Predictive Values Of Diagnostic Tests Research Articles

Epidemiology of Pathogenic Retroviruses and Domestic Cat Hepadnavirus in Community and Client-Owned Cats in Hong Kong.

Understanding the local epidemiology of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in Hong Kong will inform retrovirus prevention strategies. Domestic cat hepadnavirus (DCH), a novel hepatitis-B-like virus, is commonly detected among client-owned cats in Hong Kong, but community cats have not been studied. The aims of this study were to investigate the frequency and potential risk factors for (i) FeLV and FIV among community and client-owned cats and (ii) perform molecular detection of DCH among community cats in Hong Kong. Blood samples from 713 cats were obtained from client-owned (n = 415, residual diagnostic) and community cats (n = 298, at trap-neuter-return). Point-of-care (POC) testing for FeLV antigen and feline immunodeficiency virus (FIV) anti-p15 and p24 antibodies was performed. FeLV-positive samples were progressed to p27 sandwich enzyme-linked immunosorbent assay. Whole blood DNA was tested with qPCRs for FeLV U3 and gag, and nested PCRs where additional information was required. DCH qPCR was performed on a subset of community cats (n = 193). A single, regressive, FeLV infection was detected in a client-owned cat (1/415 FeLV U3 qPCR positive, 0.2%, 95% CI 0.0-1.3%). Five/415 client-owned cats tested presumably false FeLV-antigen positive (qPCR negative). No markers of FeLV infection were detected in community cats (0/298; 0%). FIV seroprevalence was much higher in community cats (46/298, 15.4%) than in client-owned cats (13/415, 3.1%) (p < 0.001). Mixed breed was a risk factor for FIV infection in client-owned cats. Neither sex nor age were associated with FIV infection. DCH DNA was detected in 34/193 (17.6%) community cats (median viral load 6.32 × 103 copies/reaction). FeLV infection is rare in Hong Kong, negatively impacting the positive predictive value of diagnostic tests. FeLV-antigen testing remains the screening test of choice, but confirmation of a positive result using FeLV qPCR is essential. FIV infection is common in community cats and the absence of a sex predisposition, seen previously in cats managed similarly, raises questions about virus-transmission dynamics in these groups. DCH infection is very common in Hong Kong, both in client-owned and community cats, highlighting the importance of understanding the pathogenic potential of this virus for cats.

Accuracy of Xpert MTB/RIF Ultra for the diagnosis of tuberculosis in adult patients: a retrospective cohort study

Objectives: The value of the “trace” result in Xpert Ultra for diagnosing active tuberculosis (TB) remains unclear. Our study evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) (Cepheid, Sunnyvale, USA) over Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, USA) and mycobacterial culture when compared with a composite reference standard (CRS).Methods: A retrospective single-center observational study was conducted in a tertiary care hospital in South India. Over three months, patients (aged ≥15 years) data on Xpert Ultra tests and mycobacterial culture of pulmonary and extrapulmonary samples were extracted from their electronic medical records. Patients were defined as TB cases based on the CRS criteria. Sensitivity, specificity, positive and negative predictive values of diagnostic tests were calculated by comparing them to the CRS.Results: Xpert Ultra was more sensitive (87.8%) than Xpert (72.1%) and culture (44.1%). The specificity of Xpert Ultra was lower (98.1%) than those of Xpert (100%) and culture (100%). The sensitivity (92%) and specificity (100%) of Xpert Ultra were highest when performed on pus samples.Conclusions: Xpert Ultra with the trace category is superior to the conventional Xpert, and mycobacterial culture in identifying TB.

Global Hypothesis Test to Compare the Predictive Values of Diagnostic Tests Subject to a Case-Control Design

Use of a case-control design to compare the accuracy of two binary diagnostic tests is frequent in clinical practice. This design consists of applying the two diagnostic tests to all of the individuals in a sample of those who have the disease and in another sample of those who do not have the disease. This manuscript studies the comparison of the predictive values of two diagnostic tests subject to a case-control design. A global hypothesis test, based on the chi-square distribution, is proposed to compare the predictive values simultaneously, as well as other alternative methods. The hypothesis tests studied require knowing the prevalence of the disease. Simulation experiments were carried out to study the type I errors and the powers of the hypothesis tests proposed, as well as to study the effect of a misspecification of the prevalence on the asymptotic behavior of the hypothesis tests and on the estimators of the predictive values. The proposed global hypothesis test was extended to the situation in which there are more than two diagnostic tests. The results have been applied to the diagnosis of coronary disease.

