Browsing by Subject "Sensitivity and Specificity"

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    ItemOpen Access
    An analysis from the Quality Outcomes Database, Part 1. Disability, quality of life, and pain outcomes following lumbar spine surgery: predicting likely individual patient outcomes for shared decision-making.
    (Journal of neurosurgery. Spine, 2017-10) McGirt, Matthew J; Bydon, Mohamad; Archer, Kristin R; Devin, Clinton J; Chotai, Silky; Parker, Scott L; Nian, Hui; Harrell, Frank E; Speroff, Theodore; Dittus, Robert S; Philips, Sharon E; Shaffrey, Christopher I; Foley, Kevin T; Asher, Anthony L
    OBJECTIVE Quality and outcomes registry platforms lie at the center of many emerging evidence-driven reform models. Specifically, clinical registry data are progressively informing health care decision-making. In this analysis, the authors used data from a national prospective outcomes registry (the Quality Outcomes Database) to develop a predictive model for 12-month postoperative pain, disability, and quality of life (QOL) in patients undergoing elective lumbar spine surgery. METHODS Included in this analysis were 7618 patients who had completed 12 months of follow-up. The authors prospectively assessed baseline and 12-month patient-reported outcomes (PROs) via telephone interviews. The PROs assessed were those ascertained using the Oswestry Disability Index (ODI), EQ-5D, and numeric rating scale (NRS) for back pain (BP) and leg pain (LP). Variables analyzed for the predictive model included age, gender, body mass index, race, education level, history of prior surgery, smoking status, comorbid conditions, American Society of Anesthesiologists (ASA) score, symptom duration, indication for surgery, number of levels surgically treated, history of fusion surgery, surgical approach, receipt of workers' compensation, liability insurance, insurance status, and ambulatory ability. To create a predictive model, each 12-month PRO was treated as an ordinal dependent variable and a separate proportional-odds ordinal logistic regression model was fitted for each PRO. RESULTS There was a significant improvement in all PROs (p < 0.0001) at 12 months following lumbar spine surgery. The most important predictors of overall disability, QOL, and pain outcomes following lumbar spine surgery were employment status, baseline NRS-BP scores, psychological distress, baseline ODI scores, level of education, workers' compensation status, symptom duration, race, baseline NRS-LP scores, ASA score, age, predominant symptom, smoking status, and insurance status. The prediction discrimination of the 4 separate novel predictive models was good, with a c-index of 0.69 for ODI, 0.69 for EQ-5D, 0.67 for NRS-BP, and 0.64 for NRS-LP (i.e., good concordance between predicted outcomes and observed outcomes). CONCLUSIONS This study found that preoperative patient-specific factors derived from a prospective national outcomes registry significantly influence PRO measures of treatment effectiveness at 12 months after lumbar surgery. Novel predictive models constructed with these data hold the potential to improve surgical effectiveness and the overall value of spine surgery by optimizing patient selection and identifying important modifiable factors before a surgery even takes place. Furthermore, these models can advance patient-focused care when used as shared decision-making tools during preoperative patient counseling.
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    Assessment of the Feasibility of Using Noninvasive Wearable Biometric Monitoring Sensors to Detect Influenza and the Common Cold Before Symptom Onset.
    (JAMA network open, 2021-09) Grzesiak, Emilia; Bent, Brinnae; McClain, Micah T; Woods, Christopher W; Tsalik, Ephraim L; Nicholson, Bradly P; Veldman, Timothy; Burke, Thomas W; Gardener, Zoe; Bergstrom, Emma; Turner, Ronald B; Chiu, Christopher; Doraiswamy, P Murali; Hero, Alfred; Henao, Ricardo; Ginsburg, Geoffrey S; Dunn, Jessilyn

    Importance

    Currently, there are no presymptomatic screening methods to identify individuals infected with a respiratory virus to prevent disease spread and to predict their trajectory for resource allocation.

    Objective

    To evaluate the feasibility of using noninvasive, wrist-worn wearable biometric monitoring sensors to detect presymptomatic viral infection after exposure and predict infection severity in patients exposed to H1N1 influenza or human rhinovirus.

    Design, setting, and participants

    The cohort H1N1 viral challenge study was conducted during 2018; data were collected from September 11, 2017, to May 4, 2018. The cohort rhinovirus challenge study was conducted during 2015; data were collected from September 14 to 21, 2015. A total of 39 adult participants were recruited for the H1N1 challenge study, and 24 adult participants were recruited for the rhinovirus challenge study. Exclusion criteria for both challenges included chronic respiratory illness and high levels of serum antibodies. Participants in the H1N1 challenge study were isolated in a clinic for a minimum of 8 days after inoculation. The rhinovirus challenge took place on a college campus, and participants were not isolated.

