Predictive Value Of Negative Test Research Articles

Evaluation of Sensitive Urine DNA-Based PENK Methylation Test for Detecting Bladder Cancer in Patients with Hematuria

Hematuria is a prevalent symptom associated with bladder cancer (BC). However, the invasiveness and cost of cystoscopy, the current gold standard for BC diagnosis in patients with hematuria, necessitate the development of a sensitive and accurate noninvasive test. This study introduces and validates a highly sensitive urine-based DNA methylation test. The test improves sensitivity in detecting PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR. In a case-control study comprising 175 patients with BC and 143 patients without BC with hematuria, the test's optimal cutoff value was determined by distinguishing between two groups, achieved an overall sensitivity of 86.9% and a specificity of 91.6%, with an area under the curve of 0.892. A prospective validation clinical study involving 366 patients with hematuria scheduled for cystoscopy assessed the test's performance. The test demonstrated an overall sensitivity of 84.2% in detecting 38 cases of BC, a specificity of 95.7%, and an area under the curve of 0.900. Notably, the sensitivity for detecting Ta high grade and higher stages of BC reached 92.3%. The test's negative predictive value was 98.2%, and the positive predictive value was 68.7%. These findings highlight the potential of the PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR test in urine as a promising molecular diagnostic tool for detecting primary BC in patients with hematuria, which may reduce the need for cystoscopy.

Validation of screening tool for diagnosis of childhood asthma by exclusion method

Introduction: In the 21st century, with growing concerns over over-diagnosis of asthma in children; the diagnosis of asthma is left as diagnosis by exclusion. On the same lines, an attempt had been made to device a criteria to exclude diagnosis of asthma. The criteria are labeled as other than asthma (OTA) criteria. It is assumed that if a case does not satisfy OTA tool, then it is likely to be asthma. This study had objectives of validation of screening tool by expert and validation of OTA tool by direct application on patients. Materials and Methods: This was an observational and prospective study only. Total 120 cases were enrolled. Questionnaire applied on all cases and all of the 120 cases were followed up on day 30 with clinical diagnosis and were included in results estimation. Results: According to the screening tool, out of 120 cases, 83 cases (69.2%) were found to have OTA while 37 cases (30.8%) werefound to have non-OTA. However, among this study population, 94 cases (78.3%) had non-asthma and 26 cases (21.7%) had clinical diagnosis of asthma taken as gold standard. The association between clinical diagnosis and total score based diagnosis was found to bestatistically significant (p=1.96E-07). Sensitivity was 91.57% and specificity was 51.35% which helps detect OTA cases effectively. Predictive value of positive test is 80.85% and predictive value of negative test was 73.08%. OTA category has relative risk of 3.003 for diagnosis of non-asthma as compared to 0.262 for non-OTA category being almost 3 times in comparison to non-OTA category. Thus, OTA was consistent with non-asthma diagnosis. Conclusion: On direct application of patients in prospective study, this tool has proven its value as an effective screening tool. This was the first such study to diagnose asthma by exclusion, devising a criterion for other than asthma conditions.

Skin tests in the diagnosis of food allergy

Skin tests are an important step in diagnosing food allergy. Several types of skin tests are used: prick test, intradermal, patch tests, as well as a special version of skin tests - these are tests with native (fresh allergens) – prick-prick tests. We review sensitivity, specificity, the possibility of false positive and false negative results when using natural products in testing. The safety of skin tests and certain contraindications for their use have to be considered. The advantages of using fresh products specimens for skin tests, their high sensitivity and negative predictive value of tests are described. This allows to reduce the likelihood of missing true positives:: the real patients with risk of a severe systemic reaction.

Fundamental Statistical Concepts in Clinical Trials and Diagnostic Testing.