Leptospira Seroprevalence Among Ugandan Slaughter Cattle: Comparison of Sero-Status With Renal Leptospira Infection.

Despite evidence of both human and animal Leptospira exposures in Uganda, the epidemiology of the disease is still not well-investigated. Contact with animals and their environments have been pointed out as potential source of infection with Leptospira species in humans; and cattle may be an important reservoir in Uganda. In this cross-sectional study, we estimated the prevalence of anti-Leptospira antibodies by the standard microscopic agglutination test (MAT); and associated risk factors among slaughtered cattle. We also compared the performance of the MAT used in this study against a lipL32 based real time PCR (qPCR) assay previously conducted on the kidneys and urine of the same slaughter cattle as tested in this reported study. Of 500 cattle sampled, 27.8% (95% CI 23.9–32.0) tested positive (titer ≥ 100) to at least one Leptospira serovar, with the majority of seropositive cattle reacting to serovars Tarassovi (sg Tarassovi) (11.6%), Sejroe (Sg Sejroe) (7.8%), and Australis (Sg Australis) (5.2%). Older animals had 2.8 times (95% CI 1.0–8.2, p-value 0.055) greater odds of being seropositive than younger ones (<1.5 years). The sensitivity and specificity of the MAT over the qPCR were 65.9% (95% CI 50.1–79.5) and 75.9% (95% CI 71.7–79.7), respectively; with a negative predictive value of 95.8% and positive predictive value of 20.9%. In conclusion, slaughter cattle in this study were significantly exposed to pathogenic Leptospira species of mainly the Tarassovi, Sejroe, and Australis serogroups, with seroprevalence being higher among older cattle. The high specificity and negative predictive value of MAT as used in this study when compared to the qPCR assay may imply a rather strong association between seronegativity and absence of renal Leptospira infection. However, MAT predictability for renal Leptospira infection may be interpreted cautiously since predictive values of diagnostic tests are dependent on prevalence.

A non-inferiority test and sample size determination for comparing two predictive values of diagnostic tests

Positive and negative predictive values describe the clinical performance of the diagnostic test when it is applied to a cohort of individuals. Testing non-inferiority of predictive values may be adequate in some cases due to the simplicity of the examination and the invasiveness of the test, but no non-inferiority test for predictive values has been proposed yet. In this study, we propose a non-inferiority test that investigates the non-inferiority of predictive values in paired designs, and formulae for the calculation of sample size to execute the non-inferiority test of two predictive values. Simulation studies showed that the proposed non-inferiority test is useful for comparing two predictive values in clinical trials.

Twierdzenie Bayesa w projektowaniu strategii diagnostycznych w medycynie

The paper will compare two methods used in the design of diagnostic strategies. The first one is a method that precises predictive value of diagnostic tests. The second one is based on the use of Bayes’ theorem. The main aim of this article is to identify the epistemological assumptions underlying both of these methods. For the purpose of this objective, example projects of one and multi-stage diagnostic strategy developed using both methods will be considered.

Understanding Negative Predictive Value of Diagnostic Tests Used in Clinical Practice.

Nurses review, evaluate, and use diagnostic test results on a routine basis. However, the skills necessary to evaluate a particular test using statistical outcome measures is often lacking. The purpose of this article is to examine and interpret the underlying principles for use of the statistical outcomes of diagnostic screening tests (sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values, with a discussion about use of SpPIn [Specificity, Positive test = rule in], and SnNOut [Sensitivity, Negative test = rule out]) in advanced nursing clinical practice. The authors focus on NPVs because test results with high NPV are useful to practitioners when considering unnecessary, costly, and possibly risky treatments, whether using clinical assessment tool, test, or procedure or using polymerase chain reaction analysis of DNA test results. In this article, the authors emphasize the use of NPV in treatment decisions by providing examples from critical care, neonatal, and advanced forensic nursing, which become a framework for assessing decisions in the clinical arena. This commentary stresses the importance of the NPV of tests in preventing, detecting, and ruling out disease, where PPV may not be relevant for that purpose. Negative predictive value percentages inform treatment decisions when the provider understands the biology, chemistry, and foundation for testing methods used in clinical practices. The art of diagnosis, confirmed in a test's high NPV (meaning the patient probably does not have the disease when the test is negative), reassures provider treatment stewardship to do no harm.

Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a prospective longitudinal test accuracy study to validate new risk scores in women with symptoms of suspected ovarian cancer

IntroductionOvarian cancer (OC) is associated with non-specific symptoms such as bloating, making accurate diagnosis challenging: only 1 in 3 women with OC presents through primary care referral. National Institute for...

A new likelihood approach to inference about predictive values of diagnostic tests in paired designs.

Intuitively, one only needs patients with two positive screening test results for positive predictive values comparison, and those with two negative screening test results for contrasting negative predictive values. Nevertheless, current existing methods rely on the multinomial model that includes superfluous parameters unnecessary for specific comparisons. This practice results in complex statistics formulas. We introduce a novel likelihood approach that fits the intuition by including a minimum number of parameters of interest in paired designs. It is demonstrated that our robust score test statistic is identical to a newly proposed weighted generalized score test statistic. Simulations and real data analysis are used for illustration.

Rickettsioses as causes of CNS infection in southeast Asia.

1report that scrub typhus caused by Orientia tsutsugamushi, murine typhus caused by Rickettsia typhi, and leptospirosis caused by various Leptospira species account for more than a third of CNS infections diagnosed over 8 years in Vientiane Hospital in Laos. The study is one more great contribution from this team in their investigation of undocumented syndromes, as well as in the public health challenge of rickettsial diseases in southeast Asia. The same investigators have previously reported that scrub typhus was the second most common microbial cause of fever of unknown origin in rural Laos (122 [15%] of 799 diagnosed cases). 2 In 2006, rickettsial infection was detected in 115 (27%) of 427 adults admitted to Vientiane Hospital for fever with negative blood culture. 3 The most common rickettsial agent was O tsutsugamushi followed by R typhi. Fewer data are available about the prevalence of these diseases in other southeast Asian countries. In Thailand, scrub and murine typhus has been reported 4 in 16% and 2%, respectively, of fever of unknown origin, with mortality of 3–17% for scrub typhus. Even if epidemiological data for the whole region are unavailable, the substantial presence of rickettsial infections is shown by frequent reports in travellers returning from this area. 5

OCT and NMO

OCT and NMO

Diagnostic uncertainty: dichotomies are not the answer

Over two decades ago, Alvan Feinstein, a leading figure in the development and evaluation of diagnostic research methods, argued that the binary ‘positive–negative’ framework used in test accuracy research is not representative of diagnostic decision making in clinical practice.1 In particular, he called for a move away from the dichotomisation of quantitative test scales (tests that are on a continuous or ordinal scale) and advocated an approach that allows for the explicit recognition of an ‘uncertain’ diagnostic outcome. Twenty years on and little progress has been made on this issue; reporting the accuracy of quantitative tests based on a single ‘optimal’ threshold continues to be common practice. Here we present how improving the methods for evaluating quantitative tests would be of greatest benefit to GPs, providing them with a better evidence-based toolkit of strategies for recognising and handling diagnostic uncertainty head-on. Summerton reported that failures relating to diagnosis account for nearly one-third of GP complaints.2 Diagnostic uncertainty is particularly rife in general practice due to a number of obstacles intrinsic to the clinical setting.3 First, the prevalence of serious disease is typically low in a community population, weakening the overall predictive value of diagnostic tests. Secondly, the majority of disease presenting in general practice is commonly in its early stages, when many ‘red flag’ symptoms are yet to evolve and departures from physiological normality are slight. Furthermore, many of the tests used are not disease-specific; they are typically predictive of a symptom that …

Interrelationships among enrichment with diagnostics, probability of success and demonstration of effectiveness in clinical trials

Background: Prevalence of disease phenotype in clinical practice is often not given adequate importance during formulation, validation, and implementation of diagnostic tests in clinical research and development. After promising biomarkers have been identified as potential screening diagnostics, an important strategic question for optimal decision-making in clinical development of a therapeutic is when to choose an enrichment study design over the traditional all-comer randomized control trial design. Methods: A hypothetical example of a cholesterol lowering treatment is used to illustrate influences of key statistical criteria and clinical considerations for choosing study designs. Computer simulations demonstrate how results of such analyses can aid in deciding whether or not to choose enrichment study designs. Results: This study shows how understanding of disease prevalence in practice, predictive values of diagnostic test, and prespecified establishment of a clinically meaningful minimum effectiveness all need to be integrated to insure clinical trial success and appropriate benefit to targeted patient subgroups. The most important statistical and clinical considerations were the anticipated effect size, phenotype prevalence, predictive values of diagnostics test, study power, and desired clinically meaningful difference. Conclusions: This study illustrates how successful clinical studies can be designed with careful planning and utilization of computer simulations to increase not only the probability of trial success but also to demonstrate to payers convincing evidence of clinical effectiveness. A six-step checklist is recommended as an evidence-based guideline to assist in decision-making on whether or not to adopt a diagnostics enriched clinical study design.