    Exposures

    Participants in the H1N1 challenge study were inoculated via intranasal drops of diluted influenza A/California/03/09 (H1N1) virus with a mean count of 106 using the median tissue culture infectious dose (TCID50) assay. Participants in the rhinovirus challenge study were inoculated via intranasal drops of diluted human rhinovirus strain type 16 with a count of 100 using the TCID50 assay.

    Main outcomes and measures

    The primary outcome measures included cross-validated performance metrics of random forest models to screen for presymptomatic infection and predict infection severity, including accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC).

    Results

    A total of 31 participants with H1N1 (24 men [77.4%]; mean [SD] age, 34.7 [12.3] years) and 18 participants with rhinovirus (11 men [61.1%]; mean [SD] age, 21.7 [3.1] years) were included in the analysis after data preprocessing. Separate H1N1 and rhinovirus detection models, using only data on wearble devices as input, were able to distinguish between infection and noninfection with accuracies of up to 92% for H1N1 (90% precision, 90% sensitivity, 93% specificity, and 90% F1 score, 0.85 [95% CI, 0.70-1.00] AUC) and 88% for rhinovirus (100% precision, 78% sensitivity, 100% specificity, 88% F1 score, and 0.96 [95% CI, 0.85-1.00] AUC). The infection severity prediction model was able to distinguish between mild and moderate infection 24 hours prior to symptom onset with an accuracy of 90% for H1N1 (88% precision, 88% sensitivity, 92% specificity, 88% F1 score, and 0.88 [95% CI, 0.72-1.00] AUC) and 89% for rhinovirus (100% precision, 75% sensitivity, 100% specificity, 86% F1 score, and 0.95 [95% CI, 0.79-1.00] AUC).

