) and omeprazole (20 mg daily). Analysis of variance, two-sample t-test, Blackwelder's test for equivalence, log-rank, and Cochran-Mantel-Haenszel tests were used to analyze comparisons. In the two BMI groups (<25 kg/m(2) and ≥25 kg/m(2) respectively), rabeprazole and omeprazole were equally effective for mucosal healing regardless of patient's BMI (N=542, P>0.05). However, in overweight/obese patients, rabeprazole was significantly faster than omeprazole in inducing heartburn relief during the first treatment week (P<0.0001). Results of this study show that the clinical efficacy of rabeprazole is maintained in overweight/obese patients with gastroesophageal reflux disease and suggest that this subgroup of patients may derive, from rabeprazole, even greater benefit than lean patients.

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

PubMed

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

2017-09-01

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

Marketing of Personalized Cancer Care on the Web: An Analysis of Internet Websites

PubMed Central

Cronin, Angel; Bair, Elizabeth; Lindeman, Neal; Viswanath, Vish; Janeway, Katherine A.

2015-01-01

Internet marketing may accelerate the use of care based on genomic or tumor-derived data. However, online marketing may be detrimental if it endorses products of unproven benefit. We conducted an analysis of Internet websites to identify personalized cancer medicine (PCM) products and claims. A Delphi Panel categorized PCM as standard or nonstandard based on evidence of clinical utility. Fifty-five websites, sponsored by commercial entities, academic institutions, physicians, research institutes, and organizations, that marketed PCM included somatic (58%) and germline (20%) analysis, interpretive services (15%), and physicians/institutions offering personalized care (44%). Of 32 sites offering somatic analysis, 56% included specific test information (range 1–152 tests). All statistical tests were two-sided, and comparisons of website content were conducted using McNemar’s test. More websites contained information about the benefits than limitations of PCM (85% vs 27%, P < .001). Websites specifying somatic analysis were statistically significantly more likely to market one or more nonstandard tests as compared with standard tests (88% vs 44%, P = .04). PMID:25745021

Combined Use of Tissue Morphology, Neural Network Analysis of Chromatin Texture and Clinical Variables to Predict Prostate Cancer Agressiveness from Biopsy Water

DTIC Science & Technology

2000-10-01

Purpose: To combine clinical, serum, pathologic and computer derived information into an artificial neural network to develop/validate a model to...Development of an artificial neural network (year 02). Prospective validation of this model (projected year 03). All models will be tested and

Combined Use of Tissue Morphology, Neural Network Analysis of Chromatin Texture & Clinical Variables to Predict Prostate Cancer Agressiveness from Biopsy Material

DTIC Science & Technology

1999-10-01

THE PURPOSE OF THIS REPORT IS TO COMBINE CLINICAL, SERUM, PATHOLOGICAL AND COMPUTER DERIVED INFORMATION INTO AN ARTIFICIAL NEURAL NETWORK TO DEVELOP...01). Development of a artificial neural network model (year 02). Prospective validation of this model (projected year 03). All models will be tested

Clinical Practice as Natural Laboratory for Psychotherapy Research: A Guide to Case-Based Time-Series Analysis

ERIC Educational Resources Information Center

Borckardt, Jeffrey J.; Nash, Michael R.; Murphy, Martin D.; Moore, Mark; Shaw, Darlene; O'Neil, Patrick

2008-01-01

Both researchers and practitioners need to know more about how laboratory treatment protocols translate to real-world practice settings and how clinical innovations can be systematically tested and communicated to a skeptical scientific community. The single-case time-series study is well suited to opening a productive discourse between practice…

Exploring the measurement properties of the osteopathy clinical teaching questionnaire using Rasch analysis.

PubMed

Vaughan, Brett

2018-01-01

Clinical teaching evaluations are common in health profession education programs to ensure students are receiving a quality clinical education experience. Questionnaires students use to evaluate their clinical teachers have been developed in professions such as medicine and nursing. The development of a questionnaire that is specifically for the osteopathy on-campus, student-led clinic environment is warranted. Previous work developed the 30-item Osteopathy Clinical Teaching Questionnaire. The current study utilised Rasch analysis to investigate the construct validity of the Osteopathy Clinical Teaching Questionnaire and provide evidence for the validity argument through fit to the Rasch model. Senior osteopathy students at four institutions in Australia, New Zealand and the United Kingdom rated their clinical teachers using the Osteopathy Clinical Teaching Questionnaire. Three hundred and ninety-nine valid responses were received and the data were evaluated for fit to the Rasch model. Reliability estimations (Cronbach's alpha and McDonald's omega) were also evaluated for the final model. The initial analysis demonstrated the data did not fit the Rasch model. Accordingly, modifications to the questionnaire were made including removing items, removing person responses, and rescoring one item. The final model contained 12 items and fit to the Rasch model was adequate. Support for unidimensionality was demonstrated through both the Principal Components Analysis/t-test, and the Cronbach's alpha and McDonald's omega reliability estimates. Analysis of the questionnaire using McDonald's omega hierarchical supported a general factor (quality of clinical teaching in osteopathy). The evidence for unidimensionality and the presence of a general factor support the calculation of a total score for the questionnaire as a sufficient statistic. Further work is now required to investigate the reliability of the 12-item Osteopathy Clinical Teaching Questionnaire to provide evidence for the validity argument.

Detecting Eating Psychopathology in Female Athletes by Asking About Exercise: Use of the Compulsive Exercise Test.

PubMed

Plateau, Carolyn R; Arcelus, Jon; Meyer, Caroline

2017-11-01

The present study assessed the suitability of the Compulsive Exercise Test (athlete version; CET-A) for identifying female athletes with clinically significant features related to or comparable with eating psychopathology. Three hundred and sixty-one female athletes (including 12 with a clinically diagnosed eating disorder) completed the Eating Disorders Examination Questionnaire and the CET-A. Receiver operating curve analysis was employed to identify a cut-off value on the CET-A, which could indicate clinically significant features related to or comparable with eating psychopathology among female athletes. The analysis demonstrated that a CET-A score of 10 successfully discriminated female athletes with a current eating disorder. The results suggest that the CET-A may be a suitable tool for detecting eating psychopathology in female athletes. Additional longitudinal research is needed to evaluate the predictive value of the CET-A. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Outcomes and costs of incorporating a multibiomarker disease activity test in the management of patients with rheumatoid arthritis.

PubMed

Michaud, Kaleb; Strand, Vibeke; Shadick, Nancy A; Degtiar, Irina; Ford, Kerri; Michalopoulos, Steven N; Hornberger, John

2015-09-01

The multibiomarker disease activity (MBDA) blood test has been clinically validated as a measure of disease activity in patients with RA. We aimed to estimate the effect of the MBDA test on physical function for patients with RA (based on HAQ), quality-adjusted life years and costs over 10 years. A decision analysis was conducted to quantify the effect of using the MBDA test on RA-related outcomes and costs to private payers and employers. Results of a clinical management study reporting changes to anti-rheumatic drug recommendations after use of the MBDA test informed clinical utility. The effect of treatment changes on HAQ was derived from 5 tight-control and 13 treatment-switch trials. Baseline HAQ scores and the HAQ score relationship with medical costs and quality of life were derived from published National Data Bank for Rheumatic Diseases data. Use of the MBDA test is projected to improve HAQ scores by 0.09 units in year 1, declining to 0.02 units after 10 years. Over the 10 year time horizon, quality-adjusted life years increased by 0.08 years and costs decreased by US$457 (cost savings in disability-related medical costs, US$659; in productivity costs, US$2137). The most influential variable in the analysis was the effect of the MBDA test on clinician treatment recommendations and subsequent HAQ changes. The MBDA test aids in the assessment of disease activity in patients with RA by changing treatment decisions, improving the functional status of patients and cost savings. Further validation is ongoing and future longitudinal studies are warranted. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Durability of bonds and clinical success of adhesive restorations

PubMed Central

Carvalho, Ricardo M.; Manso, Adriana P.; Geraldeli, Saulo; Tay, Franklin R.; Pashley, David H.

2013-01-01

Resin-dentin bond strength durability testing has been extensively used to evaluate the effectiveness of adhesive systems and the applicability of new strategies to improve that property. Clinical effectiveness is determined by the survival rates of restorations placed in non-carious cervical lesions (NCCL). While there is evidence that the bond strength data generated in laboratory studies somehow correlates with the clinical outcome of NCCL restorations, it is questionable whether the knowledge of bonding mechanisms obtained from laboratory testing can be used to justify clinical performance of resin-dentin bonds. There are significant morphological and structural differences between the bonding substrate used in in vitro testing versus the substrate encountered in NCCL. These differences qualify NCCL as a hostile substrate for bonding, yielding bond strengths that are usually lower than those obtained in normal dentin. However, clinical survival time of NCCL restorations often surpass the durability of normal dentin tested in the laboratory. Likewise, clinical reports on the long-term survival rates of posterior composite restorations defy the relatively rapid rate of degradation of adhesive interfaces reported in laboratory studies. This article critically analyzes how the effectiveness of adhesive systems is currently measured, to identify gaps in knowledge where new research could be encouraged. The morphological and chemical analysis of bonded interfaces of resin composite restorations in teeth that had been in clinical service for many years, but were extracted for periodontal reasons, could be a useful tool to observe the ultrastructural characteristics of restorations that are regarded as clinically acceptable. This could help determine how much degradation is acceptable for clinical success. PMID:22192252

[Design and validation of an instrument to assess families at risk for health problems].

PubMed

Puschel, Klaus; Repetto, Paula; Solar, María Olga; Soto, Gabriela; González, Karla

2012-04-01

There is a paucity of screening instruments with a high clinical predictive value to identify families at risk and therefore, develop focused interventions in primary care. To develop an easy to apply screening instrument with a high clinical predictive value to identify families with a higher health vulnerability. In the first stage of the study an instrument with a high content validity was designed through a review of existent instruments, qualitative interviews with families and expert opinions following a Delphi approach of three rounds. In the second stage, concurrent validity was tested through a comparative analysis between the pilot instrument and a family clinical interview conducted to 300 families randomly selected from a population registered at a primary care clinic in Santiago. The sampling was blocked based on the presence of diabetes, depression, child asthma, behavioral disorders, presence of an older person or the lack of previous conditions among family members. The third stage, was directed to test the clinical predictive validity of the instrument by comparing the baseline vulnerability obtained by the instrument and the change in clinical status and health related quality of life perceptions of the family members after nine months of follow-up. The final SALUFAM instrument included 13 items and had a high internal consistency (Cronbach's alpha: 0.821), high test re-test reproducibility (Pearson correlation: 0.84) and a high clinical predictive value for clinical deterioration (Odds ratio: 1.826; 95% confidence intervals: 1.101-3.029). SALUFAM instrument is applicable, replicable, has a high content validity, concurrent validity and clinical predictive value.

News from the Breath Analysis Summit 2011.

PubMed

Corradi, Massimo; Mutti, Antonio

2012-06-01

This special section highlights some of the important work presented at the Breath Analysis Summit 2011, which was held in Parma (Italy) from 11 to 14 September 2011. The meeting, which was jointly organized by the International Association for Breath Research and the University of Parma, was attended by more than 250 delegates from 33 countries, and offered 34 invited lectures and 64 unsolicited scientific contributions. The summit was organized to provide a forum to scientists, engineers and clinicians to present their latest findings and to meet industry executives and entrepreneurs to discuss key trends, future directions and technologies available for breath analysis. A major focus was on nitric oxide, exhaled breath condensate, electronic nose, mass spectrometry and newer sensor technologies. Medical applications ranged from asthma and other respiratory diseases to gastrointestinal disease, occupational diseases, critical care and cancer. Most people identify breath tests with breathalysers used by police to estimate ethanol concentration in blood. However, breath testing has far more sophisticated applications. Breath analysis is rapidly evolving as a new frontier in medical testing for disease states in the lung and beyond. Every individual has a breath fingerprint-or 'breathprint'-that can provide useful information about his or her state of health. This breathprint comprises the many thousands of molecules that are expelled with each breath we exhale. Breath research in the past few years has uncovered the scientific and molecular basis for such clinical observations. Relying on mass spectrometry, we have been able to identify many such unique substances in exhaled breath, including gases, such as nitric oxide (NO) and carbon monoxide (CO), and a wide array of volatile organic compounds. Exhaled breath also carries aerosolized droplets that can be collected as an exhaled breath condensate that contains endogenously produced non-volatile compounds. Breath analysis is now used to diagnose and monitor asthma, check for transplant organ rejection, detect lung cancer and test for Helicobacter pyloriinfection-and the list is growing. A major milestone in the scientific study of breath was marked in the 1970s when Linus Pauling demonstrated that there is more to exhaled breath than the classic gases of nitrogen, oxygen, carbon dioxide and water vapour-a lot more. Based on the gas-liquid partition chromatography analysis, Pauling reported the presence of 250 substances in exhaled breath. We now have the technology to test for any and all of these components. The field of breath analysis has made considerable advances in the 21st century and the utility of breath analysis in health care is advancing quickly. The science is rapidly expanding, the technology is improving and several new applications have been developed or are under commercial development. Breath analysis may rely on both direct (on line) and indirect (off line) reading methods: in the on-line method, breath analysis is immediately available, whereas the use of indirect methods generally involves collecting and trapping the breath sample and subsequently transferring it to an analytical instrument for analysis. Various kinds of breath samples have been used in biological monitoring, including mixed expired air and end expired air: end exhaled air represents the alveolar air concentration and mixed exhaled air represents the gas mixture coming from the dead space of the bronchial tree and the alveolar gas-exchange space. Exhaled breath analysis is an area where the modern day advances in technology and engineering meet the ever expanding need in medicine for more sensitive, specific and non-invasive tests which makes this area a major front in the interface between medicine and engineering. A major breakthrough over the past decade has been the increase in breath-based tests approved by the US Food and Drug Administration (FDA). Devices measuring common breath gases (oxygen, nitrogen, water vapour and CO(2)) in patient respiratory monitoring have served as a platform for technological growth in clinical breath-testing applications. A few exhaled breath tests have demonstrated clinical utility and are in widespread use, and several FDA-approved devices are available. These widely used exhaled breath tests include detection of blood alcohol concentration and exhaled CO(2). Other clinical applications of exhaled breath analysis include testing for H. pylori infection, lactose intolerance, heart transplant rejection and, more recently, monitoring of airway inflammation by means of exhaled NO. Examination of exhaled breath has the potential to change the existing routine approaches in human medicine. The rapidly developing new analytical and computer technologies along with novel, unorthodox ideas are prerequisites for future advances in this field. Scientists who participated in the Breath Analysis Summit 2011 were invited to submit a full length paper to the Journal of Breath Research and this issue includes eight articles which describe the different applications of breath analysis. We thank all the authors for their valuable contribution and we trust that this collection will provide useful information and an update to this rapidly evolving field, giving an example of integration among scientists who address the same topic-breath analysis-from different and complementary perspectives, from basic to clinical research.

Rapid extraction, identification and quantification of drugs of abuse in hair by immunoassay and ultra-performance liquid chromatography tandem mass spectrometry.

PubMed

Pichini, Simona; Gottardi, Massimo; Marchei, Emilia; Svaizer, Fiorenza; Pellegrini, Manuela; Rotolo, Maria Concetta; Algar, Oscar García; Pacifici, Roberta

2014-05-01

Drug testing in hair is a unique analysis in pharmacotoxicology for establishing a past repeated history of consumption or passive exposure to psychotropic substances. A rather lengthy sample treatment is usually required before parent drugs and eventual metabolites are amenable to quali-quantitative analysis. We evaluated a high throughput screening and confirmation analysis of drugs of abuse in hair by immunoassay and a validated ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after applying a rapid digestion of the keratin matrix with VMA-T reagent before screening assay and M3 reagent before confirmatory analysis. Samples digestion with VMA-T reagent and immunometric screening analysis of hair calibrators, controls and clinical samples for a total of 150 samples was completed in 4 h. No false-positive and -negative results were found for the control material. UPLC-MS/MS analysis confirmed all of the 31 adult hair samples positive to the screening test using internationally established cut-offs, and identified and quantified drugs of abuse in 32 pediatric hair samples, applying lower limits of quantification from 0.01 to 0.1 ng analyte per mg hair. Analytical recovery was between 70.9% and 100.7%. Intra- and inter-assay imprecision and inaccuracy were always lower than 10%. Rapid extraction, identification and quantification of drugs of abuse in hair by immunoassay and UPLC-MS/MS was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in hair in epidemiological studies.

Improvement of long-term outcomes in pancreatic cancer and its associated factors within the gemcitabine era: a collaborative retrospective multicenter clinical review of 1,082 patients.

PubMed

Kuroda, Taira; Kumagi, Teru; Yokota, Tomoyuki; Seike, Hirotaka; Nishiyama, Mari; Imai, Yusuke; Inada, Nobu; Shibata, Naozumi; Imamine, Satoshi; Okada, Shin-ichi; Koizumi, Mitsuhito; Yamanishi, Hirofumi; Azemoto, Nobuaki; Miyaike, Jiro; Tanaka, Yoshinori; Tatsukawa, Haruka; Utsunomiya, Hiroki; Ohno, Yoshinori; Miyake, Teruki; Hirooka, Masashi; Furukawa, Shinya; Abe, Masanori; Ikeda, Yoshiou; Matsuura, Bunzo; Hiasa, Yoichi; Onji, Morikazu

2013-08-31

Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era. A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student's t-test, and Mann-Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test. The distribution of clinical stages was: I, 2.2% II, 3.4% III, 13% IVa, 27% and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001-2005, n=406) and B (2006-2010, n=676). However, group B included more patients who underwent chemotherapy (P<0.0001) and fewer treated with best supportive care (P=0.0004), mirroring improvements in this group's long-term outcomes (P=0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P<0.0001), location of the tumor (P=0.0294) and treatments (surgery, chemotherapy) (<0.0001). Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best supportive care. Most patients are still diagnosed at an advanced stage, making clinical strategy development for diagnosing pancreatic cancer at earlier stages essential.

Preliminary report of a Web-based instrument to assess and teach knowledge and clinical thinking to medical student

PubMed Central

Tokunaga, Hironobu; Ando, Hirotaka; Obika, Mikako; Miyoshi, Tomoko; Tokuda, Yasuharu; Bautista, Miho; Kataoka, Hitomi; Terasawa, Hidekazu

2014-01-01

Objectives We report the preliminary development of a unique Web-based instrument for assessing and teaching knowledge and developing clinical thinking called the “Sequential Questions and Answers” (SQA) test. Included in this feasibility report are physicians’ answers to the Sequential Questions and Answers pre- and posttests and their brief questionnaire replies. Methods The authors refined the SQA test case scenario for content, ease of modifications of case scenarios, test uploading and answer retrieval. Eleven geographically distant physicians evaluated the SQA test, taking the pretest and posttest within two weeks. These physicians completed a brief questionnaire about the SQA test. Results Eleven physicians completed the SQA pre- and posttest; all answers were downloaded for analysis. They reported the ease of website login and navigating within the test module together with many helpful suggestions. Their average posttest score gain was 53% (p=0.012). Conclusions We report the successful launch of a unique Web-based instrument referred to as the Sequential Questions and Answers test. This distinctive test combines teaching organization of the clinical narrative into an assessment tool that promotes acquiring medical knowledge and clinical thinking. We successfully demonstrated the feasibility of geographically distant physicians to access the SQA instrument. The physicians’ helpful suggestions will be added to future SQA test versions. Medical schools might explore the integration of this multi-language-capable SQA assessment and teaching instrument into their undergraduate medical curriculum. PMID:25341203

Clinical Functional Capacity Testing in Patients With Facioscapulohumeral Muscular Dystrophy: Construct Validity and Interrater Reliability of Antigravity Tests.

PubMed

Rijken, Noortje H; van Engelen, Baziel G; Weerdesteyn, Vivian; Geurts, Alexander C

2015-12-01

To evaluate the construct validity and interrater reliability of 4 simple antigravity tests in a small group of patients with facioscapulohumeral muscular dystrophy (FSHD). Case-control study. University medical center. Patients with various severity levels of FSHD (n=9) and healthy control subjects (n=10) were included (N=19). Not applicable. A 4-point ordinal scale was designed to grade performance on the following 4 antigravity tests: sit to stance, stance to sit, step up, and step down. In addition, the 6-minute walk test, 10-m walking test, Berg Balance Scale, and timed Up and Go test were administered as conventional tests. Construct validity was determined by linear regression analysis using the Clinical Severity Score (CSS) as the dependent variable. Interrater agreement was tested using a κ analysis. Patients with FSHD performed worse on all 4 antigravity tests compared with the controls. Stronger correlations were found within than between test categories (antigravity vs conventional). The antigravity tests revealed the highest explained variance with regard to the CSS (R(2)=.86, P=.014). Interrater agreement was generally good. The results of this exploratory study support the construct validity and interrater reliability of the proposed antigravity tests for the assessment of functional capacity in patients with FSHD taking into account the use of compensatory strategies. Future research should further validate these results in a larger sample of patients with FSHD. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

High-resolution melting analysis of gyrA codon 84 and grlA codon 80 mutations conferring resistance to fluoroquinolones in Staphylococcus pseudintermedius isolates from canine clinical samples.

PubMed

Loiacono, Monica; Martino, Piera A; Albonico, Francesca; Dell'Orco, Francesca; Ferretti, Manuela; Zanzani, Sergio; Mortarino, Michele

2017-09-01

Staphylococcus pseudintermedius is an opportunistic pathogen of dogs and cats. A high-resolution melting analysis (HRMA) protocol was designed and tested on 42 clinical isolates with known fluoroquinolone (FQ) susceptibility and gyrA codon 84 and grlA codon 80 mutation status. The HRMA approach was able to discriminate between FQ-sensitive and FQ-resistant strains and confirmed previous reports that the main mutation site associated with FQ resistance in S. pseudintermedius is located at position 251 (Ser84Leu) of gyrA. Routine, HRMA-based FQ susceptibility profiles may be a valuable tool to guide therapy. The FQ resistance-predictive power of the assay should be tested in a significantly larger number of isolates.

99mTc-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant chemotherapy in locally advanced breast cancer: A quantitative analysis

PubMed Central

KOGA, KATIA HIROMOTO; MORIGUCHI, SONIA MARTA; NETO, JORGE NAHÁS; PERES, STELA VERZINHASSE; SILVA, EDUARDO TINÓIS DA; SARRI, ALMIR JOSÉ; MICHELIN, ODAIR CARLITO; MARQUES, MARIANGELA ESTHER ALENCAR; GRIVA, BEATRIZ LOTUFO

2010-01-01

To evaluate the tumor response to neoadjuvant chemotherapy, 99mTc-sestamibi breast scintigraphy was proposed as a quantitative method. Fifty-five patients with ductal carcinoma were studied. They underwent breast scintigraphy before and after neoadjuvant chemotherapy, along with clinical assessment and surgical specimen analysis. The regions of interest on the lesion and contralateral breast were identified, and the pixel counts were used to evaluate lesion uptake in relation to background radiation. The ratio of these counts before to after neoadjuvant chemotherapy was assessed. The decrease in uptake rate due to chemotherapy characterized the scintigraphy tumor response. The Kruskal-Wallis test was used to compare the mean scintigraphic tumor response and histological type. Dunn’s multiple comparison test was used to detect differences between histological types. The Mann-Whitney test was used to compare means between quantitative and qualitative variables: scintigraphic tumor response vs. clinical response and uptake before chemotherapy vs. scintigraphic tumor response. The Spearman’s test was used to correlate the quantitative variables of clinical reduction in tumor size and scintigraphic tumor response. All of the variables compared presented significant differences. The change in 99mTc-sestamibi uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy, may be used as an effective method for evaluating the response to neoadjuvant chemotherapy, since this quantification reflects the biological behavior of the tumor towards the chemotherapy regimen. Furthermore, additional analysis on the uptake rate before chemotherapy may accurately predict treatment response. PMID:22966312

Applications of commercial biosensors in clinical, food, environmental, and biothreat/biowarfare analyses.

PubMed

Bahadır, Elif Burcu; Sezgintürk, Mustafa Kemal

2015-06-01

The lack of specific, low-cost, rapid, sensitive, and easy detection of biomolecules has resulted in the development of biosensor technology. Innovations in biosensor technology have enabled many biosensors to be commercialized and have enabled biomolecules to be detected onsite. Moreover, the emerging technologies of lab-on-a-chip microdevices and nanosensors offer opportunities for the development of new biosensors with much better performance. Biosensors were first introduced into the laboratory by Clark and Lyons. They developed the first glucose biosensor for laboratory conditions. Then in 1973, a glucose biosensor was commercialized by Yellow Springs Instruments. The commercial biosensors have small size and simple construction and they are ideal for point-of-care biosensing. In addition to glucose, a wide variety of metabolites such as lactate, cholesterol, and creatinine can be detected by using commercial biosensors. Like the glucose biosensors (tests) other commercial tests such as for pregnancy (hCG), Escherichia coli O157, influenza A and B viruses, Helicobacter pylori, human immunodeficiency virus, tuberculosis, and malaria have achieved success. Apart from their use in clinical analysis, commercial tests are also used in environmental (such as biochemical oxygen demand, nitrate, pesticide), food (such as glutamate, glutamine, sucrose, lactose, alcohol, ascorbic acid), and biothreat/biowarfare (Bacillus anthracis, Salmonella, Botulinum toxin) analysis. In this review, commercial biosensors in clinical, environmental, food, and biowarfare analysis are summarized and the commercial biosensors are compared in terms of their important characteristics. This is the first review in which all the commercially available tests are compiled together. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and Taxonomic Status of Pathogenic Nonpigmented or Late-Pigmenting Rapidly Growing Mycobacteria

PubMed Central

Brown-Elliott, Barbara A.; Wallace, Richard J.

2002-01-01

The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on the Mycobacterium fortuitum group, including M. fortuitum, M. peregrinum, and the unnamed third biovariant complex with its recent taxonomic changes and newly recognized species (including M. septicum, M. mageritense, and proposed species M. houstonense and M. bonickei). The clinical and taxonomic status of M. chelonae, M. abscessus, and M. mucogenicum is also detailed, along with that of the closely related new species, M. immunogenum. Additionally, newly recognized species, M. wolinskyi and M. goodii, as well as M. smegmatis sensu stricto, are included in a discussion of the M. smegmatis group. Laboratory diagnosis of RGM using phenotypic methods such as biochemical testing and high-performance liquid chromatography and molecular methods of diagnosis are also discussed. The latter includes PCR-restriction fragment length polymorphism analysis, hybridization, ribotyping, and sequence analysis. Susceptibility testing and antibiotic susceptibility patterns of the RGM are also annotated, along with the current recommendations from the National Committee for Clinical Laboratory Standards (NCCLS) for mycobacterial susceptibility testing. PMID:12364376

Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria.

PubMed

Brown-Elliott, Barbara A; Wallace, Richard J

2002-10-01

The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of disease are also described. Special emphasis is on the Mycobacterium fortuitum group, including M. fortuitum, M. peregrinum, and the unnamed third biovariant complex with its recent taxonomic changes and newly recognized species (including M. septicum, M. mageritense, and proposed species M. houstonense and M. bonickei). The clinical and taxonomic status of M. chelonae, M. abscessus, and M. mucogenicum is also detailed, along with that of the closely related new species, M. immunogenum. Additionally, newly recognized species, M. wolinskyi and M. goodii, as well as M. smegmatis sensu stricto, are included in a discussion of the M. smegmatis group. Laboratory diagnosis of RGM using phenotypic methods such as biochemical testing and high-performance liquid chromatography and molecular methods of diagnosis are also discussed. The latter includes PCR-restriction fragment length polymorphism analysis, hybridization, ribotyping, and sequence analysis. Susceptibility testing and antibiotic susceptibility patterns of the RGM are also annotated, along with the current recommendations from the National Committee for Clinical Laboratory Standards (NCCLS) for mycobacterial susceptibility testing.

