scholarly journals The Confirmation Rate of Primary Hits: A Predictive Model

2002 ◽  
Vol 7 (3) ◽  
pp. 175-190 ◽  
Author(s):  
Paul Fogel ◽  
Pascal Collette ◽  
Alain Dupront ◽  
Tina Garyantes ◽  
Denis Guédini
Keyword(s):  
Predictive Model ◽  
False Positive ◽  
False Negative ◽  
Individual Compound ◽  
Additional Advantage ◽  
Primary Screening ◽  
Alternative Approach ◽  
Compound Screening ◽  
Calculated Probability

HTS data from primary screening are usually analyzed by setting a cutoff for activity, in order to minimize both false-negative and false-positive rates. An alternative approach, based on a calculated probability of being active, is presented here. Given the predicted confirmation rate derived from this probability, the number of primary positives selected for follow-up can be optimized to maximize the number of true positives without picking too many false positives. Typical cutoff-determining methods are more serendipitous in their nature and not easily optimized in an effort to optimize screening efforts. An additional advantage of calculating a probability of being active for each compound screened is that orthogonal mixtures can be deconvoluted without presetting a deconvolution threshold. An important consequence of using the probability of being active with orthogonal mixtures is that individual compound screening results can be recorded irrespective of whether the assays were performed on single compounds or on cocktails.

Probing the Primary Screening Efficiency by Multiple Replicate Testing: A Quantitative Analysis of Hit Confirmation and False Screening Results of a Biochemical Assay

2005 ◽  
Vol 10 (7) ◽  
pp. 695-704 ◽  
Author(s):  
Ji-hu Zhang ◽  
Xiang Wu ◽  
Matthew A. Sills
Keyword(s):  
False Positive ◽  
High Throughput Screening ◽  
Quantitative Estimation ◽  
False Negative ◽  
Large Body ◽  
Screening Process ◽  
Measurement Variability ◽  
Primary Screening ◽  
Assay Optimization ◽  
Screening Efficiency

Despite a large body of references on assay development, assay optimization, strategies, and methodologies for high-throughput screening (HTS), there have been few reports on investigations of the efficiency of primary screening in a systematic and quantitative manner for a typical HTS process. Recently, the authors investigated the primary hit comparison and the effect of measurement variability by screening a library of approximately 25,000 random compounds in multiple replicate tests in a nuclear receptor recruitment assay with 2 different assay detection technologies. In this report, we utilized these sets of multiple replicate screening data from a different perspective and conducted a systematic data analysis in order to gain some insights into the hit-finding efficiency of a typical primary screening process. Specifically, hit confirmation, false-positive (declaration) rates, and false-negative rates at different hit cutoff limits were explored and calculated from the 2 different assay formats. Results and analyses provided some quantitative estimation regarding the reliability and efficiency of the primary screening process. For the 2 assay formats tested in this report, the confirmation rate (activity repeated at or above a certain hit limit) was found to be 65% or above. It was also suggested that, at least in this case, applying some hit-selection strategies, it is possible to decrease the number of false-negative or false-positive hits without significantly increasing the efforts in primary screening.

scholarly journals False Covid-19 Test Results – Could We Do Things Better? A Personal Opinion

2020 ◽  
Vol 8 (5) ◽  
Author(s):  
Suzanne Lisbeth Ekelund
Keyword(s):  
False Positive ◽  
False Negative ◽  
Test Results ◽  
Negative Results ◽  
False Negative Results ◽  
Personal Opinion ◽  
Potential Problems

This paper describes the problems with false covid-19 test results, both false positive and false negative results. The problems are related to the quality of tests, test sampling and the currently limited follow-up procedures. A test and follow-up strategy that could decrease the potential problems is suggested.