    Conclusions and relevance

    This cohort study suggests that the use of a noninvasive, wrist-worn wearable device to predict an individual's response to viral exposure prior to symptoms is feasible. Harnessing this technology would support early interventions to limit presymptomatic spread of viral respiratory infections, which is timely in the era of COVID-19.
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    Biomarkers to help guide management of patients with pulmonary nodules.
    (Am J Respir Crit Care Med, 2013-08-15) Patz, Edward F; Campa, Michael J; Gottlin, Elizabeth B; Trotter, Priscilla R; Herndon, James E; Kafader, Don; Grant, Russell P; Eisenberg, Marcia
    RATIONALE: Indeterminate pulmonary nodules are a common radiographic finding and require further evaluation because of the concern for lung cancer. OBJECTIVES: We developed an algorithm to assign patients to a low- or high-risk category for lung cancer, based on a combination of serum biomarker levels and nodule size. METHODS: For the serum biomarker assay, we determined levels of carcinoembryonic antigen, α1-antitrypsin, and squamous cell carcinoma antigen. Serum data and nodule size from a training set of 509 patients with (n = 298) and without (n = 211) lung cancer were subjected to classification and regression tree and logistic regression analyses. Multiple models were developed and tested in an independent, masked validation set for their ability to categorize patients with (n = 203) or without (n = 196) lung cancer as being low- or high-risk for lung cancer. MEASUREMENTS AND MAIN RESULTS: In all models, a large percentage of individuals in the validation study with small nodules (<1 cm) were assigned to the low-risk group, and a large percentage of individuals with large nodules (≥3 cm) were assigned to the high-risk group. In the validation study, the classification and regression tree algorithm had overall sensitivity, specificity, and positive and negative predictive values for determining lung cancer of 88%, 82%, 84%, and 87%, respectively. The logistic regression model had overall sensitivity, specificity, and positive and negative predictive values of 80%, 89%, 89%, and 81%, respectively. CONCLUSION: Integration of biomarkers with lung nodule size has the potential to help guide the management of patients with indeterminate pulmonary nodules.
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    Brief Report: Diagnostic Accuracy of Oral Mucosal Transudate Tests Compared with Blood-Based Rapid Tests for HIV Among Children Aged 18 Months to 18 Years in Kenya and Zimbabwe.
    (Journal of acquired immune deficiency syndromes (1999), 2019-12) Dziva Chikwari, Chido; Njuguna, Irene N; Neary, Jillian; Rainer, Crissi; Chihota, Belinda; Slyker, Jennifer A; Katz, David A; Wamalwa, Dalton C; Oyiengo, Laura; Bandason, Tsitsi; McHugh, Grace; Dauya, Ethel; Mujuru, Hilda; Stewart, Kearsley A; John-Stewart, Grace C; Ferrand, Rashida A; Wagner, Anjuli D
    BACKGROUND:Gaps persist in HIV testing for children who were not tested in prevention of mother-to-child HIV transmission programs. Oral mucosal transudate (OMT) rapid HIV tests have been shown to be highly sensitive in adults, but their performance has not been established in children. METHODS:Antiretroviral therapy-naive children aged 18 months to 18 years in Kenya and Zimbabwe were tested for HIV using rapid OraQuick ADVANCE Rapid HIV-1/2 Antibody test on oral fluids (OMT) and blood-based rapid diagnostic testing (BBT). BBT followed Kenyan and Zimbabwean national algorithms. Sensitivity and specificity were calculated using the national algorithms as the reference standard. RESULTS:A total of 1776 children were enrolled; median age was 7.3 years (interquartile range: 4.7-11.6). Among 71 children positive by BBT, all 71 were positive by OMT (sensitivity: 100% [97.5% confidence interval (CI): 94.9% to 100%]). Among the 1705 children negative by BBT, 1703 were negative by OMT (specificity: 99.9% [95% CI: 99.6% to 100.0%]). Due to discrepant BBT and OMT results, 2 children who initially tested BBT-negative and OMT-positive were subsequently confirmed positive within 1 week by further tests. Excluding these 2 children, the sensitivity and specificity of OMT compared with those of BBT were each 100% (97.5% CI: 94.9% to 100% and 99.8% to 100%, respectively). CONCLUSIONS:Compared to national algorithms, OMT did not miss any HIV-positive children. These data suggest that OMTs are valid in this age range. Future research should explore the acceptability and uptake of OMT by caregivers and health workers to increase pediatric HIV testing coverage.
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    CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.
    (PLoS One, 2015) Peeling, Rosanna W; Sollis, Kimberly A; Glover, Sarah; Crowe, Suzanne M; Landay, Alan L; Cheng, Ben; Barnett, David; Denny, Thomas N; Spira, Thomas J; Stevens, Wendy S; Crowley, Siobhan; Essajee, Shaffiq; Vitoria, Marco; Ford, Nathan
    BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.
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    Clinical assessment and characterization of a dual tube kilovoltage X-ray localization system in the radiotherapy treatment room.
    (Journal of applied clinical medical physics, 2008-01-13) Lee, Sung-Woo; Jin, Jian-Yue; Guan, Huaiqun; Martin, Flavious; Kim, Jae Ho; Yin, Fang-Fang
    INTRODUCTION:Although flat-panel based X-ray imaging has been well tested in diagnostic radiology, its use as an image-guided-radiotherapy (IGRT) system in a treatment room is new and requires systematic assessment. MATERIALS AND METHODS:BrainLab Novalis IGRT system was used for this study. It consists of two floor mounted kV X-ray tubes projecting obliquely into two flat-panel detectors mounted on the ceiling. The system automatically fuses the 2D localization images with 3D simulation CT image to provide positioning guidance. The following characteristics of the system were studied: (1) Coincidence of the isocenters between the IGRT and Linac; (2) Image quality; (3) Exposure; (4) Linearity, uniformity and repeatability. RESULTS:(1) Localization accuracy and coincidence of the isocenters between the IGRT and Linac was better than 1-mm. (2) The spatial resolution was quantified using the relative modulation-transfer-function with f50=0.7-0.9 lp/mm. The variation of contrast-noise-ratio with technical settings was measured. (3) The maximal exposure of an image was less than 95 mR. An empirical relation between the exposure and the X-ray technical setting was derived. (4) The linearity, uniformity and repeatability of the system generally meet the requirements. CONCLUSION:The system can be safely and reliably used as a target localization device.