This article explores basic statistical concepts of clinical trial design and diagnostic testing, or how one starts with a question, formulates it into a hypothesis on which a clinical trial is then built, and integrates it with statistics and probability, such as determining the probability of rejecting the null hypothesis when it is actually true (type I error) and the probability of failing to reject the null hypothesis when it is false (type II error). There are a variety of tests for different types of data, and the appropriate test must be chosen for which the sample data meet the assumptions. Correcting type I error in the presence of multiple testing is needed to control the error's inflation. Within diagnostic testing, identifying false-positive and false-negative results is critical to understanding the performance of a test. These are used to determine the sensitivity and specificity of a test along with the test's negative predictive value and positive predictive value. These quantities, specifically sensitivity and specificity, are used to determine the accuracy of a diagnostic test using receiver-operating-characteristic curves. These concepts are briefly introduced to provide a basic understanding of clinical trial design and analysis, with references to allow the reader to explore various concepts at a more detailed level if desired.

NESTROFT AS SCREENING TEST FOR BETA THALASSEMIA TRAIT

Objective: To evaluate the utility of NESTROFT as a screening test for Beta Thalassemia Trait. Material and Methods: A Prospective study of total 137 clinically normal siblings of thalassemia major patients registered at thalassemia clinic in department of pediatrics, Govt. medical college, Kota were selected randomly for the study. All cases were investigated for CBC, Mentzer’s index, NESTROFT and HbA2 estimation by HPLC method. Result: Total 137 cases were screened for thalassemia carrier by HbA2 estimation using HPLC technique. Total 67 (48.90%) cases having HbA2 level ≥3.5 % considered as carrier whereas rest 70 (51.10%) cases were normal. In this study 95 cases showed MCV<80. Out of them 59 cases were carrier and 36 cases were normal. The Sensitivity, specificity, positive predictive value and negative predictive value of MCV<80 are 90.12%, 49.71%, 63.78% and 84.68% respectively. The Sensitivity, specificity, positive predictive value and negative predictive value of Mentzer index are 85.25%, 97.16%, 96.45% and 89.19 % respectively. In present study, NESTROFT were done in all cases, the sensitivity of NESTROF test is 94.21%, specificity is 89.72%, Predictive value of positive test is 89.17% and Predictive value of negative test is 93.75%. So NESTROFT is better test for screening for Beta Thalassemia trait. Conclusion: NESTROF test is reliable, cost effective and better screening test for Thalassemia carrier detection. Positive cases can be confirmed by HPLC. NESTROFT can be used as mass screening programme for hemoglobinopathies.

Assessment of transvaginal ultrasound measurement of cervical length for prediction of spontaneous onset of labor at term

The objective of this study was to measure the cervical length by transvaginal sonography at term to predict onset and course of spontaneous labor. One hundred and nighty nine pregnant women between 37 to 40 weeks of gestation who fulfilled the inclusion criteria were enrolled in this prospective observational study conducted in department of obstetrics and gynecology of IGGMC, NAGPUR. Out of 199 pregnant women, 154 women had full term vaginal delivery and 45 women underwent emergency cesarean section. The mean cervical length was 2.58cm in women who had vaginal birth and was 3.45cm in women who underwent emergency cesarean section. The best cutoff of transvaginal cervical length was 2.7cm for predicting the spontaneous onset of labor within 7 days, having sensitivity of 90.91% and specificity of 84%.The positive predictive value was 84.9% and negative predictive value of test 90.3%, with diagnostic accuracy of 87.4%. When cervical length is less, then chances of vaginal delivery are significantly higher. Transvaginal cervical length measurement between 37 to 40 weeks is useful test for predicting spontaneous onset of labor within 7 days. It helps women and healthcare providers to plan vaginal birth and also timely decision of referral of those cases requiring immediate care to higher centres for better maternal and foetal outcome.

Drug Challenge Tests With General Anesthetics: Predictive Value of Skin Tests.

The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.

The efficacy and reliability of Solubility test followed by High-Performance Liquid Chromatography (HPLC) for sickle cell disorders in Gujarat- An original research article