Assessment of the total cost of FNAC as a diagnostic tool in patients with thyroid nodules

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6628-6628
Author(s):  
I. Borget ◽  
P. Vielh ◽  
M. Allyn ◽  
M. Schlumberger ◽  
G. De Pouvourville
Keyword(s):  
False Positive ◽  
Thyroid Nodules ◽  
Unit Cost ◽  
False Negative ◽  
Final Diagnosis ◽  
Sensitivity Analyses ◽  
Markov Modelling ◽  
Total Cost ◽  
Number Of Patients

6628 Background: The prevalence of thyroid nodules in the general population ranges from 4 to 7% and fine-needle aspiration cytology (FNAC) is a widely used diagnostic procedure. As the final diagnosis is based on post-surgical pathology of the lesion, a number of patients with nodules classified as benign or indeterminate by cytology may have a postponed final diagnosis, impacting the procedure cost. This study aims to determine the total cost of FNAC, by taking into account of diagnostic mistakes (false-positive and false-negative), failures of FNAC (indeterminate results) and the follow-up of non operated patients. Methods: A Markov model was built to describe the management of patients through time, from the first FNA-t. We derived estimates for diagnostic accuracy values and follow-up from a retrospective study, including all patients who had their first FNAC from 2003 to 2005 at Institut Gustave Roussy. Costs were computed from the viewpoint of the hospital. A microcosting study was performed to determine the unit cost of FNAC. Sensitivity analyses were performed. Results: Out of the 624 patients who had FNAC, 15 were cytologically classified as malignant, 57 as suspicious and 171 as indeterminate. Surgical excision was carried on in 155 cases. The unit cost of FNAC was 121 €. Markov modelling showed that the mean total cost of a true diagnosis including unnecessary surgeries, repeat FNAC and follow-up was 1,145 Euros. The number of false negative and false positive cases had little impact on total cost, whereas it was significantly affected by the percentage (27%) of unsatisfactory specimens. The absence of such specimens would reduce the total cost to 738 Euros (35%). Conclusions: The cost of FNAC exceeds its unit production cost. It depends on the performance of the cytologist and on the rate of indeterminate results that might be reduced by routine ultrasound-guidance. No significant financial relationships to disclose.

Accuracy of Fine-Needle Aspiration of Thyroid

2001 ◽  
Vol 125 (4) ◽  
pp. 484-488 ◽  
Author(s):  
Mojghan Amrikachi ◽  
Ibrahim Ramzy ◽  
Sheldon Rubenfeld ◽  
Thomas M. Wheeler
Keyword(s):  
Fine Needle Aspiration ◽  
False Positive ◽  
Thyroid Nodules ◽  
False Negative ◽  
Cost Effective ◽  
Needle Aspiration ◽  
Follicular Neoplasm ◽  
Follicular Variant ◽  
Fine Needle

Abstract Context.—Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules. Objectives.—To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls. Design, Setting, and Participants.—Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982–1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes. Results.—The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29.5%) unsatisfactory. Most of the cases with negative or unsatisfactory aspirates were followed clinically or by repeat fine-needle aspiration. We identified 11 false-negative and 7 false-positive diagnoses. For aspirates considered sufficient for diagnosis, the sensitivity and specificity levels were 93% and 96%, respectively. Conclusions.—Fine-needle aspiration of the thyroid gland is highly accurate and has a low rate of false-negative and false-positive diagnoses. The major diagnostic problems are caused by diagnosis using a marginally adequate specimen, diagnosis of malignancy based on just 1 or 2 atypical cytologic features, or overlapping cytologic features of follicular neoplasm with those of follicular variant of papillary carcinoma.

FDG-PET for Staging and Follow-up of HIV-Infected Patients with Non Hodgkin Lymphoma and Hodgkin Lymphoma: A Single Center Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5014-5014
Author(s):  
Silvia Cantoni ◽  
Erika Ravelli ◽  
Maria Cristina Moioli ◽  
Chiara Rusconi ◽  
Vittorio Ruggero Zilioli ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Ct Scan ◽  
Hodgkin Lymphoma ◽  
False Positive ◽  
Fdg Pet ◽  
False Negative ◽  
Hiv Positive ◽  
Number Of Patients ◽  
Positive Results