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    Clinically Adjudicated Reference Standards for Evaluation of Infectious Diseases Diagnostics.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023-03) Patel, Robin; Tsalik, Ephraim L; Evans, Scott; Fowler, Vance G; Doernberg, Sarah B; Antibacterial Resistance Leadership Group
    Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an imperfect reference, rather than correctness, because the right answer is unknown. Solutions consist of multitest comparators, including those that involve a test under evaluation if multiple new tests are being evaluated together, using latent class modeling, and clinically adjudicated reference standards. Clinically adjudicated reference standards may be considered as comparator methods when no predefined test or composite of tests is sufficiently accurate; they emulate clinical practice in that multiple data pieces are clinically assessed together.
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    Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates.
    (Journal of clinical microbiology, 2018-08) Stone, Mars; Bainbridge, John; Sanchez, Ana M; Keating, Sheila M; Pappas, Andrea; Rountree, Wes; Todd, Chris; Bakkour, Sonia; Manak, Mark; Peel, Sheila A; Coombs, Robert W; Ramos, Eric M; Shriver, M Kathleen; Contestable, Paul; Nair, Sangeetha Vijaysri; Wilson, David H; Stengelin, Martin; Murphy, Gary; Hewlett, Indira; Denny, Thomas N; Busch, Michael P
    Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening, and next-generation assays. Three-hundred-member panels of 20 serially diluted well-characterized antibody-negative HIV isolates for which the researchers were blind to the results (blind panels) were distributed to manufacturers and end-user labs to assess the relative analytic sensitivity of currently approved and preapproved clinical HIV fourth-generation Ag/Ab combo or p24 Ag-alone immunoassays for the detection of diverse subtypes. The limits of detection (LODs) of virus were estimated for different subtypes relative to confirmed viral loads. Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blind panel. On the basis of the proportion of positive results on 300 observations, all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half-log LODs, illustrating the similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo assays performed poorly. The similar performance of the different commercially available fourth-generation assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next-generation preclinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while rapid fourth-generation assays performed poorly for p24 Ag detection.
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    Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells.
    (Nature genetics, 2017-12) Meyers, Robin M; Bryan, Jordan G; McFarland, James M; Weir, Barbara A; Sizemore, Ann E; Xu, Han; Dharia, Neekesh V; Montgomery, Phillip G; Cowley, Glenn S; Pantel, Sasha; Goodale, Amy; Lee, Yenarae; Ali, Levi D; Jiang, Guozhi; Lubonja, Rakela; Harrington, William F; Strickland, Matthew; Wu, Ting; Hawes, Derek C; Zhivich, Victor A; Wyatt, Meghan R; Kalani, Zohra; Chang, Jaime J; Okamoto, Michael; Stegmaier, Kimberly; Golub, Todd R; Boehm, Jesse S; Vazquez, Francisca; Root, David E; Hahn, William C; Tsherniak, Aviad
    The CRISPR-Cas9 system has revolutionized gene editing both at single genes and in multiplexed loss-of-function screens, thus enabling precise genome-scale identification of genes essential for proliferation and survival of cancer cells. However, previous studies have reported that a gene-independent antiproliferative effect of Cas9-mediated DNA cleavage confounds such measurement of genetic dependency, thereby leading to false-positive results in copy number-amplified regions. We developed CERES, a computational method to estimate gene-dependency levels from CRISPR-Cas9 essentiality screens while accounting for the copy number-specific effect. In our efforts to define a cancer dependency map, we performed genome-scale CRISPR-Cas9 essentiality screens across 342 cancer cell lines and applied CERES to this data set. We found that CERES decreased false-positive results and estimated sgRNA activity for both this data set and previously published screens performed with different sgRNA libraries. We further demonstrate the utility of this collection of screens, after CERES correction, for identifying cancer-type-specific vulnerabilities.
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    Contrast in intracardiac acoustic radiation force impulse images of radiofrequency ablation lesions.
    (Ultrason Imaging, 2014-04) Eyerly, Stephanie A; Bahnson, Tristram D; Koontz, Jason I; Bradway, David P; Dumont, Douglas M; Trahey, Gregg E; Wolf, Patrick D
    We have previously shown that intracardiac acoustic radiation force impulse (ARFI) imaging visualizes tissue stiffness changes caused by radiofrequency ablation (RFA). The objectives of this in vivo study were to (1) quantify measured ARFI-induced displacements in RFA lesion and unablated myocardium and (2) calculate the lesion contrast (C) and contrast-to-noise ratio (CNR) in two-dimensional ARFI and conventional intracardiac echo images. In eight canine subjects, an ARFI imaging-electroanatomical mapping system was used to map right atrial ablation lesion sites and guide the acquisition of ARFI images at these sites before and after ablation. Readers of the ARFI images identified lesion sites with high sensitivity (90.2%) and specificity (94.3%) and the average measured ARFI-induced displacements were higher at unablated sites (11.23 ± 1.71 µm) than at ablated sites (6.06 ± 0.94 µm). The average lesion C (0.29 ± 0.33) and CNR (1.83 ± 1.75) were significantly higher for ARFI images than for spatially registered conventional B-mode images (C = -0.03 ± 0.28, CNR = 0.74 ± 0.68).
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    Correlation between quantitative whole-body muscle magnetic resonance imaging and clinical muscle weakness in Pompe disease.
    (Muscle & nerve, 2015-05) Horvath, Jeffrey J; Austin, Stephanie L; Case, Laura E; Greene, Karla B; Jones, Harrison N; Soher, Brian J; Kishnani, Priya S; Bashir, Mustafa R