Introduction: Sickle cell anemia (SCA) is a genetic disorder characterized by severe hemolytic anemia. Diagnosis is an important aspect of the management of the disease. In the present study, the efficacy of the solubility test was assessed and High-performance liquid chromatography (HPLC) in the diagnosis of Sickle cell disorders. Material and Methods: A total of 1890 patients were screened. Among them, 1022 samples were tested positive for Sickle cell disorders. All the samples were observed for peripheral smear, subjected to solubility test and were further analyzed on HPLC ‘BIO-RAD’ analyzer for the confirmation along with the distinction of Sickle cell trait (SCT), sickle cell disease (homozygous) and Heterozygous sickle cell and beta-thalassemia. Results: Out of all 1890 patients screened, 1022 samples were found to be positive with the solubility test. A total of 686 samples were diagnosed as Sickle cell Trait, 247 for sickle cell disease (homozygous) and 89 samples were diagnosed as Sickle cell beta-thalassemia (heterozygous) with HPLC. Conclusion: Solubility test is very effective with 96.8% sensitivity. Specificity calibrated was on average 29.6%, with the predictive value of positive test 87.9% and a predictive value of negative test 64.0%. The most commonly used method now in Gujarat is HPLC although the solubility test is also sensitive and cheap.

The Usefulness of Indirect Immunofluorescence in Pemphigus and the Natural History of Patients With Initial False-Positive Results: A Retrospective Cohort Study.

The specificity and the predictive values of indirect immunofluorescence (IIF) in real-life settings is yet to be firmly established. The natural history of patients with false-positive results has not been sufficiently elucidated. The primary aim of the current study is to evaluate the diagnostic value of IIF analysis on monkey esophagus in pemphigus, utilizing a large cohort arising from the real-life experience of a tertiary referral center. The secondary endpoint was to determine the clinical outcomes of patients with false-positive results. This was a retrospective cohort study including all patients who were tested for the presence of intercellular autoantibodies by IIF on monkey esophagus between 2000 and 2017. Overall, 770 sera from different individuals were tested by IIF microscopy. Of those, 176 patients had been diagnosed with pemphigus vulgaris (PV) and 29 patients with pemphigus foliaceus (PF). The sensitivity of this immunoassay was significantly higher for the diagnosis of PV (87.4%; 95% CI, 81.5–91.9%) as compared to PF (69.0%; 95% CI, 49.2–84.7%; P = 0.018). The specificity for the diagnosis of pemphigus was 93.5% (95% CI, 91.1–95.4%). Patients with false-positive results (n = 37) were followed for a median duration of 5.3 years contributing 280.8 person-years. Thirty patients (81.1%) were eventually diagnosed clinically and immunopathologically with subepidermal autoimmune bullous diseases, whereas the remaining patients (18.9%) were diagnosed clinically and histologically with other inflammatory dermatoses, but none of them developed pemphigus during the follow-up duration. Of note, 7.0% (n = 23) of all patients diagnosed with bullous pemphigoid (BP) in the same period (n = 328) were tested positive for IgG intercellular antibodies. Histopathological review of the biopsy specimens of these patients did not reveal acantholysis. In conclusion, the predictive value of negative test in IIF on monkey esophagus is particularly reliable to exclude a diagnosis of pemphigus. Individuals tested positive for intercellular antibodies without an initial overt pemphigus did not show an increased risk for developing pemphigus subsequently. A sizable fraction of patients with BP showed circulating intercellular autoantibodies by IIF, without a histopathological evidence for acantholysis.

Loop-Mediated Isothermal Amplification Assay for Rapid and Reliable Detection of Mycobacterium tuberculosis in Sputum Samples

