Variation of a test's sensitivity and specificity with disease prevalence

BACKGROUND Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. METHODS We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. RESULTS Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. INTERPRETATION The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

Evaluation of PCR electrospray-ionization mass spectrometry for rapid molecular diagnosis of bovine mastitis

Bovine mastitis, an inflammatory disease of the mammary gland, is one of the most costly diseases affecting the dairy industry. The treatment and prevention of this disease is linked heavily to the use of antibiotics in agriculture and early detection of the primary pathogen is essential to control the disease. Milk samples (n=67) from cows suffering from mastitis were analyzed for the presence of pathogens using PCR electrospray-ionization mass spectrometry (PCR/ESI-MS) and were compared with standard culture diagnostic methods. Concurrent identification of the primary mastitis pathogens was obtained for 64% of the tested milk samples, whereas divergent results were obtained for 27% of the samples. The PCR/ESI-MS failed to identify some of the primary pathogens in 18% of the samples, but identified other pathogens as well as microorganisms in samples that were negative by culture. The PCR/ESI-MS identified bacteria to the species level as well as yeasts and molds in samples that contained a mixed bacterial culture (9%). The sensitivity of the PCR/ESI-MS for the most common pathogens ranged from 57.1 to 100% and the specificity ranged from 69.8 to 100% using culture as gold standard. The PCR/ESI-MS also revealed the presence of the methicillin-resistant gene mecA in 16.2% of the milk samples, which correlated with the simultaneous detection of staphylococci including Staphylococcus aureus. We demonstrated that PCR/ESI-MS, a more rapid diagnostic platform compared with bacterial culture, has the significant potential to serve as an important screening method in the diagnosis of bovine clinical mastitis and has the capacity to be used in infection control programs for both subclinical and clinical disease.

Prevalence and risk factors of methicillin-resistant Staphylococcus aureus in critically-ill hospitalized patients in a tertiary care center in Houston, Texas: An active surveillance pilot project

Objective. The objective of this study is to determine the prevalence of MRSA colonization in adult patients admitted to intensive care units at an urban tertiary care hospital in Houston, Texas and to evaluate the risk factors associated with colonization during a three month active-screening pilot project. Design. This study used secondary data from a small cross-sectional pilot project. Methods. All patients admitted to the seven specialty ICUs were screened for MRSA by nasal culture. Results were obtained utilizing the BD GeneOhm™ IDI-MRSA assay in vitro diagnostic test, for rapid MRSA detection. Statistical analysis was performed using the STATA 10, Epi Info, and JavaStat. Results . 1283/1531 (83.4%) adult ICU admissions were screened for nasal MRSA colonization. Of those screened, demographic and risk factor data was available for 1260/1283 (98.2%). Unresolved results were obtained for 73 patients. Therefore, a total of 1187/1531 (77.5%) of all ICU admissions during the three month study period are described in this analysis. Risk factors associated with colonization included the following: hospitalization within the last six months (odds ratio 2.48 [95% CI, 1.70-3.63], p=0.000), hospitalization within the last 12 months, (odds ratio 2.27 [95% CI, 1.57-3.80], p=0.000), and having diabetes mellitus (odds ratio 1.63 [95% CI, 1.14-2.32], p=0.007). Conclusion. Based on the literature, the prevalence of MRSA for this population is typical of other prevalence studies conducted in the United States and coincides with the continual increasing trend of MRSA colonization. Significant risk factors were similar to those found in previous studies. Overall, the active surveillance screening pilot project has provided valuable information on a population not widely addressed. These findings can aid in future interventions for the education, control, prevention, and treatment of MRSA. ^

POPULATION ASSESSMENTS OF INFECTION WITH SCHISTOSOMA MANSONI: EFFECTS OF BIAS CAUSED BY THE RELATIVE SENSITIVITY OF DIAGNOSTIC TECHNIQUES (PUERTO RICO)