Digital subtraction radiographic analysis of the combination of bioabsorbable membrane and bovine morphogenetic protein pool in human periodontal infrabony defects

PubMed Central

GUIMARÃES, Maria do Carmo Machado; PASSANEZI, Euloir; SANT’ANA, Adriana Campos Passanezi; GREGHI, Sebastião Luiz Aguiar; TABA JUNIOR, Mario

2010-01-01

Objectives This study assessed the bone density gain and its relationship with the periodontal clinical parameters in a case series of a regenerative therapy procedure. Material and Methods Using a split-mouth study design, 10 pairs of infrabony defects from 15 patients were treated with a pool of bovine bone morphogenetic proteins associated with collagen membrane (test sites) or collagen membrane only (control sites). The periodontal healing was clinically and radiographically monitored for six months. Standardized presurgical and 6-month postoperative radiographs were digitized for digital subtraction analysis, which showed relative bone density gain in both groups of 0.034 ± 0.423 and 0.105 ± 0.423 in the test and control group, respectively (p>0.05). Results As regards the area size of bone density change, the influence of the therapy was detected in 2.5 mm2 in the test group and 2 mm2 in the control group (p>0.05). Additionally, no correlation was observed between the favorable clinical results and the bone density gain measured by digital subtraction radiography (p>0.05). Conclusions The findings of this study suggest that the clinical benefit of the regenerative therapy observed did not come with significant bone density gains. Long-term evaluation may lead to a different conclusions. PMID:20835573

Testing and screening for chlamydia in general practice: a cross-sectional analysis.

PubMed

Thomson, Allison; Morgan, Simon; Henderson, Kim; Tapley, Amanda; Spike, Neil; Scott, John; van Driel, Mieke; Magin, Parker

2014-12-01

Chlamydia screening is widely advocated. General practice registrars are an important stage of clinical behaviour development. This study aimed to determine rates of, and factors associated with, registrars' chlamydia testing including asymptomatic screening. A cross-sectional analysis of data from Registrars Clinical Encounters in Training (ReCEnT), a cohort study of registrars' consultations. Registrars record details of 60 consecutive consultations in each GP-term of training. Outcome factors were chlamydia testing, asymptomatic screening and doctor-initiated screening. Testing occurred in 2.5% of 29,112 consultations (398 registrars) and in 5.8% of patients aged 15-25. Asymptomatic screening comprised 47.5% of chlamydia tests, and 55.6% of screening tests were doctor-initiated. Chlamydia testing was associated with female gender of doctor and patient, younger patient age, and patients new to doctor or practice. Asymptomatic screening was associated with practices where patients incur no fees, and in patients new to doctor or practice. Screening of female patients was more often doctor-initiated. GP registrars screen for chlamydia disproportionately in younger females and new patients. Our findings highlight potential opportunities to improve uptake of screening for chlamydia, including targeted education and training for registrars, campaigns targeting male patients, and addressing financial barriers to accessing screening services. © 2014 Public Health Association of Australia.

The VI-SENSE-vaginal discharge self-test to facilitate management of vaginal symptoms.

PubMed

Geva, Adam; Bornstein, Jacob; Dan, Michael; Shoham, Hadar Kessary; Sobel, Jack D

2006-11-01

This study was undertaken to evaluate a diagnostic panty liner (VI-SENSE) (Common Sense, Caesarea, Israel) developed to facilitate diagnosis of vaginal infections by detecting disordered acidity level. Five hundred sixteen women with vulvovaginal symptoms were enrolled. Final clinical diagnosis included Amsel criteria, Gram stain analysis, pH determination, and Trichomonas vaginalis and Candida culture. VI-SENSE strip color status estimated by patients was compared with clinical diagnosis and pH measurement by using nitrazine paper. Statistical analysis included sensitivity and specificity calculations. The VI-SENSE test was positive in 226 of 249 patients (90.8%) with bacterial vaginosis or trichomoniasis. Nitrazine pH paper revealed elevated pH in 165 (66.5%) and the amine test was positive in 160 (64.3%) patients. The VI-SENSE test was negative in 217 of 267 patients (81.3%) without trichomoniasis or bacterial vaginosis. The VI-SENSE was positive in 85 of 92 women (92%), with mixed vaginal infection including Candida and bacterial vaginosis or trichomoniasis. Amine test, nitrazine pH paper and physician diagnosis relying only on speculum examination were inferior and positive in only 65 (70%), 59 (64%), and 66 (72%) patients, respectively. The VI-SENSE test was found to be superior to traditional individual tests in facilitating preliminary diagnosis of vaginal infections.

A comparison of two forms of teaching instruction: video vs. live lecture for education in clinical periodontology.

PubMed

Ramlogan, S; Raman, V; Sweet, J

2014-02-01

This crossover controlled study aimed to compare the knowledge and skill attained by third-year dental students in three clinical exercises in the discipline of periodontology through video and live lecture instruction. Students (n = 35) segregated into two group either viewed a video or attended a live lecture repeated over three clinical teaching sessions. Pre-test and post-test written assessments were completed and comparisons between video and live lecture done (analysis of variance, P < 0.05). Students were assessed on clinic by a simple checklist. A questionnaire was administered after all three sessions to determine preferences and opinions on video and live lecture. For the combined three sessions, both video (n = 48) and live lecture (n = 47) groups attained similar mean pre-test scores. The mean post-test score was statistically significantly greater (P = 0.049) for the live lecture (74.9%, SD 14.9) compared to the video group (68.6%, SD 16.3). All students attained clinical proficiency via the simple checklist. In adding to their clinical skill, more students favoured video (97%) vs. live lecture (78.8%). Most students (97%) favoured a future combination of video and lecture. While students were deemed clinically competent via a simple checklist, the live lecture group performed better than the video group via the in-depth post-test assessment. Students had a preference for video and would like it integrated in the lecture rather than act as a substitute for the lecture. The use of video alone in clinical periodontology training may have limitations unless supplemented by appropriate learning activities. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The value of routine polymerase chain reaction analysis of intraocular fluid specimens in the diagnosis of infectious posterior uveitis.

PubMed

Scheepers, Marius A; Lecuona, Karin A; Rogers, Graeme; Bunce, Catey; Corcoran, Craig; Michaelides, Michel

2013-01-01

To assess the value of routine polymerase chain reaction (PCR) analysis on intraocular fluid from patients presenting with a first episode of suspected active infectious posterior uveitis in a population with a high prevalence of human immunodeficiency virus infection. Retrospective, interventional case series. Participants. 159 consecutive patients presenting at a tertiary care hospital over a five-year period. PCR analysis was performed for cytomegalovirus, varicella zoster virus, herpes simplex virus types 1 and 2, Toxoplasma gondii, and Mycobacterium tuberculosis. PCR analysis confirmed the initial clinical diagnosis in 55 patients (35%) and altered the initial clinical diagnosis in 36 patients (23%). The clinical diagnosis prior to PCR testing was nonspecific (uncertain) in 51 patients (32%), with PCR providing a definitive final diagnosis in 20 of these patients (39%); necrotizing herpetic retinopathy and ocular toxoplasmosis were particularly difficult to diagnose correctly without the use of PCR analysis. The clinical phenotype alone was unreliable in diagnosing the underlying infectious cause in a quarter of patients in this study. Since the outcome of incorrectly treated infective uveitis can be blinding, PCR analysis of ocular fluids is recommended early in the disease even in resource poor settings.

The Frequency of Optical Coherence Tomography Testing in Glaucoma at a Single Academic Medical Center.

PubMed

Griffith, Joseph F; Goldberg, Jeffrey L

2016-03-01

To determine the frequency of optical coherence tomography (OCT) examinations compared with clinical examinations and visual field (VF) tests in patients with 5 types of glaucoma. A retrospective, longitudinal cohort study was conducted of 5154 patients treated between 2003 and 2010 at a single academic medical center. Patients were classified using billing records as having primary open-angle glaucoma, low-tension open-angle glaucoma (NTG), pigmentary open-angle glaucoma, chronic angle-closure glaucoma, or pseudoexfoliation glaucoma. Analysis of variance, χ test, and exact χ test were performed to identify associations between glaucoma type and test frequency. Pigmentary open-angle glaucoma and NTG patients had a higher rate of undergoing at least 2 VFs (94.4%, 94.9%), and chronic angle-closure glaucoma patients had a lower rate of undergoing at least 2 OCTs (25.3%) than all other glaucoma types. NTG patients also had the highest rate of undergoing at least 2 OCTs and at least 2 VFs (36.6%). Overall, the rate of clinical examinations (2.68 examinations/y) exceeded the rates of OCTs (1.39 examinations/y), which exceeded the rate of VF tests (1.24 tests/y). There were no differences in OCT frequency between glaucoma types (0.91 to 1.63 OCTs/y). Within each glaucoma diagnosis, patients had clinical examinations more frequently than OCTs and clinical examinations more frequently than VFs. Primary open-angle glaucoma and pseudoexfoliation glaucoma patients also had OCTs more frequently than VFs. More patients had at least 2 VF tests than at least 2 OCTs (4481 vs. 1679). The relative use of clinical examinations, VF testing, and OCT imaging varies among glaucoma diagnoses.

Frequency and determinants of consistent STI/HIV testing among men who have sex with men testing at STI outpatient clinics in the Netherlands: a longitudinal study.

PubMed

Visser, Maartje; Heijne, Janneke C M; Hogewoning, Arjan A; van Aar, Fleur

2017-09-01

Men who have sex with men (MSM) are at highest risk for STIs and HIV infections in the Netherlands. However, official guidelines on STI testing among MSM are lacking. They are advised to test for STIs at least every six months, but their testing behaviour is not well known. This study aimed to get insight into the proportion and determinants of consistent 6-monthly STI testing among MSM testing at STI outpatient clinics in the Netherlands. This study included longitudinal surveillance data of STI consultations among MSM from all 26 STI outpatient clinics in the Netherlands between 1 June 2014 and 31 December 2015. Multinomial logistic regression analysis was used to identify determinants of consistent 6-monthly testing compared with single testing and inconsistent testing. Determinants of time between consultations among men with multiple consultations were analysed using a Cox Prentice-Williams-Peterson gap-time model. A total of 34 605 STI consultations of 18 634 MSM were included. 8966 (48.1%) men had more than one consultation, and 3516 (18.9%) men tested consistently 6-monthly. Indicators of high sexual risk behaviour, including having a history of STI, being HIV positive and having more than 10 sex partners, were positively associated with both being a consistent tester and returning to the STI clinic sooner. Men who were notified by a partner or who reported STI symptoms were also more likely to return to the STI clinic sooner, but were less likely to be consistent testers, identifying a group of event-driven testers. The proportion of consistent 6-monthly testers among MSM visiting Dutch STI outpatient clinics was low. Testing behaviour was associated with sexual risk behaviour, but exact motives to test consistently remain unclear. Evidence-based testing guidelines are needed to achieve optimal reductions in STI transmission in the future. 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/.

Genetic and clinical characteristics of Chinese children with Glucokinase-maturity-onset diabetes of the young (GCK-MODY).

PubMed

Li, Xiuzhen; Ting, Tzer Hwu; Sheng, Huiying; Liang, Cui Li; Shao, Yongxian; Jiang, Minyan; Xu, Aijing; Lin, Yunting; Liu, Li

2018-03-06

There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. The aim of the study was to investigate the clinical and molecular characteristics of Chinese children with GCK-MODY. Eleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children's hospital in South China. Clinical data were obtained from medical records. Blood was collected from the patients and their parents for glucokinase (GCK) gene analysis. Parents without diabetes were tested for fasting glucose and HbA1c. Clinical information and blood for GCK gene analysis were obtained from grandparents with diabetes. GCK gene mutational analysis was performed by polymerase chain reaction and direct sequencing. Patients without a GCK gene mutation were screened by targeted next-generation sequencing (NGS) technology for other MODY genes. Nine children tested positive for GCK gene mutations while two were negative. The nine GCK-MODY patients were from unrelated families, aged 1 month to 9 years and 1 month at first detection of hyperglycaemia. Fasting glucose was elevated (6.1-8.5 mmol/L), HbA1c 5.2-6.7% (33.3-49.7 mmol/mol), both remained stable on follow-up over 9 months to 5 years. Five detected mutations had been previously reported: p.Val182Met, c.679 + 1G > A, p.Gly295Ser, p.Arg191Gln and p.Met41Thr. Four mutations were novel: c.483 + 2 T > A, p.Ser151del, p.Met57GlyfsX29 and p.Val374_Ala377del. No mutations were identified in the other two patients, who were also tested by NGS. GCK gene mutations are detected in Chinese children and their family members with typical clinical features of GCK-MODY. Four novel mutations are detected.

Effectiveness of a Risk Screener in Identifying Hepatitis C Virus in a Primary Care Setting

PubMed Central

Litwin, Alain H.; Smith, Bryce D.; Koppelman, Elisa A.; McKee, M. Diane; Christiansen, Cindy L.; Gifford, Allen L.; Weinbaum, Cindy M.; Southern, William N.

2012-01-01

Objectives. We evaluated an intervention designed to identify patients at risk for hepatitis C virus (HCV) through a risk screener used by primary care providers. Methods. A clinical reminder sticker prompted physicians at 3 urban clinics to screen patients for 12 risk factors and order HCV testing if any risks were present. Risk factor data were collected from the sticker; demographic and testing data were extracted from electronic medical records. We used the t test, χ2 test, and rank-sum test to compare patients who had and had not been screened and developed an analytic model to identify the incremental value of each element of the screener. Results. Among screened patients, 27.8% (n = 902) were identified as having at least 1 risk factor. Of screened patients with risk factors, 55.4% (n = 500) were tested for HCV. Our analysis showed that 7 elements (injection drug use, intranasal drug use, elevated alanine aminotransferase, transfusions before 1992, ≥ 20 lifetime sex partners, maternal HCV, existing liver disease) accounted for all HCV infections identified. Conclusions. A brief risk screener with a paper-based clinical reminder was effective in increasing HCV testing in a primary care setting. PMID:22994166

CK-MB mass test in ischemic myocardial injury. Comparison of two tests: BioMerieux Vidas and sanofi access immunoassays.

PubMed

Poirey, S; Polge, A; Bertinchant, J P; Bancel, E; Boyer, J C; Fabbro-Peray, P; de Bornier, B M; Ledermann, B; Bonnier, M; Bali, J P

2000-01-01

The analytical and clinical performances of the new fluorescent immunoassay (CK-MB mass Vidas-BioMerieux) were examined and compared to the chemiluminescent test (CK-MB mass Access-Sanofi-Pasteur). Assay precisions of the CK-MB Vidas test within-assay or between-assay were less than 5.4 and 5.3%, respectively. Linearity was tested up to 214 microg/L. The CK-MB Vidas test was free of interference with CK-BB, CK-MM, and macro-CK. One hundred nineteen blood samples from patients with ischemic myocardial injury (IMI): acute myocardial infarction (AMI), suspected myocardial contusion (SMC), and unstable angina pectoris (UA), were tested using both immunoassays. In AMI, a good correlation was found (Y [CK-MB Access] = 1.1372 x [CK-MB Vidas] - 6.3902; r(2) = 0.96). In UA and SMC, low values were observed and both methods were well correlated (Y [CK-MB Access] = 1.3662 x [CK-MB Vidas] + 0.0671; r(2) = 0.97). Clinical data were in good agreement with both immunoassays. ROC analysis performed in AMI demonstrated that the clinical performances of the two assays were similar. Copyright 2000 Wiley-Liss, Inc.

Academic performance of ethnic minority candidates and discrimination in the MRCGP examinations between 2010 and 2012: analysis of data.

PubMed

Esmail, Aneez; Roberts, Chris

2013-09-26

To determine the difference in failure rates in the postgraduate examination of the Royal College of General Practitioners (MRCGP) by ethnic or national background, and to identify factors associated with pass rates in the clinical skills assessment component of the examination. Analysis of data provided by the Royal College of General Practitioners and the General Medical Council. Cohort of 5095 candidates sitting the applied knowledge test and clinical skills assessment components of the MRCGP examination between November 2010 and November 2012. A further analysis was carried out on 1175 candidates not trained in the United Kingdom, who sat an English language capability test (IELTS) and the Professional and Linguistic Assessment Board (PLAB) examination (as required for full medical registration), controlling for scores on these examinations and relating them to pass rates of the clinical skills assessment. United Kingdom. After controlling for age, sex, and performance in the applied knowledge test, significant differences persisted between white UK graduates and other candidate groups. Black and minority ethnic graduates trained in the UK were more likely to fail the clinical skills assessment at their first attempt than their white UK colleagues (odds ratio 3.536 (95% confidence interval 2.701 to 4.629), P<0.001; failure rate 17% v 4.5%). Black and minority ethnic candidates who trained abroad were also more likely to fail the clinical skills assessment than white UK candidates (14.741 (11.397 to 19.065), P<0.001; 65% v 4.5%). For candidates not trained in the UK, black or minority ethnic candidates were more likely to fail than white candidates, but this difference was no longer significant after controlling for scores in the applied knowledge test, IELTS, and PLAB examinations (adjusted odds ratio 1.580 (95% confidence interval 0.878 to 2.845), P=0.127). Subjective bias due to racial discrimination in the clinical skills assessment may be a cause of failure for UK trained candidates and international medical graduates. The difference between British black and minority ethnic candidates and British white candidates in the pass rates of the clinical skills assessment, despite controlling for prior attainment, suggests that subjective bias could also be a factor. Changes to the clinical skills assessment could improve the perception of the examination as being biased against black and minority ethnic candidates. The difference in training experience and other cultural factors between candidates trained in the UK and abroad could affect outcomes. Consideration should be given to strengthening postgraduate training for international medical graduates.

Qualifying and quantifying minimal hepatic encephalopathy.

PubMed

Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A; Jackson, Clive D; Kircheis, Gerald; Lauridsen, Mette M; Montagnese, Sara; Schiff, Sami; Weissenborn, Karin

2016-12-01

Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is no gold standard for the diagnosis of this syndrome. As these patients have, by definition, no recognizable clinical features of brain dysfunction, the primary prerequisite for the diagnosis is careful exclusion of clinical symptoms and signs. A large number of psychometric tests/test systems have been evaluated in this patient group. Of these the best known and validated is the Portal Systemic Hepatic Encephalopathy Score (PHES) derived from a test battery of five paper and pencil tests; normative reference data are available in several countries. The electroencephalogram (EEG) has been used to diagnose hepatic encephalopathy since the 1950s but, once popular, the technology is not as accessible now as it once was. The performance characteristics of the EEG are critically dependent on the type of analysis undertaken; spectral analysis has better performance characteristics than visual analysis; evolving analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test together with one of the validated alternative techniques or the EEG. Minimal hepatic encephalopathy has a detrimental effect on the well-being of patients and their care-givers. It responds well to treatment with resolution of test abnormalities and the associated detrimental effects on quality of life, liver-related mortality and morbidity. Patients will only benefit in this way if they can be effectively diagnosed. Corporate efforts and consensus agreements are needed to develop effective diagnostic algorithms.

Which physical examination tests provide clinicians with the most value when examining the shoulder? Update of a systematic review with meta-analysis of individual tests.

PubMed

Hegedus, Eric J; Goode, Adam P; Cook, Chad E; Michener, Lori; Myer, Cortney A; Myer, Daniel M; Wright, Alexis A

2012-11-01

To update our previously published systematic review and meta-analysis by subjecting the literature on shoulder physical examination (ShPE) to careful analysis in order to determine each tests clinical utility. This review is an update of previous work, therefore the terms in the Medline and CINAHL search strategies remained the same with the exception that the search was confined to the dates November, 2006 through to February, 2012. The previous study dates were 1966 - October, 2006. Further, the original search was expanded, without date restrictions, to include two new databases: EMBASE and the Cochrane Library. The Quality Assessment of Diagnostic Accuracy Studies, version 2 (QUADAS 2) tool was used to critique the quality of each new paper. Where appropriate, data from the prior review and this review were combined to perform meta-analysis using the updated hierarchical summary receiver operating characteristic and bivariate models. Since the publication of the 2008 review, 32 additional studies were identified and critiqued. For subacromial impingement, the meta-analysis revealed that the pooled sensitivity and specificity for the Neer test was 72% and 60%, respectively, for the Hawkins-Kennedy test was 79% and 59%, respectively, and for the painful arc was 53% and 76%, respectively. Also from the meta-analysis, regarding superior labral anterior to posterior (SLAP) tears, the test with the best sensitivity (52%) was the relocation test; the test with the best specificity (95%) was Yergason's test; and the test with the best positive likelihood ratio (2.81) was the compression-rotation test. Regarding new (to this series of reviews) ShPE tests, where meta-analysis was not possible because of lack of sufficient studies or heterogeneity between studies, there are some individual tests that warrant further investigation. A highly specific test (specificity >80%, LR+ ≥ 5.0) from a low bias study is the passive distraction test for a SLAP lesion. This test may rule in a SLAP lesion when positive. A sensitive test (sensitivity >80%, LR- ≤ 0.20) of note is the shoulder shrug sign, for stiffness-related disorders (osteoarthritis and adhesive capsulitis) as well as rotator cuff tendinopathy. There are six additional tests with higher sensitivities, specificities, or both but caution is urged since all of these tests have been studied only once and more than one ShPE test (ie, active compression, biceps load II) has been introduced with great diagnostic statistics only to have further research fail to replicate the results of the original authors. The belly-off and modified belly press tests for subscapularis tendinopathy, bony apprehension test for bony instability, olecranon-manubrium percussion test for bony abnormality, passive compression for a SLAP lesion, and the lateral Jobe test for rotator cuff tear give reason for optimism since they demonstrated both high sensitivities and specificities reported in low bias studies. Finally, one additional test was studied in two separate papers. The dynamic labral shear may be sensitive for SLAP lesions but, when modified, be diagnostic of labral tears generally. Based on data from the original 2008 review and this update, the use of any single ShPE test to make a pathognomonic diagnosis cannot be unequivocally recommended. There exist some promising tests but their properties must be confirmed in more than one study. Combinations of ShPE tests provide better accuracy, but marginally so. These findings seem to provide support for stressing a comprehensive clinical examination including history and physical examination. However, there is a great need for large, prospective, well-designed studies that examine the diagnostic accuracy of the many aspects of the clinical examination and what combinations of these aspects are useful in differentially diagnosing pathologies of the shoulder.

A tool for the economic analysis of mass prophylaxis operations with an application to H1N1 influenza vaccination clinics.

PubMed

Cho, Bo-Hyun; Hicks, Katherine A; Honeycutt, Amanda A; Hupert, Nathaniel; Khavjou, Olga; Messonnier, Mark; Washington, Michael L

2011-01-01

This article uses the 2009 H1N1 influenza vaccination program experience to introduce a cost analysis approach that may be relevant for planning mass prophylaxis operations, such as vaccination clinics at public health centers, work sites, schools, or pharmacy-based clinics. These costs are important for planning mass influenza vaccination activities and are relevant for all public health emergency preparedness scenarios requiring countermeasure dispensing. We demonstrate how costs vary depending on accounting perspective, staffing composition, and other factors. We also describe a mass vaccination clinic budgeting tool that clinic managers may use to estimate clinic costs and to examine how costs vary depending on the availability of volunteers or donated supplies and on the number of patients vaccinated per hour. Results from pilot tests with school-based H1N1 influenza vaccination clinic managers are described. The tool can also contribute to planning efforts for universal seasonal influenza vaccination.

A comparison of manual and quantitative elbow strength testing.

PubMed

Shahgholi, Leili; Bengtson, Keith A; Bishop, Allen T; Shin, Alexander Y; Spinner, Robert J; Basford, Jeffrey R; Kaufman, Kenton R

2012-10-01

The aim of this study was to compare the clinical ratings of elbow strength obtained by skilled clinicians with objective strength measurement obtained through quantitative testing. A retrospective comparison of subject clinical records with quantitative strength testing results in a motion analysis laboratory was conducted. A total of 110 individuals between the ages of 8 and 65 yrs with traumatic brachial plexus injuries were identified. Patients underwent manual muscle strength testing as assessed on the 5-point British Medical Research Council Scale (5/5, normal; 0/5, absent) and quantitative elbow flexion and extension strength measurements. A total of 92 subjects had elbow flexion testing. Half of the subjects clinically assessed as having normal (5/5) elbow flexion strength on manual muscle testing exhibited less than 42% of their age-expected strength on quantitative testing. Eighty-four subjects had elbow extension strength testing. Similarly, half of those displaying normal elbow extension strength on manual muscle testing were found to have less than 62% of their age-expected values on quantitative testing. Significant differences between manual muscle testing and quantitative findings were not detected for the lesser (0-4) strength grades. Manual muscle testing, even when performed by experienced clinicians, may be more misleading than expected for subjects graded as having normal (5/5) strength. Manual muscle testing estimates for the lesser strength grades (1-4/5) seem reasonably accurate.

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

PubMed

Alagrund, Katariina; Orpana, Arto K

2014-01-01

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

PROSPECTIVE MULTICENTER SURVEY ON PREDICTIVE FACTORS FOR POSITIVE ORAL FOOD CHALLENGE TESTS IN DIAGNOSIS OF GASTROINTESTINAL FOOD ALLERGY IN NEONATES.

PubMed

Miyazawa, Tokuo; Imai, Takanori; Itabashi, Kazuo

2016-01-01

To assess predictors of positive oral food challenge test (OFC) in neonates that are suggestive of gastrointestinal food allergy. A prospective case accumulations study on neonates suspected of having gastrointestinal food allergy was conducted in 126 neonatal intensive care units in Japan between April 2010 and September 2011. Neonates who underwent an OFC for the diagnosis of gastrointestinal food allergy were enrolled. Clinical backgrounds, clinical symptoms, and laboratory findings were compared between neonates with a positive OFC and those with a negative OFC. An analysis was performed in 32 neonates. The OFC results were positive in 9 neonates (28.1%), pseudo-positive in 4, and negative in 19. There were no significant differences in clinical backgrounds between the positive OFC group and the negative OFC group. Vomiting and bloody stool were frequently observed in both groups (approximately 70%), although there were no significant differences in the clinical symptoms between the two groups. Additional diagnostic tests included those for eosinophils in the peripheral blood and stool mucus and allergen-specific lymphocyte stimulation test. There were no significant differences in laboratory findings between the two groups, and many neonates showed pseudo-positive in all of the tests. It was difficult to predict OFC results based on clinical symptoms and additional diagnostic test results. In order to obtain an accurate diagnosis of gastrointestinal food allergy in neonates, OFC should be performed proactively under conditions that enable complete understanding of risks to neonates.

Assessing the readiness of precision medicine interoperabilty: An exploratory study of the National Institutes of Health genetic testing registry.