Umgang mit diagnostischer Unsicherheit in der Hausarztpraxis

In general, the prevalence of diseases is low in primary care. Therefore, the positive predictive value of diagnostic tests is lower than in hospitals where patients are highly selected. In addition, the patients present with milder forms of disease; and many diseases might hide behind the initial symptom(s). These facts lead to diagnostic uncertainty which is somewhat inherent to general practice. This narrative review discusses different sources of and reasons for uncertainty and strategies to deal with it in the context of the current literature. Fear of uncertainty correlates with higher diagnostic activities. The attitude towards uncertainty correlates with the choice of medical speciality by vocational trainees or medical students. An intolerance of uncertainty, which still increases as medicine is making steady progress, might partly explain the growing shortage of general practitioners. The bio-psycho-social context appears to be important to diagnostic decision-making. The effect of intuition and heuristics are investigated by cognitive psychologists. It is still unclear whether these aspects are prone to bias or useful, which might depend on the context of medical decisions. Good communication is of great importance to share uncertainty with the patients in a transparent way and to alleviate shared decision-making. Dealing with uncertainty should be seen as an important core component of general practice and needs to be investigated in more detail to improve the respective medical decisions.

A weighted generalized score statistic for comparison of predictive values of diagnostic tests

Positive and negative predictive values are important measures of a medical diagnostic test performance. We consider testing equality of two positive or two negative predictive values within a paired design in which all patients receive two diagnostic tests. The existing statistical tests for testing equality of predictive values are either Wald tests based on the multinomial distribution or the empirical Wald and generalized score tests within the generalized estimating equations (GEE) framework. As presented in the literature, these test statistics have considerably complex formulas without clear intuitive insight. We propose their re-formulations that are mathematically equivalent but algebraically simple and intuitive. As is clearly seen with a new re-formulation we presented, the generalized score statistic does not always reduce to the commonly used score statistic in the independent samples case. To alleviate this, we introduce a weighted generalized score (WGS) test statistic that incorporates empirical covariance matrix with newly proposed weights. This statistic is simple to compute, always reduces to the score statistic in the independent samples situation, and preserves type I error better than the other statistics as demonstrated by simulations. Thus, we believe that the proposed WGS statistic is the preferred statistic for testing equality of two predictive values and for corresponding sample size computations. The new formulas of the Wald statistics may be useful for easy computation of confidence intervals for difference of predictive values. The introduced concepts have potential to lead to development of the WGS test statistic in a general GEE setting.

Bivariate meta-analysis of predictive values of diagnostic tests can be an alternative to bivariate meta-analysis of sensitivity and specificity

ObjectiveMeta-analysis of predictive values is usually discouraged because these values are directly affected by disease prevalence, but sensitivity and specificity sometimes show substantial heterogeneity as well. We propose a bivariate random-effects logitnormal model for the meta-analysis of the positive predictive value (PPV) and negative predictive value (NPV) of diagnostic tests. Study Design and SettingTwenty-three meta-analyses of diagnostic accuracy were reanalyzed. With separate models, we calculated summary estimates of the PPV and NPV and summary estimates of sensitivity and specificity. We compared these summary estimates, the goodness of fit of the two models, and the amount of heterogeneity of both approaches. ResultsThere were no substantial differences in the goodness of fit or amount of heterogeneity between both models. The median absolute difference between the projected PPV and NPV from the summary estimates of sensitivity and specificity and the summary estimates of PPV and NPV was 1% point (interquartile range, 0–2% points). ConclusionA model for the meta-analysis of predictive values fitted the data from a range of systematic reviews equally well as meta-analysis of sensitivity and specificity. The choice for either model could be guided by considerations of the design used in the primary studies and sources of heterogeneity.

Evidence‐Based Medicine in Otolaryngology, Part 3: Everyday Probabilities

Recent studies have demonstrated that the majority of physicians cannot accurately determine the predictive values of diagnostic tests. Physicians must understand the predictive probabilities associated with diagnostic testing in order to convey accurate information to patients, a key aspect of evidence-based practice. While sensitivity and specificity are widely understood, predictive values require a further understanding of conditional probabilities, pretest probabilities, and the prevalence of disease. Therefore, this third installment of the series "Evidence-Based Medicine in Otolaryngology" focuses on understanding the probabilities needed to accurately convey the results of dichotomous diagnostic tests in everyday practice.