This study establishes the extent and relevance of bias of population estimates of prevalence, incidence, and intensity of infection with Schistosoma mansoni caused by the relative sensitivity of stool examination techniques. The population studied was Parcelas de Boqueron in Las Piedras, Puerto Rico, where the Centers for Disease Control, had undertaken a prospective community-based study of infection with S. mansoni in 1972. During each January of the succeeding years stool specimens from this population were processed according to the modified Ritchie concentration (MRC) technique. During January 1979 additional stool specimens were collected from 30 individuals selected on the basis of their mean S. mansoni egg output during previous years. Each specimen was divided into ten 1-gm aliquots and three 42-mg aliquots. The relationship of egg counts obtained with the Kato-Katz (KK) thick smear technique as a function of the mean of ten counts obtained with the MRC technique was established by means of regression analysis. Additionally, the effect of fecal sample size and egg excretion level on technique sensitivity was evaluated during a blind assessment of single stool specimen samples, using both examination methods, from 125 residents with documented S. mansoni infections. The regression equation was: Ln KK = 2.3324 + 0.6319 Ln MRC, and the coefficient of determination (r('2)) was 0.73. The regression equation was then utilized to correct the term "m" for sample size in the expression P ((GREATERTHEQ) 1 egg) = 1 - e('-ms), which estimates the probability P of finding at least one egg as a function of the mean S. mansoni egg output "m" of the population and the effective stool sample size "s" utilized by the coprological technique. This algorithm closely approximated the observed sensitivity of the KK and MRC tests when these were utilized to blindly screen a population of known parasitologic status for infection with S. mansoni. In addition, the algorithm was utilized to adjust the apparent prevalence of infection for the degree of functional sensitivity exhibited by the diagnostic test. This permitted the estimation of true prevalence of infection and, hence, a means for correcting estimates of incidence of infection. ^

Should an oral glucose tolerance test be performed routinely in all renal transplant recipients?

Posttransplantation diabetes (PTD) contributes to cardiovascular disease and graft loss in renal transplant recipients (RTR). Current recommendations advise fasting blood glucose (FBG) as the screening and diagnostic test of choice for PTD. This study sought to determine (1) the predictive power of FBG with respect to 2-h blood glucose (2HBG) and (2) the prevalence of PTD using FBG and 2HBG compared with that using FBG alone, in prevalent RTR. A total of 200 RTR (mean age 52 yr; 59% male; median transplant duration 6.6 yr) who were >6 mo posttransplantation and had no known history of diabetes were studied. Patients with FBG

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

RATIONALE: Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. OBJECTIVES: We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. METHODS: The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. MEASUREMENTS AND MAIN RESULTS: In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved. CONCLUSIONS: Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development.

Development of a Durability Test for Asphalts, HR-124, Progress Report No. 3., 1969

Research Project HR-124, "Development of a Laboratory Durability Test for Asphalts," was initiated in 1966 as a long range comprehensive program. Its ultimate objective was to develop a simple, rapid laboratory test that could be used by highway engineers to select paving asphalt according to quality, to identify inferior asphalts, and to reasonably predict the useful life of asphalts once they were incorporated in the pavements. This report, designated Progress Report No. 3, summarizes the work accomplished during the second year of the HR-124 extension (1967 - 1969), i. e., the period from 1 October 1968 to 31 October 1969.

Diagnostic Tests and their Application in the Management of Soil- and Water-borne Oomycete Pathogen Species