PubMed

Ronquillo, Jay G; Weng, Chunhua; Lester, William T

2017-11-17

  Precision medicine involves three major innovations currently taking place in healthcare:  electronic health records, genomics, and big data.  A major challenge for healthcare providers, however, is understanding the readiness for practical application of initiatives like precision medicine.   To better understand the current state and challenges of precision medicine interoperability using a national genetic testing registry as a starting point, placed in the context of established interoperability formats.   We performed an exploratory analysis of the National Institutes of Health Genetic Testing Registry.  Relevant standards included Health Level Seven International Version 3 Implementation Guide for Family History, the Human Genome Organization Gene Nomenclature Committee (HGNC) database, and Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT).  We analyzed the distribution of genetic testing laboratories, genetic test characteristics, and standardized genome/clinical code mappings, stratified by laboratory setting. There were a total of 25472 genetic tests from 240 laboratories testing for approximately 3632 distinct genes.  Most tests focused on diagnosis, mutation confirmation, and/or risk assessment of germline mutations that could be passed to offspring.  Genes were successfully mapped to all HGNC identifiers, but less than half of tests mapped to SNOMED CT codes, highlighting significant gaps when linking genetic tests to standardized clinical codes that explain the medical motivations behind test ordering.  Conclusion:  While precision medicine could potentially transform healthcare, successful practical and clinical application will first require the comprehensive and responsible adoption of interoperable standards, terminologies, and formats across all aspects of the precision medicine pipeline.

Cost-effectiveness of the Carbon-13 Urea Breath Test for the Detection of Helicobacter Pylori

PubMed Central

Masucci, L; Blackhouse, G; Goeree, R

2013-01-01

Objectives This analysis aimed to evaluate the cost-effectiveness of various testing strategies for Helicobacter pylori in patients with uninvestigated dyspepsia and to calculate the budgetary impact of these tests for the province of Ontario. Data Sources Data on the sensitivity and specificity were obtained from the clinical evidence-based analysis. Resource items were obtained from expert opinion, and costs were applied on the basis of published sources as well as expert opinion. Review Methods A decision analytic model was constructed to compare the costs and outcomes (false-positive results, false-negative results, and misdiagnoses avoided) of the carbon-13 (13C) urea breath test (UBT), enzyme-linked immunosorbent assay (ELISA) serology test, and a 2-step strategy of an ELISA serology test and a confirmatory 13C UBT based on the sensitivity and specificity of the tests and prevalence estimates. Results The 2-step strategy is more costly and more effective than the ELISA serology test and results in $210 per misdiagnosis case avoided. The 13C UBT is dominated by the 2-step strategy, i.e., it is more costly and less effective. The budget impact analysis indicates that it will cost $7.9 million more to test a volume of 129,307 patients with the 13C UBT than with ELISA serology, and $4.7 million more to test these patients with the 2-step strategy. Limitations The clinical studies that were pooled varied in the technique used to perform the breath test and in reference standards used to make comparisons with the breath test. However, these parameters were varied in a sensitivity analysis. The economic model was designed to consider intermediate outcomes only (i.e., misdiagnosed cases) and was not a complete model with final patient outcomes (e.g., quality-adjusted life years). Conclusions Results indicate that the 2-step strategy could be economically attractive for the testing of H. pylori. However, testing with the 2-step strategy will cost the Ministry of Health and Long-Term Care $4.7 million more than with the ELISA serology test. PMID:24228083

Potential surrogate endpoints for prostate cancer survival: analysis of a phase III randomized trial.

PubMed

Ray, Michael E; Bae, Kyounghwa; Hussain, Maha H A; Hanks, Gerald E; Shipley, William U; Sandler, Howard M

2009-02-18

The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial. Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided. At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria. Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions

PubMed Central

Mamiya, Yasuyuki; Nishio, Yoshiyuki; Watanabe, Hiroyuki; Yokoi, Kayoko; Uchiyama, Makoto; Baba, Toru; Iizuka, Osamu; Kanno, Shigenori; Kamimura, Naoto; Kazui, Hiroaki; Hashimoto, Mamoru; Ikeda, Manabu; Takeshita, Chieko; Shimomura, Tatsuo; Mori, Etsuro

2016-01-01

Background Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test. Methods The pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer’s disease (AD) and 20 healthy controls (HCs). We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC) and the concurrent validity using the Neuropsychiatric Inventory (NPI) hallucinations score as a reference. A receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs. Results The pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82), and moderately correlated with the NPI hallucinations score (rs = 0.42). Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%. Conclusions Our study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB. PMID:27171377

Genetic testing for hearing impairment.

PubMed

Topsakal, V; Van Camp, G; Van de Heyning, P

2005-01-01

For some patients, genetic testing can reveal the etiology of their hearing impairment, and can provide evidence for a medical diagnosis. However, a gap between fundamental genetic research on hereditary deafness and clinical otology emerges because of the steadily increasing number of discovered genes for hereditary hearing impairment (HHI) and the comparably low clinical differentiation of the HHIs. In an attempt to keep up with the scientific progress, this article enumerates the indications of genetic testing for HHI from a clinical point of view and describes the most frequently encountered HHIs in Belgium. Domains of recent scientific interest, molecular biological aspects, and some pitfalls with HHIs are highlighted. The overview comprises bilateral congenital hearing loss, late-onset progressive high frequency hearing loss, progressive bilateral cochleo-vestibular deficit, and progressive low frequency hearing loss. Also, several syndromal forms of HHI are summarized, and the availability of genetic tests mentioned. Finally, the requirements for successful linkage analysis, an important genetic research tool for localizing the potential genes of a trait on a chromosome, are briefly described.

Modest rise in chlamydia and gonorrhoea testing did not increase case detection in a clinical HIV cohort in Ontario, Canada

PubMed Central

Burchell, Ann N; Grewal, Ramandip; Allen, Vanessa G; Gardner, Sandra L; Moravan, Veronika; Bayoumi, Ahmed M; Kaul, Rupert; McGee, Frank; Millson, Margaret (Peggy) E; Remis, Robert S; Raboud, Janet; Mazzulli, Tony; Rourke, Sean B

2014-01-01

Objectives We described patterns of testing for chlamydia and gonorrhoea infection among persons in specialty HIV care in Ontario, Canada, from 2008 to 2011. Methods We analysed data from 3165 participants in the OHTN Cohort Study attending one of seven specialty HIV care clinics. We obtained chlamydia and gonorrhoea test results via record linkage with the provincial public health laboratory. We estimated the proportion of participants who underwent testing annually, the positivity rate among those tested and the proportion diagnosed with chlamydia or gonorrhoea among all under observation. We explored risk factors for testing and diagnosis using multiple logistic regression analysis. Results The proportion tested annually rose from 15.2% (95% CI 13.6% to 16.7%) in 2008 to 27.0% (95% CI 25.3% to 28.6%) in 2011 (p<0.0001). Virtually all were urine-based nucleic acid amplification tests. Testing was more common among men who have sex with men (MSM), younger adults, Toronto residents, persons attending primary care clinics and persons who had tested in the previous year or who had more clinic visits in the current year. We observed a decrease in test positivity rates over time. However, the annual proportion diagnosed remained stable and in 2011 this was 0.97% (95% CI 0.61% to 1.3%) and 0.79% (95% CI 0.46% to 1.1%) for chlamydia and gonorrhoea, respectively. Virtually all cases were among MSM. Conclusions Chlamydia and gonorrhoea testing increased over time while test positivity rates declined and the overall proportion diagnosed remained stable, suggesting that the modest increase in testing did not improve case detection. PMID:25178285

Psychometric properties of the Chinese version of the Obsessive Beliefs Questionnaire-44 (OBQ-44).

PubMed

Wang, Jing; Wei, Zhen; Wang, He; Jiang, Zeyu; Peng, Ziwen

2015-08-04

The Obsessive Beliefs Questionnaire-44 (OBQ-44) is originally developed by the Obsessive Compulsive Cognitions Working Group and has been translated into several languages. This paper is aimed to investigate the psychometric properties of the Chinese version of the Obsessive Beliefs Questionnaire-44 (OBQ-44) in both clinical and non-clinical samples. Five hundred and sixty-nine undergraduate volunteers and sixty-six OCD patients were included in the study. All participants have completed Chinese version of OBQ-44, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and Beck Depression Inventory (BDI). Confirmatory factor analysis was conducted to examine the construct validity of Chinese version of OBQ-44. The internal consistency and test-retest reliabilities at 4-week interval were examined in both non-clinical and clinical groups. The confirmatory factor analysis of the non-clinical sample confirmed a 3-factor model which was suggested by the original authors of the instrument (χ (2)/d.f = 2.96, GFI = 0.83, NFI = 0.82, CFI = 0.88 and RMSEA = 0.06). The internal consistency and test-retest reliability were at an acceptable range for the two samples. The Chinese version of OBQ-44 is a valid and reliable instrument for assessing dysfunctional beliefs related to the etiology and maintenance of obsessions and compulsions.

Randomization in cancer clinical trials: permutation test and development of a computer program.

PubMed Central

Ohashi, Y

1990-01-01

When analyzing cancer clinical trial data where the treatment allocation is done using dynamic balancing methods such as the minimization method for balancing the distribution of important prognostic factors in each arm, conservativeness occurs if such a randomization scheme is ignored and a simple unstratified analysis is carried out. In this paper, the above conservativeness is demonstrated by computer simulation, and the development of a computer program that carries out permutation tests of the log-rank statistics for clinical trial data where the allocation is done by the minimization method or a stratified permuted block design is introduced. We are planning to use this program in practice to supplement a usual stratified analysis and model-based methods such as the Cox regression. The most serious problem in cancer clinical trials in Japan is how to carry out the quality control or data management in trials that are initiated and conducted by researchers without support from pharmaceutical companies. In the final section of this paper, one international collaborative work for developing international guidelines on data management in clinical trials of bladder cancer is briefly introduced, and the differences between the system adopted in US/European statistical centers and the Japanese system is described. PMID:2269216

Evaluation of the three-dimensional accuracy of implant impression techniques in two simulated clinical conditions by optical scanning.

PubMed

Sabouhi, Mahmoud; Bajoghli, Farshad; Abolhasani, Majid

2015-01-01

The success of an implant-supported prosthesis is dependent on the passive fit of its framework fabricated on a precise cast. The aim of this in vitro study was to digitally compare the three-dimensional accuracy of implant impression techniques in partially and completely edentulous conditions. The master model simulated two clinical conditions. The first condition was a partially edentulous mandibular arch with an anterior edentulous space (D condition). Two implant analogs were inserted in bilateral canine sites. After elimination of the teeth, the model was converted to a completely edentulous condition (E condition). Three different impression techniques were performed (open splinted [OS], open unsplinted [OU], closed [C]) for each condition. Six groups of casts (DOS, DOU, DC, EOS, EOU, EC) (n = 8), totaling 48 casts, were made. Two scan bodies were secured onto the master edentulous model and onto each test cast and digitized by an optical scanning system. The related scans were superimposed, and the mean discrepancy for each cast was determined. The statistical analysis showed no significant difference in the accuracy of casts as a function of model status (P = .78, analysis of variance [ANOVA] test), impression technique (P = .57, ANOVA test), or as the combination of both (P = .29, ANOVA test). The distribution of data was normal (Kolmogorov-Smirnov test). Model status (dentate or edentulous) and impression technique did not influence the precision of the casts. There is no difference among any of the impression techniques in either simulated clinical condition.

A novel hypothesis on the sensitivity of the fecal occult blood test: Results of a joint analysis of 3 randomized controlled trials.

PubMed

Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Boer, Rob; Zauber, Ann; Habbema, J Dik F

2009-06-01

Estimates of the fecal occult blood test (FOBT) (Hemoccult II) sensitivity differed widely between screening trials and led to divergent conclusions on the effects of FOBT screening. We used microsimulation modeling to estimate a preclinical colorectal cancer (CRC) duration and sensitivity for unrehydrated FOBT from the data of 3 randomized controlled trials of Minnesota, Nottingham, and Funen. In addition to 2 usual hypotheses on the sensitivity of FOBT, we tested a novel hypothesis where sensitivity is linked to the stage of clinical diagnosis in the situation without screening. We used the MISCAN-Colon microsimulation model to estimate sensitivity and duration, accounting for differences between the trials in demography, background incidence, and trial design. We tested 3 hypotheses for FOBT sensitivity: sensitivity is the same for all preclinical CRC stages, sensitivity increases with each stage, and sensitivity is higher for the stage in which the cancer would have been diagnosed in the absence of screening than for earlier stages. Goodness-of-fit was evaluated by comparing expected and observed rates of screen-detected and interval CRC. The hypothesis with a higher sensitivity in the stage of clinical diagnosis gave the best fit. Under this hypothesis, sensitivity of FOBT was 51% in the stage of clinical diagnosis and 19% in earlier stages. The average duration of preclinical CRC was estimated at 6.7 years. Our analysis corroborated a long duration of preclinical CRC, with FOBT most sensitive in the stage of clinical diagnosis. (c) 2009 American Cancer Society.

Content Analysis of Informed Consent for Whole Genome Sequencing Offered by Direct-to-Consumer Genetic Testing Companies.

PubMed

Niemiec, Emilia; Borry, Pascal; Pinxten, Wim; Howard, Heidi Carmen

2016-12-01

Whole exome sequencing (WES) and whole genome sequencing (WGS) have become increasingly available in the research and clinical settings and are now also being offered by direct-to-consumer (DTC) genetic testing (GT) companies. This offer can be perceived as amplifying the already identified concerns regarding adequacy of informed consent (IC) for both WES/WGS and the DTC GT context. We performed a qualitative content analysis of Websites of four companies offering WES/WGS DTC regarding the following elements of IC: pre-test counseling, benefits and risks, and incidental findings (IFs). The analysis revealed concerns, including the potential lack of pre-test counseling in three of the companies studied, missing relevant information in the risks and benefits sections, and potentially misleading information for consumers. Regarding IFs, only one company, which provides opportunistic screening, provides basic information about their management. In conclusion, some of the information (and related practices) present on the companies' Web pages salient to the consent process are not adequate in reference to recommendations for IC for WGS or WES in the clinical context. Requisite resources should be allocated to ensure that commercial companies are offering high-throughput sequencing under responsible conditions, including an adequate consent process. © 2016 WILEY PERIODICALS, INC.

Shoe contact dermatitis from dimethyl fumarate: clinical manifestations, patch test results, chemical analysis, and source of exposure.

PubMed

Giménez-Arnau, Ana; Silvestre, Juan Francisco; Mercader, Pedro; De la Cuadra, Jesus; Ballester, Isabel; Gallardo, Fernando; Pujol, Ramón M; Zimerson, Erik; Bruze, Magnus

2009-11-01

The methyl ester form of fumaric acid named dimethyl fumarate (DMF) is an effective mould-growth inhibitor. Its irritating and sensitizing properties were demonstrated in animal models. Recently, DMF has been identified as responsible for furniture contact dermatitis in Europe. To describe the clinical manifestations, patch test results, shoe chemical analysis, and source of exposure to DMF-induced shoe contact dermatitis. Patients with suspected shoe contact dermatitis were studied in compliance with the Declaration of Helsinki. Patch test results obtained with their own shoe and the European baseline series, acrylates and fumaric acid esters (FAE), were recorded according to international guidelines. The content of DMF in shoes was analysed with gas chromatography and mass spectrometry. Acute, immediate irritant contact dermatitis and non-immunological contact urticaria were observed in eight adults and two children, respectively. All the adult patients studied developed a delayed sensitization demonstrated by a positive patch testing to DMF < or = 0.1% in pet. Cross-reactivity with other FAEs and acrylates was observed. At least 12 different shoe brands were investigated. The chemical analysis from the available shoes showed the presence of DMF. DMF in shoes was responsible for severe contact dermatitis. Global preventive measures for avoiding contact with DMF are necessary.

Systems consultation: protocol for a novel implementation strategy designed to promote evidence-based practice in primary care.

PubMed

Quanbeck, Andrew; Brown, Randall T; E Zgierska, Aleksandra; A Johnson, Roberta; Robinson, James M; Jacobson, Nora

2016-01-27

Adoption of evidence-based practices takes place at a glacial place in healthcare. This research will pilot test an innovative implementation strategy - systems consultation -intended to speed the adoption of evidence-based practice in primary care. The strategy is based on tenets of systems engineering and has been extensively tested in addiction treatment. Three innovations have been included in the strategy - translation of a clinical practice guideline into a checklist-based implementation guide, the use of physician peer coaches ('systems consultants') to help clinics implement the guide, and a focus on reducing variation in practices across prescribers and clinics. The implementation strategy will be applied to improving opioid prescribing practices in primary care, which may help ultimately mitigate the increasing prevalence of opioid abuse and addiction. The pilot test will compare four intervention clinics to four control clinics in a matched-pairs design. A leading clinical guideline for opioid prescribing has been translated into a checklist-based implementation guide in a systematic process that involved experts who wrote the guideline in consultation with implementation experts and primary care physicians. Two physicians with expertise in family and addiction medicine are serving as the systems consultants. Each systems consultant will guide two intervention clinics, using two site visits and follow-up communication by phone and email, to implement the translated guideline. Mixed methods will be used to test the feasibility, acceptability, and preliminary effectiveness of the implementation strategy in an evaluation that meets standards for 'fully developed use' of the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance). The clinic will be the primary unit of analysis. The systems consultation implementation strategy is intended to generalize to the adoption of other clinical guidelines. This pilot test is intended to prepare for a large randomized clinical trial that will test the strategy against other implementation strategies, such as audit/feedback and academic detailing, used to close the gap between knowledge and practice. The systems consultation approach has the potential to shorten the famously long time it takes to implement evidence-based practices and clinical guidelines in healthcare.

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

PubMed

Zenner, Dominik; Nacul, Luis

2012-03-12

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

Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.

PubMed

Martino, David; Dang, Thanh; Sexton-Oates, Alexandra; Prescott, Susan; Tang, Mimi L K; Dharmage, Shyamali; Gurrin, Lyle; Koplin, Jennifer; Ponsonby, Anne-Louise; Allen, Katrina J; Saffery, Richard

2015-05-01

The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital.

PubMed

Yao, H; Jiang, F; Hu, H; Gao, Y; Zhu, Z; Zhang, H; Wang, Y; Guo, Y; Liu, L; Yuan, Y; Zhou, L; Wang, J; Du, B; Qu, N; Zhang, R; Dong, Y; Xu, H; Chen, F; Jiang, H; Liu, Y; Zhang, L; Tian, Z; Liu, Q; Zhang, C; Pan, X; Yang, S; Zhao, L; Wang, W; Liang, Z

2014-07-01

To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients. This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options. Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases. Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

[The clinicopathological analysis of 88 patients with abnormal liver function test of unknown etiology].

PubMed

Pang, Shu-zhen; Ou, Xiao-juan; Shi, Xiao-yan; Wang, Tai-ling; Duan, Wei-jia; Jia, Ji-dong

2011-01-01

To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis. Patients with abnormal liver function test hospitalized and had liver biopsies during 2008 - 2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis, space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M(2) positive of primary biliary cirrhosis (PBC), the clinical and histological characteristics were evaluated. Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with drug-induced liver injury (DILI) [34.09% (30/88)], autoimmune liver diseases [22.73% (20/88)], and nonalcoholic fatty liver disease (NAFLD) [12.50% (11/88)] being the most common causes, following by genetic and other rare diseases. DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metabolic liver disease also represent a considerable proportion in patients with abnormal liver function test.

Learning the facts in medical school is not enough: which factors predict successful application of procedural knowledge in a laboratory setting?

PubMed Central

2013-01-01

Background Medical knowledge encompasses both conceptual (facts or “what” information) and procedural knowledge (“how” and “why” information). Conceptual knowledge is known to be an essential prerequisite for clinical problem solving. Primarily, medical students learn from textbooks and often struggle with the process of applying their conceptual knowledge to clinical problems. Recent studies address the question of how to foster the acquisition of procedural knowledge and its application in medical education. However, little is known about the factors which predict performance in procedural knowledge tasks. Which additional factors of the learner predict performance in procedural knowledge? Methods Domain specific conceptual knowledge (facts) in clinical nephrology was provided to 80 medical students (3rd to 5th year) using electronic flashcards in a laboratory setting. Learner characteristics were obtained by questionnaires. Procedural knowledge in clinical nephrology was assessed by key feature problems (KFP) and problem solving tasks (PST) reflecting strategic and conditional knowledge, respectively. Results Results in procedural knowledge tests (KFP and PST) correlated significantly with each other. In univariate analysis, performance in procedural knowledge (sum of KFP+PST) was significantly correlated with the results in (1) the conceptual knowledge test (CKT), (2) the intended future career as hospital based doctor, (3) the duration of clinical clerkships, and (4) the results in the written German National Medical Examination Part I on preclinical subjects (NME-I). After multiple regression analysis only clinical clerkship experience and NME-I performance remained independent influencing factors. Conclusions Performance in procedural knowledge tests seems independent from the degree of domain specific conceptual knowledge above a certain level. Procedural knowledge may be fostered by clinical experience. More attention should be paid to the interplay of individual clinical clerkship experiences and structured teaching of procedural knowledge and its assessment in medical education curricula. PMID:23433202

An inexpensive modification of the laboratory computer display changes emergency physicians' work habits and perceptions.

PubMed

Marinakis, Harry A; Zwemer, Frank L

2003-02-01

Little is known about how the availability of laboratory data affects emergency physicians' practice habits and satisfaction. We modified our clinical information system to display laboratory test status with continuous updates, similar to an airport arrival display. The objective of this study was to determine whether the laboratory test status display altered emergency physicians' work habits and increased satisfaction compared with the time period before implementation of laboratory test status. A retrospective analysis was performed of emergency physicians' actual use of the clinical information system before and after implementation of the laboratory test status display. Emergency physicians were retrospectively surveyed regarding the effect of laboratory test status display on their practice habits and clinical information system use. Survey responses were matched with actual use of the clinical information system. Data were analyzed by using dependent t tests and Pearson correlation coefficients. The study was conducted at a university hospital. Clinical information system use by 46 emergency physicians was analyzed. Twenty-five surveys were returned (71.4% of available emergency physicians). All emergency physicians perceived fewer clinical information system log ons per day after laboratory test status display. The actual average decrease was 19%. Emergency physicians who reported the greatest decrease in log ons per day tended to have the greatest actual decrease (r =-0.36). There was no significant correlation between actual and perceived total time logged on (r =0.08). In regard to effect on emergency physicians' practice habits, 95% reported increased efficiency, 80% reported improved satisfaction with data access, and 65% reported improved communication with patients. An inexpensive computer modification, laboratory test status display, significantly increased subjective efficiency, changed work habits, and improved satisfaction regarding data access and patient communication among emergency physicians. Knowledge of the test queue changed emergency physician behavior and improved satisfaction.

Testing homogeneity of proportion ratios for stratified correlated bilateral data in two-arm randomized clinical trials.

PubMed

Pei, Yanbo; Tian, Guo-Liang; Tang, Man-Lai

2014-11-10

Stratified data analysis is an important research topic in many biomedical studies and clinical trials. In this article, we develop five test statistics for testing the homogeneity of proportion ratios for stratified correlated bilateral binary data based on an equal correlation model assumption. Bootstrap procedures based on these test statistics are also considered. To evaluate the performance of these statistics and procedures, we conduct Monte Carlo simulations to study their empirical sizes and powers under various scenarios. Our results suggest that the procedure based on score statistic performs well generally and is highly recommended. When the sample size is large, procedures based on the commonly used weighted least square estimate and logarithmic transformation with Mantel-Haenszel estimate are recommended as they do not involve any computation of maximum likelihood estimates requiring iterative algorithms. We also derive approximate sample size formulas based on the recommended test procedures. Finally, we apply the proposed methods to analyze a multi-center randomized clinical trial for scleroderma patients. Copyright © 2014 John Wiley & Sons, Ltd.

Real-Time PCR in Clinical Microbiology: Applications for Routine Laboratory Testing

PubMed Central

Espy, M. J.; Uhl, J. R.; Sloan, L. M.; Buckwalter, S. P.; Jones, M. F.; Vetter, E. A.; Yao, J. D. C.; Wengenack, N. L.; Rosenblatt, J. E.; Cockerill, F. R.; Smith, T. F.

2006-01-01

Real-time PCR has revolutionized the way clinical microbiology laboratories diagnose many human microbial infections. This testing method combines PCR chemistry with fluorescent probe detection of amplified product in the same reaction vessel. In general, both PCR and amplified product detection are completed in an hour or less, which is considerably faster than conventional PCR detection methods. Real-time PCR assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible. The combination of excellent sensitivity and specificity, low contamination risk, and speed has made real-time PCR technology an appealing alternative to culture- or immunoassay-based testing methods for diagnosing many infectious diseases. This review focuses on the application of real-time PCR in the clinical microbiology laboratory. PMID:16418529

The impact of an online learning platform about nursing education on enrolled nurse preceptor teaching capabilities: a pre-post-test evaluation.

PubMed

Ryan, Colleen; Young, Louise; McAllister, Margaret

2017-06-01

Enrolled nurses (ENs) across Australia precept nursing students in the clinical field. Yet learning about the preceptoring role is not widely available to ENs. Educational innovation: EN's in this study participated in a professional development project that utilised the material of an online learning resource, originally designed to inspire clinical registered nurses (RNs), and RN teachers, to develop teaching innovations in their role. The aim of this paper is to report the results of a pre-post-test questionnaire designed to evaluate the impact of the professional development intervention. The analysis showed high scoring means with many items in the questionnaire statistically significant (p < .05, CI 95%). Results indicated positive differences in a number of teaching capabilities between pre- and post-test scores. This suggests ENs appreciate education that extends beyond clinical skills and that professional development should include the nursing education role.

C-reactive protein as a predictor of chorioamnionitis.

PubMed

Smith, Erik J; Muller, Corinna L; Sartorius, Jennifer A; White, David R; Maslow, Arthur S

2012-10-01

Chorioamnionitis (CAM) affects many pregnancies complicated by preterm premature rupture of membranes (PPROM). Finding a serum factor that could accurately predict the presence of CAM could potentially lead to more efficient management of PPROM and improved neonatal outcomes. To determine if C-reactive protein (CRP) is an effective early marker of CAM in patients with PPROM. A retrospective evaluation of pregnant women with PPROM at Geisinger Medical Center in Danville, Pennsylvania, between January 2005 and January 2009. Nonparametric statistical tests (ie, Wilcoxon rank sum and Spearman rank correlation) were used to compare distributions that were skewed. Characteristics of the study population were compared using 2-sample t tests for continuous variables and Fisher exact tests for discrete variables. Logistic regression analysis was used to generate receiver operating characteristic curves and obtain area under the curve estimates in stepwise fashion for predicting histologic CAM. A secondary analysis compared the characteristics among patients with clinical CAM, histologic CAM, or non-CAM. The total population of 73 women was subdivided into patients with histologic CAM (n=26) and patients without histologic CAM (ie, no evidence of CAM on placental pathology; n=47). There was no difference between groups in CRP levels, days of pregnancy latency, white blood cell count, smoking status, antibiotic administration, or steroid benefit. The group with histologic CAM delivered at earlier gestational ages: mean (standard deviation) age was 29.5 (4.4) weeks vs 31.9 (3.5) weeks (P=.02). For our primary analysis, we found no difference in CRP levels (P=.32). Receiver operating characteristic curve plots of CRP levels, temperature at delivery, and white blood cell count resulted in an area under the curve estimate of 0.696, which was 70% predictive of histologic CAM. In the secondary analysis, after adjusting for gestational age, the estimated hazard ratio for CRP change was 1.05 (95% confidence interval, 1.02-1.08; P=.001). Therefore, increasing CRP levels from PPROM was statistically significant in predicting clinical CAM development over time. C-reactive protein levels were not effective independent predictors of clinical or histologic CAM, nor was sequential CRP testing statistically significant for the identification of clinical or histologic CAM in patients with PPROM.