    Introduction

    Previous examination of whole-body muscle involvement in Pompe disease has been limited to physical examination and/or qualitative magnetic resonance imaging (MRI). In this study we assess the feasibility of quantitative proton-density fat-fraction (PDFF) whole-body MRI in late-onset Pompe disease (LOPD) and compare the results with manual muscle testing.

    Methods

    Seven LOPD patients and 11 disease-free controls underwent whole-body PDFF MRI. Quantitative MR muscle group assessments were compared with physical testing of muscle groups.

    Results

    The 95% upper limits of confidence intervals for muscle groups were 4.9-12.6% in controls and 6.8-76.4% in LOPD patients. LOPD patients showed severe and consistent tongue and axial muscle group involvement, with less marked involvement of peripheral musculature. MRI was more sensitive than physical examination for detection of abnormality in multiple muscle groups.

    Conclusion

    This integrated, quantitative approach to muscle assessment provides more detailed data than physical examination and may have clinical utility for monitoring disease progression and treatment response.
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    Cost-effectiveness analysis of the diagnosis of meniscus tears.
    (Am J Sports Med, 2015-01) Mather, Richard C; Garrett, William E; Cole, Brian J; Hussey, Kristen; Bolognesi, Michael P; Lassiter, Tally; Orlando, Lori A
    BACKGROUND: Diagnostic imaging represents the fastest growing segment of costs in the US health system. This study investigated the cost-effectiveness of alternative diagnostic approaches to meniscus tears of the knee, a highly prevalent disease that traditionally relies on MRI as part of the diagnostic strategy. PURPOSE: To identify the most efficient strategy for the diagnosis of meniscus tears. STUDY DESIGN: Economic and decision analysis; Level of evidence, 1. METHODS: A simple-decision model run as a cost-utility analysis was constructed to assess the value added by MRI in various combinations with patient history and physical examination (H&P). The model examined traumatic and degenerative tears in 2 distinct settings: primary care and orthopaedic sports medicine clinic. Strategies were compared using the incremental cost-effectiveness ratio (ICER). RESULTS: In both practice settings, H&P alone was widely preferred for degenerative meniscus tears. Performing MRI to confirm a positive H&P was preferred for traumatic tears in both practice settings, with a willingness to pay of less than US$50,000 per quality-adjusted life-year. Performing an MRI for all patients was not preferred in any reasonable clinical scenario. The prevalence of a meniscus tear in a clinician's patient population was influential. For traumatic tears, MRI to confirm a positive H&P was preferred when prevalence was less than 46.7%, with H&P preferred above that. For degenerative tears, H&P was preferred until the prevalence reaches 74.2%, and then MRI to confirm a negative was the preferred strategy. In both settings, MRI to confirm positive physical examination led to more than a 10-fold lower rate of unnecessary surgeries than did any other strategy, while MRI to confirm negative physical examination led to a 2.08 and 2.26 higher rate than H&P alone in primary care and orthopaedic clinics, respectively. CONCLUSION: For all practitioners, H&P is the preferred strategy for the suspected degenerative meniscus tear. An MRI to confirm a positive H&P is preferred for traumatic tears for all practitioners. Consideration should be given to implementing alternative diagnostic strategies as well as enhancing provider education in physical examination skills to improve the reliability of H&P as a diagnostic test. CLINICAL RELEVANCE: Alternative diagnostic strategies that do not include the use of MRI may result in decreased health care costs without harm to the patient and could possibly reduce unnecessary procedures.
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    Critical Review of Current Approaches for Echocardiographic Reproducibility and Reliability Assessment in Clinical Research.
    (Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 2016-12) Crowley, Anna Lisa; Yow, Eric; Barnhart, Huiman X; Daubert, Melissa A; Bigelow, Robert; Sullivan, Daniel C; Pencina, Michael; Douglas, Pamela S

    Background

    There is no broadly accepted standard method for assessing the quality of echocardiographic measurements in clinical research reports, despite the recognized importance of this information in assessing the quality of study results.

    Methods

    Twenty unique clinical studies were identified reporting echocardiographic data quality for determinations of left ventricular (LV) volumes (n = 13), ejection fraction (n = 12), mass (n = 9), outflow tract diameter (n = 3), and mitral Doppler peak early velocity (n = 4). To better understand the range of possible estimates of data quality and to compare their utility, reported reproducibility measures were tabulated, and de novo estimates were then calculated for missing measures, including intraclass correlation coefficient (ICC), 95% limits of agreement, coefficient of variation (CV), coverage probability, and total deviation index, for each variable for each study.

    Results

    The studies varied in approaches to reproducibility testing, sample size, and metrics assessed and values reported. Reported metrics included mean difference and its SD (n = 7 studies), ICC (n = 5), CV (n = 4), and Bland-Altman limits of agreement (n = 4). Once de novo estimates of all missing indices were determined, reasonable reproducibility targets for each were identified as those achieved by the majority of studies. These included, for LV end-diastolic volume, ICC > 0.95, CV < 7%, and coverage probability > 0.93 within 30 mL; for LV ejection fraction, ICC > 0.85, CV < 8%, and coverage probability > 0.85 within 10%; and for LV mass, ICC > 0.85, CV < 10%, and coverage probability > 0.60 within 20 g.