Introduction: Tuberculosis (TB) remains a major global health problem. The most common method for diagnosing TB in developing countries is sputum smear microscopy; however, the sensitivity of this test is relatively lower. Detection of Mycobacterium tuberculosis using conventional culture and biochemical-based assays is time-consuming and laborious. Polymerase Chain Reaction (PCR) is also available for diagnosis of Mycobacterium tuberculosis. However, the PCR assay requires an expensive thermal cycler to amplify the DNA fragment in multiple temperature-dependent steps. Therefore, a simple and sensitive method for rapid detection has been anxiously awaited. The loop-mediated isothermal amplification (LAMP) assay is a diagnostic technique which can aid in the fight against TB in resource-poor countries. The LAMP assay can amplify a targeted sequence at a constant temperature. Therefore, a large and costly thermal cycler is not necessary for a LAMP assay.Objectives: The objective of this study was to identify Mycobacterium tuberculosis directly from sputum by LAMP and to compare its efficacy over routinely used methods.Methods: A total of 106 (53 fluorochrome staining positive and 53 fluorochrome staining negative) sputum samples were collected in this study. Mycobacterial DNA was extracted from concentrated sputum samples by freezing and boiling method. LAMP assay using a set of six specific primers targeting the M. tuberculosis 16S rRNA gene with high sensitivity was used to analyze sputum samples. The results were then compared with that of the culture method, which was considered as the gold standard method.Results: Among total of 106 samples studied by microscopy and culture, 53 were positive by both, whole four were positive by culture but negative by microscopy. With reference to culture, the microscopy had sensitivity 92.98%, specificity 100%, and predictive value of positive test 100%, predictive value of negative test 92.5%. Out of 106 samples subjected to culture and LAMP for the diagnosis of TB, 55 samples were positive by both tests and two were positive only in culture, while 48 were negative in both tests and one was negative only in culture. While comparing the LAMP with culture as a gold standard, the sensitivity of LAMP was 96.49%, specificity was 97.95%, predictive value of positive test was 98.21%, predictive value of negative test was 96%.Conclusions: Comparative experiments showed that the LAMP assay is a rapid, sensitive, and specific method to detect M. tuberculosis infection. Indeed, an inexpensive LAMP assay would be potential as a diagnostic test for tuberculosis, especially in resource-limited settings. J-GMC-N | Volume 11 | Issue 01 | January-June 2018, Page: 27-34

UJI KESAHIHAN (VALIDITAS) PEMERIKSAAN D-DIMER CARA MENYARING KEKEBALAN (METODE IMUNOFILTRASI) DAN CARA MENGUKUR IMUNOTURBIDIMETRI

D-Dimer parameter is the most usefull laboratory assay to detect the present of activated coagulation. The D-Dimer fragment directlyindicate the fibrinolitic proccess whereas the increasing mark of D-Dimer is the most hemostatic parameter that was used to detectthe early stage of Disseminated Intravascular Coagulation (DIC) and has a correlation with the patient prognosis. D-Dimer assay byimmunoturbidimetric method was used to detect antigen-antibody reaction automatically and it can detect D-Dimer concentration lessthan 0.5 μg/mL. The immunoturbidimetric method has a good correlation with the ELISA method, but the proccess is complicated, ishigh costed, and need the competence of practical human resource. D-Dimer assay with immunofiltration method has the same principleas immunoturbidimetric method, but it's work more simpler, low cost and does not need the competence of practical human resource.The aim of this study is to compare the D-Dimer assay concentration between immunofltration and immunoturbidimetric method. Therewere 30 plasma samples assayed with these two methods (immunoturbidimetric and immunofiltration), and then compared betweenthem. The samples were collected between November until December 2008 at Rumah Sakit dr. Hasan Sadikin Bandung. The validity ofD-Dimer using immunofiltration method showed sensitivity 74%, specificity 95%, predictive value of negative test (PV-) 22%, predictivevalue of positive test (PV+) 95% with likelihood ratio 5.2. The conclusion of this study so far that the immunofiltration method has agood validity for diagnosing. D-Dimer work rapidly with low cost laboratory assay than the immunoturbidimetric method.

Study on early warning threshold values for 7 common communicable diseases in Gansu province, 2016