Abstract Abstract 5014 Introduction Risk of developing non Hodgkin lymphomas (NHL) is known to be increased among patients (pts) infected by HIV-1 and sporadic non-HIV related cases of Hodgking lymphomas (HL) are also described. HIV-positive pts also feature a virus-related systemic lymphoadenopathy which makes nodal involvement by lymphoma difficult to evaluate using conventional imaging. The role of positron-emission tomography using 18F-fluorodeoxyglucose (FDG-PET) in the staging and evaluation of response to treatment of pts with NHL and HL is well established in immunocompetent pts, while only limited information is available on lymphomas arising in the setting of HIV infection. We report on a retrospective analysis of FDG-PET results in a group of HIV pts with lymphoma, both NHL and HL, followed-up at our hospital. Patients and methods Twelve HIV-positive male pts with a diagnosis of lymphoma (7 high grade and 1 follicular NHL, 4 HL) underwent a total of 22 PET scans. PET results were compared with those obtained by computed tomography (CT). Nine PET were performed at staging, 7 at restaging following chemotherapy, and 6 at follow-up. At diagnosis of lymphoma: median CD4 count was 200 cells/mcL (range 98-451); HIV genome was undetectable in 5/9 pts, in the remaining 4 pts for whom the data was available viral loads ranged from 103 to 1,452,720 copies/mL; 10/12 pts were already receiving HAART, while the remaining 2 pts started treatment upon diagnosis of lymphoma. Results In the majority of cases (17/22 = 77%) results of PET, CT scan and clinical status were concordant, being diagnostic of either lymphoma presence (11/17) or absence (6/17). No false positive results were recorded at follow-up. In 5/22 cases (23%) PET and CT scan were discordant. In 4 cases PET yielded a false negative result; in 2 cases at diagnosis (2 pts with HL) and in 2 cases at follow-up (both in the pt with follicular lymphoma). In the remaining case, a PET-negative CT-positive adenopathy was demonstrated which proved to be reactive in nature at biopsy. Discussion Our results suggest that FDG-PET is useful in the evaluation of lymphoma in the setting of HIV infection, similarly to what has been observed among immunocompetent pts. Although the number of patients is limited, in our experience PET proved to be able to discriminate between reactive and lymphomatous involvement of lymphoid tissue as demonstrated by absence of false positive results in pts evaluated at follow-up. These results need to be confirmed by larger clinical trials. Disclosures No relevant conflicts of interest to declare.

Is there a need for rescreening of patients treated for genital chlamydial infections?

2002 ◽  
Vol 13 (6) ◽  
pp. 363-367 ◽  
Author(s):  
Per-Anders Mårdh ◽  
Kenneth Persson
Keyword(s):  
False Positive ◽  
Diagnostic Tests ◽  
False Negative ◽  
Partner Notification ◽  
Drug Intake ◽  
Concomitant Therapy ◽  
Present Communication ◽  
Development Of Resistance ◽  
Wrong Dose

The present communication reviews reasons to perform rescreening of chlamydia-infected persons. It brings up difficulties to differentiate between relapse and reinfection. Studies on follow-up of chlamydia-positive cases after therapy are reviewed. It also highlights reasons for therapeutic failure, like compliance, pharmacological factors, including poor bioavailability, wrong dose regimens, lack of adherence to drug intake, neglect of partner notification and concomitant therapy in consorts, possible development of resistance to drugs generally prescribed, false negative or false positive diagnostic tests and reinfection from extra-genital not 'cured' sites. The review points to the need to establish programmes for routine rescreening of chlamydia-infected persons.

scholarly journals Diagnostic Value of MRI for Detecting Recurrent Soft-Tissue Sarcoma in a Long-Term Analysis at a Multidisciplinary Sarcoma Center

2020 ◽  
Author(s):  
Sam Sedaghat ◽  
Maya Sedaghat ◽  
Jens Meschede ◽  
Olav Jansen ◽  
Marcus Both
Keyword(s):  
Radiation Therapy ◽  
Soft Tissue ◽  
Diagnostic Accuracy ◽  
False Positive ◽  
False Negative ◽  
True Positive ◽  
Primary Tumors ◽  
Negative Results