    Conclusions

    Assessment of data quality in echocardiographic clinical research is infrequent, and methods vary substantially. A first step to standardizing echocardiographic quality reporting is to standardize assessments and reporting metrics. Potential benefits include clearer communication of data quality and the identification of achievable targets to benchmark quality improvement initiatives.
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    Delivery efficiency of an Elekta linac under gated operation.
    (Journal of applied clinical medical physics, 2014-09-08) Cui, Guoqiang; Housley, David J; Chen, Fan; Mehta, Vivek K; Shepard, David M
    In this study, we have characterized the efficiency of an Elekta linac in the delivery of gated radiotherapy. We have explored techniques to reduce the beam-on delay and to improve the delivery efficiency, and have investigated the impact of frequent beam interruptions on the dosimetric accuracy of gated deliveries. A newly available gating interface was installed on an Elekta Synergy. Gating signals were generated using a surface mapping system in conjunction with a respiratory motion phantom. A series of gated deliveries were performed using volumetric modulated arc therapy (VMAT) treatment plans previously generated for lung cancer patients treated with stereotactic body radiotherapy. Baseline values were determined for the delivery times. The machine was then tuned in an effort to minimize beam-on delays and improve delivery efficiency. After that process was completed, the dosimetric accuracy of the gated deliveries was evaluated by comparing the measured and the planned coronal dose distributions using gamma index analyses. Comparison of the gated and the non-gated deliveries were also performed. The results demonstrated that, with the optimal machine settings, the average beam-on delay was reduced to less than 0.22 s. High dosimetric accuracy was demonstrated with gamma index passing rates no lower than 99.0% for all tests (3%/3 mm criteria). Consequently, Elekta linacs can provide a practical solution for gated VMAT treatments with high dosimetric accuracy and only a moderate increase in the overall delivery time.
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    Design and in vivo evaluation of more efficient and selective deep brain stimulation electrodes.
    (Journal of neural engineering, 2015-08) Howell, Bryan; Huynh, Brian; Grill, Warren M

    Objective

    Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, the efficiency and selectivity of DBS can be improved. Our objective was to design electrode geometries that increased the efficiency and selectivity of DBS.

    Approach

    We coupled computational models of electrodes in brain tissue with cable models of axons of passage (AOPs), terminating axons (TAs), and local neurons (LNs); we used engineering optimization to design electrodes for stimulating these neural elements; and the model predictions were tested in vivo.

    Main results

    Compared with the standard electrode used in the Medtronic Model 3387 and 3389 arrays, model-optimized electrodes consumed 45-84% less power. Similar gains in selectivity were evident with the optimized electrodes: 50% of parallel AOPs could be activated while reducing activation of perpendicular AOPs from 44 to 48% with the standard electrode to 0-14% with bipolar designs; 50% of perpendicular AOPs could be activated while reducing activation of parallel AOPs from 53 to 55% with the standard electrode to 1-5% with an array of cathodes; and, 50% of TAs could be activated while reducing activation of AOPs from 43 to 100% with the standard electrode to 2-15% with a distal anode. In vivo, both the geometry and polarity of the electrode had a profound impact on the efficiency and selectivity of stimulation.