Objective: To optimize the warning threshold values of common communicable diseases in Gansu province, and improve the early warning effect. Method: An early warning model was set up for influenza, scarlet fever, other infectious diarrheal diseases, dysentery, typhoid and paratyphoid, viral hepatitis type E and hand foot and mouth disease (HFMD) respectively in Gansu by using the moving percentile method and cumulative sum method. By calculating the sensitivity, specificity, predictive value of positive test, predictive value of negative test, Youden' index and receiver-operating characteristic curve, the optimum early warning threshold values for communicable diseases in Gansu were selected. Results: The optimum early warning boundary values of influenza, scarlet fever, other infectious diarrheal diseases, dysentery, typhoid and paratyphoid, and viral hepatitis type E were P(90), P(80), P(95), P(90), P(80) and P(90) respectively. The optimum early warning parameters of HFMD were k=1.2, H=5σ. Under the optimum early warning boundary values/parameters, the early warning sensitivities of influenza, scarlet fever, other infectious diarrheal diseases, dysentery, typhoid and paratyphoid, viral hepatitis type E and HFMD were 86.67%, 100.00%, 91.67%, 100.00%, 100.00%, 100.00% and 100.00%, the specificities were 86.49%, 62.22%, 75.00%, 100.00%, 97.92%, 89.13% and 74.47%. The predictive values of positive test were 72.22%, 29.17%, 52.38%, 100.00%, 80.00%, 54.55% and 29.41%, and the predictive values of negative test were 94.12%, 100.00%, 96.77%, 100.00%, 100.00%, 100.00% and 100.00%, and the Youden' indexes were 0.73, 0.62, 0.67, 1.00, 0.98,0.89 and 0.74. Receiver-operating characteristic curve showed that the values/parameters of this warning boundary were the points closest to the upper left of the coordinate diagram. Conclusion: The early warning thresholds of influenza, other infectious diarrheal diseases, dysentery and hepatitis E in Gansu may be raised appropriately and the early warning parameters of HFMD need to be adjusted to improve the effectiveness of early warning.

Age-Adjusted D-Dimer Cut-Off Levels to Rule-out Venous Thromboembolism in Patients with Non-High Pre-Test Probability. Clinical Performance and Cost-Effectiveness Analysis

BackgroundD-dimer levels below a well-defined cut-off level enable to safely rule out VTE in patients with a low or intermediate pre-test probability (PTP), as the test negative predictive value (NPV) was high. As ageing is associated with increased D-dimer levels, the question was raised of the usefulness of their measurement to rule out VTE in elderly patients. Various attempts were made in the recent years to address that issue, particularly the use of age-adjusted cut-off values calculated by multiplying the patient's age by 10, in patients aged over 50.Aim of that studyThe aim of the study was to validate such a strategy, and to evaluate its economic impact in unselected outpatients referred to the emergency departments of 5 French centres (2 university hospitals, and 3 general hospitals).Patients, Materials and MethodsAfter exclusion of those on anticoagulant treatment at the time of the diagnosis (n=23), a total of 1255 consecutive patients with a non-high PTP of VTE were included in the study. The same standardized procedure was used in the 5 centres, i.e. D-dimer measurement in patients with a non-high PTP, and imaging techniques (usually computed pulmonary angiography in case of suspected PE and Doppler ultrasonography in case of suspected DVT) only when D-dimer was above the cut-off level.D-dimer was evaluated using the same latex-based fully automated assay (HemosIL D-dimer HS500 assay, Instrumentation Laboratory). Test results were expressed in ng/mL fibrinogen equivalent units (FEU), and the traditional cut-off level for VTE exclusion was 500 ng/mL.ResultsVTE was diagnosed in 105 patients of the 1255 included patients (8.4%): 88 patients were diagnosed out of the 1082 patients referred for suspected PE and 27 out the 173 referred for suspected DVT. D-dimer levels were above 500 ng/mL in all patients with VTE and in 521 of the 1150 patients without VTE (45.3%). The test NPV was 100% as well as its sensitivity. If the overall test specificity was 54.7%, it significantly decreased in an age-dependent manner over 70 years, related to a high percentage of increased D-dimer levels in elderly patients, particularly in those above 80 years.Using age-adjusted cut-off levels, calculated by multiplying the patient's age by 10, induced a significantly improvement in test specificity, particularly in very old patients with an overall NPV=60.2% vs. 54.7% using the fixed cut-off value. The overall NPV remained high (99.9%), even if a 78 y-old female with a low PTP of PE would have been misdiagnosed as her D-dimer level (540 ng/mL) was above 500 ng/mL but below the age-adjusted cut-off value. Such an improvement in test performance was found both in patients with suspected PE and DVT (Table).As this increase in test specificity would have led to exclude VTE in a higher percentage of patients in the studied population, we evaluated the cost-effectiveness of that strategy, taking into account the local cost of D-dimer testing, angiography and Doppler US (16.20, 58.72, and 75.60 Euros respectively). In the case of suspected PE, the economic impact of the proposed diagnosis strategy was a decreased of 6.9% of total costs (45,023.4 vs. 48,356.4 Euros). In the case of DVT, the overall saving was 5.1% (9,909 vs. 10,438.2 Euros). If such an analysis was used in the US, where angiography and Doppler US were more expensive (648 and 226 US$ respectively), and D-dimer less costly (14 US$), the cost savings would have been even higher (-11.0% for PE, and -6.3% for DVT).ConclusionsThe use age-adjusted cut-off levels for D-dimer, in patients aged over 50 years old, leaded to a significant increase in the test specificity, but correlatively to slightly decreased NPV and sensitivity, as some patients with D-dimer levels above 500 ng/mL but below the age-adjusted cut-off value could be misdiagnosed. However such a strategy was found to be safe in our studied populations, as the NPV remained high (99.9%), and cost-effective. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