Abstract Background: To assess the long-term diagnostic accuracy of MRI for detecting recurrent soft-tissue sarcoma at a multidisciplinary sarcoma center.Methods: In all, 1055 postoperative follow-up MRIs of 204 patients were included in the study. MRI follow-up scans were systematically reviewed for true-positive/-negative and false-positive/-negative results in detecting recurrent tumor. Available pathological reports and follow-up MRIs were set as reference. Results: The median age of the patients was 55.3±18.2 years. Of the patients, 34.8% presented with recurrences. Here, 65 follow-up scans were true positive, 23 false positive, 6 false negative, and 961 true negative. The overall sensitivity and specificity of MRI for detecting recurrences were 92% and 98%, respectively, with an accuracy of 97%. For intramuscular lesions and after surgery alone the sensitivity was higher (95% and 97%) than for subcutaneous lesions and surgery with additional radiation therapy (83% and 86%, respectively), at similarly high specificities (96-98%). The 6 false-negative results were found in streaky (n=2) and small ovoid/nodular (n=4) recurring lesions. The false-positive lesions imitated streaky (n=14), ovoid/nodular (n=8), and polycyclic/multilobulated recurring tumors (n=1). All false-positive results were found in patients in whom the primary tumors were polycyclic/multilobulated in appearance.Conclusion: MRI shows a high diagnostic accuracy for detecting recurrent STS, with a high sensitivity and specificity. The diagnostic accuracy decreases in subcutaneous lesions and after surgery with radiation therapy, compared to intramuscular lesions and surgery alone. Radiologists should pay particular attention to streaky and small ovoid/nodular recurring lesions and patients with polycyclic/multilobulated primary tumors.

Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long-term follow-up results

2009 ◽  
Vol 150 (47) ◽  
pp. 2133-2138
Author(s):  
Zsuzsa Molnár ◽  
Zsófia Simon ◽  
Zita Borbényi ◽  
Beáta Deák ◽  
LászLÓ Galuska ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Predictive Value ◽  
False Positive ◽  
Fdg Pet ◽  
Clinical Stage ◽  
False Negative ◽  
True Negative ◽  
Significant Difference ◽  
The Difference

In the past few decades Hodgkin lymphoma (HL) has become a highly curable malignant disease, as a result of using modern polychemotherapy and irradiation. Differentiation of active tumor from fibrosis or necrosis within residual radiographic masses represents a problem of interpretation. Aims: The aim of this retrospective study is to assess the value of FDG-PET for prediction of remission or relapse in HL. Patients and methods: Data of 128 patients, who had residual masses on CT after completion of their planned treatment, have been analyzed. FDG-PET was performed between January 1995 and February 2005. Results: The median duration of the follow-up from PET was 75.5 months (range: 20–180 months). 89 (70%) patients had negative and 39 (30%) patients had positive FDG-PET results. The numbers of true-positive, true-negative, false-positive and false-negative subjects were 29, 83, 10 and 6, respectively. Sensitivity of post-treatment FDG-PET was 83%, specificity 93%, positive predictive value 74%, negative predictive value 93%, and accuracy 88%. The difference between the event free survival of PET positive and negative cases is highly significant (p = 0.0000), according to the Mantel-Cox test. Conclusion: Our results, in accordance with literature, clearly indicate that patients with negative FDG-PET results are unlikely to progress or relapse during a long follow-up. However, false positive uptake is a problem. We have investigated the effect of age, histological subtype, clinical stage and the type of treatment on the accuracy, but on the basis of these facts we could not find any significant difference. However, the date of the investigation influenced the results: before 2000 the number of false results was significantly higher than after that time, which shows the importance of investigators’ experience.

scholarly journals Clinical effectiveness of the Manchester Glaucoma Enhanced Referral Scheme