Oomycete diseases cause significant losses across a broad range of crop and aquaculture commodities worldwide. These losses can be greatly reduced by disease management practices steered by accurate and early diagnoses of pathogen presence. Determinations of disease potential can help guide optimal crop rotation regimes, varietal selections, targeted control measures, harvest timings and crop post-harvest handling. Pathogen detection prior to infection can also reduce the incidence of disease epidemics. Classical methods for the isolation of oomycete pathogens are normally deployed only after disease symptom appearance. These processes are often-time consuming, relying on culturing the putative pathogen(s) and the availability of expert taxonomic skills for accurate identification; a situation that frequently results in either delayed application, or routine ‘blanket’ over-application of control measures. Increasing concerns about pesticides in the environment and the food chain, removal or restriction of their usage combined with rising costs have focussed interest in the development and improvement of disease management systems. To be effective, these require timely, accurate and preferably quantitatve diagnoses. A wide range of rapid diagnostic tools, from point of care immunodiagnostic kits to next generation nucleotide sequencing have potential application in oomycete disease management. Here we review currently-available as well as promising new technologies in the context of commercial agricultural production systems, considering the impacts of specific biotic and abiotic and other important factors such as speed and ease of access to information and cost effectiveness

Recommended reporting standards for test accuracy studies of infectious diseases of finfish, amphibians, molluscs and crustaceans: the STRADAS-aquatic checklist

Complete and transparent reporting of key elements of diagnostic accuracy studies for infectious diseases in cultured and wild aquatic animals benefits end-users of these tests, enabling the rational design of surveillance programs, the assessment of test results from clinical cases and comparisons of diagnostic test performance. Based on deficiencies in the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines identified in a prior finfish study (Gardner et al. 2014), we adapted the Standards for Reporting of Animal Diagnostic Accuracy Studies—paratuberculosis (STRADAS-paraTB) checklist of 25 reporting items to increase their relevance to finfish, amphibians, molluscs, and crustaceans and provided examples and explanations for each item. The checklist, known as STRADAS-aquatic, was developed and refined by an expert group of 14 transdisciplinary scientists with experience in test evaluation studies using field and experimental samples, in operation of reference laboratories for aquatic animal pathogens, and in development of international aquatic animal health policy. The main changes to the STRADAS-paraTB checklist were to nomenclature related to the species, the addition of guidelines for experimental challenge studies, and the designation of some items as relevant only to experimental studies and ante-mortem tests. We believe that adoption of these guidelines will improve reporting of primary studies of test accuracy for aquatic animal diseases and facilitate assessment of their fitness-for-purpose. Given the importance of diagnostic tests to underpin the Sanitary and Phytosanitary agreement of the World Trade Organization, the principles outlined in this paper should be applied to other World Organisation for Animal Health (OIE)-relevant species.

Evaluación del desempeño de pruebas diagnósticas de tuberculosis en pacientes VIH positivo en dos hospitales públicos de Bogotá

La tuberculosis TB es una de las principales causas de muerte en el mundo en individuos con infección por VIH. En Colombia esta coinfección soporta una carga importante en la población general convirtiéndose en un problema de salud pública. En estos pacientes las pruebas diagnósticas tienen sensibilidad inferior y la enfermedad evoluciona con mayor frecuencia hacia formas diseminadas y rápidamente progresivas y su diagnóstico oportuno representa un reto en Salud. El objetivo de este proyecto es evaluar el desempeño de las pruebas diagnósticas convencionales y moleculares, para la detección de TB latente y activa pacientes con VIH, en dos hospitales públicos de Bogotá. Para TB latente se evaluó la concordancia entre las pruebas QuantiFERON-TB (QTF) y Tuberculina (PPD), sugiriendo superioridad del QTF sobre la PPD. Se evaluaron tres pruebas diagnósticas por su sensibilidad y especificidad, baciloscopia (BK), GenoType®MTBDR plus (Genotype) y PCR IS6110 teniendo como estándar de oro el cultivo. Los resultados de sensibilidad (S) y especificidad (E) de cada prueba con una prevalencia del 19,4 % de TB pulmonar y extrapulmonar en los pacientes que participaron del estudio fue: BK S: 64% E: 99,1%; Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 73% E: 95,5%, de la misma forma se determinaron los valores predictivos positivos y negativos (VPP y VPN) BK: 88,9% y 94,8%, Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 90% y 95,7%. Se concluyó bajo análisis de curva ROC que las pruebas muestran un rendimiento diagnóstico similar por separado en el diagnóstico de TB en pacientes con VIH, aumentando su rendimiento diagnostico cuando se combinan