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EVALUATION OF LEUKOCYTE ESTERASE REAGENT STRIPS TEST IN THE DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS IN CHILDREN WITH CIRRHOSIS.

Spontaneous bacterial peritonitis is defined as an ascetic fluid infection without an evident intra-abdominal surgically treatable source. Spontaneous bacterial peritonitis is one of the severe complications in patients with cirrhosis and ascites. Without early antibiotic treatment, this complication is associated with high mortality rate; therefore, early diagnosis and treatment of spontaneous bacterial peritonitis is necessary for survival. Leukocyte esterase reagent can rapidly diagnose the spontaneous bacterial peritonitis. This study aimed to find out the diagnostic accuracy of leukocyte esterase dipstick test for the diagnosis of spontaneous bacterial peritonitis. A single centered hospital-based cross-sectional study was conducted during July 2013 to August 2014 on children with cirrhotic liver disease and ascites who were admitted in the Department of Pediatric Gastroenterology in Nemazee Hospital affiliated to Shiraz University of Medical Sciences (Iran). All patients underwent abdominal paracentesis, and the ascitic fluid was processed for cell count, leukocyte esterase reagent strip test (Combiscreen SL10) and culture. Spontaneous bacterial peritonitis was defined as having a polymorphonuclear count (PMN ≥250/m3) in ascitic fluid. Sensitivity, specificity, positive predictive value and negative predictive value of leukocyte esterase test were calculated according to the formula. Totally, 150 ascitic fluid sample of cirrhotic male patients (53.2%) and their mean age (4.33±1.88 years) were analyzed. Biliary atresia (n=44, 29.4%) and idiopathic neonatal hepatitis (n=29, 19.3%) were the most frequent etiology of cirrhosis. Also, abdominal pain (68.6%) and distension (64%) were the most common presenting complaint. Of all cases, 41 patients (27.35%) were diagnosed to have spontaneous bacterial peritonitis (PMN ≥250/mm3). Sensitivity and specificity of leukocyte esterase reagent test according to PMNs ≥250 mm3 were 87.80% and 91.74%, also on ascitic fluid culture results were 88.23% and 77.44%. Positive predictive value and negative predictive value of this test in PMNs ≥250 mm3 were 80% and 95.23% and in cases with positive culture 33.33% and 98.09% were obtained, respectively. Efficiency of leukocyte esterase reagent test in diagnosing spontaneous bacterial peritonitis, according to PMNs ≥250 mm3 and culture results were 90.66% and 78.66%. The leukocyte esterase strip test may be used as rapid test for diagnosis of spontaneous bacterial peritonitis due to its high diagnostic validity.

THE COMBINATION OF CAROTID ULTRASOUND PLAQUE QUANTIFICATION AND STRESS TESTING ENHANCES PATIENT SELECTION FOR CORONARY ANGIOGRAPHY