    Significance

    Model-based design is a powerful tool that can be used to improve the efficiency and selectivity of DBS electrodes.
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    Detection of depression in low resource settings: validation of the Patient Health Questionnaire (PHQ-9) and cultural concepts of distress in Nepal.
    (BMC Psychiatry, 2016-03-08) Kohrt, Brandon A; Luitel, Nagendra P; Acharya, Prakash; Jordans, Mark JD
    BACKGROUND: Despite recognition of the burden of disease due to mood disorders in low- and middle-income countries, there is a lack of consensus on best practices for detecting depression. Self-report screening tools, such as the Patient Health Questionnaire (PHQ-9), require modification for low literacy populations and to assure cultural and clinical validity. An alternative approach is to employ idioms of distress that are locally salient, but these are not synonymous with psychiatric categories. Therefore, our objectives were to evaluate the validity of the PHQ-9, assess the added value of using idioms of distress, and develop an algorithm for depression detection in primary care. METHODS: We conducted a transcultural translation of the PHQ-9 in Nepal using qualitative methods to achieve semantic, content, technical, and criterion equivalence. Researchers administered the Nepali PHQ-9 to randomly selected patients in a rural primary health care center. Trained psychosocial counselors administered a validated Nepali depression module of the Composite International Diagnostic Interview (CIDI) to validate the Nepali PHQ-9. Patients were also assessed for local idioms of distress including heart-mind problems (Nepali, manko samasya). RESULTS: Among 125 primary care patients, 17 (14 %) were positive for a major depressive episode in the prior 2 weeks based on CIDI administration. With a Nepali PHQ-9 cutoff ≥ 10: sensitivity = 0.94, specificity = 0.80, positive predictive value (PPV) =0.42, negative predictive value (NPV) =0.99, positive likelihood ratio = 4.62, and negative likelihood ratio = 0.07. For heart-mind problems: sensitivity = 0.94, specificity = 0.27, PPV = 0.17, NPV = 0.97. With an algorithm comprising two screening questions (1. presence of heart-mind problems and 2. function impairment due to heart-mind problems) to determine who should receive the full PHQ-9, the number of patients requiring administration of the PHQ-9 could be reduced by 50 %, PHQ-9 false positives would be reduced by 18 %, and 88 % of patients with depression would be correctly identified. CONCLUSION: Combining idioms of distress with a transculturally-translated depression screener increases efficiency and maintains accuracy for high levels of detection. The algorithm reduces the time needed for primary healthcare staff to verbally administer the tool for patients with limited literacy. The burden of false positives is comparable to rates in high-income countries and is a limitation for universal primary care screening.
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    Development of a TaqMan Array Card for Acute-Febrile-Illness Outbreak Investigation and Surveillance of Emerging Pathogens, Including Ebola Virus.
    (J Clin Microbiol, 2016-01) Liu, Jie; Ochieng, Caroline; Wiersma, Steve; Ströher, Ute; Towner, Jonathan S; Whitmer, Shannon; Nichol, Stuart T; Moore, Christopher C; Kersh, Gilbert J; Kato, Cecilia; Sexton, Christopher; Petersen, Jeannine; Massung, Robert; Hercik, Christine; Crump, John A; Kibiki, Gibson; Maro, Athanasia; Mujaga, Buliga; Gratz, Jean; Jacob, Shevin T; Banura, Patrick; Scheld, W Michael; Juma, Bonventure; Onyango, Clayton O; Montgomery, Joel M; Houpt, Eric; Fields, Barry
    Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis), and 3 protozoa (Leishmania spp., Plasmodium spp., and Trypanosoma brucei). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus.
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    Diagnostic Accuracy of Electrographic Seizure Detection by Neurophysiologists and Non-Neurophysiologists in the Adult ICU Using a Panel of Quantitative EEG Trends.
    (J Clin Neurophysiol, 2015-08) Swisher, Christa B; White, Corey R; Mace, Brian E; Dombrowski, Keith E; Husain, Aatif M; Kolls, Bradley J; Radtke, Rodney R; Tran, Tung T; Sinha, Saurabh R
    PURPOSE: To evaluate the sensitivity and specificity of a panel of quantitative EEG (qEEG) trends for seizure detection in adult intensive care unit (ICU) patients when reviewed by neurophysiologists and non-neurophysiologists. METHODS: One hour qEEG panels (n = 180) were collected retrospectively from 45 ICU patients and were distributed to 5 neurophysiologists, 7 EEG technologists, and 5 Neuroscience ICU nurses for evaluation of seizures. Each panel consisted of the following qEEG tools, displayed separately for left and right hemisphere electrodes: rhythmicity spectrogram (rhythmic run detection and display; Persyst Inc), color density spectral array, EEG asymmetry index, and amplitude integrated EEG. The reviewers did not have access to the raw EEG data. RESULTS: For the reviewer's ability to detect the presence of seizures on qEEG panels when compared with the gold standard of independent raw EEG review, the sensitivities and specificities are as follows: neurophysiologists 0.87 and 0.61, EEG technologists 0.80 and 0.80, and Neuroscience ICU nurses 0.87 and 0.61, respectively. There was no statistical difference among the three groups regarding sensitivity. CONCLUSIONS: Quantitative EEG display panels are a promising tool to aid detection of seizures by non-neurophysiologists as well as by neurophysiologists. However, even when used as a panel, qEEG trends do not appear to be adequate as the sole method for reviewing continuous EEG data.