Determination of moxifloxacin anaerobic susceptibility breakpoints according to the Clinical and Laboratory Standards Institute guidelines.

PubMed

Ambler, Jane; Rennie, Robert; Poupard, James; Koeth, Laura; Stass, Heino; Endermann, Rainer; Choudhri, Shurjeel

2008-05-01

A summary of the key data presented to Clinical and Laboratory Standards Institute (CLSI, formerly National Committee for Clinical and Laboratory Standards) in determination of moxifloxacin anaerobic breakpoints is presented. The breakpoint analysis required review of a variety of data, including bacteriologic and clinical outcomes by MIC of anaerobic isolates from prospective clinical trials in patients with complicated intra-abdominal infections, human and animal pharmacokinetic/pharmacodynamic (PK/PD) information and in vitro models, MIC distributions of indicated organisms, and animal model efficacy data for strains with MIC values around prospective breakpoints. The compilation of the various components of this breakpoint analysis supports the US Food and Drug Administration (FDA) and CLSI moxifloxacin anaerobic breakpoints of < or =2 mg/L (susceptible), 4 mg/L (intermediate), and > or =8 mg/L (resistant), and provides information to European investigators for interpretation of MICs prior to establishment of the European Committee on Antimicrobial Susceptibility Testing breakpoints.

Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X.

2015-12-01

Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia.

PubMed

Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X

2015-12-01

Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

Anterior cruciate ligament reconstruction with 4-strand hamstring autograft and accelerated rehabilitation: a 10-year prospective study on clinical results, knee osteoarthritis and its predictors.

PubMed

Janssen, Rob P A; du Mée, Arthur W F; van Valkenburg, Juliette; Sala, Harm A G M; Tseng, Carroll M

2013-09-01

Analysis of long-term clinical and radiological outcomes after anterior cruciate ligament (ACL) reconstruction with special attention to knee osteoarthritis and its predictors. A prospective, consecutive case series of 100 patients. Arthroscopic transtibial ACL reconstruction was performed using 4-strand hamstring tendon autografts with a standardized accelerated rehabilitation protocol. Analysis was performed preoperatively and 10 years postoperatively. Clinical examination included Lysholm and Tegner scores, IKDC, KT-1000 testing (MEDmetric Co., San Diego, CA, USA) and leg circumference measurements. Radiological evaluation included AP weight bearing, lateral knee, Rosenberg and sky view X-rays. Radiological classifications were according to Ahlbäck and Kellgren & Lawrence. Statistical analysis included univariate and multivariate logistic regressions. RESULTS CLINICAL OUTCOME: A significant improvement (p < 0.001) between preoperative and postoperative measurements could be demonstrated for the Lysholm and Tegner scores, IKDC patient subjective assessment, KT-1000 measurements, pivot shift test, IKDC score and one-leg hop test. A pivot shift phenomenon (glide) was still present in 43 (50%) patients and correlated with lower levels of activity (p < 0.022). Radiological outcome: At follow-up, 46 (53.5%) patients had signs of osteoarthritis (OA). In this group, 33 patients (72%) had chondral lesions (≥grade 2) at the time of ACL reconstruction. A history of medial meniscectomy before or at the time of ACL reconstruction increased the risk of knee OA 4 times (95% CI 1.41-11.5). An ICRS grade 3 at the time of ACL reconstruction increased the risk of knee OA by 5.2 times (95% CI 1.09-24.8). There was no correlation between OA and activity level (Tegner score ≥6) nor between OA and a positive pivot shift test. Transtibial ACL reconstruction with 4-strand hamstring autograft and accelerated rehabilitation restored anteroposterior knee stability. Clinical parameters and patient satisfaction improved significantly. At 10-year follow-up, radiological signs of OA were present in 53.5 % of the subjects. Risk factors for OA were meniscectomy prior to or at the time of ACL reconstruction and chondral lesions at the time of ACL reconstruction. II.

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service

PubMed Central

Kaur, Kulvinder; Camps, Carme; Kaisaki, Pamela; Gupta, Avinash; Talbot, Denis; Middleton, Mark; Henderson, Shirley; Cutts, Anthony; Vavoulis, Dimitrios V.; Housby, Nick; Taylor, Jenny C.; Schuh, Anna

2017-01-01

Background Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing. Methods and findings We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of “real world” data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds. Conclusions This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers. PMID:28196074

Clinical and Molecular Consequences of NF1 Microdeletion

DTIC Science & Technology

2006-05-01

service based on meta -PCR/sequencing, dosage analysis , and loss of heterozygosity analysis . Genet Test 2004;8(4):368-80. 51. Kluwe L, Mautner VF. Mosaicism...neurofibromin in normal centrosome function and in maintaining genome stability. Our detailed analysis of human and chimpanzee genome sequences were...chromosomes and DNA fibers (1). Tandem duplication of the region would have significant impact on many aspects of NF1 research, e.g., mutational analysis

Analysis and visualization of intracardiac electrograms in diagnosis and research: Concept and application of KaPAVIE.

PubMed

Oesterlein, Tobias Georg; Schmid, Jochen; Bauer, Silvio; Jadidi, Amir; Schmitt, Claus; Dössel, Olaf; Luik, Armin

2016-04-01

Progress in biomedical engineering has improved the hardware available for diagnosis and treatment of cardiac arrhythmias. But although huge amounts of intracardiac electrograms (EGMs) can be acquired during electrophysiological examinations, there is still a lack of software aiding diagnosis. The development of novel algorithms for the automated analysis of EGMs has proven difficult, due to the highly interdisciplinary nature of this task and hampered data access in clinical systems. Thus we developed a software platform, which allows rapid implementation of new algorithms, verification of their functionality and suitable visualization for discussion in the clinical environment. A software for visualization was developed in Qt5 and C++ utilizing the class library of VTK. The algorithms for signal analysis were implemented in MATLAB. Clinical data for analysis was exported from electroanatomical mapping systems. The visualization software KaPAVIE (Karlsruhe Platform for Analysis and Visualization of Intracardiac Electrograms) was implemented and tested on several clinical datasets. Both common and novel algorithms were implemented which address important clinical questions in diagnosis of different arrhythmias. It proved useful in discussions with clinicians due to its interactive and user-friendly design. Time after export from the clinical mapping system to visualization is below 5min. KaPAVIE(2) is a powerful platform for the development of novel algorithms in the clinical environment. Simultaneous and interactive visualization of measured EGM data and the results of analysis will aid diagnosis and help understanding the underlying mechanisms of complex arrhythmias like atrial fibrillation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genetic mouse embryo assay: improving performance and quality testing for assisted reproductive technology (ART) with a functional bioassay.

PubMed

Gilbert, Rebecca S; Nunez, Brandy; Sakurai, Kumi; Fielder, Thomas; Ni, Hsiao-Tzu

2016-03-24

Growing concerns about safety of ART on human gametes, embryos, clinical outcomes and long-term health of offspring require improved methods of risk assessment to provide functionally relevant assays for quality control testing and pre-clinical studies prior to clinical implementation. The one-cell mouse embryo assay (MEA) is the most widely used for development and quality testing of human ART products; however, concerns exist due to the insensitivity/variability of this bioassay which lacks standardization and involves subjective analysis by morphology alone rather than functional analysis of the developing embryos. We hypothesized that improvements to MEA by the use of functional molecular biomarkers could enhance sensitivity and improve detection of suboptimal materials/conditions. Fresh one-cell transgenic mouse embryos with green fluorescent protein (GFP) expression driven by Pou6f1 or Cdx2 control elements were harvested and cultured to blastocysts in varied test and control conditions to compare assessment by standard morphology alone versus the added dynamic expression of GFP for screening and selection of critical raw materials and detection of suboptimal culture conditions. Transgenic mouse embryos expressing functionally relevant biomarkers of normal early embryo development can be used to monitor the developmental impact of culture conditions. This novel approach provides a superior MEA that is more meaningful and sensitive for detection of embryotoxicity than morphological assessment alone.

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

PubMed

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

2017-08-01

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

Two simple clinical tests for predicting onset of medial tibial stress syndrome: shin palpation test and shin oedema test.

PubMed

Newman, Phil; Adams, Roger; Waddington, Gordon

2012-09-01

To examine the relationship between two clinical test results and future diagnosis of (Medial Tibial Stress Syndrome) MTSS in personnel at a military trainee establishment. Data from a preparticipation musculoskeletal screening test performed on 384 Australian Defence Force Academy Officer Cadets were compared against 693 injuries reported by 326 of the Officer Cadets in the following 16 months. Data were held in an Injury Surveillance database and analysed using χ² and Fisher's Exact tests, and Receiver Operating Characteristic Curve analysis. Diagnosis of MTSS, confirmed by an independent blinded health practitioner. Both the palpation and oedema clinical tests were each found to be significant predictors for later onset of MTSS. Specifically: Shin palpation test OR 4.63, 95% CI 2.5 to 8.5, Positive Likelihood Ratio 3.38, Negative Likelihood Ratio 0.732, Pearson χ² p<0.001; Shin oedema test OR 76.1 95% CI 9.6 to 602.7, Positive Likelihood Ratio 7.26, Negative Likelihood Ratio 0.095, Fisher's Exact p<0.001; Combined Shin Palpation Test and Shin Oedema Test Positive Likelihood Ratio 7.94, Negative Likelihood Ratio <0.001, Fisher's Exact p<0.001. Female gender was found to be an independent risk factor (OR 2.97, 95% CI 1.66 to 5.31, Positive Likelihood Ratio 2.09, Negative Likelihood Ratio 0.703, Pearson χ² p<0.001) for developing MTSS. The tests for MTSS employed here are components of a normal clinical examination used to diagnose MTSS. This paper confirms that these tests and female gender can also be confidently applied in predicting those in an asymptomatic population who are at greater risk of developing MTSS symptoms with activity at some point in the future.

CallWall: tracking resident calls to improve clinical utilization of pathology laboratories.

PubMed

Buck, Thomas P; Connor, Ian M; Horowitz, Gary L; Arnaout, Ramy A

2011-07-01

Clinical pathology (CP) laboratories are used for millions of tests each year. These lead to thousands of calls to CP residents. However, although laboratory utilization is a frequent topic of study, clinical utilization--the content of the interactions between clinicians and CP residents--is not. Because it reflects questions about laboratory utilization, clinical utilization could suggest ways to improve both training and care by reducing diagnostic error. To build and implement a secure, scalable Web-based system to allow CP residents at any hospital to track the calls they receive, the interaction's context, and the action taken as a result, with evidence where applicable, and to use this system to report on clinical utilization at a major academic hospital. Entries were analyzed from a nearly year-long period to describe the clinical utilization of CP at a large academic teaching hospital. Sixteen residents logged 847 calls during 10 months, roughly evenly distributed among transfusion medicine, chemistry, microbiology, and hematopathology. Calls covered 94 different analytes in chemistry and 71 different organisms or tests in microbiology. Analysis revealed areas where CP can improve clinical care through educating the clinical services, for example, about ordering Rh immune globulin, testosterone testing, and diagnosis of tick-borne diseases. Documenting calls also highlighted patterns among residents. Clinical utilization is a potentially rich knowledge base for improving patient care and resident training. Our resident call-tracking system is a useful way for measuring clinical utilization and mining it for actionable information.

Assessment of the influence of test characteristics on the clinical and cost impacts of methicillin-resistant Staphylococcus aureus screening programs in US hospitals.

PubMed

Olchanski, Natalia; Mathews, Charles; Fusfeld, Lauren; Jarvis, William

2011-03-01

To compare the impacts of different methicillin-resistant Staphylococcus aureus (MRSA) screening test options (eg, polymerase chain reaction [PCR], rapid culture) and program characteristics on the clinical outcomes and budget of a typical US hospital. We developed an Excel-based decision-analytic model, using published literature to calculate and compare hospital costs and MRSA infection rates for PCR- or culture-based MRSA screening and then used multivariate sensitivity analysis to evaluate key variables. Same-day PCR testing for a representative 370-bed teaching hospital in the United States was assessed in different populations (high-risk patients, intensive care unit [ICU] patients, or all patients) and compared with other test options. Different screening program populations (all patients, high-risk patients, ICU patients, or patients with previous MRSA colonization or infection only) represented a potential savings of $12,158-$76,624 per month over no program ($188,618). Analysis of multiple test options in high-risk population screening indicated that same-day PCR testing of high-risk patients resulted in fewer infections over 1,720 patient-days (2.9, compared with 3.5 for culture on selective media and 3.8 for culture on nonselective media) and the lowest total cost ($112,012). The costs of other testing approaches ranged from $113,742 to $123,065. Sensitivity analysis revealed that variations in transmission rate, conversion to infection, prevalence increases, and hospital size are important to determine program impact. Among test characteristics, turnaround time is highly influential. All screening options showed reductions in infection rates and cost impact improvement over no screening program. Among the options, same-day PCR testing for high-risk patients slightly edges out the others in terms of fewest infections and greatest potential cost savings.

A Streamlined Protocol for Molecular Testing of the DMD Gene within a Diagnostic Laboratory: A Combination of Array Comparative Genomic Hybridization and Bidirectional Sequence Analysis

PubMed Central

Marquis-Nicholson, Renate; Lai, Daniel; Love, Jennifer M.; Love, Donald R.

2013-01-01

Purpose. The aim of this study was to develop a streamlined mutation screening protocol for the DMD gene in order to confirm a clinical diagnosis of Duchenne or Becker muscular dystrophy in affected males and to clarify the carrier status of female family members. Methods. Sequence analysis and array comparative genomic hybridization (aCGH) were used to identify mutations in the dystrophin DMD gene. We analysed genomic DNA from six individuals with a range of previously characterised mutations and from eight individuals who had not previously undergone any form of molecular analysis. Results. We successfully identified the known mutations in all six patients. A molecular diagnosis was also made in three of the four patients with a clinical diagnosis who had not undergone prior genetic screening, and testing for familial mutations was successfully completed for the remaining four patients. Conclusion. The mutation screening protocol described here meets best practice guidelines for molecular testing of the DMD gene in a diagnostic laboratory. The aCGH method is a superior alternative to more conventional assays such as multiplex ligation-dependent probe amplification (MLPA). The combination of aCGH and sequence analysis will detect mutations in 98% of patients with the Duchenne or Becker muscular dystrophy. PMID:23476807

The clinical learning environment and supervision by staff nurses: developing the instrument.

PubMed

Saarikoski, Mikko; Leino-Kilpi, Helena

2002-03-01

The aims of this study were (1) to describe students' perceptions of the clinical learning environment and clinical supervision and (2) to develop an evaluation scale by using the empirical results of this study. The data were collected using the Clinical Learning Environment and Supervision instrument (CLES). The instrument was based on the literature review of earlier studies. The derived instrument was tested empirically in a study involving nurse students (N=416) from four nursing colleges in Finland. The results demonstrated that the method of supervision, the number of separate supervision sessions and the psychological content of supervisory contact within a positive ward atmosphere are the most important variables in the students' clinical learning. The results also suggest that ward managers can create the conditions of a positive ward culture and a positive attitude towards students and their learning needs. The construct validity of the instrument was analysed by using exploratory factor analysis. The analysis indicated that the most important factor in the students' clinical learning is the supervisory relationship. The two most important factors constituting a 'good' clinical learning environment are the management style of the ward manager and the premises of nursing on the ward. The results of the factor analysis support the theoretical construction of the clinical learning environment modelled by earlier empirical studies.

RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy

PubMed Central

Lo, Kitty K.; Boustred, Christopher; Chitty, Lyn S.; Plagnol, Vincent

2014-01-01

Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex. RAPIDR has been extensively tested with a large sample set as part of the RAPID project in the UK. The package contains quality control steps to make it robust for use in the clinical setting. Availability and implementation: RAPIDR is implemented in R and can be freely downloaded via CRAN from here: http://cran.r-project.org/web/packages/RAPIDR/index.html. Contact: kitty.lo@ucl.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24990604

The Yale-Brown Obsessive Compulsive Scale: A Reliability Generalization Meta-Analysis.

PubMed

López-Pina, José Antonio; Sánchez-Meca, Julio; López-López, José Antonio; Marín-Martínez, Fulgencio; Núñez-Núñez, Rosa Maria; Rosa-Alcázar, Ana I; Gómez-Conesa, Antonia; Ferrer-Requena, Josefa

2015-10-01

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the most frequently applied test to assess obsessive compulsive symptoms. We conducted a reliability generalization meta-analysis on the Y-BOCS to estimate the average reliability, examine the variability among the reliability estimates, search for moderators, and propose a predictive model that researchers and clinicians can use to estimate the expected reliability of the Y-BOCS. We included studies where the Y-BOCS was applied to a sample of adults and reliability estimate was reported. Out of the 11,490 references located, 144 studies met the selection criteria. For the total scale, the mean reliability was 0.866 for coefficients alpha, 0.848 for test-retest correlations, and 0.922 for intraclass correlations. The moderator analyses led to a predictive model where the standard deviation of the total test and the target population (clinical vs. nonclinical) explained 38.6% of the total variability among coefficients alpha. Finally, clinical implications of the results are discussed. © The Author(s) 2014.

[The clinical economic analysis of the methods of ischemic heart disease diagnostics].

PubMed

Kalashnikov, V Iu; Mitriagina, S N; Syrkin, A L; Poltavskaia, M G; Sorokina, E G

2007-01-01

The clinical economical analysis was applied to assess the application of different techniques of ischemic heart disease diagnostics - the electro-cardiographic monitoring, the treadmill-testing, the stress-echo cardiographic with dobutamine, the single-photon computerized axial tomography with load, the multi-spiral computerized axial tomography with coronary arteries staining in patients with different initial probability of disease occurrence. In all groups, the best value of "cost-effectiveness" had the treadmill-test. The patients with low risk needed 17.4 rubles to precise the probability of ischemic heart disease occurrence at 1%. In the group with medium and high risk this indicator was 9.4 and 24.7 rubles correspondingly. It is concluded that to precise the probability of ischemic heart disease occurrence after tredmil-test in the patients with high probability it is appropriate to use the single-photon computerized axial tomography with load and in the case of patients with low probability the multi-spiral computerized axial tomography with coronary arteries staining.

Unified Approach to the Biomechanics of Dental Implantology

NASA Technical Reports Server (NTRS)

Grenoble, D. E.; Knoell, A. C.

1973-01-01

The human need for safe and effective dental implants is well-recognized. Although many implant designs have been tested and are in use today, a large number have resulted in clinical failure. These failures appear to be due to biomechanical effects, as well as biocompatibility and surgical factors. A unified approach is proposed using multidisciplinary systems technology, for the study of the biomechanical interactions between dental implants and host tissues. The approach progresses from biomechanical modeling and analysis, supported by experimental investigations, through implant design development, clinical verification, and education of the dental practitioner. The result of the biomechanical modeling, analysis, and experimental phases would be the development of scientific design criteria for implants. Implant designs meeting these criteria would be generated, fabricated, and tested in animals. After design acceptance, these implants would be tested in humans, using efficient and safe surgical and restorative procedures. Finally, educational media and instructional courses would be developed for training dental practitioners in the use of the resulting implants.

Social Problem Solving and Depressive Symptoms over Time: A Randomized Clinical Trial of Cognitive-Behavioral Analysis System of Psychotherapy, Brief Supportive Psychotherapy, and Pharmacotherapy

ERIC Educational Resources Information Center

Klein, Daniel N.; Leon, Andrew C.; Li, Chunshan; D'Zurilla, Thomas J.; Black, Sarah R.; Vivian, Dina; Dowling, Frank; Arnow, Bruce A.; Manber, Rachel; Markowitz, John C.; Kocsis, James H.

2011-01-01

Objective: Depression is associated with poor social problem solving, and psychotherapies that focus on problem-solving skills are efficacious in treating depression. We examined the associations between treatment, social problem solving, and depression in a randomized clinical trial testing the efficacy of psychotherapy augmentation for…

Development and psychometric evaluation of the nursing instructors' clinical teaching performance inventory.

PubMed

A Farahani, Mansoureh; Emamzadeh Ghasemi, Hormat Sadat; Nikpaima, Nasrin; Fereidooni, Zhila; Rasoli, Maryam

2014-10-29

Evaluation of nursing instructors' clinical teaching performance is a prerequisite to the quality assurance of nursing education. One of the most common procedures for this purpose is using student evaluations. This study was to develop and evaluate the psychometric properties of Nursing Instructors' Clinical Teaching Performance Inventory (NICTPI). The primary items of the inventory were generated by reviewing the published literature and the existing questionnaires as well as consulting with the members of the Faculties Evaluation Committee of the study setting. Psychometric properties were assessed by calculating its content validity ratio and index, and test-retest correlation coefficient as well as conducting an exploratory factor analysis and an internal consistency assessment. The content validity ratios and indices of the items were respectively higher than 0.85 and 0.79. The final version of the inventory consisted of 25 items, and in the exploratory factor analysis, items were loaded on three factors which jointly accounting for 72.85% of the total variance. The test-retest correlation coefficient and the Cronbach's alpha of the inventory were 0.93 and 0.973, respectively. The results revealed that the developed inventory is an appropriate, valid, and reliable instrument for evaluating nursing instructors' clinical teaching performance.

Could texture features from preoperative CT image be used for predicting occult peritoneal carcinomatosis in patients with advanced gastric cancer?

PubMed

Kim, Hae Young; Kim, Young Hoon; Yun, Gabin; Chang, Won; Lee, Yoon Jin; Kim, Bohyoung

2018-01-01

To retrospectively investigate whether texture features obtained from preoperative CT images of advanced gastric cancer (AGC) patients could be used for the prediction of occult peritoneal carcinomatosis (PC) detected during operation. 51 AGC patients with occult PC detected during operation from January 2009 to December 2012 were included as occult PC group. For the control group, other 51 AGC patients without evidence of distant metastasis including PC, and whose clinical T and N stage could be matched to those of the patients of the occult PC group, were selected from the period of January 2011 to July 2012. Each group was divided into test (n = 41) and validation cohort (n = 10). Demographic and clinical data of these patients were acquired from the hospital database. Texture features including average, standard deviation, kurtosis, skewness, entropy, correlation, and contrast were obtained from manually drawn region of interest (ROI) over the omentum on the axial CT image showing the omentum at its largest cross sectional area. After using Fisher's exact and Wilcoxon signed-rank test for comparison of the clinical and texture features between the two groups of the test cohort, conditional logistic regression analysis was performed to determine significant independent predictor for occult PC. Using the optimal cut-off value from receiver operating characteristic (ROC) analysis for the significant variables, diagnostic sensitivity and specificity were determined in the test cohort. The cut-off value of the significant variables obtained from the test cohort was then applied to the validation cohort. Bonferroni correction was used to adjust P value for multiple comparisons. Between the two groups, there was no significant difference in the clinical features. Regarding the texture features, the occult PC group showed significantly higher average, entropy, standard deviation, and significantly lower correlation (P value < 0.004 for all). Conditional logistic regression analysis demonstrated that entropy was significant independent predictor for occult PC. When the cut-off value of entropy (> 7.141) was applied to the validation cohort, sensitivity and specificity for the prediction of occult PC were 80% and 90%, respectively. For AGC patients whose PC cannot be detected with routine imaging such as CT, texture analysis may be a useful adjunct for the prediction of occult PC.

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.

PubMed

Ramkumar, Hema L; Gudiseva, Harini V; Kishaba, Kameron T; Suk, John J; Verma, Rohan; Tadimeti, Keerti; Thorson, John A; Ayyagari, Radha

2017-02-01

To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

The challenge of defining and treating anemia and iron deficiency in pregnancy: A study of New Zealand midwives' management of iron status in pregnancy and the postpartum period.

PubMed

Calje, Esther; Skinner, Joan

2017-06-01

Early recognition and management of low maternal iron status is associated with improved maternal, fetal, and neonatal outcomes. However, existing international guidelines for the testing and management of maternal iron-deficiency anemia are variable, with no national guideline for New Zealand midwives. Clinical management is complicated by normal physiological hemodilution, and complicated further by the effects of inflammation on iron metabolism, especially in populations with a high prevalence of obesity or infection. This study describes how midwives in one New Zealand area diagnose and treat anemia and iron deficiency, in the absence of established guidelines. Data on demographics, laboratory results, and documented clinical management were retrospectively collected from midwives (n=21) and women (n=189), from September to December 2013. Analysis was predominantly descriptive. A secondary analysis of iron status and body mass index (BMI) was undertaken. A total of 46% of 186 women, with hemoglobin testing at booking, did not have ferritin tested; 86% (of 385) of ferritin tests were not concurrently tested with C-reactive protein. Despite midwives prescribing iron for 48.7% of second trimester women, 47.1% still had low iron status before birth. Only 22.8% of women had hemoglobin testing postpartum. There was a significant difference between third trimester median ferritin levels in women with BMI ≥25.00 (14 μg/L) and BMI <25.00 (18 μg/L) (P=.05). There was a wide range in the midwives' practice. Maternal iron status was difficult to categorize, because of inconsistent testing. This study indicates the need for an evidence-based clinical guideline for New Zealand midwives and maternity care providers. © 2017 Wiley Periodicals, Inc.

Usability testing of Avoiding Diabetes Thru Action Plan Targeting (ADAPT) decision support for integrating care-based counseling of pre-diabetes in an electronic health record.