BACKGROUND: Stress testing is commonly used to select patients for angiography. Recent studies have shown that up to 25% of angiograms may be unnecessarily conducted whereas some patients requiring angiography may not be referred, reflecting the limitations of stress testing and traditional risk factor scores. Our objective was to determine whether addition of carotid ultrasound to stress testing enhanced sensitivity for the prediction of coronary artery disease (CAD) and improved selection of patients requiring angiogram. METHODS: Carotid ultrasound was performed in 209 consecutive outpatients undergoing same-day angiography. All patients had received an imaging based stress test within 3 months. Mean far distal carotid intima-media thickness (CIMT) and maximal plaque height (thickness) were measured and compared to angiographic scores for prediction of CAD. Significant CAD was defined as presence of at least one major epicardial coronary vessel with 50% luminal narrowing. Literature threshold values for increased CIMT ( 0.8 mm) and plaque definition ( 1.5 mm) were used as cut-offs for stratifying patients as low or high risk for CAD. Stress test and ultrasound results, alone or combined, were analyzed for accuracy in stratifying risk. RESULTS: Plaque height by carotid ultrasound, in addition to stress testing, increased the overall test negative predictive value (NPV) from 28% to 71%, increased the sensitivity from 78% to 99%, and improved the negative likelihood ratio (LR-) from 1.27 to 0.20 for the detection of CAD. The combination of stress testing with carotid ultrasound would have appropriately re-stratified 34 out of 36 patients (who had received negative/equivocal stress test results) from low risk to high risk, as confirmed by coronary angiography. See Table 1. CONCLUSION: In symptomatic patients undergoing stress testing, both CIMT and carotid plaque quantification improves the identification of patients with significant coronary stenosis. Carotid plaque height quantification is superior to CIMT, and improves the NPV of stress testing by 43%. The combination of carotid ultrasound with stress testing is a potential clinical tool to rule out significant CAD and enhance selection of patients requiring angiography.

A non-invasive strategy for haemoglobin screening of blood donors.

Assessing blood-donor haemoglobin (Hb) is a worldwide screening requirement against inappropriate donation. The pre-donation Hb (which should be at least 12.5 g/dL in women and 13.5 g/dL in men) is usually determined in capillary blood from a finger prick, using a spectrophotometer which reveals the absorbance of blood haemolysed in a microcuvette. New non-invasive methods of measuring Hb are now available. In the first semester of 3 consecutive years three different strategies were employed to screen donors for anaemia at the moment of donation. In 2011 all whole-blood donors underwent the finger-prick method using azide-methaemoglobin: the test's negative predictive value (NPV) was determined by comparison with the sub-threshold Hb values ascertained by haemocytometry of test-tube blood drawn at the start of the donation. In 2012 the donor evaluation was based on NBM 200 occlusion spectrophotometry. The same approach was kept in 2013, but a haemocytometry test was added on a pre-donation venous sample drawn from donors who, though fit to donate, had previous critical Hb values in their clinical records. In 2011, the NPV (in 3,856 donors) was 86% for women and 95% for men; in 2012 (3,966 donors), the values were 85% and 95%, respectively, and in 2013 (3,995 donors) they were 91% and 97%, respectively. Fisher's test for contingency tables revealed no statistically significant differences between 2011 and 2012, but the 2013 results were a significant improvement. Measuring Hb by finger prick is not wholly satisfactory since, above all in women, the result of this screening may subsequently be belied by the haemocytometry finding of an unacceptable Hb value. Using a non-invasive method does not diminish the selective efficiency. In women, in particular, adding a haemocytometric test on a venous sample significantly improves donor selection and avoids the risk of inappropriate donation or blood-letting.

Molecular sex identification of dry human teeth specimens from Sokoto, Northwestern Nigeria.

Background:The advent of molecular techniques has revolutionized the ability of scientists to estimate the sex of individuals. Forensic odontology plays an important role in establishing the sex of victims with bodies mutilated beyond recognition due to major disaster. The genetic difference between males and females is defined by the presence or absence of the Y-chromosome. The use of alphoid-repeat primers in sex estimation was first applied on dried blood. Generally, the X, Y alphoid repeats blind test attest to the accuracy of genetic testing, and also point the potential for occasional error in morphometric sexing.Aim:To estimate genetic sex of dry human teeth specimens from Sokoto, Northwestern Nigeria, using polymerase chain reaction (PCR).Materials and Methods:A single-blind study of DNA analysis for sex estimation of nine dry human teeth specimens from Sokoto, Northwestern Nigeria, through PCR, using alphoid repeats primers, was undertaken.Results:The genetic sex of each group of the teeth samples were accurately (100%) identified. For each group of teeth, PCR Sensitivity = 100%, Specificity = 0%, Predictive value of positive test = 100%, Predictive value of negative test = 0%, False positive rate = 0%, False negative rate = 0%, Efficiency of test = 100%. Fisher's exact probability test P = 1. Z-test: z- and P values were invalid.Conclusion:This study has demonstrated the successful use of alphoid-repeat primers in genetic sex identification of human dry teeth samples from Sokoto, Northwestern Nigeria. This is the first known study estimating the sex of human dry teeth specimens by means of PCR in Nigeria. There is need for further studies in Nigeria to complement the findings of this study.