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    Efficacy of High-Sensitivity Troponin T in Identifying Very-Low-Risk Patients With Possible Acute Coronary Syndrome.
    (JAMA cardiology, 2018-02) Peacock, W Frank; Baumann, Brigette M; Bruton, Deborah; Davis, Thomas E; Handy, Beverly; Jones, Christopher W; Hollander, Judd E; Limkakeng, Alexander T; Mehrotra, Abhi; Than, Martin; Ziegler, Andre; Dinkel, Carina
    Importance:Physicians need information on how to use the first available high-sensitivity troponin (hsTnT) assay in the United States to identify patients at very low risk for 30-day adverse cardiac events (ACE). Objective:To determine whether a negative hsTnT assay at 0 and 3 hours following emergency department presentation could identify patients at less than 1% risk of a 30-day ACE. Design, Setting, and Participants:A prospective, observational study at 15 emergency departments in the United States between 2011 and 2015 that included individuals 21 years and older, presenting to the emergency department with suspected acute coronary syndrome. Of 1690 eligible individuals, 15 (no cardiac troponin T measurement) and 320 (missing a 0-hour or 3-hour sample) were excluded from the analyses. Exposures:Serial hsTnT measurements (fifth-generation Roche Elecsys hsTnT assay). Main Outcomes and Measures:Serial blood samples from each patient were collected after emergency department presentation (once identified as a potential patient with acute coronary syndrome) and 3 hours, 6 to 9 hours, and 12 to 24 hours later. Adverse cardiac events were defined as myocardial infarction, urgent revascularization, or death. The upper reference level for the hsTnT assay, defined as the 99th percentile, was established as 19 ng/L in a separate healthy US cohort. Patients were considered ruled out for acute myocardial infarction if their hsTnT level at 0 hours and 3 hours was less than the upper reference level. Gold standard diagnoses were determined by a clinical end point committee. Evaluation of assay clinical performance for acute myocardial infarction rule-out was prespecified; the hypothesis regarding 30-day ACE was formulated after data collection. Results:In 1301 healthy volunteers (50.4% women; median age, 48 years), the upper reference level was 19 ng/L. In 1600 patients with suspected acute coronary syndrome (48.4% women; median age, 55 years), a single hsTnTlevel less than 6 ng/L at baseline had a negative predictive value for AMI of 99.4%. In 974 patients (77.1%) with both 0-hour and 3-hour hsTnT levels of 19 ng/L or less, the negative predictive value for 30-day ACE was 99.3% (95% CI, 99.1-99.6). Using sex-specific cutpoints, C statistics for women (0.952) and men (0.962) were similar for acute myocardial infarction. Conclusions and Relevance:A single hsTnT level less than 6 ng/L was associated with a markedly decreased risk of AMI, while serial levels at 19 ng/L or less identified patients at less than 1% risk of 30-day ACE.
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    Emergency department point-of-care ultrasound in out-of-hospital and in-ED cardiac arrest.
    (Resuscitation, 2016-12) Gaspari, Romolo; Weekes, Anthony; Adhikari, Srikar; Noble, Vicki E; Nomura, Jason T; Theodoro, Daniel; Woo, Michael; Atkinson, Paul; Blehar, David; Brown, Samuel M; Caffery, Terrell; Douglass, Emily; Fraser, Jacqueline; Haines, Christine; Lam, Samuel; Lanspa, Michael; Lewis, Margaret; Liebmann, Otto; Limkakeng, Alexander; Lopez, Fernando; Platz, Elke; Mendoza, Michelle; Minnigan, Hal; Moore, Christopher; Novik, Joseph; Rang, Louise; Scruggs, Will; Raio, Christopher
    Point-of-care ultrasound has been suggested to improve outcomes from advanced cardiac life support (ACLS), but no large studies have explored how it should be incorporated into ACLS. Our aim was to determine whether cardiac activity on ultrasound during ACLS is associated with improved survival.We conducted a non-randomized, prospective, protocol-driven observational study at 20 hospitals across United States and Canada. Patients presenting with out-of-hospital arrest or in-ED arrest with pulseless electrical activity or asystole were included. An ultrasound was performed at the beginning and end of ACLS. The primary outcome was survival to hospital admission. Secondary outcomes included survival to hospital discharge and return of spontaneous circulation.793 patients were enrolled, 208 (26.2%) survived the initial resuscitation, 114 (14.4%) survived to hospital admission, and 13 (1.6%) survived to hospital discharge. Cardiac activity on US was the variable most associated with survival at all time points. On multivariate regression modeling, cardiac activity was associated with increased survival to hospital admission (OR 3.6, 2.2-5.9) and hospital discharge (OR 5.7, 1.5-21.9). No cardiac activity on US was associated with non-survival, but 0.6% (95% CI 0.3-2.3) survived to discharge. Ultrasound identified findings that responded to non-ACLS interventions. Patients with pericardial effusion and pericardiocentesis demonstrated higher survival rates (15.4%) compared to all others (1.3%).Cardiac activity on ultrasound was the variable most associated with survival following cardiac arrest. Ultrasound during cardiac arrest identifies interventions outside of the standard ACLS algorithm.