PubMed

Chrimes, Dillon; Kitos, Nicole R; Kushniruk, Andre; Mann, Devin M

2014-09-01

Usability testing can be used to evaluate human-computer interaction (HCI) and communication in shared decision making (SDM) for patient-provider behavioral change and behavioral contracting. Traditional evaluations of usability using scripted or mock patient scenarios with think-aloud protocol analysis provide a way to identify HCI issues. In this paper we describe the application of these methods in the evaluation of the Avoiding Diabetes Thru Action Plan Targeting (ADAPT) tool, and test the usability of the tool to support the ADAPT framework for integrated care counseling of pre-diabetes. The think-aloud protocol analysis typically does not provide an assessment of how patient-provider interactions are effected in "live" clinical workflow or whether a tool is successful. Therefore, "Near-live" clinical simulations involving applied simulation methods were used to compliment the think-aloud results. This complementary usability technique was used to test the end-user HCI and tool performance by more closely mimicking the clinical workflow and capturing interaction sequences along with assessing the functionality of computer module prototypes on clinician workflow. We expected this method to further complement and provide different usability findings as compared to think-aloud analysis. Together, this mixed method evaluation provided comprehensive and realistic feedback for iterative refinement of the ADAPT system prior to implementation. The study employed two phases of testing of a new interactive ADAPT tool that embedded an evidence-based shared goal setting component into primary care workflow for dealing with pre-diabetes counseling within a commercial physician office electronic health record (EHR). Phase I applied usability testing that involved "think-aloud" protocol analysis of eight primary care providers interacting with several scripted clinical scenarios. Phase II used "near-live" clinical simulations of five providers interacting with standardized trained patient actors enacting the clinical scenario of counseling for pre-diabetes, each of whom had a pedometer that recorded the number of steps taken over a week. In both phases, all sessions were audio-taped and motion screen-capture software was activated for onscreen recordings. Transcripts were coded using iterative qualitative content analysis methods. In Phase I, the impact of the components and layout of ADAPT on user's Navigation, Understandability, and Workflow were associated with the largest volume of negative comments (i.e. approximately 80% of end-user commentary), while Usability and Content of ADAPT were representative of more positive than negative user commentary. The heuristic category of Usability had a positive-to-negative comment ratio of 2.1, reflecting positive perception of the usability of the tool, its functionality, and overall co-productive utilization of ADAPT. However, there were mixed perceptions about content (i.e., how the information was displayed, organized and described in the tool). In Phase II, the duration of patient encounters was approximately 10 min with all of the Patient Instructions (prescriptions) and behavioral contracting being activated at the end of each visit. Upon activation, providers accepted the pathway prescribed by the tool 100% of the time and completed all the fields in the tool in the simulation cases. Only 14% of encounter time was spent using the functionality of the ADAPT tool in terms of keystrokes and entering relevant data. The rest of the time was spent on communication and dialog to populate the patient instructions. In all cases, the interaction sequence of reviewing and discussing exercise and diet of the patient was linked to the functionality of the ADAPT tool in terms of monitoring, response-efficacy, self-efficacy, and negotiation in the patient-provider dialog. There was a change from one-way dialog to two-way dialog and negotiation that ended in a behavioral contract. This change demonstrated the tool's sequence, which supported recording current exercise and diet followed by a diet and exercise goal setting procedure to reduce the risk of diabetes onset. This study demonstrated that "think-aloud" protocol analysis with "near-live" clinical simulations provided a successful usability evaluation of a new primary care pre-diabetes shared goal setting tool. Each phase of the study provided complementary observations on problems with the new onscreen tool and was used to show the influence of the ADAPT framework on the usability, workflow integration, and communication between the patient and provider. The think-aloud tests with the provider showed the tool can be used according to the ADAPT framework (exercise-to-diet behavior change and tool utilization), while the clinical simulations revealed the ADAPT framework to realistically support patient-provider communication to obtain behavioral change contract. SDM interactions and mechanisms affecting protocol-based care can be more completely captured by combining "near-live" clinical simulations with traditional "think-aloud analysis" which augments clinician utilization. More analysis is required to verify if the rich communication actions found in Phase II compliment clinical workflows. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Clinical application of antenatal genetic diagnosis of osteogenesis imperfecta type IV.

PubMed

Yuan, Jing; Li, Song; Xu, YeYe; Cong, Lin

2015-04-02

Clinical analysis and genetic testing of a family with osteogenesis imperfecta type IV were conducted, aiming to discuss antenatal genetic diagnosis of osteogenesis imperfecta type IV. Preliminary genotyping was performed based on clinical characteristics of the family members and then high-throughput sequencing was applied to rapidly and accurately detect the changes in candidate genes. Genetic testing of the III5 fetus and other family members revealed missense mutation in c.2746G>A, pGly916Arg in COL1A2 gene coding region and missense and synonymous mutation in COL1A1 gene coding region. Application of antenatal genetic diagnosis provides fast and accurate genetic counseling and eugenics suggestions for patients with osteogenesis imperfecta type IV and their families.

User-centered design to improve clinical decision support in primary care.

PubMed

Brunner, Julian; Chuang, Emmeline; Goldzweig, Caroline; Cain, Cindy L; Sugar, Catherine; Yano, Elizabeth M

2017-08-01

A growing literature has demonstrated the ability of user-centered design to make clinical decision support systems more effective and easier to use. However, studies of user-centered design have rarely examined more than a handful of sites at a time, and have frequently neglected the implementation climate and organizational resources that influence clinical decision support. The inclusion of such factors was identified by a systematic review as "the most important improvement that can be made in health IT evaluations." (1) Identify the prevalence of four user-centered design practices at United States Veterans Affairs (VA) primary care clinics and assess the perceived utility of clinical decision support at those clinics; (2) Evaluate the association between those user-centered design practices and the perceived utility of clinical decision support. We analyzed clinic-level survey data collected in 2006-2007 from 170 VA primary care clinics. We examined four user-centered design practices: 1) pilot testing, 2) provider satisfaction assessment, 3) formal usability assessment, and 4) analysis of impact on performance improvement. We used a regression model to evaluate the association between user-centered design practices and the perceived utility of clinical decision support, while accounting for other important factors at those clinics, including implementation climate, available resources, and structural characteristics. We also examined associations separately at community-based clinics and at hospital-based clinics. User-centered design practices for clinical decision support varied across clinics: 74% conducted pilot testing, 62% conducted provider satisfaction assessment, 36% conducted a formal usability assessment, and 79% conducted an analysis of impact on performance improvement. Overall perceived utility of clinical decision support was high, with a mean rating of 4.17 (±.67) out of 5 on a composite measure. "Analysis of impact on performance improvement" was the only user-centered design practice significantly associated with perceived utility of clinical decision support, b=.47 (p<.001). This association was present in hospital-based clinics, b=.34 (p<.05), but was stronger at community-based clinics, b=.61 (p<.001). Our findings are highly supportive of the practice of analyzing the impact of clinical decision support on performance metrics. This was the most common user-centered design practice in our study, and was the practice associated with higher perceived utility of clinical decision support. This practice may be particularly helpful at community-based clinics, which are typically less connected to VA medical center resources. Published by Elsevier B.V.

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT)

PubMed Central

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

2018-01-01

Introduction The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Methods Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2–4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods—pertussis culture as the “gold standard,” composite reference standard analysis (CRS), and latent class analysis (LCA). Results Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Conclusions Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis. PMID:29652945

At-Home Versus In-Clinic INR Monitoring: A Cost-Utility Analysis from The Home INR Study (THINRS).

PubMed

Phibbs, Ciaran S; Love, Sean R; Jacobson, Alan K; Edson, Robert; Su, Pon; Uyeda, Lauren; Matchar, David B

2016-09-01

Effective management of patients using warfarin is resource-intensive, requiring frequent in-clinic testing of the international normalized ratio (INR). Patient self-testing (PST) using portable at-home INR monitoring devices has emerged as a convenient alternative. As revealed by The Home INR Study (THINRS), event rates for PST were not significantly different from those for in-clinic high-quality anticoagulation management (HQACM), and a cumulative gain in quality of life was observed for patients undergoing PST. To perform a cost-utility analysis of weekly PST versus monthly HQACM and to examine the sensitivity of these results to testing frequency. In this study, 2922 patients taking warfarin for atrial fibrillation or mechanical heart valve, and who demonstrated PST competence, were randomized to either weekly PST (n = 1465) or monthly in-clinic testing (n = 1457). In a sub-study, 234 additional patients were randomized to PST once every 4 weeks (n = 116) or PST twice weekly (n = 118). The endpoints were quality of life (measured by the Health Utilities Index), health care utilization, and costs over 2 years of follow-up. PST and HQACM participants were similar with regard to gender, age, and CHADS2 score. The total cost per patient over 2 years of follow-up was $32,484 for HQACM and $33,460 for weekly PST, representing a difference of $976. The incremental cost per quality-adjusted life year gained with PST once weekly was $5566 (95 % CI, -$11,490 to $25,142). The incremental cost-effectiveness ratio (ICER) was sensitive to testing frequency: weekly PST dominated PST twice weekly and once every 4 weeks. Compared to HQACM, weekly PST was associated with statistically significant and clinically meaningful improvements in quality of life. The ICER for weekly PST versus HQACM was well within accepted standards for cost-effectiveness, and was preferred over more or less frequent PST. These results were robust to sensitivity analyses of key assumptions. Weekly PST is a cost-effective alternative to monthly HQACM and a preferred testing frequency compared to twice weekly or monthly PST.

Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count Tests: A Comprehensive Systematic Review with Meta-Analysis

PubMed Central

Weymann, Alexander; Ali-Hasan-Al-Saegh, Sadeq; Sabashnikov, Anton; Popov, Aron-Frederik; Mirhosseini, Seyed Jalil; Liu, Tong; Lotfaliani, Mohammadreza; de Oliveira Sá, Michel Pompeu Barros; Baker, William L.; Yavuz, Senol; Zeriouh, Mohamed; Jang, Jae-Sik; Dehghan, Hamidreza; Meng, Lei; Testa, Luca; D’Ascenzo, Fabrizio; Benedetto, Umberto; Tse, Gary; Nombela-Franco, Luis; Dohmen, Pascal M.; Deshmukh, Abhishek J.; Linde, Cecilia; Biondi-Zoccai, Giuseppe; Stone, Gregg W.; Calkins, Hugh

2017-01-01

Background Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and is routinely used in the workup of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of hematological parameters in the CBC test with new-onset and recurrent AF. Material/Methods We conducted a meta-analysis of observational studies evaluating hematologic parameters in patients with new-onset AF and recurrent AF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. Results The literature search of all major databases retrieved 2150 studies. After screening, 70 studies were analyzed in the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of −26.39×109/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001), white blood cell (WBC) (WMD=−0.005×109/L and p=0.83), neutrophil to lymphocyte ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW) (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF revealed PC (WMD=−2.71×109/L and p=0.59), WBC (WMD=0.20×109/L (95% CI: 0.08 to 0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001). Conclusions Hematological parameters have significant ability to predict occurrence and recurrence of AF. Therefore, emphasizing the potential predictive role of hematological parameters for new-onset and recurrent AF, we recommend adding the CBC test to the diagnostic modalities of AF in clinical practice. PMID:28496093

Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count Tests: A Comprehensive Systematic Review with Meta-Analysis.

PubMed

Weymann, Alexander; Ali-Hasan-Al-Saegh, Sadeq; Sabashnikov, Anton; Popov, Aron-Frederik; Mirhosseini, Seyed Jalil; Liu, Tong; Lotfaliani, Mohammadreza; Sá, Michel Pompeu Barros de Oliveira; Baker, William L L; Yavuz, Senol; Zeriouh, Mohamed; Jang, Jae-Sik; Dehghan, Hamidreza; Meng, Lei; Testa, Luca; D'Ascenzo, Fabrizio; Benedetto, Umberto; Tse, Gary; Nombela-Franco, Luis; Dohmen, Pascal M; Deshmukh, Abhishek J; Linde, Cecilia; Biondi-Zoccai, Giuseppe; Stone, Gregg W; Calkins, Hugh; Surgery And Cardiology-Group Imcsc-Group, Integrated Meta-Analysis Of Cardiac

2017-05-12

BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and is routinely used in the workup of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of hematological parameters in the CBC test with new-onset and recurrent AF. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating hematologic parameters in patients with new-onset AF and recurrent AF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS The literature search of all major databases retrieved 2150 studies. After screening, 70 studies were analyzed in the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of -26.39×10^9/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001), white blood cell (WBC) (WMD=-0.005×10^9/L and p=0.83), neutrophil to lymphocyte ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW) (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF revealed PC (WMD=-2.71×109/L and p=0.59), WBC (WMD=0.20×10^9/L (95% CI: 0.08 to 0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001). CONCLUSIONS Hematological parameters have significant ability to predict occurrence and recurrence of AF. Therefore, emphasizing the potential predictive role of hematological parameters for new-onset and recurrent AF, we recommend adding the CBC test to the diagnostic modalities of AF in clinical practice.

Self-reported use of complementary and alternative medicine therapies in a reflexology randomized clinical trial.

PubMed

Wyatt, Gwen; Sikorskii, Alla; You, Mei

2013-01-01

According to the National Center for Complementary and Alternative Medicine (NCCAM), about one-third of American cancer patients have used complementary and alternative medicine (CAM). The objective of this secondary analysis was an assessment of the use of other CAM by women with advanced breast cancer who were undergoing chemotherapy and who participated in a randomized clinical trial (RCT) studying the safety and efficacy of reflexology. For this secondary analysis, the research team hypothesized an increased CAM use due to exposure to the reflexology trial. For this secondary analysis, the team conducted telephone interviews at baseline, wk 5, and wk 11 to assess the use of 23 common CAM therapies. The study took place at 14 medical oncology clinics across the Midwestern United States. Participants included women with advanced breast cancer who were undergoing chemotherapy and/or hormonal therapy. In the study related to this secondary analysis, the research team randomly assigned the women to one of three primary groups: (1) reflexology; (2) lay foot manipulation (LFM); and (3) control. In addition, the research team used two test groups to establish the study's protocol: (1) test reflexology and (2) test LFM. For this secondary analysis, the research team considered the two reflexology groups (test and intervention) and the two LFM groups (test and intervention) to be the active groups, comparing their use of CAM to the control group's use at the selected time points. The research team used a linear, mixed-effects model to analyze the number of therapies used at the three time points. The team performed t tests to compare therapy use at baseline for those women who completed the study vs those who dropped out. The team used the CAM-use instrument. In total, 385 women participated. The research team found no differences in CAM use for the active groups vs the control group over time or in those women who stayed in the study vs those who dropped out. The team found an increase in CAM use at wk 5 compared to baseline, followed by a decrease at wk 11; however, the time trends were the same in the active groups and the control group In women with advanced breast cancer, researchers can rely upon one assessment of CAM use during an RCT of a CAM therapy.

Variation in esophageal physiology testing in clinical practice: Results from an international survey.

PubMed

Sweis, R; Heinrich, H; Fox, M

2018-03-01

Advances in clinical measurement of esophageal motility and function have improved the assessment of swallowing disorders and reflux symptoms. Variation in data acquisition, analysis, and reporting exists and impacts on diagnosis and management. This study examined variation in esophageal manometry methodology between institutions to establish the status in current practice. A structured survey was distributed through international NGM societies using an Internet-based platform. Questions explored infrastructure, technology, analysis, and reporting. Responses were received from 91 centers from 29 countries. Eighteen (20%) centers used "conventional" manometry, 75 (82%) high-resolution manometry, and 53 (58%) HR impedance manometry. All centers documented motility for single water swallows. The Chicago Classification was applied by 65 (71.4%) centers. In contrast, analysis of EGJ morphology varied widely. Adjunctive testing was often applied: multiple rapid swallows (77%), rapid drink challenge (77%), single solid swallows (63%), and a standard test meal (18%). Of 86 (94.5%) units that offered pH impedance (pH-Z) studies, approximately half (53.5%) performed tests on acid-suppressant medication in patients with a high pretest probability (eg, erosive esophagitis). Most (75.6%) centers manually reviewed every reflux event. Others examined pH-Z data only prior to symptoms. To assess symptom association with reflux events, 73.6% centers analyzed each symptom separately, whereas 29.7% centers pooled symptoms. There is marked variation in the data acquisition, analysis, and reporting of esophageal manometry studies. Further efforts to improve quality and uniformity in testing and reporting are required. This survey provides information upon which best-practice guidelines can be developed. © 2017 John Wiley & Sons Ltd.

Clinical Performance of an Ultrahigh Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders.

PubMed

Ho, Karen S; Twede, Hope; Vanzo, Rena; Harward, Erin; Hensel, Charles H; Martin, Megan M; Page, Stephanie; Peiffer, Andreas; Mowery-Rushton, Patricia; Serrano, Moises; Wassman, E Robert

2016-01-01

Copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) significantly contribute to the etiology of neurodevelopmental disorders, such as developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD). This study summarizes the results of 3.5 years of CMA testing by a CLIA-certified clinical testing laboratory 5487 patients with neurodevelopmental conditions were clinically evaluated for rare copy number variants using a 2.8-million probe custom CMA optimized for the detection of CNVs associated with neurodevelopmental disorders. We report an overall detection rate of 29.4% in our neurodevelopmental cohort, which rises to nearly 33% when cases with DD/ID and/or MCA only are considered. The detection rate for the ASD cohort is also significant, at 25%. Additionally, we find that detection rate and pathogenic yield of CMA vary significantly depending on the primary indications for testing, the age of the individuals tested, and the specialty of the ordering doctor. We also report a significant difference between the detection rate on the ultrahigh resolution optimized array in comparison to the array from which it originated. This increase in detection can significantly contribute to the efficient and effective medical management of neurodevelopmental conditions in the clinic.

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

PubMed

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

2005-11-01

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

Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia

PubMed Central

Claus, Rainer; Lucas, David M.; Stilgenbauer, Stephan; Ruppert, Amy S.; Yu, Lianbo; Zucknick, Manuela; Mertens, Daniel; Bühler, Andreas; Oakes, Christopher C.; Larson, Richard A.; Kay, Neil E.; Jelinek, Diane F.; Kipps, Thomas J.; Rassenti, Laura Z.; Gribben, John G.; Döhner, Hartmut; Heerema, Nyla A.; Marcucci, Guido; Plass, Christoph; Byrd, John C.

2012-01-01

Purpose Increased ZAP-70 expression predicts poor prognosis in chronic lymphocytic leukemia (CLL). Current methods for accurately measuring ZAP-70 expression are problematic, preventing widespread application of these tests in clinical decision making. We therefore used comprehensive DNA methylation profiling of the ZAP-70 regulatory region to identify sites important for transcriptional control. Patients and Methods High-resolution quantitative DNA methylation analysis of the entire ZAP-70 gene regulatory regions was conducted on 247 samples from patients with CLL from four independent clinical studies. Results Through this comprehensive analysis, we identified a small area in the 5′ regulatory region of ZAP-70 that showed large variability in methylation in CLL samples but was universally methylated in normal B cells. High correlation with mRNA and protein expression, as well as activity in promoter reporter assays, revealed that within this differentially methylated region, a single CpG dinucleotide and neighboring nucleotides are particularly important in ZAP-70 transcriptional regulation. Furthermore, by using clustering approaches, we identified a prognostic role for this site in four independent data sets of patients with CLL using time to treatment, progression-free survival, and overall survival as clinical end points. Conclusion Comprehensive quantitative DNA methylation analysis of the ZAP-70 gene in CLL identified important regions responsible for transcriptional regulation. In addition, loss of methylation at a specific single CpG dinucleotide in the ZAP-70 5′ regulatory sequence is a highly predictive and reproducible biomarker of poor prognosis in this disease. This work demonstrates the feasibility of using quantitative specific ZAP-70 methylation analysis as a relevant clinically applicable prognostic test in CLL. PMID:22564988

Standardization of clinical enzyme analysis using frozen human serum pools with values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures.

PubMed

Tong, Qing; Chen, Baorong; Zhang, Rui; Zuo, Chang

Variation in clinical enzyme analysis, particularly across different measuring systems and laboratories, represents a critical but long-lasting problem in diagnosis. Calibrators with traceability and commutability are imminently needed to harmonize analysis in laboratory medicine. Fresh frozen human serum pools were assigned values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), creatine kinase (CK) and lactate dehydrogenase (LDH) by six laboratories with established International Federation of Clinical Chemistry and Laboratory Medicine reference measurement procedures. These serum pools were then used across 76 laboratories as a calibrator in the analysis of five enzymes. Bias and imprecision in the measurement of the five enzymes tested were significantly reduced by using the value-assigned serum in analytical systems with open and single-point calibration. The median (interquartile range) of the relative biases of ALT, AST, GGT, CK and LDH were 2.0% (0.6-3.4%), 0.8% (-0.8-2.3%), 1.0% (-0.5-2.0%), 0.2% (-0.3-1.0%) and 0.2% (-0.9-1.1%), respectively. Before calibration, the interlaboratory coefficients of variation (CVs) in the analysis of patient serum samples were 8.0-8.2%, 7.3-8.5%, 8.1-8.7%, 5.1-5.9% and 5.8-6.4% for ALT, AST, GGT, CK and LDH, respectively; after calibration, the CVs decreased to 2.7-3.3%, 3.0-3.6%, 1.6-2.1%, 1.8-1.9% and 3.3-3.5%, respectively. The results suggest that the use of fresh frozen serum pools significantly improved the comparability of test results in analytical systems with open and single-point calibration.

A web-based system for neural network based classification in temporomandibular joint osteoarthritis.

PubMed

de Dumast, Priscille; Mirabel, Clément; Cevidanes, Lucia; Ruellas, Antonio; Yatabe, Marilia; Ioshida, Marcos; Ribera, Nina Tubau; Michoud, Loic; Gomes, Liliane; Huang, Chao; Zhu, Hongtu; Muniz, Luciana; Shoukri, Brandon; Paniagua, Beatriz; Styner, Martin; Pieper, Steve; Budin, Francois; Vimort, Jean-Baptiste; Pascal, Laura; Prieto, Juan Carlos

2018-07-01

The purpose of this study is to describe the methodological innovations of a web-based system for storage, integration and computation of biomedical data, using a training imaging dataset to remotely compute a deep neural network classifier of temporomandibular joint osteoarthritis (TMJOA). This study imaging dataset consisted of three-dimensional (3D) surface meshes of mandibular condyles constructed from cone beam computed tomography (CBCT) scans. The training dataset consisted of 259 condyles, 105 from control subjects and 154 from patients with diagnosis of TMJ OA. For the image analysis classification, 34 right and left condyles from 17 patients (39.9 ± 11.7 years), who experienced signs and symptoms of the disease for less than 5 years, were included as the testing dataset. For the integrative statistical model of clinical, biological and imaging markers, the sample consisted of the same 17 test OA subjects and 17 age and sex matched control subjects (39.4 ± 15.4 years), who did not show any sign or symptom of OA. For these 34 subjects, a standardized clinical questionnaire, blood and saliva samples were also collected. The technological methodologies in this study include a deep neural network classifier of 3D condylar morphology (ShapeVariationAnalyzer, SVA), and a flexible web-based system for data storage, computation and integration (DSCI) of high dimensional imaging, clinical, and biological data. The DSCI system trained and tested the neural network, indicating 5 stages of structural degenerative changes in condylar morphology in the TMJ with 91% close agreement between the clinician consensus and the SVA classifier. The DSCI remotely ran with a novel application of a statistical analysis, the Multivariate Functional Shape Data Analysis, that computed high dimensional correlations between shape 3D coordinates, clinical pain levels and levels of biological markers, and then graphically displayed the computation results. The findings of this study demonstrate a comprehensive phenotypic characterization of TMJ health and disease at clinical, imaging and biological levels, using novel flexible and versatile open-source tools for a web-based system that provides advanced shape statistical analysis and a neural network based classification of temporomandibular joint osteoarthritis. Published by Elsevier Ltd.

The "Chaos Theory" and nonlinear dynamics in heart rate variability analysis: does it work in short-time series in patients with coronary heart disease?

PubMed

Krstacic, Goran; Krstacic, Antonija; Smalcelj, Anton; Milicic, Davor; Jembrek-Gostovic, Mirjana

2007-04-01

Dynamic analysis techniques may quantify abnormalities in heart rate variability (HRV) based on nonlinear and fractal analysis (chaos theory). The article emphasizes clinical and prognostic significance of dynamic changes in short-time series applied on patients with coronary heart disease (CHD) during the exercise electrocardiograph (ECG) test. The subjects were included in the series after complete cardiovascular diagnostic data. Series of R-R and ST-T intervals were obtained from exercise ECG data after sampling digitally. The range rescaled analysis method determined the fractal dimension of the intervals. To quantify fractal long-range correlation's properties of heart rate variability, the detrended fluctuation analysis technique was used. Approximate entropy (ApEn) was applied to quantify the regularity and complexity of time series, as well as unpredictability of fluctuations in time series. It was found that the short-term fractal scaling exponent (alpha(1)) is significantly lower in patients with CHD (0.93 +/- 0.07 vs 1.09 +/- 0.04; P < 0.001). The patients with CHD had higher fractal dimension in each exercise test program separately, as well as in exercise program at all. ApEn was significant lower in CHD group in both RR and ST-T ECG intervals (P < 0.001). The nonlinear dynamic methods could have clinical and prognostic applicability also in short-time ECG series. Dynamic analysis based on chaos theory during the exercise ECG test point out the multifractal time series in CHD patients who loss normal fractal characteristics and regularity in HRV. Nonlinear analysis technique may complement traditional ECG analysis.

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

PubMed

Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M; Papatheodorou, Efstathios; Ware, James S; Papadakis, Michael; Tadros, Rafik; Cole, Della; Skinner, Jonathan R; Crawford, Jackie; Love, Donald R; Pua, Chee J; Soh, Bee Y; Bhalshankar, Jaydutt D; Govind, Risha; Tfelt-Hansen, Jacob; Winkel, Bo G; van der Werf, Christian; Wijeyeratne, Yanushi D; Mellor, Greg; Till, Jan; Cohen, Marta C; Tome-Esteban, Maria; Sharma, Sanjay; Wilde, Arthur A M; Cook, Stuart A; Bezzina, Connie R; Sheppard, Mary N; Behr, Elijah R

2017-05-02

Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10 -5 ). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Misleading biochemical laboratory test results

PubMed Central

Nanji, Amin A.

1984-01-01

This article reviews the general and specific factors that interfere with the performance of common biochemical laboratory tests and the interpretation of their results. The clinical status of the patient, drug interactions, and in-vivo and in-vitro biochemical interactions and changes may alter the results obtained from biochemical analysis of blood constituents. Failure to recognize invalid laboratory test results may lead to injudicious and dangerous management of patients. PMID:6375845

USAFSAM Review and Analysis of Radiofrequency Radiation Bioeffects Literature.

DTIC Science & Technology

1981-11-01

less than 0.2 mW/cm . Clinical tests included ophthalmoscopic examination and a neurologic check-up supplemented by psychologic tests and EEG...34). These 12 studies are assessed individually and collectively below, followed by the analyses of each per se. Collective Summary In Lilienfeld et al...hours/workday). Electrocardiograms, heart and lung X-rays, eryth- rocyte sedimentation rates, urinalyses, and liver function tests were conducted as well

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

PubMed

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

2017-01-01

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

Clinical flow cytometric screening of SAP and XIAP expression accurately identifies patients with SH2D1A and XIAP/BIRC4 mutations.

PubMed

Gifford, Carrie E; Weingartner, Elizabeth; Villanueva, Joyce; Johnson, Judith; Zhang, Kejian; Filipovich, Alexandra H; Bleesing, Jack J; Marsh, Rebecca A

2014-07-01

X-linked lymphoproliferative disease is caused by mutations in two genes, SH2D1A and XIAP/BIRC4. Flow cytometric methods have been developed to detect the gene products, SAP and XIAP. However, there is no literature describing the accuracy of flow cytometric screening performed in a clinical lab setting. We reviewed the clinical flow cytometric testing results for 656 SAP and 586 XIAP samples tested during a 3-year period. Genetic testing was clinically performed as directed by the managing physician in 137 SAP (21%) and 115 XIAP (20%) samples. We included these samples for analyses of flow cytometric test accuracy. SH2D1A mutations were detected in 15/137 samples. SAP expression was low in 13/15 (sensitivity 87%, CI 61-97%). Of the 122 samples with normal sequencing, SAP was normal in 109 (specificity 89%, CI 82-94%). The positive predictive values (PPVs) and the negative predictive values (NPVs) were 50% and 98%, respectively. XIAP/BIRC4 mutations were detected in 19/115 samples. XIAP expression was low in 18/19 (sensitivity 95%, CI 73-100%). Of the 96 samples with normal sequencing, 59 had normal XIAP expression (specificity 61%, CI 51-71%). The PPVs and NPVs were 33% and 98%, respectively. Receiver-operating characteristic analysis was able to improve the specificity to 75%. Clinical flow cytometric screening tests for SAP and XIAP deficiencies offer good sensitivity and specificity for detecting genetic mutations, and are characterized by high NPVs. We recommend these tests for patients suspected of having X-linked lymphoproliferative disease type 1 (XLP1) or XLP2. © 2014 Clinical Cytometry Society.