Abstract 498: Age-adjusted Cut-off Levels Improve Test Performance in the Diagnosis Strategy of Venous Thromboembolism in Elderly Patients With a Non-high Pre-test Probability

Background D-dimer levels below a well defined cut-off level enable to safely rule out VTE in patients with non-high PTP. Ageing is associated with higher levels of D-dimer. To address the issue of their usefulness in elderly patients, we firstly managed data from 644 out-patients with non-high PTP included in a multicenter management study of a D-dimer assay (C.Legnani et al. 2010). We then validated our results in a cohort of 1,042 consecutive patients investigated using another assay. Results In the first part, D-dimer level, evaluated using the HemosIL D-dimer HS500 assay (Instrumentation Laboratory), was above the cut-off level (500 ng/ml) in all 88 patients with VTE and in 299 of those without (53.8%). Test negative predictive value (NPV) and sensitivity were 100%. Overall test specificity was 46.2%, but decreased in an age-dependent manner over 70 y. ROC-analysis of test results obtained in patients classified according to age allowed us to propose an age- adjustment of the cut-off level calculated by increasing its level by 100 ng/ml per 10 y-increments in patients aged over 59 y e.g. 600 ng/ml between 60 et 69 y, 700 ng/ml between 70 et 79 y. Using those age-adjusted cut-off levels yielded to significantly improve test specificity (56.1%), particularly in old patients. If an 84 y old patient (D-dimer=625 ng/ml) was missed, NPV remained high (99.6%). That strategy was then validated by evaluating data from 1,042 consecutive out-patients, investigated using the Vidas D-dimer assay (BioMérieux). When applied, that age- adjusted cut-off levels leaded to improve test specificity 62.2% vs. 55.1% using the fixed cut-off level. 3 additional patients, with D-dimer >500 ng/ml but below age- adjusted cut-off level, were missed but overall NPV remained high 99.0% vs. 99.4%. Conclusions Age-adjusted cut-off levels for D-dimer, calculated by increasing the traditional cut- off level (500 ng/ml) by 100 ng/ml per 10 y-increments in patients aged over 59 y, significantly increased the test specificity. Correlatively, NPV and sensitivity were slightly decreased, as some patients, with D-dimer above 500 ng/ml but below the age-adjusted cut-off level, could be misdiagnosed. However such a strategy was safe, as NPV remained above 99% in our studied populations.

Fetal fibronectin test on Chinese women with symptoms of preterm labour: a pilot study

The fetal fibronectin test is advocated to facilitate the management of women presenting with threatened preterm labour, but is underutilised in Hong Kong. This study aimed to provide experience with this test and evaluate its utility in a local setting. Prospective cohort study. A university-affiliated hospital in Hong Kong. Women presenting with symptoms of preterm labour were recruited from 1 January 2011 to 30 June 2012. The sensitivity, specificity, positive predictive value, and negative predictive value of the fetal fibronectin test to predict delivery within 24 hours, 48 hours, 7 days, and 14 days. A total of 22 women were recruited; 12 (55%) of whom had a negative fetal fibronectin test, none of whom delivered within 7 days; six received corticosteroids and tocolysis, one of whom delivered within 14 days. The 10 remaining women had a positive fetal fibronectin test. Five of whom delivered within 7 days and two within 14 days; all of them had received corticosteroids and tocolysis. For predicting delivery within 7 days, the sensitivity and negative predictive value of the test were both 100%. Our study demonstrated the high negative predictive value of the fetal fibronectin test in our local setting, which suggests that it should be utilised more readily in women presenting with threatened preterm labour.