Prior probability (the pretest best guess) affects predictive values of diagnostic tests

Authors who publish evaluations of dichotomous (yes/no) diagnostic tests often include the predictive values of their test at a single prior probability (eg, the prevalence of the target disease within the evaluation data set). The objectives of this technical note are to demonstrate why single-probability predictive values are misleading and to show a better way to display positive predictive values (PPV) and negative predictive values (NPV) for a newly evaluated test. Secondly, this technical note will show readers how to calculate predictive values from only sensitivity and specificity for any desired prior probability. As prior probability increases from 0% to 100%, PPV increases from 0% to 100%, but NPV goes in the opposite direction (drops from 100% to 0%). Because prior probabilities vary so greatly across situations, predictive values should be provided in publications for the full range of potential prior probabilities (if provided at all). This is easily done with a 2-curve graph displaying the predictive values (y-axis) against the prior probability (x-axis).

Analisis coste-efectividad de distintos métodos de diagnóstico por imagen del tromboembolismo pulmonar agudo

The optimal diagnostic test for detecting acute pulmonary embolism (APE) is still under discussion. The ventilation /perfusion scanning has been the preferred examination for several decades, but with the development of new tests the diagnostic possibilities have increased. It is necessary to evaluate them from the cost-effectiveness perspective. The goal of this study was to evaluate several methods of imaging diagnosis so as to determine the most cost-effective for detecting APE. Cost-effectiveness (CE) analysis using a decision tree to model various diagnostic test (V/Q lung scan, spiral CT, angiography by MDCT, MRI and conventional arteriography). Sensitivity and specificity values, and positive and negative predictive values of diagnostic tests were calculated. Expected outcome: "new APE case detected." The direct costs were evaluated in eurosos (euros), including the secondary complications of diagnostic methods. To assess the robustness of the findings, a one way sensitivity analysis was performed. The most cost-effective diagnostic test was angiography by MDCT. No diagnostic test were eliminated by extended dominance. The crude rate of CE for MDCT was 486 euros per case of APE detected. The marginal cost between spiral CT and V / Q lung scan was euros 103 for 8 cases of APE detected additionally, while the marginal cost between MDCT and spiral CT was 229 euros to detect an additional case of APE. The most cost-effective diagnostic test was the MDCT; this finding showed to be robust in relationship to sensitivity, specificity and costs changes. However, the incremental C-E analysis showed that MDCT was capable to detect only one additional case of APE than spiral CT, with an incremental cost of 229 euros. When peripheral branches are affected, high negative predictive value of the MDCT justify its conduct.

Treatment of Chronic Recurrent Abdominal Pain: Laparoscopy or Hypnosis?

Functional chronic recurrent abdominal pain (FCRAP) is long lasting, intermittent, or constant pain affecting 15-30% of children ages 4-18 and presents a diagnostic and treatment challenge to the physician. The predictive value of diagnostic tests is questionable, and studies of the treatment of chronic abdominal pain show inconclusive evidence regarding diet regimens as well as medical and surgical treatments. However, there is evidence that cognitive-behavioral therapy may be useful in improving pain and disability outcome. Increasing the understanding of the neural-pain pathways and research in cognitive modulation of pain led to the application of behavioral strategies in children with FCRAP with variable success. However, the use of hypnotherapy in children with recurrent abdominal pain is not common. During the last 3 years, we have implemented hypnosis as the preferred treatment for patients with FCRAP. In the current study, we aimed to summarize our experience with hypnosis for the treatment of FCRAP in children. Twenty patients who met the criteria for FCRAP were candidates for hypnosis. Hypnosis or imagery was offered to the families, of whom 3 refused. Seventeen patients underwent just one single session of hypnosis. A possible nonorganic etiology for the abdominal pain was revealed in all cases. In 14 adolescents, all clinical symptoms resolved. Hypnosis was not effective in 3 cases, in whom secondary gain was probably responsible for their symptoms. No side effects have been noted during and after the study. Follow-up was available for a period of 4-24 months. Although effective in the management of acute pain and distress in pediatric cancer patients, the use of hypnotherapy in children with FCRAP is not a common practice. The current study highly supports the use of hypnosis as a part of the biobehavioral approach for this dilemma.