The Impact of a Social Marketing Campaign on HIV and Sexually Transmissible Infection Testing Among Men Who Have Sex With Men in Australia.

PubMed

Wilkinson, Anna L; Pedrana, Alisa E; El-Hayek, Carol; Vella, Alyce M; Asselin, Jason; Batrouney, Colin; Fairley, Christopher K; Read, Tim R H; Hellard, Margaret; Stoové, Mark

2016-01-01

In response to increasing HIV and other sexually transmissible infection (HIV/STI) notifications in Australia, a social marketing campaign Drama Downunder (DDU) was launched in 2008 to promote HIV/STI testing among men who have sex with men (MSM). We analyzed prospective data from (1) an online cohort of MSM and (2) clinic-level HIV/STI testing to evaluate the impact of DDU on HIV, syphilis, gonorrhea, and chlamydia testing. (1) Cohort participants who completed 3 surveys (2010-2014) contributed to a Poisson regression model examining predictors of recent HIV testing.(2) HIV, syphilis, gonorrhea, and chlamydia tests among MSM attending high caseload primary care clinics (2007-2013) were included in an interrupted time series analysis. (1) Although campaign awareness was high among 242 MSM completing 726 prospective surveys, campaign recall was not associated with self-reported HIV testing. Reporting previous regular HIV testing (adjusted incidence rate ratio, 2.4; 95% confidence interval, 1.3-4.4) and more than 10 partners in the previous 6 months (adjusted incidence rate ratio, 1.2; 95% confidence interval, 1.1-1.4) was associated with recent HIV testing. (2) Analysis of 257,023 tests showed increasing monthly HIV, syphilis, gonorrhea, and chlamydia tests pre-DDU. Post-DDU, gonorrhea test rates increased significantly among HIV-negative MSM, with modest and nonsignificant increasing rates of HIV, syphilis, and chlamydia testing. Among HIV-positive MSM, no change in gonorrhea or chlamydia testing occurred and syphilis testing declined significantly. Increasing HIV/STI testing trends among MSM occurred pre- and post-DDU, coinciding with other plausible drivers of testing. Modest changes in HIV testing post-DDU suggest that structural changes to improve testing access may need to occur alongside health promotion to increase testing frequency.

The Relevance of Proprioception to Chronic Neck Pain: A Correlational Analysis of Flexor Muscle Size and Endurance, Clinical Neck Pain Characteristics, and Proprioception.

PubMed

Amiri Arimi, Somayeh; Ghamkhar, Leila; Kahlaee, Amir H

2018-01-02

Impairment in the cervical proprioception and deep flexor muscle function and morphology have been regarded to be associated with chronic neck pain (CNP).  The aim of the study is to assess the relationship between proprioception and flexor endurance capacity and size and clinical CNP characteristics.  This was an observational, cross-sectional study.  Rehabilitation hospital laboratory.  Sixty subjects with or without CNP participated in the study.  Joint position error, clinical deep flexor endurance test score, longus colli/capitis and sternocleidomastoid muscle size, pain intensity, neck pain-related disability, and fear of movement were assessed. Multivariate analysis of variance and Pearson correlation tests were used to compare the groups and quantify the strength of the associations among variables, respectively. Logistic regression analysis was performed to test the predictive value of the dependent variables for the development of neck pain.  CNP patients showed lower flexor endurance (P = 0.01) and smaller longus colli size (P < 0.01). The joint position error was not statistically different between the groups. Longus colli size was correlated with local flexor endurance in both CNP (P = 0.01) and control (P = 0.04) groups. Among clinical CNP characteristics, kinesiophobia showed fair correlation with joint position error (r = 0.39, P = 0.03). Left rotation error and local flexor endurance were significant predictors of CNP development (β = 1.22, P = 0.02, and β = 0.97, P = 0.02, respectively).  The results indicated that cervical proprioception was associated neither with deep flexor muscle structure/function nor with clinical CNP characteristics. Left rotation error and local flexor endurance were found relevant to neck pain development. © 2017 American Academy of Pain Medicine. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Mild clinical behaviour of Crohn disease in elderly patients in a Latin American country: A case-control study.

PubMed

Yamamoto-Furusho, Jesús K; Sarmiento-Aguilar, Andrea

2015-01-01

Crohn disease is characterized by fluctuating clinical behaviour, which is influenced by various factors. There are no data from Latin America that evaluate the clinical behaviour of Crohn disease in elderly patients. To evaluate the clinical course of elderly onset Crohn disease compared with younger onset in the Mexican population. The present analysis was a case-control study that included 132 patients with a histopathological diagnosis of Crohn disease between 1983 and 2013 in an inflammatory bowel disease clinic of a tertiary care centre. Statistical analysis was performed using SPSS version 17 (IBM Corporation, USA) and descriptive statistics, χ2 and Fisher's exact test for categorical variables and Student's t test for numerical variables. Univariate and multivariate analysis were performed to identify associated risk factors and OR was calculated. A total of 132 patients (73 men and 59 women) were divided into two groups according to age at diagnosis: 27 cases (>60 years of age) and 105 controls (≤60 years of age). Factors influencing the clinical course of Crohn disease in the elderly were: female sex (OR 2.55 [95% CI 1.06 to 6.10]; P=0.02); colonic location (OR 0.22 [95% CI 0.03 to 0.89]; P=0.02); mild clinical behaviour of disease (OR 10.08 [95% CI 3.74 to 27.17]; P=0.0001); response to medical treatment (OR 2.85 [95% CI 1.08 to 7.48]; P=0.02); frequent use of sulfasalazine (OR 4.46 [95% CI 1.22 to 16.28]; P=0.03); less use of azathioprine (OR 0.38 [95% CI 0.13 to 1.03]; P=0.04); and long-term remission (OR 4.96 [95% CI 1.70 to 14.48]; P=0.002). Elderly patients with Crohn disease had a mild clinical course characterized by the lack of escalation to immunosuppressive and anti-tumour necrosis factor therapy, as well as long-term remission.

Mathematical Modelling of the Infusion Test

NASA Astrophysics Data System (ADS)

Cieslicki, Krzysztof

2007-01-01

The objective of this paper was to improve the well established in clinical practice Marmarou model for intracranial volume-pressure compensation by adding the pulsatile components. It was demonstrated that complicated pulsation and growth in intracranial pressure during infusion test could be successfully modeled by the relatively simple analytical expression derived in this paper. The CSF dynamics were tested in 25 patients with clinical symptoms of hydrocephalus. Basing on the frequency spectrum of the patient's baseline pressure and identified parameters of CSF dynamic, for each patient an "ideal" infusion test curve free from artefacts and slow waves was simulated. The degree of correlation between simulated and real curves obtained from clinical observations gave insight into the adequacy of assumptions of Marmarou model. The proposed method of infusion tests analysis designates more exactly the value of the reference pressure, which is usually treated as a secondary and of uncertain significance. The properly identified value of the reference pressure decides on the degree of pulsation amplitude growth during IT, as well as on the value of elastance coefficient. The artificially generated tests with various pulsation components were also applied to examine the correctness of the used algorithm of identification of the original Marmarou model parameters.

Privacy-preserving Kruskal-Wallis test.

PubMed

Guo, Suxin; Zhong, Sheng; Zhang, Aidong

2013-10-01

Statistical tests are powerful tools for data analysis. Kruskal-Wallis test is a non-parametric statistical test that evaluates whether two or more samples are drawn from the same distribution. It is commonly used in various areas. But sometimes, the use of the method is impeded by privacy issues raised in fields such as biomedical research and clinical data analysis because of the confidential information contained in the data. In this work, we give a privacy-preserving solution for the Kruskal-Wallis test which enables two or more parties to coordinately perform the test on the union of their data without compromising their data privacy. To the best of our knowledge, this is the first work that solves the privacy issues in the use of the Kruskal-Wallis test on distributed data. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Parents' Perceptions of the Usefulness of Chromosomal Microarray Analysis for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Reiff, Marian; Giarelli, Ellen; Bernhardt, Barbara A.; Easley, Ebony; Spinner, Nancy B.; Sankar, Pamela L.; Mulchandani, Surabhi

2015-01-01

Clinical guidelines recommend chromosomal microarray analysis (CMA) for all children with autism spectrum disorders (ASDs). We explored the test's perceived usefulness among parents of children with ASD who had undergone CMA, and received a result categorized as pathogenic, variant of uncertain significance, or negative. Fifty-seven parents…

Exploring examinee behaviours as validity evidence for multiple-choice question examinations.

PubMed

Surry, Luke T; Torre, Dario; Durning, Steven J

2017-10-01

Clinical-vignette multiple choice question (MCQ) examinations are used widely in medical education. Standardised MCQ examinations are used by licensure and certification bodies to award credentials that are meant to assure stakeholders as to the quality of physicians. Such uses are based on the interpretation of MCQ examination performance as giving meaningful information about the quality of clinical reasoning. There are several assumptions foundational to these interpretations and uses of standardised MCQ examinations. This study explores the implicit assumption that cognitive processes elicited by clinical-vignette MCQ items are like the processes thought to occur with 'real-world' clinical reasoning as theorised by dual-process theory. Fourteen participants (three medical students, five residents and six staff physicians) completed three sets of five timed MCQ items (total 15) from the Medical Knowledge Self-Assessment Program (MKSAP). Upon answering a set of MCQs, each participant completed a retrospective think aloud (TA) protocol. Using constant comparative analysis (CCA) methods sensitised by dual-process theory, we performed a qualitative thematic analysis. Examinee behaviours fell into three categories: clinical reasoning behaviours, test-taking behaviours and reactions to the MCQ. Consistent with dual-process theory, statements about clinical reasoning behaviours were divided into two sub-categories: analytical reasoning and non-analytical reasoning. Each of these categories included several themes. Our study provides some validity evidence that test-takers' descriptions of their cognitive processes during completion of high-quality clinical-vignette MCQs align with processes expected in real-world clinical reasoning. This supports one of the assumptions important for interpretations of MCQ examination scores as meaningful measures of clinical reasoning. Our observations also suggest that MCQs elicit other cognitive processes, including certain test-taking behaviours, that seem 'inauthentic' to real-world clinical reasoning. Further research is needed to explore if similar themes arise in other contexts (e.g. simulated patient encounters) and how observed behaviours relate to performance on MCQ-based assessments. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

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

PubMed

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

2016-09-22

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

The Brief Fear of Negative Evaluation Scale (BFNE): translation and validation study of the Iranian version.

PubMed

Tavoli, Azadeh; Melyani, Mahdiyeh; Bakhtiari, Maryam; Ghaedi, Gholam Hossein; Montazeri, Ali

2009-07-09

The Brief Fear of Negative Evaluation Scale (BFNE) is a commonly used instrument to measure social anxiety. This study aimed to translate and to test the reliability and validity of the BFNE in Iran. The English language version of the BFNE was translated into Persian (Iranian language) and was used in this study. The questionnaire was administered to a consecutive sample of 235 students with (n = 33, clinical group) and without social phobia (n = 202, non-clinical group). In addition to the BFNE, two standard instruments were used to measure social phobia severity: the Social Phobia Inventory (SPIN), and the Social Interaction Anxiety Scale (SIAS). All participants completed a brief background information questionnaire, the SPIN, the SIAS and the BFNE scales. Statistical analysis was performed to test the reliability and validity of the BFNE. In all 235 students were studied (111 male and 124 female). The mean age for non-clinical group was 22.2 (SD = 2.1) years and for clinical sample it was 22.4 (SD = 1.8) years. Cronbach's alpha coefficient (to test reliability) was acceptable for both non-clinical and clinical samples (alpha = 0.90 and 0.82 respectively). In addition, 3-week test-retest reliability was performed in non-clinical sample and the intraclass correlation coefficient (ICC) was quite high (ICC = 0.71). Validity as performed using convergent and discriminant validity showed satisfactory results. The questionnaire correlated well with established measures of social phobia such as the SPIN (r = 0.43, p < 0.001) and the SIAS (r = 0.54, p < 0.001). Also the BFNE discriminated well between men and women with and without social phobia in the expected direction. Factor analysis supported a two-factor solution corresponding to positive and reverse-worded items. This validation study of the Iranian version of BFNE proved that it is an acceptable, reliable and valid measure of social phobia. However, since the scale showed a two-factor structure and this does not confirm to the theoretical basis for the BFNE, thus we suggest the use of the BFNE-II when it becomes available in Iran. The validation study of the BFNE-II is in progress.

Flow cytometric analysis of lymphocyte proliferative responses to food allergens in dogs with food allergy.

PubMed

Fujimura, Masato; Masuda, Kenichi; Hayashiya, Makio; Okayama, Taro

2011-10-01

Two different allergy tests, antigen-specific immunoglobulin E quantification (IgE test) and flow cytometric analysis of antigen-specific proliferation of peripheral lymphocytes (lymphocyte proliferation test), were performed to examine differences in allergic reactions to food allergens in dogs with food allergy (FA). Thirteen dogs were diagnosed as FA based on clinical findings and elimination diet trials. Seven dogs clinically diagnosed with canine atopic dermatitis (CAD) were used as a disease control group, and 5 healthy dogs were used as a negative control group. In the FA group, 19 and 33 allergen reactions were identified using the serum IgE test and the lymphocyte proliferation test, respectively. Likewise, in the CAD group, 12 and 6 allergen reactions and in the healthy dogs 3 and 0 allergen reactions were identified by each test, respectively. A significant difference was found between FA and healthy dogs in terms of positive allergen detection by the lymphocyte proliferation test, suggesting that the test can be useful to differentiate FA from healthy dogs but not from CAD. Both tests were repeated in 6 of the dogs with FA after a 1.5- to 5-month elimination diet trial. The IgE concentrations in 9 of 11 of the positive reactions decreased by 20-80%, whereas all the positive reactions in the lymphocyte proliferation test decreased to nearly zero (P<0.05), suggesting that lymphocytes against food allergens may be involved in the pathogenesis of canine FA.

Novel splice mutation in microthalmia-associated transcription factor in Waardenburg Syndrome.

PubMed

Brenner, Laura; Burke, Kelly; Leduc, Charles A; Guha, Saurav; Guo, Jiancheng; Chung, Wendy K

2011-01-01

Waardenburg Syndrome (WS) is a syndromic form of hearing loss associated with mutations in six different genes. We identified a large family with WS that had previously undergone clinical testing, with no reported pathogenic mutation. Using linkage analysis, a region on 3p14.1 with an LOD score of 6.6 was identified. Microthalmia-Associated Transcription Factor, a gene known to cause WS, is located within this region of linkage. Sequencing of Microthalmia-Associated Transcription Factor demonstrated a c.1212 G>A synonymous variant that segregated with the WS in the family and was predicted to cause a novel splicing site that was confirmed with expression analysis of the mRNA. This case illustrates the need to computationally analyze novel synonymous sequence variants for possible effects on splicing to maximize the clinical sensitivity of sequence-based genetic testing.

A five-year self-sustainability analysis of nurse-administered HIV rapid testing in Veterans Affairs primary care.

PubMed

Knapp, Herschel; Hagedorn, Hildi; Anaya, Henry D

2014-10-01

In 2008, nurse-administered HIV oral rapid testing (RT) was introduced at the Veterans Affairs Primary Care Clinic in Downtown Los Angeles. Analysis at five years revealed variable yet increasing rates of HIV RT at that facility despite the fact that no post-launch support was provided by the implementation team. Qualitative interviews among stakeholders conducted at five years revealed the pre-existing implementation practices endemic to this clinic that facilitated this unprecedented success (e.g. history of positive quality improvement implementations, leadership support, clinician involvement at each step of the process to facilitate empowerment, ownership and feasible customisation of the implementation, cohesive communication among clinicians and leadership, training, efficient supply pathway, progressive performance feedback and ongoing encouragement). © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Design and analysis of submarine radome

NASA Astrophysics Data System (ADS)

Sandeep, C. Satya; Prasad, U. Shiva; Suresh, R.; Rathan, A.; Sravanthi, G.; Govardhan, D.

2017-07-01

Radomes are the electromagnetic windows that protect microwave sub-systems from the environmental effects. The major requirement of radome is its transparency to microwaves and for most of the cases mechanical properties are also equally important. Radome for underwater applications has to withstand high water pressure of the order of 45 bars. Composite materials owing to their high strength to weight ratio, high stiffness and better corrosion resistance are potential source for under water applications. The concept of 'tailoring' the material properties to suit the radome is obtained by selecting proper reinforcement, resin matrix and their compositions. The mechanical properties of composite material, evaluated by testing specimens as per ASTM standards, are utilized in designing the radome. The modulus properties calculated using classical theories of composite materials and compared with test results. ANSYS a Finite Element software package used to analyse the problem. As the cross sectional thickness of radome varies, the complexity in fabrication is overcome by adopting matched die techniques. The radome design and finite element analysis validation concluded by conducting the pressure test on radome. On the design a modal analysis is also carried to check for the natural frequency, So that resonance does not occur if the natural frequency of the radome coincides with the excitation frequency of the submarine Clinical information system (CIS) for UNRWA is a computerized distributed application that used in clinics which follows the United Nations Relief and Works Agency (UNRWA) to manage the clinical requirements and services.

[Hierarchical assessment of balance and mobility : German translation and cross-cultural adaptation].

PubMed

Braun, Tobias; Rieckmann, Alina; Grüneberg, Christian; Marks, Detlef; Thiel, Christian

2016-07-01

The hierarchical assessment of balance and mobility (HABAM) is an internationally established clinical mobility test which has good psychometric properties, allows an easy assessment of mobility and the graphical illustration of change over time in geriatric patients. The aims of this study were the translation and cross-cultural adaptation of the English original HABAM into the German language as well as a preliminary analysis of the practicability and construct validity of the HABAM. The HABAM was translated into German following international guidelines. A prefinal version was clinically tested by physiotherapists in two geriatric hospitals over a period of 5 weeks. In order to make a final revision of the German HABAM version, structured in-depth feedback was obtained from the seven therapists who had used the HABAM most often. A total of 18 physiotherapists used the HABAM for 47 elderly inpatients for the initial assessment. The translated items and instructions seemed comprehensible but problems occurred concerning the conducting and documentation of the HABAM. Modifications led to the final German HABAM version and 85 % of the HABAM assessments were performed within ≤ 10 min. There was a correlation of rs= 0.71 with the Tinetti test and of rs = 0.68 with the Barthel index. A German HABAM version is now accessible for use in clinical practice. The results of a preliminary psychometric analysis indicate a potentially good practicability and sufficient construct validity. A comprehensive analysis of psychometric properties is pending.

Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases.

PubMed

Plaiasu, Vasilica; Ochiana, Diana; Motei, Gabriela; Anca, Ioana; Georgescu, Adrian

2010-07-01

Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management.

Qualitative computer aided evaluation of dental impressions in vivo.

PubMed

Luthardt, Ralph G; Koch, Rainer; Rudolph, Heike; Walter, Michael H

2006-01-01

Clinical investigations dealing with the precision of different impression techniques are rare. Objective of the present study was to develop and evaluate a procedure for the qualitative analysis of the three-dimensional impression precision based on an established in-vitro procedure. The zero hypothesis to be tested was that the precision of impressions does not differ depending on the impression technique used (single-step, monophase and two-step-techniques) and on clinical variables. Digital surface data of patient's teeth prepared for crowns were gathered from standardized manufactured master casts after impressions with three different techniques were taken in a randomized order. Data-sets were analyzed for each patient in comparison with the one-step impression chosen as the reference. The qualitative analysis was limited to data-points within the 99.5%-range. Based on the color-coded representation areas with maximum deviations were determined (preparation margin and the mantle and occlusal surface). To qualitatively analyze the precision of the impression techniques, the hypothesis was tested in linear models for repeated measures factors (p < 0.05). For the positive 99.5% deviations no variables with significant influence were determined in the statistical analysis. In contrast, the impression technique and the position of the preparation margin significantly influenced the negative 99.5% deviations. The influence of clinical parameter on the deviations between impression techniques can be determined reliably using the 99.5 percentile of the deviations. An analysis regarding the areas with maximum deviations showed high clinical relevance. The preparation margin was pointed out as the weak spot of impression taking.

Profile Analysis of the Woodcock-Johnson III Tests of Cognitive Abilities with Gifted Students.

ERIC Educational Resources Information Center

Rizza, Mary G.; McIntosh, David E.; McCunn, Alice

2001-01-01

The Cattell-Horn-Carroll (CHC) factor clusters of the Woodcock-Johnson III Tests of Cognitive Abilities (WJ III COG) were studied with a group of gifted and nongifted individuals. Results found both groups display similar patterns of performance across the CHC factor clusters. Discusses clinical and educational considerations when using the WJ III…

Microarray as a First Genetic Test in Global Developmental Delay: A Cost-Effectiveness Analysis

ERIC Educational Resources Information Center

Trakadis, Yannis; Shevell, Michael

2011-01-01

Aim: Microarray technology has a significantly higher clinical yield than karyotyping in individuals with global developmental delay (GDD). Despite this, it has not yet been routinely implemented as a screening test owing to the perception that this approach is more expensive. We aimed to evaluate the effect that replacing karyotype with…

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

PubMed

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

2016-01-01

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

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

PubMed

Dolled-Filhart, Marisa P; Gustavson, Mark D

2012-11-01

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

Digital vs. conventional implant prosthetic workflows: a cost/time analysis.

PubMed

Joda, Tim; Brägger, Urs

2015-12-01

The aim of this prospective cohort trial was to perform a cost/time analysis for implant-supported single-unit reconstructions in the digital workflow compared to the conventional pathway. A total of 20 patients were included for rehabilitation with 2 × 20 implant crowns in a crossover study design and treated consecutively each with customized titanium abutments plus CAD/CAM-zirconia-suprastructures (test: digital) and with standardized titanium abutments plus PFM-crowns (control conventional). Starting with prosthetic treatment, analysis was estimated for clinical and laboratory work steps including measure of costs in Swiss Francs (CHF), productivity rates and cost minimization for first-line therapy. Statistical calculations were performed with Wilcoxon signed-rank test. Both protocols worked successfully for all test and control reconstructions. Direct treatment costs were significantly lower for the digital workflow 1815.35 CHF compared to the conventional pathway 2119.65 CHF [P = 0.0004]. For subprocess evaluation, total laboratory costs were calculated as 941.95 CHF for the test group and 1245.65 CHF for the control group, respectively [P = 0.003]. The clinical dental productivity rate amounted to 29.64 CHF/min (digital) and 24.37 CHF/min (conventional) [P = 0.002]. Overall, cost minimization analysis exhibited an 18% cost reduction within the digital process. The digital workflow was more efficient than the established conventional pathway for implant-supported crowns in this investigation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel methods of imaging and analysis for the thermoregulatory sweat test.

PubMed

Carroll, Michael Sean; Reed, David W; Kuntz, Nancy L; Weese-Mayer, Debra Ellyn

2018-06-07

The thermoregulatory sweat test (TST) can be central to the identification and management of disorders affecting sudomotor function and small sensory and autonomic nerve fibers, but the cumbersome nature of the standard testing protocol has prevented its widespread adoption. A high resolution, quantitative, clean and simple assay of sweating could significantly improve identification and management of these disorders. Images from 89 clinical TSTs were analyzed retrospectively using two novel techniques. First, using the standard indicator powder, skin surface sweat distributions were determined algorithmically for each patient. Second, a fundamentally novel method using thermal imaging of forced evaporative cooling was evaluated through comparison with the standard technique. Correlation and receiver operating characteristic analyses were used to determine the degree of match between these methods, and the potential limits of thermal imaging were examined through cumulative analysis of all studied patients. Algorithmic encoding of sweating and non-sweating regions produces a more objective analysis for clinical decision making. Additionally, results from the forced cooling method correspond well with those from indicator powder imaging, with a correlation across spatial regions of -0.78 (CI: -0.84 to -0.71). The method works similarly across body regions, and frame-by-frame analysis suggests the ability to identify sweating regions within about 1 second of imaging. While algorithmic encoding can enhance the standard sweat testing protocol, thermal imaging with forced evaporative cooling can dramatically improve the TST by making it less time-consuming and more patient-friendly than the current approach.

Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost.

PubMed

Pellet, Andrew C; Erten, Mujde Z; James, Ted A

2016-06-01

Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy test of a toothpaste in reducing extrinsic dental stain

NASA Astrophysics Data System (ADS)

Agustanti, A.; Ramadhani, S. A.; Adiatman, M.; Rahardjo, A.; Callea, M.; Yavuz, I.; Maharani, D. A.

2017-08-01

This clinical trial compared the external dental stain reduction achieved by tested toothpaste versus placebo in adult patients. In this double-blind, parallel, randomised clinical trial, 45 female volunteers with a mean age of 20 years old were included. All study subjects front teeth were topically applicated with Silver Diamine Fluoride (SDF) to create external dental stains. Subjects were randomized into test (n=22) and control (n=23) groups. Toothpastes were used for two days to analyse the effects of removing external stains on the labial surfaces of all anterior teeth. VITA Easyshade Advance 4.0 was used to measure dental extrinsic stains changes. The analysis showed statistically significant efficacy of the tested toothpaste in reducing external dental stain caused by SDF, comparing to the placebo toothpaste, after one and two days of usage. The tested toothpaste was effective in reducing dental stain.

Allergenicity of orange juice and orange seeds: a clinical study.

PubMed

Zhu, S L; Ye, S T; Yu, Y

1989-06-01

Oranges are considered to be common allergenic fruits in China. They may induce severe food allergy in sensitive individuals. Allergic histories were analyzed in 26 orange-sensitive patients. Intradermal tests with extracts of orange juice and seeds were performed in 16 out of the 26 patients. P-K test was performed in one patient. The allergic history analysis suggested that clinical symptoms of some orange-allergic subjects were different from other fruit allergies but similar to nut and other oil plant seed allergies. The skin test and P-K test showed that the major allergenic components of orange reside in orange seeds instead of orange juice. Systemic reactions developed in 5 patients after intradermal tests with 1:20-200 (w/v) orange seed extracts. We considered that orange seed contains high potent allergens which may induce orange sensitivity due to careless chewing of orange seeds.

LabRS: A Rosetta stone for retrospective standardization of clinical laboratory test results.

PubMed

Hauser, Ronald George; Quine, Douglas B; Ryder, Alex

2018-02-01

Clinical laboratories in the United States do not have an explicit result standard to report the 7 billion laboratory tests results they produce each year. The absence of standardized test results creates inefficiencies and ambiguities for secondary data users. We developed and tested a tool to standardize the results of laboratory tests in a large, multicenter clinical data warehouse. Laboratory records, each of which consisted of a laboratory result and a test identifier, from 27 diverse facilities were captured from 2000 through 2015. Each record underwent a standardization process to convert the original result into a format amenable to secondary data analysis. The standardization process included the correction of typos, normalization of categorical results, separation of inequalities from numbers, and conversion of numbers represented by words (eg, "million") to numerals. Quality control included expert review. We obtained 1.266 × 109 laboratory records and standardized 1.252 × 109 records (98.9%). Of the unique unstandardized records (78.887 × 103), most appeared <5 times (96%, eg, typos), did not have a test identifier (47%), or belonged to an esoteric test with <100 results (2%). Overall, these 3 reasons accounted for nearly all unstandardized results (98%). Current results suggest that the tool is both scalable and generalizable among diverse clinical laboratories. Based on observed trends, the tool will require ongoing maintenance to stay current with new tests and result formats. Future work to develop and implement an explicit standard for test results would reduce the need to retrospectively standardize test results. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Marketing of personalized cancer care on the web: an analysis of Internet websites.