2018 ◽  
Vol 103 (8) ◽  
pp. 1066-1071 ◽  
Author(s):  
Patrick J G Gunn ◽  
Joanne R Marks ◽  
Evgenia Konstantakopoulou ◽  
David F Edgar ◽  
John G Lawrenson ◽  
...  
Keyword(s):  
Usual Care ◽  
False Positive ◽  
False Negative ◽  
Clinical Effectiveness ◽  
Outcome Data ◽  
Reference Standard ◽  
Referral Criteria ◽  
Standard Assessment ◽  
The Uk

BackgroundGlaucoma referral filtering schemes have operated in the UK for many years. However, there is a paucity of data on the false-negative (FN) rate. This study evaluated the clinical effectiveness of the Manchester Glaucoma Enhanced Referral Scheme (GERS), estimating both the false-positive (FP) and FN rates.MethodOutcome data were collected for patients newly referred through GERS and assessed in ‘usual-care’ clinics to determine the FP rate (referred patients subsequently discharged at their first visit). For the FN rate, glaucoma suspects deemed not requiring referral following GERS assessment were invited to attend for a ‘reference standard’ examination including all elements of assessment recommended by National Institute for Health and Care Excellence (NICE) by a glaucoma specialist optometrist. A separate 33 cases comprising randomly selected referred and non-referred cases were reviewed independently by two glaucoma specialist consultant ophthalmologists to validate the reference standard assessment.Results1404 patients were evaluated in GERS during the study period; 651 (46.3%) were referred to the Hospital Eye Service (HES) and 753 (53.6%) were discharged. The FP rate in 307 assessable patients referred to the HES was 15.5%. This study reviewed 131 (17.4%) of those patients not referred to the HES through the GERS scheme; 117 (89.3%) were confirmed as not requiring hospital follow-up; 14 (10.7%) required follow-up, including 5 (3.8%) offered treatment. Only one patient (0.8%) in this sample met the GERS referral criteria and was not referred (true FN). There were no cases of missed glaucoma or non-glaucomatous pathology identified within our sample.ConclusionThe Manchester GERS is an effective glaucoma filtering scheme with a low FP and FN rate.

Carcinoembryonic Antigen (CEA), α-fetoprotein, CA 19.9 and CA 125 in Advanced Colorectal Cancer (ACC)

1993 ◽  
Vol 8 (2) ◽  
pp. 88-93 ◽  
Author(s):  
N. Tsavaris ◽  
K. Vonorta ◽  
H. Tsoutsos ◽  
D. Kozatsani-Halividi ◽  
N. Mylonakis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
False Positive ◽  
Advanced Colorectal Cancer ◽  
False Negative ◽  
Response To Treatment ◽  
Ca 125 ◽  
Clinical Parameters ◽  
Response To Chemotherapy ◽  
Ca 19.9

In 111 patients with ACC we studied CEA, FP, CA-125 and CA 19.9 during therapy and follow-up. Marker determination was performed every two months. CEA was elevated (> 5 ng/ml) in 82%, αFP(> 15 ng/ml) in 0%, CA-125 (>38 U/ml) in 37%, CA 19.9 (> 30 U/ml) in 64% of the patients. We did not find significant differences between the sensititivity of CEA alone and that of the combination of CEA + CA-125 (86%), CEA + CA 19.9 (87%), CA-125 + CA-19.9 (71%) and CEA + CA-125 + CA 19.9 (88%). We did not find any correlation between the level of positivity of the markers and the clinical parameters we examined. When serial determinations were carried out, CEA showed the best indication of response to treatment, followed by CA 19.9. In the evaluation of the response to chemotherapy we found that CA 125 presented significant percentages of false-positive (9%) (P < 0.008) and false-negative (8.1%) (P < 0.008) results, compared to CEA and CA 19.9. CA 125 did not demonstrate any utility for the follow-up of patients with colorectal cancer although increased values were found in 37%. We conclude that CEA is currently the best marker for the follow-up of patients with colorectal cancer. The combination of CEA and CA 19.9 had some utility in follow-up, without significantly improving CEA results

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