PubMed

Gray, Stacy W; Cronin, Angel; Bair, Elizabeth; Lindeman, Neal; Viswanath, Vish; Janeway, Katherine A

2015-05-01

Internet marketing may accelerate the use of care based on genomic or tumor-derived data. However, online marketing may be detrimental if it endorses products of unproven benefit. We conducted an analysis of Internet websites to identify personalized cancer medicine (PCM) products and claims. A Delphi Panel categorized PCM as standard or nonstandard based on evidence of clinical utility. Fifty-five websites, sponsored by commercial entities, academic institutions, physicians, research institutes, and organizations, that marketed PCM included somatic (58%) and germline (20%) analysis, interpretive services (15%), and physicians/institutions offering personalized care (44%). Of 32 sites offering somatic analysis, 56% included specific test information (range 1-152 tests). All statistical tests were two-sided, and comparisons of website content were conducted using McNemar's test. More websites contained information about the benefits than limitations of PCM (85% vs 27%, P < .001). Websites specifying somatic analysis were statistically significantly more likely to market one or more nonstandard tests as compared with standard tests (88% vs 44%, P = .04). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Strategy for allergenicity assessment of 'natural novel foods': clinical and molecular investigation of exotic vegetables (water spinach, hyacinth bean and Ethiopian eggplant).

PubMed

Gubesch, M; Theler, B; Dutta, M; Baumer, B; Mathis, A; Holzhauser, T; Vieths, S; Ballmer-Weber, B K

2007-11-01

Foods not commonly consumed in the European Union must be proven safe before being brought to market, including an assessment of allergenicity. We present a three-stepwise strategy for allergenicity assessment of natural novel foods using three novel vegetables, namely, water spinach, hyacinth bean, Ethiopian eggplant. First, vegetable extracts were analyzed for the presence of pan-allergens [Bet v 1 homologous proteins, profilins, nonspecific lipid transfer proteins (LTP)] by immunoblot analysis with specific animal antibodies. Secondly, the IgE-binding of the food extracts was investigated by EAST (Enzyme-allergosorbent test) and immunoblot analysis using sera with IgE-reactivity to known pan-allergens or to phylogenetically related foods from subjects (i) allergic to birch, grass and mugwort pollen, (ii) with food allergy to soy, peanut, tomato, multiple pollen-related foods and (iii) sensitized to LTP. Thirdly, the clinical relevance of IgE-binding was assessed in vivo by skin prick testing (SPT) and open oral food challenges (OFC). Profilin and LTP were detected by animal antibodies in all vegetables, a Bet v 1 homologue selectively in hyacinth bean. IgE-binding to LTP, profilin and a Bet v 1 homologue was proven by immunoblot analysis and EAST. Positive SPT and OFC results were observed for all vegetables in pollen-allergic patients. Our stepwise procedure confirmed the presence and IgE-binding capacity of novel vegetable proteins homologous to known allergens in endemic vegetable foods. In vivo testing proved the potential of the novel vegetables to elicit clinical allergy. Hence, our described algorithm seems to be applicable for allergenicity testing of natural novel foods.

Can we predict urinary stress incontinence by using demographic, clinical, imaging and urodynamic data?

PubMed

Wlaźlak, Edyta; Surkont, Grzegorz; Shek, Ka L; Dietz, Hans P

2015-10-01

It has been claimed that urethral hypermobility and resting urethral pressure can largely explain stress incontinence in women. In this study we tried to replicate these findings in an unselected cohort of women seen for urodynamic testing, including as many potential confounders as possible. This study is a retrospective analysis of data obtained from 341 women. They attended for urodynamic testing due to symptoms of pelvic floor dysfunction. We excluded from the analysis women with a history of previous anti-incontinence and prolapse surgery. All patients had a standardised clinical assessment, 4D transperineal pelvic floor ultrasound and multichannel urodynamic testing. Urodynamic stress incontinence (USI) was diagnosed by multichannel urodynamic testing. Its severity was subjectively graded as mild, moderate and severe. Candidate variables were: age, BMI, symptoms of prolapse, vaginal parity, significant prolapse (compartment-specific), levator avulsion, levator hiatal area, Oxford grading, midurethral mobility, maximum urethral pressure (MUP), maximum cough pressure and maximum Valsalva pressure reached. On binary logistic regression, the following parameters were statistically significant in predicting urodynamic stress incontinence: age (P=0.03), significant rectocele (P=0.02), max. abdominal pressure reached (negatively, P<0.0001), midurethral mobility (P=0.0004) and MUP (negatively, P<0.0001). On multivariate analysis, accounting for multiple interdependencies, the following predictors remained significant: max. abdominal pressure reached (negatively, P<0.0001), cough pressure (P=0.006), midurethral mobility (P=0.003) and MUP (negatively, P<0.0001), giving an R(2) of 0.24. Mid-urethral mobility and MUP are the main predictors of USI. Demographic and clinical data are at best weak predictors. Our results suggest the presence of major unrecognised confounders. Copyright © 2015. Published by Elsevier Ireland Ltd.

Detection of anti-neutrophil antibodies in autoimmune neutropenia of infancy: a multicenter study.

PubMed

Sella, Ruti; Flomenblit, Lena; Goldstein, Itamar; Kaplinsky, Chaim

2010-02-01

Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN is characterized by neutrophil count < 500 ml and a benign self-limiting course. Detecting specific antibodies against the polymorphic human neutrophil antigen usually confirms the diagnosis. Current available tests, however, are expensive and inapplicable in many laboratories as they require the use of isolated and fixed granulocytes obtained from donors pretyped for their distinct HNA alloform. To assess the performance of a modified test to identify by FACS-analysis granulocyte-specific antibodies in the sera of neutropenic children. We evaluated 120 children with a clinical suspicion of AIN, whose sera were analyzed by flow cytometry for the presence of autoantibodies using the indirect granulocyte immunofluorescence test. In contrast to the traditional tests, the sera were tested against randomly selected untyped neutrophils derived from a batch of 10 anonymous healthy subjects, presumably including the common HNA alloforms. Control sera samples were from patients with chemotherapy-induced, familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded. Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods. The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective tool for clinical decision making.

Using Theater to Teach Clinical Empathy: A Pilot Study

PubMed Central

Leong, David; Anderson, Aaron; Wenzel, Richard P.

2007-01-01

Background Clinical empathy, a critical skill for the doctor–patient relationship, is infrequently taught in graduate medical education. No study has tested if clinical empathy can be taught effectively. Objective To assess whether medicine residents can learn clinical empathy techniques from theater professors. Design A controlled trial of a clinical empathy curriculum taught and assessed by 4 theater professors. Setting Virginia Commonwealth University, Richmond, Virginia, a large urban university and health system. Participants Twenty Internal Medicine residents: 14 in the intervention group, 6 in the control group. Intervention Six hours of classroom instruction and workshop time with professors of theater. Measurements Scores derived from an instrument with 6 subscores designed to measure empathy in real-time patient encounters. Baseline comparisons were made using two-sample T tests. A mixed-effects analysis of variance model was applied to test for significance between the control and intervention groups. Results The intervention group demonstrated significant improvement (p ≤ .011) across all 6 subscores between pre-intervention and post-intervention observations. Compared to the control group, the intervention group had better posttest scores in 5 of 6 subscores (p ≤ .01). Limitations The study was neither randomized nor blinded. Conclusions Collaborative efforts between the departments of theater and medicine are effective in teaching clinical empathy techniques. PMID:17486385

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

PubMed

Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

2015-10-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol

PubMed Central

Koth, Laura L.; Maier, Lisa A.; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K.; Collman, Ronald G.; Hamzeh, Nabeel; Sweiss, Nadera J.; Zhang, Yingze; O’Neal, Scott; Senior, Robert M.; Becich, Michael; Hochheiser, Harry S.; Kaminski, Naftali; Wisniewski, Stephen R.; Gibson, Kevin F.

2015-01-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant’s clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis. PMID:26193069

A tool to include gamma analysis software into a quality assurance program.

PubMed

Agnew, Christina E; McGarry, Conor K

2016-03-01

To provide a tool to enable gamma analysis software algorithms to be included in a quality assurance (QA) program. Four image sets were created comprising two geometric images to independently test the distance to agreement (DTA) and dose difference (DD) elements of the gamma algorithm, a clinical step and shoot IMRT field and a clinical VMAT arc. The images were analysed using global and local gamma analysis with 2 in-house and 8 commercially available software encompassing 15 software versions. The effect of image resolution on gamma pass rates was also investigated. All but one software accurately calculated the gamma passing rate for the geometric images. Variation in global gamma passing rates of 1% at 3%/3mm and over 2% at 1%/1mm was measured between software and software versions with analysis of appropriately sampled images. This study provides a suite of test images and the gamma pass rates achieved for a selection of commercially available software. This image suite will enable validation of gamma analysis software within a QA program and provide a frame of reference by which to compare results reported in the literature from various manufacturers and software versions. Copyright © 2015. Published by Elsevier Ireland Ltd.

Supporting nursing student supervision: An assessment of an innovative approach to supervisor support.

PubMed

Browning, Mark; Pront, Leeanne

2015-06-01

The responsibility for clinical supervision is recognised by both the nursing literature and the Australian Nursing and Midwifery Council, through an expectation that RNs will provide support and facilitate student learning in the clinical environment (Atack et al., 2000; Gray and Smith, 2000; Brammer, 2005; Australian Nursing and Midwifery Council, 2006; Hallin and Danielson, 2008). RNs identify with and acknowledge the need for the supervisory role and are willing participants however, request strategies to guide and support students in the clinical environment (Bourbonnais and Kerr, 2007; Hallin and Danielson, 2008). The aim of this study was to provide a means of support to clinical supervisors of nursing students through a computer-based clinical supervisor educational package (CSEP) and to test the effectiveness of the CSEP. The effectiveness of the CSEP was determined by a pre-test-post-test evaluation sheet that included open and Likert scale questions. 4 regional hospitals in South Australia, Australia. 28 participants completed the questionnaire on their experience with the CSEP. Analysis of quantitative data utilised non-parametric testing with SPSS version 20. A Wilcoxon Signed Rank Test was performed on the Likert scale questions to establish any significant difference between the pre- and post-tests. The responses to the open-ended questions were thematically analysed separately by the two authors. The themes were then amalgamated. The results were then compared to find similarities or differences. The CSEP is an effective education package in promoting increased preparedness to supervise and increased confidence to promote learning. Copyright © 2015 Elsevier Ltd. All rights reserved.

EMG of the hip adductor muscles in six clinical examination tests.

PubMed

Lovell, Gregory A; Blanch, Peter D; Barnes, Christopher J

2012-08-01

To assess activation of muscles of hip adduction using EMG and force analysis during standard clinical tests, and compare athletes with and without a prior history of groin pain. Controlled laboratory study. 21 male athletes from an elite junior soccer program. Bilateral surface EMG recordings of the adductor magnus, adductor longus, gracilis and pectineus as well as a unilateral fine-wire EMG of the pectineus were made during isometric holds in six clinical examination tests. A load cell was used to measure force data. Test type was a significant factor in the EMG output for all four muscles (all muscles p < 0.01). EMG activation was highest in Hips 0 or Hips 45 for adductor magnus, adductor longus and gracilis. EMG activation for pectineus was highest in Hips 90. Injury history was a significant factor in the EMG output for the adductor longus (p < 0.05), pectineus (p < 0.01) and gracilis (p < 0.01) but not adductor magnus. For force data, clinical test type was a significant factor (p < 0.01) with Hips 0 being significantly stronger than Hips 45, Hips 90 and Side lay. BMI (body mass index) was a significant factor (p < 0.01) for producing a higher force. All other factors had no significant effect on the force outputs. Hip adduction strength assessment is best measured at hips 0 (which produced most force) or 45° flexion (which generally gave the highest EMG output). Muscle EMG varied significantly with clinical test position. Athletes with previous groin injury had a significant fall in some EMG outputs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Northwestern University Flexible Subischial Vacuum Socket for persons with transfemoral amputation: Part 2 Description and Preliminary evaluation

PubMed Central

Fatone, Stefania; Caldwell, Ryan

2017-01-01

Background: Current transfemoral prosthetic sockets are problematic as they restrict function, lack comfort, and cause residual limb problems. Development of a subischial socket with lower proximal trim lines is an appealing way to address this problem and may contribute to improving quality of life of persons with transfemoral amputation. Objectives: The purpose of this study was to illustrate the use of a new subischial socket in two subjects. Study design: Case series. Methods: Two unilateral transfemoral prosthesis users participated in preliminary socket evaluations comparing functional performance of the new subischial socket to ischial containment sockets. Testing included gait analysis, socket comfort score, and performance-based clinical outcome measures (Rapid-Sit-To-Stand, Four-Square-Step-Test, and Agility T-Test). Results: For both subjects, comfort was better in the subischial socket, while gait and clinical outcomes were generally comparable between sockets. Conclusion: While these evaluations are promising regarding the ability to function in this new socket design, more definitive evaluation is needed. Clinical relevance Using gait analysis, socket comfort score and performance-based outcome measures, use of the Northwestern University Flexible Subischial Vaccum Socket was evaluated in two transfemoral prosthesis users. Socket comfort improved for both subjects with comparable function compared to ischial containment sockets. PMID:28132589

On the design and analysis of clinical trials with correlated outcomes

PubMed Central

Follmann, Dean; Proschan, Michael

2014-01-01

SUMMARY The convention in clinical trials is to regard outcomes as independently distributed, but in some situations they may be correlated. For example, in infectious diseases, correlation may be induced if participants have contact with a common infectious source, or share hygienic tips that prevent infection. This paper discusses the design and analysis of randomized clinical trials that allow arbitrary correlation among all randomized volunteers. This perspective generalizes the traditional perspective of strata, where patients are exchangeable within strata, and independent across strata. For theoretical work, we focus on the test of no treatment effect μ1 − μ0 = 0 when the n dimensional vector of outcomes follows a Gaussian distribution with known n × n covariance matrix Σ, where the half randomized to treatment (placebo) have mean response μ1 (μ0). We show how the new test corresponds to familiar tests in simple situations for independent, exchangeable, paired, and clustered data. We also discuss the design of trials where Σ is known before or during randomization of patients and evaluate randomization schemes based on such knowledge. We provide two complex examples to illustrate the method, one for a study of 23 family clusters with cardiomyopathy, the other where the malaria attack rates vary within households and clusters of households in a Malian village. PMID:25111420

Biochemical and Molecular Analysis of Staphylococcus aureus Clinical Isolates from Hospitalized Patients.

PubMed

Karmakar, Amit; Dua, Parimal; Ghosh, Chandradipa

2016-01-01

Staphylococcus aureus is opportunistic human as well as animal pathogen that causes a variety of diseases. A total of 100 Staphylococcus aureus isolates were obtained from clinical samples derived from hospitalized patients. The presumptive Staphylococcus aureus clinical isolates were identified phenotypically by different biochemical tests. Molecular identification was done by PCR using species specific 16S rRNA primer pairs and finally 100 isolates were found to be positive as Staphylococcus aureus. Screened isolates were further analyzed by several microbiological diagnostics tests including gelatin hydrolysis, protease, and lipase tests. It was found that 78%, 81%, and 51% isolates were positive for gelatin hydrolysis, protease, and lipase activities, respectively. Antibiogram analysis of isolated Staphylococcus aureus strains with respect to different antimicrobial agents revealed resistance pattern ranging from 57 to 96%. Our study also shows 70% strains to be MRSA, 54.3% as VRSA, and 54.3% as both MRSA and VRSA. All the identified isolates were subjected to detection of mecA, nuc, and hlb genes and 70%, 84%, and 40% were found to harbour mecA, nuc, and hlb genes, respectively. The current investigation is highly important and informative for the high level multidrug resistant Staphylococcus aureus infections inclusive also of methicillin and vancomycin.

Analysis of risk factors for mild cognitive impairment based on word list memory test results and questionnaire responses in healthy Japanese individuals registered in an online database.

PubMed

Ogawa, Masayo; Sone, Daichi; Maruo, Kazushi; Shimada, Hiroyuki; Suzuki, Keisuke; Watanabe, Hiroshi; Matsuda, Hiroshi; Mizusawa, Hidehiro

2018-01-01

Although the development of effective therapeutic drugs and radical treatment options for dementia and Alzheimer's disease (AD) remains urgent, progress in recent clinical trials of AD drugs has been less than adequate. In order to advance the progress of clinical trials, it is necessary to establish more efficient methods of recruitment. In Japan, there are registration systems stratified by mild cognitive impairment and preclinical and clinical stages of early and advanced stage dementia, but there is no registration system for healthy individuals yet. Therefore, in the present study, we developed a large-scale, internet-based health registry to investigate factors associated with cognitive function among registered participants. A total of 1038 participants completed the initial questionnaire and word list memory test. Among these participants, 353 individuals completed a second questionnaire and memory test. Stepwise multiple regression analysis was performed using IBM SPSS version 23.0 for Windows at a statistical significance level of p<0.05. We found that mood, motivation, and a decreased ability to perform activities of daily living were significantly associated with cognitive function. The results of the present study suggest that maintaining social involvement is important to prevent decreases in physical activity, daily function, mood, and motivation.

Procuring interoperability at the expense of usability: a case study of UK National Programme for IT assurance process.

PubMed

Krause, Paul; de Lusignan, Simon

2010-01-01

The allure of interoperable systems is that they should improve patient safety and make health services more efficient. The UK's National Programme for IT has made great strides in achieving interoperability; through linkage to a national electronic spine. However, there has been criticism of the usability of the applications in the clinical environment. Analysis of the procurement and assurance process to explore whether they predetermine usability. Processes separate developers from users, and test products against theoretical assurance models of use rather than simulate or pilot in a clinical environment. The current process appears to be effective for back office systems and high risk applications, but too inflexible for developing applications for the clinical setting. For clinical applications agile techniques are more appropriate. Usability testing should become an integrated part of the contractual process and be introduced earlier in the development process.

Assessing the Effectiveness of a School-Based Dental Clinic on the Oral Health of Children Who Lack Access to Dental Care: A Program Evaluation

ERIC Educational Resources Information Center

Carpino, Rachel; Walker, Mary P.; Liu, Ying; Simmer-Beck, Melanie

2017-01-01

This program evaluation examines the effectiveness of a school-based dental clinic. A repeated-measures design was used to longitudinally examine secondary data from participants (N = 293). Encounter intensity was developed to normalize data. Multivariate analysis of variance and Kruskal-Wallis test were used to investigate the effect of encounter…

Cleveland Clinic Rehabilitation Research Program

DTIC Science & Technology

2014-10-01

risks have been identified that would require a new risk analysis. The study is now registered as a pilot clinical trial. Use of tDCS , TMS and structural...using behavioral recording and electroencephalographic ( EEG ) recording and results were published. Study 2: The motor cortex (M1) and the...four pilot projects. Study 1: Magnetic stimulation and epilepsy In this study, transcranial magnetic stimulation ( TMS ) will be tested for its

Stakeholder attitudes and needs regarding cell-free fetal DNA testing.

PubMed

Hill, Melissa; Lewis, Celine; Chitty, Lyn S

2016-04-01

To explore stakeholder views on cell-free DNA testing and highlight findings important for successful implementation and the provision of best practice in counseling. Noninvasive tests based on the analysis of cell-free fetal DNA are now widely available in clinical practice and applications are expanding rapidly. It is essential that stakeholder views are considered in order to identify and address any ethical and social issues. We provide an overview of stakeholder viewpoints and then focus on the key issues of informed decision making, test uptake, service delivery and information sources. Stakeholders are positive about the introduction of cell-free fetal DNA testing into clinical practice. They describe both practical and psychological benefits arising from tests that are safe and can potentially be performed earlier in pregnancy. Key concerns, which include the potential for these tests to have a negative impact on informed decision making and increased societal pressure to have testing, can be addressed through careful parent-directed counseling. As applications for these tests expand it is increasingly important to develop innovative approaches to facilitate good understanding for parents who are offered noninvasive prenatal testing.

MTB-DR-RIF 9G test: Detection and discrimination of tuberculosis and multi-drug resistant tuberculosis strains.

PubMed

Song, Keum-Soo; Nimse, Satish Balasaheb; Cho, Nam Hoon; Sung, Nackmoon; Kim, Hee-Jin; Yang, Jeongseong; Kim, Taisun

2015-12-01

This report describes the evaluation of the novel MTB-DR-RIF 9G test for the accurate detection and discrimination of Mycobacterium tuberculosis (MTB) and rifampicin-resistant M. tuberculosis (MTB-DR-RIF) in the clinical samples. The procedure included the amplification of a nucleotide fragment of the rpoB gene of the MTB and MTB-DR-RIF strains and their hybridization with the immobilized probes. The MTB-DR-RIF 9G test was evaluated for its ability to detect and discriminate MTB and MTB-DR-RIF strains in 113 known clinical samples. The accuracy of the MTB-DR-RIF 9G test was determined by comparing its results with sequencing analysis and drug susceptibility testing. The sensitivity and specificity of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 95.4% (89.5-98.5) and 100% (69.2-100), respectively. The positive predictive value and negative predictive value of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 100% (85.0-95.9) and 66.7% (38.4-88.18), respectively. Sequencing analysis of all samples indicated that the mutations present in the regions identified with the MTB-DR-RIF 9G assay can be detected accurately. Copyright © 2015 Elsevier Ltd. All rights reserved.

Studies and applications of NiTi shape memory alloys in the medical field in China.

PubMed

Dai, K; Chu, Y

1996-01-01

The biomedical study of NiTi shape memory alloys has been undertaken in China since 1978. A series of stimulating corrosion tests, histological observations, toxicity tests, carcinogenicity tests, trace nickel elements analysis and a number of clinical trials have been conducted. The results showed that the NiTi shape memory alloy is a good biomaterial with good biocompatibility and no obvious local tissue reaction, carcinogenesis or erosion of implants were found experimentally or clinically. In 1981, on the basis of fundamental studies, a shape memory staple was used for the first time inside the human body. Subsequently, various shape memory devices were designed and applied clinically for internal fixation of fractures, spine surgery, endoprostheses, gynaecological and craniofacial surgery. Since 1990, a series of internal stents have been developed for the management of biliary, tracheal and esophageal strictures and urethrostenosis as well as vascular obturator for tumour management. Several thousand cases have been treated and had a 1-10 year follow-up and good clinical results with a rather low complication rate were obtained.

From differences in means between cases and controls to risk stratification: a business plan for biomarker development.

PubMed

Wentzensen, Nicolas; Wacholder, Sholom

2013-02-01

Researchers developing biomarkers for early detection can determine the potential for clinical benefit at early stages of development. We provide the theoretical background showing the quantitative connection between biomarker levels in cases and controls and clinically meaningful risk measures, as well as a spreadsheet for researchers to use in their own research. We provide researchers with tools to decide whether a test is useful, whether it needs technical improvement, whether it may work only in specific populations, or whether any further development is futile. The methods described here apply to any method that aims to estimate risk of disease based on biomarkers, clinical tests, genetics, environment, or behavior. Many efforts go into futile biomarker development and premature clinical testing. In many instances, predictions for translational success or failure can be made early, simply based on critical analysis of case–control data. Our article presents well-established theory in a form that can be appreciated by biomarker researchers. Furthermore, we provide an interactive spreadsheet that links biomarker performance with specific disease characteristics to evaluate the promise of biomarker candidates at an early stage.

Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios

PubMed Central

Majzoub, Ahmad; Esteves, Sandro C.; Ko, Edmund; Ramasamy, Ranjith; Zini, Armand

2016-01-01

Sperm DNA fragmentation (SDF) has been generally acknowledged as a valuable tool for male fertility evaluation. While its detrimental implications on sperm function were extensively investigated, little is known about the actual indications for performing SDF analysis. This review delivers practice based recommendations on commonly encountered scenarios in the clinic. An illustrative description of the different SDF measurement techniques is presented. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. High SDF is also linked with recurrent spontaneous abortion (RSA) and can influence outcomes of different assisted reproductive techniques. Several studies have shown some benefit in using testicular sperm rather than ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with evidence of exposure to pollutants can benefit from sperm DNA testing as it can help reinforce the importance of lifestyle modification (e.g., cessation of cigarette smoking, antioxidant therapy), predict fertility and monitor the patient’s response to intervention. PMID:28078226

Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis.

PubMed

Nolan, Danielle; Carlson, Martha

2016-06-01

Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype-based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations. © The Author(s) 2016.

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group

PubMed Central

Frerichs, Inéz; Amato, Marcelo B P; van Kaam, Anton H; Tingay, David G; Zhao, Zhanqi; Grychtol, Bartłomiej; Bodenstein, Marc; Gagnon, Hervé; Böhm, Stephan H; Teschner, Eckhard; Stenqvist, Ola; Mauri, Tommaso; Torsani, Vinicius; Camporota, Luigi; Schibler, Andreas; Wolf, Gerhard K; Gommers, Diederik; Leonhardt, Steffen; Adler, Andy

2017-01-01

Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology. PMID:27596161

Association factor analysis between osteoporosis with cerebral artery disease: The STROBE study.

PubMed

Jin, Eun-Sun; Jeong, Je Hoon; Lee, Bora; Im, Soo Bin

2017-03-01

The purpose of this study was to determine the clinical association factors between osteoporosis and cerebral artery disease in Korean population. Two hundred nineteen postmenopausal women and men undergoing cerebral computed tomography angiography were enrolled in this study to evaluate the cerebral artery disease by cross-sectional study. Cerebral artery disease was diagnosed if there was narrowing of 50% higher diameter in one or more cerebral vessel artery or presence of vascular calcification. History of osteoporotic fracture was assessed using medical record, and radiographic data such as simple radiography, MRI, and bone scan. Bone mineral density was checked by dual-energy x-ray absorptiometry. We reviewed clinical characteristics in all patients and also performed subgroup analysis for total or extracranial/ intracranial cerebral artery disease group retrospectively. We performed statistical analysis by means of chi-square test or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon's rank sum test for continuous variables. We also used univariate and multivariate logistic regression analyses were conducted to assess the factors associated with the prevalence of cerebral artery disease. A two-tailed p-value of less than 0.05 was considered as statistically significant. All statistical analyses were performed using R (version 3.1.3; The R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 14.0; SPSS, Inc, Chicago, Ill, USA). Of the 219 patients, 142 had cerebral artery disease. All vertebral fracture was observed in 29 (13.24%) patients. There was significant difference in hip fracture according to the presence or absence of cerebral artery disease. In logistic regression analysis, osteoporotic hip fracture was significantly associated with extracranial cerebral artery disease after adjusting for multiple risk factors. Females with osteoporotic hip fracture were associated with total calcified cerebral artery disease. Some clinical factors such as age, hypertension, and osteoporotic hip fracture, smoking history and anti-osteoporosis drug use were associated with cerebral artery disease.

Clinical experience using a 5-week treadmill training program with virtual reality to enhance gait in an ambulatory physical therapy service.

PubMed

Shema, Shirley Roth; Brozgol, Marina; Dorfman, Moran; Maidan, Inbal; Sharaby-Yeshayahu, Lior; Malik-Kozuch, Hila; Wachsler Yannai, Orly; Giladi, Nir; Hausdorff, Jeffrey M; Mirelman, Anat

2014-09-01

Current literature views safe gait as a complex task, relying on motor and cognitive resources. The use of virtual reality (VR) in gait training offers a multifactorial approach, showing positive effects on mobility, balance, and fall risk in elderly people and individuals with neurological disorders. This form of training has been described as a viable research tool; however, it has not been applied routinely in clinical practice. Recently, VR was used to develop an adjunct training method for use by physical therapists in an ambulatory clinical setting. The aim of this article is to describe the initial clinical experience of applying a 5-week VR clinical service to improve gait and mobility in people with a history of falls, poor mobility, or postural instability. A retrospective data analysis was conducted. The clinical records of the first 60 patients who completed the VR gait training program were examined. Training was provided 3 times per week for 5 weeks, with each session lasting approximately 1 hour and consisting of walking on a treadmill while negotiating virtual obstacles. Main outcome measures were compared across time and included the Timed "Up & Go" Test (TUG), the Two-Minute Walk Test (2MWT), and the Four Square Step Test (FSST). After 5 weeks of training, time to complete the TUG decreased by 10.3%, the distance walked during the 2MWT increased by 9.5%, and performance on the FSST improved by 13%. Limitations of the study include the use of a retrospective analysis with no control group and the lack of objective cognitive assessment. Treadmill training with VR appears to be an effective and practical tool that can be applied in an outpatient physical therapy clinic. This training apparently leads to improvements in gait, mobility, and postural control. It, perhaps, also may augment cognitive and functional aspects. © 2014 American Physical Therapy Association.

Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool.

PubMed

Ramsey, Danielle; Scoto, Mariacristina; Mayhew, Anna; Main, Marion; Mazzone, Elena S; Montes, Jacqueline; de Sanctis, Roberto; Dunaway Young, Sally; Salazar, Rachel; Glanzman, Allan M; Pasternak, Amy; Quigley, Janet; Mirek, Elizabeth; Duong, Tina; Gee, Richard; Civitello, Matthew; Tennekoon, Gihan; Pane, Marika; Pera, Maria Carmela; Bushby, Kate; Day, John; Darras, Basil T; De Vivo, Darryl; Finkel, Richard; Mercuri, Eugenio; Muntoni, Francesco

2017-01-01

Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are 'fit for purpose'. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials.

The construct validity of the Major Depression Inventory: A Rasch analysis of a self-rating scale in primary care.

PubMed

Nielsen, Marie Germund; Ørnbøl, Eva; Vestergaard, Mogens; Bech, Per; Christensen, Kaj Sparle

2017-06-01

We aimed to assess the measurement properties of the ten-item Major Depression Inventory when used on clinical suspicion in general practice by performing a Rasch analysis. General practitioners asked consecutive persons to respond to the web-based Major Depression Inventory on clinical suspicion of depression. We included 22 practices and 245 persons. Rasch analysis was performed using RUMM2030 software. The Rasch model fit suggests that all items contribute to a single underlying trait (defined as internal construct validity). Mokken analysis was used to test dimensionality and scalability. Our Rasch analysis showed misfit concerning the sleep and appetite items (items 9 and 10). The response categories were disordered for eight items. After modifying the original six-point to a four-point scoring system for all items, we achieved ordered response categories for all ten items. The person separation reliability was acceptable (0.82) for the initial model. Dimensionality testing did not support combining the ten items to create a total score. The scale appeared to be well targeted to this clinical sample. No significant differential item functioning was observed for gender, age, work status and education. The Rasch and Mokken analyses revealed two dimensions, but the Major Depression Inventory showed fit to one scale if items 9 and 10 were excluded. Our study indicated scalability problems in the current version of the Major Depression Inventory. The conducted analysis revealed better statistical fit when items 9 and 10 were excluded. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurocognitive function in clinically stable individuals with long-term bipolar I disorder: Comparisons with schizophrenia patients and controls.

PubMed

Lin, Pei-Yun; Wang, Peng-Wei; Chen, Cheng-Sheng; Yen, Cheng-Fang

2017-05-01

This study compared the levels of the five domains of neurocognitive function-executive function, attention, memory, verbal comprehension, and perceptual organization-among clinically stable individuals with long-term bipolar I disorder, individuals with long-term schizophrenia, and a group of controls. We recruited a total of 93 clinically stable individuals with bipolar I disorder, 94 individuals with schizophrenia, and 106 controls in this study. Their neurocognitive function was measured using a series of neurocognitive function tests: the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), Line Cancellation Test, Visual Form Discrimination, Controlled Oral Word Association Test, Wisconsin Card Sorting Test, Continuous Performance Task, and Wechsler Memory Scale-Third Edition. Neurocognitive function was compared among the three groups through a multivariate analysis of variance. The results indicated that when the effect of age was controlled, clinically stable individuals with bipolar I disorder and those with schizophrenia demonstrated poor neurocognitive function on all tests except for the WAIS-III Similarity and Information and the Line Cancellation Test. The individuals with bipolar I disorder had similar levels of neurocognitive function compared with the schizophrenia group, but higher levels of neurocognitive function on the WAIS-III Comprehension, Controlled Oral Word Association Test, and Wechsler Memory Scale-Third Edition Auditory Immediate and Delayed Index and Visual Immediate and Delayed Index. The conclusions of this study suggest that compared with controls, individuals with long-term bipolar I disorder and those with long-term schizophrenia have poorer neurocognitive function, even when clinically stable. Individuals with long-term bipolar I disorder and those with long-term schizophrenia have similar levels of deficits in several domains of neurocognitive function. Copyright © 2017. Published by Elsevier Taiwan.

Monothermal caloric screening test performance: a relative operating characteristic curve analysis.

PubMed

Murnane, Owen D; Akin, Faith W; Lynn, Susan G; Cyr, David G

2009-06-01

The objective of the present study was to evaluate the performance of the monothermal caloric screening test in a large sample of patients. A retrospective analysis of the medical records of 1002 consecutive patients who had undergone vestibular assessment at the Mayo Clinic during the years 1989 and 1990 was conducted. Patients with incomplete alternate binaural bithermal (ABB) caloric testing, congenital or periodic alternating nystagmus, or bilateral vestibular loss were excluded from the study. Clinical decision theory analyses (relative operating characteristic curves) were used to determine the accuracy with which the monothermal warm (MWST) and monothermal cool (MCST) caloric screening tests predicted the results of the ABB caloric test. Cumulative distributions were constructed as a function of the cutoff points for monothermal interear difference (IED) to select the cutoff point associated with any combination of true-positive and false-positive rates. Both MWST and MCST performed well above chance level. The test performance for the MWST was significantly better than that of the MCST for three of the four ABB gold standards. A 10% IED cutoff point for the MWST yielded a false-negative rate of either 1% (UW >or=25%) or 3% (UW >or=20%). The use of a 10% IED (UW >or=25%) for the MWST would have resulted in a 40% reduction (N = 294) in the number of ABB caloric tests performed on patients without a unilateral weakness. The results of this study indicated that the MWST decreases test time without sacrificing the sensitivity of the ABB caloric test.

Challenges of Maintaining Good Clinical Laboratory Practices in Low-Resource Settings:  A Health Program Evaluation Framework Case Study From East Africa.

PubMed

Zhang, Helen L; Omondi, Michael W; Musyoka, Augustine M; Afwamba, Isaac A; Swai, Remigi P; Karia, Francis P; Muiruri, Charles; Reddy, Elizabeth A; Crump, John A; Rubach, Matthew P

2016-08-01

Using a clinical research laboratory as a case study, we sought to characterize barriers to maintaining Good Clinical Laboratory Practice (GCLP) services in a developing world setting. Using a US Centers for Disease Control and Prevention framework for program evaluation in public health, we performed an evaluation of the Kilimanjaro Christian Medical Centre-Duke University Health Collaboration clinical research laboratory sections of the Kilimanjaro Clinical Research Institute in Moshi, Tanzania. Laboratory records from November 2012 through October 2014 were reviewed for this analysis. During the 2-year period of study, seven instrument malfunctions suspended testing required for open clinical trials. A median (range) of 9 (1-55) days elapsed between instrument malfunction and biomedical engineer service. Sixteen (76.1%) of 21 suppliers of reagents, controls, and consumables were based outside Tanzania. Test throughput among laboratory sections used a median (range) of 0.6% (0.2%-2.7%) of instrument capacity. Five (55.6%) of nine laboratory technologists left their posts over 2 years. These findings demonstrate that GCLP laboratory service provision in this setting is hampered by delays in biomedical engineer support, delays and extra costs in commodity procurement, low testing throughput, and high personnel turnover. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Correlation of clinical examination characteristics with three sources of chronic low back pain.

PubMed

Young, Sharon; Aprill, Charles; Laslett, Mark

2003-01-01

Research has demonstrated some progress in using a clinical examination to predict discogenic or sacroiliac (SI) joint sources of pain. No clear predictors of symptomatic lumbar zygapophysial joints have yet been demonstrated. To identify significant components of a clinical examination that are associated with symptomatic lumbar discs, zygapophysial joints and SI joints. A prospective, criterion-related concurrent validity study performed at a private radiology practice specializing in spinal diagnostics. The sample consisted of 81 patients with chronic lumbopelvic pain referred for diagnostic injections. Contingency tables were constructed for nine features of the clinical evaluation compared with the results of diagnostic injections. Statistical analysis included chi-squared test for independence, phi and odds ratios with confidence intervals. Patients received blinded clinical examinations by physical therapists, and diagnostic injections were used as the criterion standard. Significant relationships were found between discogenic pain and centralization of pain during repeated movement testing, and pain when rising from sitting. Lumbar zygapophysial joint pain was associated with absence of pain when rising from sitting. Sacroiliac joint pain was related to three or more positive pain provocation tests, pain when rising from sitting, unilateral pain and absence of lumbar pain. Significant correlations exist between clinical examination findings and symptomatic lumbar discs, zygapophysial and SI joints. The strongest relationships were seen between SI joint pain and three or more positive pain provocation tests, centralization of pain for symptomatic discs and absence of pain when rising from sitting for symptomatic lumbar zygapophysial joints.

Lesion correlates of patholinguistic profiles in chronic aphasia: comparisons of syndrome-, modality- and symptom-level assessment.

PubMed

Henseler, Ilona; Regenbrecht, Frank; Obrig, Hellmuth

2014-03-01

One way to investigate the neuronal underpinnings of language competence is to correlate patholinguistic profiles of aphasic patients to corresponding lesion sites. Constituting the beginnings of aphasiology and neurolinguistics over a century ago, this approach has been revived and refined in the past decade by statistical approaches mapping continuous variables (providing metrics that are not simply categorical) on voxel-wise lesion information (voxel-based lesion-symptom mapping). Here we investigate whether and how voxel-based lesion-symptom mapping allows us to delineate specific lesion patterns for differentially fine-grained clinical classifications. The latter encompass 'classical' syndrome-based approaches (e.g. Broca's aphasia), more symptom-oriented descriptions (e.g. agrammatism) and further refinement to linguistic sub-functions (e.g. lexico-semantic deficits for inanimate versus animate items). From a large database of patients treated for aphasia of different aetiologies (n = 1167) a carefully selected group of 102 first ever ischaemic stroke patients with chronic aphasia (∅ 12 months) were included in a VLSM analysis. Specifically, we investigated how performance in the Aachen Aphasia Test-the standard clinical test battery for chronic aphasia in German-relates to distinct brain lesions. The Aachen Aphasia Test evaluates aphasia on different levels: a non-parametric discriminant procedure yields probabilities for the allocation to one of the four 'standard' syndromes (Broca, Wernicke, global and amnestic aphasia), whereas standardized subtests target linguistic modalities (e.g. repetition), or even more specific symptoms (e.g. phoneme repetition). Because some subtests of the Aachen Aphasia Test (e.g. for the linguistic level of lexico-semantics) rely on rather coarse and heterogeneous test items we complemented the analysis with a number of more detailed clinically used tests in selected mostly mildly affected subgroups of patients. Our results indicate that: (i) Aachen Aphasia Test-based syndrome allocation allows for an unexpectedly concise differentiation between 'Broca's' and 'Wernicke's' aphasia corresponding to non-overlapping anterior and posterior lesion sites; whereas (ii) analyses for modalities and specific symptoms yielded more circumscribed but partially overlapping lesion foci, often cutting across the above syndrome territories; and (iii) especially for lexico-semantic capacities more specialized clinical test-batteries are required to delineate precise lesion patterns at this linguistic level. In sum this is the first report on a successful lesion-delineation of syndrome-based aphasia classification highlighting the relevance of vascular distribution for the syndrome level while confirming and extending a number of more linguistically motivated differentiations, based on clinically used tests. We consider such a comprehensive view reaching from the syndrome to a fine-grained symptom-oriented assessment mandatory to converge neurolinguistic, patholinguistic and clinical-therapeutic knowledge on language-competence and impairment.

The combination of pH monitoring in the most distal esophagus and symptom association analysis markedly improves the clinical value of esophageal pH tests.

PubMed

Hall, Mats Guerrero Garcia; Wenner, Jörgen; Öberg, Stefan

2016-01-01

The poor sensitivity of esophageal pH monitoring substantially limits the clinical value of the test. The aim of this study was to compare the diagnostic accuracy of esophageal pH monitoring and symptom association analysis performed at the conventional level with that obtained in the most distal esophagus. Eighty-two patients with typical reflux symptoms and 49 asymptomatic subjects underwent dual 48-h pH monitoring with the electrodes positioned immediately above, and 6 cm above the squamo-columnar junction (SCJ). The degree of esophageal acid exposure and the temporal relationship between reflux events and symptoms were evaluated. The sensitivity of pH recording and the diagnostic yield of Symptom Association Probability (SAP) were significantly higher for pH monitoring performed at the distal compared with the conventional level (82% versus 65%, p<0.001 and 74% versus 62%, p<0.001, respectively). The greatest improvement was observed in patients with non-erosive disease. In this group, the sensitivity increased from 46% at the standard level to 66% immediately above the SCJ, and with the combination of a positive SAP as a marker for a positive pH test, the diagnostic yield further increased to 94%. The diagnostic accuracy of esophageal pH monitoring in the most distal esophagus is superior to that performed at the conventional level and it is further improved with the combination of symptom association analysis. PH monitoring with the pH electrode positioned immediately above the SCJ should be introduced in clinical practice and always combined with symptom association analysis.

Progressive resistance training in Parkinson's disease: a systematic review and meta-analysis

PubMed Central

Saltychev, Mikhail; Bärlund, Esa; Paltamaa, Jaana; Katajapuu, Niina; Laimi, Katri

2016-01-01

Objectives To investigate if there is evidence on effectiveness of progressive resistance training in rehabilitation of Parkinson disease. Design Systematic review and meta-analysis. Data sources: Central, Medline, Embase, Cinahl, Web of Science, Pedro until May 2014. Randomised controlled or controlled clinical trials. The methodological quality of studies was assessed according to the Cochrane Collaboration's domain-based evaluation framework. Data synthesis: random effects meta-analysis with test for heterogeneity using the I² and pooled estimate as the raw mean difference. Participants Adults with primary/idiopathic Parkinson's disease of any severity, excluding other concurrent neurological condition. Interventions Progressive resistance training defined as training consisting of a small number of repetitions until fatigue, allowing sufficient rest between exercises for recovery, and increasing the resistance as the ability to generate force improves. Comparison Progressive resistance training versus no treatment, placebo or other treatment in randomised controlled or controlled clinical trials. Primary and secondary outcome measures Any outcome. Results Of 516 records, 12 were considered relevant. Nine of them had low risk of bias. All studies were randomised controlled trials conducted on small samples with none or 1 month follow-up after the end of intervention. Of them, six were included in quantitative analysis. Pooled effect sizes of meta-analyses on fast and comfortable walking speed, the 6 min walking test, Timed Up and Go test and maximal oxygen consumption were below the level of minimal clinical significance. Conclusions There is so far no evidence on the superiority of progressive resistance training compared with other physical training to support the use of this technique in rehabilitation of Parkinson's disease. Systematic review registration number PROSPERO 2014:CRD42014009844. PMID:26743698

Identification of Clinical Isolates of Mycobacteria with Gas-Liquid Chromatography Alone

PubMed Central

Tisdall, Philip A.; Roberts, Glenn D.; Anhalt, John P.

1979-01-01

Identification of 18 mycobacterial species was performed by analysis of profiles obtained by using gas-liquid chromatography. Organisms were saponified in methanolic NaOH, and the reaction mixture was treated with BF3 in methanol and extracted with a hexane-chloroform mixture. An identification scheme was developed from 128 stock strains and tested against a collection of 79 clinical isolates. By using gas-liquid chromatographic profiles alone, 58% of specimens were correctly identified to species level, and an additional 41% were correctly identified to a group of two or three organisms. Use in a clinical laboratory over a 2-month period proved chromatography to be as accurate as and more rapid than concurrent biochemical testing. Of 81 isolates tested, 64% were identified to species level by chromatography alone. An additional 35% were differentiated to the same groups of two or three organisms as found in our analysis of stock strains. These groups consisted of: Mycobacterium tuberculosis, M. bovis, and M. xenopi; M. avium complex, M. gastri, and M. scrofulaceum; or M. fortuitum and M. chelonei. Identification to species level from these groups could usually be done by colonial morphology alone and could always be done by the addition of one selected biochemical test. This study demonstrated the practical application of gas-liquid chromatography in the identification of mycobacteria in a clinical laboratory. In particular, all strains of M. gordonae and M. kansasii were identified to species level. M. tuberculosis was definitively identified in 85% of cases. When it could not be definitely identified, the only alternatives were M. bovis and M. xenopi, both of which are rare causes of infection. PMID:118984

Tips and Tricks for Successful Application of Statistical Methods to Biological Data.

PubMed

Schlenker, Evelyn

2016-01-01

This chapter discusses experimental design and use of statistics to describe characteristics of data (descriptive statistics) and inferential statistics that test the hypothesis posed by the investigator. Inferential statistics, based on probability distributions, depend upon the type and distribution of the data. For data that are continuous, randomly and independently selected, as well as normally distributed more powerful parametric tests such as Student's t test and analysis of variance (ANOVA) can be used. For non-normally distributed or skewed data, transformation of the data (using logarithms) may normalize the data allowing use of parametric tests. Alternatively, with skewed data nonparametric tests can be utilized, some of which rely on data that are ranked prior to statistical analysis. Experimental designs and analyses need to balance between committing type 1 errors (false positives) and type 2 errors (false negatives). For a variety of clinical studies that determine risk or benefit, relative risk ratios (random clinical trials and cohort studies) or odds ratios (case-control studies) are utilized. Although both use 2 × 2 tables, their premise and calculations differ. Finally, special statistical methods are applied to microarray and proteomics data, since the large number of genes or proteins evaluated increase the likelihood of false discoveries. Additional studies in separate samples are used to verify microarray and proteomic data. Examples in this chapter and references are available to help continued investigation of experimental designs and appropriate data analysis.

Psychosocial and Clinical Factors Associated with Family Communication of Cancer Genetic Test Results Among Women Diagnosed with Breast Cancer at a Young Age

PubMed Central

Elrick, Ashley; Ashida, Sato; Ivanovich, Jennifer; Lyons, Sarah; Biesecker, Barbara B.; Goodman, Melody S.; Kaphingst, Kimberly A.

2016-01-01

Genetic test results have medical implications beyond the patient that extend to biological family members. We examined psychosocial and clinical factors associated with communication of genetic test results within families. Women (N=1080) diagnosed with breast cancer at age 40 or younger completed an online survey; 920 women that reported prior cancer genetic testing were included in analysis. We examined the proportion of immediate family members to whom they communicated genetic test results, and built multivariable regression models to examine clinical and psychosocial variables associated with the proportion score. Participants were most likely to communicate test results to their mother (83%) and least likely to their son (45%). Participants who carried a BRCA mutation (OR=1.34; 95% CI = 1.06, 1.70), had higher interest in genomic information (OR=1.55; 95% CI = 1.26, 1.91) and lower genetic worry (OR=0.91; 95% CI = 0.86, 0.96) communicated genetic test results to a greater proportion of their immediate family members. Participants with a BRCA1/2 mutation shared their genetic test results with more male family members (OR=1.72; 95% CI = 1.02, 2.89). Our findings suggest that patients with high worry about genetic risks, low interest in genomic information, or receive a negative genetic test result will likely need additional support to encourage family communication. PMID:27422778

Non-invasive prenatal testing for single gene disorders: exploring the ethics.

PubMed

Deans, Zuzana; Hill, Melissa; Chitty, Lyn S; Lewis, Celine

2013-07-01

Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for 'information only', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care.

Validation of a next-generation sequencing assay for clinical molecular oncology.

PubMed

Cottrell, Catherine E; Al-Kateb, Hussam; Bredemeyer, Andrew J; Duncavage, Eric J; Spencer, David H; Abel, Haley J; Lockwood, Christina M; Hagemann, Ian S; O'Guin, Stephanie M; Burcea, Lauren C; Sawyer, Christopher S; Oschwald, Dayna M; Stratman, Jennifer L; Sher, Dorie A; Johnson, Mark R; Brown, Justin T; Cliften, Paul F; George, Bijoy; McIntosh, Leslie D; Shrivastava, Savita; Nguyen, Tudung T; Payton, Jacqueline E; Watson, Mark A; Crosby, Seth D; Head, Richard D; Mitra, Robi D; Nagarajan, Rakesh; Kulkarni, Shashikant; Seibert, Karen; Virgin, Herbert W; Milbrandt, Jeffrey; Pfeifer, John D

2014-01-01

Currently, oncology testing includes molecular studies and cytogenetic analysis to detect genetic aberrations of clinical significance. Next-generation sequencing (NGS) allows rapid analysis of multiple genes for clinically actionable somatic variants. The WUCaMP assay uses targeted capture for NGS analysis of 25 cancer-associated genes to detect mutations at actionable loci. We present clinical validation of the assay and a detailed framework for design and validation of similar clinical assays. Deep sequencing of 78 tumor specimens (≥ 1000× average unique coverage across the capture region) achieved high sensitivity for detecting somatic variants at low allele fraction (AF). Validation revealed sensitivities and specificities of 100% for detection of single-nucleotide variants (SNVs) within coding regions, compared with SNP array sequence data (95% CI = 83.4-100.0 for sensitivity and 94.2-100.0 for specificity) or whole-genome sequencing (95% CI = 89.1-100.0 for sensitivity and 99.9-100.0 for specificity) of HapMap samples. Sensitivity for detecting variants at an observed 10% AF was 100% (95% CI = 93.2-100.0) in HapMap mixes. Analysis of 15 masked specimens harboring clinically reported variants yielded concordant calls for 13/13 variants at AF of ≥ 15%. The WUCaMP assay is a robust and sensitive method to detect somatic variants of clinical significance in molecular oncology laboratories, with reduced time and cost of genetic analysis allowing for strategic patient management. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

[The interpretation of attachment in the Szondi test and in the questionnaire processes of attachment theory].

PubMed

Török I, András; Vincze, Gábor

2011-01-01

[corrected] The Szondi-test is widely applied in clinical diagnostics in Hungary too, and the evidence resulting from the theory is that we can get information about attachment during its interpreting. Its validity is proven by empirical research and clinical experiences. By analyzing the modern attachment theory more thoroughly, it becomes clear in what ways the Szondi-test constellations regarding attachment are different from the classificationbased on questionnaires, allowing the discrete measurement of the attachment style. With the Szondi-test the classification to attachment style is more insecure, but if it is completed with exploration, it is more informative in vector C (vector of relation, attachment information), while short questionnaires make the classification to attachment style possible. In our empirical analysis we represent the integration of the above mentioned clinical and theoretical experiences. In the present analysis we compare the vector C and S constellation of the two-profile Szondi-test of 80 persons with the dimensions of ECR-R questionnaire and with Collins and Read's questionnaire classification regarding attachment style. The statistical results refer to the fact that there is a legitimacy to compare questionnaire processes allowing the discrete classification of attachment and the Szondi-test's information content regarding attachment. With applying the methods together, we get a unique, complementary section of the information relating to attachment. Comparing the two methods (projective and questionnaire) establishes the need of theoretical integration as well. We also make an attempt to explain Fraley's evolutionary non-adaptivity of avoidant attachment, in the case of whose presence adaptivity of early attachment, counterbalancing the exploration and security need, and providing closeness--farness loses its balance.

Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1.

PubMed

van der Vaart, Thijs; Rietman, André B; Plasschaert, Ellen; Legius, Eric; Elgersma, Ype; Moll, Henriëtte A

2016-01-12

To evaluate the appropriateness of cognitive and behavioral outcome measures in clinical trials in neurofibromatosis type 1 (NF1) by analyzing the degree of deficits compared to reference groups, test-retest reliability, and how scores correlate between outcome measures. Data were analyzed from the Simvastatin for cognitive deficits and behavioral problems in patients with neurofibromatosis type 1 (NF1-SIMCODA) trial, a randomized placebo-controlled trial of simvastatin for cognitive deficits and behavioral problems in children with NF1. Outcome measures were compared with age-specific reference groups to identify domains of dysfunction. Pearson r was computed for before and after measurements within the placebo group to assess test-retest reliability. Principal component analysis was used to identify the internal structure in the outcome data. Strongest mean score deviations from the reference groups were observed for full-scale intelligence (-1.1 SD), Rey Complex Figure Test delayed recall (-2.0 SD), attention problems (-1.2 SD), and social problems (-1.1 SD). Long-term test-retest reliability were excellent for Wechsler scales (r > 0.88), but poor to moderate for other neuropsychological tests (r range 0.52-0.81) and Child Behavioral Checklist subscales (r range 0.40-0.79). The correlation structure revealed 2 strong components in the outcome measures behavior and cognition, with no correlation between these components. Scores on psychosocial quality of life correlate strongly with behavioral problems and less with cognitive deficits. Children with NF1 show distinct deficits in multiple domains. Many outcome measures showed weak test-retest correlations over the 1-year trial period. Cognitive and behavioral outcomes are complementary. This analysis demonstrates the need to include reliable outcome measures on a variety of cognitive and behavioral domains in clinical trials for NF1. © 2015 American Academy of Neurology.

Psychometric Properties of the Arabic Version of the Drug Use Disorders Identification Test (DUDIT) in Clinical, Prison Inmate, and Student Samples.

PubMed

Sfendla, Anis; Zouini, Btissame; Lemrani, Dina; Berman, Anne H; Senhaji, Meftaha; Kerekes, Nóra

2017-04-01

The study aimed to validate the Arabic version of the Drug Use Disorders Identification Test (DUDIT) by (1) assessing its factor structure, (2) determining structural validity, (3) evaluating item-total and inter-item correlation, and (4) assessing its predictive validity. The study population included 169 prison inmates, 51 patients with clinical diagnosis of substance used disorder, and 53 students (N = 273). All participants completed the self-report version of the Arabic DUDIT. After exploratory factor analysis, internal consistency of the Arabic DUDIT was determined and external validation was performed. Principal factor analysis showed that Arabic DUDIT exhibited only one factor, which explained 66.9% of the variance. Reliability based on Cronbach's alpha was .95. When compared to the DSM-IV substance use disorder diagnosis in a clinical sample, DUDIT had an area under the curve (AUC) of .98, with a sensitivity of .98 and a specificity of .90. The Arabic version of DUDIT is a valid and reliable tool for screening for drug use in Arabic-speaking countries.