Identification of Neoplasias of Breast Tissues Using a Powder Diffractometer

An investigation was carried out to study the potential use of the angular distribution of scattered photons by human breast samples for a rapid identification of neoplasias of breast tissues. This technique has possible applications as diagnostic aid for breast cancer. In this work, a commercial powder diffractometer was used to obtain the scattering profiles from breast tissues histopathologically classified as normal breast tissues, fibroadenomas (benign breast diseases) and carcinomas (malignant breast diseases), in the interval 0.02 angstrom(-1) < x < 0.62 angstrom(-1). The experimental methods and data corrections are discussed in detail, and they included background subtraction, polarization, self-attenuation and geometric effects. The validation of the experimental procedure was achieved through an analysis of water sample. The results showed that the scattering profile is a unique impression of each type of tissue, being correlated with their microscopic morphological features. Multivariate analysis was applied to these profiles in order to verify if the information carried by these scattering profiles allow the differentiation between normal, benign and malignant breast tissues. The statistical analysis results showed that a correct identification of 75% of the analyzed samples is accomplished. The values of sensibility and specificity of this method in correctly differentiating between normal and neoplastic samples were 95.6% and 82.3%, respectively, while the values for differentiation between benign and malignant neoplasias were 78.6% and 62.5%. These initial results indicate the feasible use of commercial powder diffractometer to provide a rapid diagnostic with a high sensitivity.

Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole, bismuth suticitrate, furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success. METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens. The therapeutic regimen consisted of 20 mg omeprazole, 240 mg colloidal bismuth subcitrate, 1000 mg amoxicillin, and 200 mg furazolidone, taken twice a day for 7 d. Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology). Safety was determined by the presence of adverse effects. RESULTS: Fifty-one patients were enrolled. The eradication rate was 68.8% (31/45). Adverse effects were reported by 31.4% of the patients, and these were usually considered to be slight or moderate in the majority of the cases. Three patients had to withdraw from the treatment due to the presence of severe adverse effects. CONCLUSION: The association of bismuth, furazolidone, amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens. It is an effective, cheap and safe option for salvage therapy of positive patients. (C) 2008 The WJG Press. All rights reserved.

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication

Background: Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen. Methods: This study included 48 patients with peptic ulcer disease. Helicobacter pylori infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use. Results: Only one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI-89%-99%) and 88% (88-92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-nave patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002). Conclusion: An empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of Helicobacter pylori, particularly in patients that have failed one prior eradication therapy.

Utility of Quantitative Ultrasound of the Calcaneus in Diagnosing Osteoporosis in Spinal Cord Injury Patients

Bittar CK, Cliquet A Jr, dos Santos Floter M: Utility of quantitative ultrasound of the calcaneus in diagnosing osteoporosis in spinal cord injury patients. Am J Phys Med Rehabil 2011;90:477-481. Objective: The aim of this study was to assess the utility of quantitative ultrasound of the calcaneus in diagnosing osteoporosis in spinal cord injury patients in a Brazilian Teaching Hospital. Design: This is a diagnostic test criterion standard comparison study. Between January 2008 and October 2009, the bone density of 15 spinal cord injury patients was assessed for analysis before beginning rehabilitation using muscle stimulation. The bone density was assessed using bone densitometry examination (DEXA) and ultrasound examination of the calcaneus (QUS). The measurements acquired using QUS and DEXA were compared between patients with spinal cord injury and a control group of ten healthy individuals. Results: The T-score values for femoral neck using DEXA (P < 0.0022) and those using QUS of the calcaneus (P < 0.0005) differed significantly between the groups, and the means in the normal subjects were higher than those in spinal cord injury patients who would receive electrical stimulation. In spinal cord injury patients, the significant differences were found between the QUS T-score for calcaneus and the DEXA scores for the lumbar spine and femoral neck. Conclusions: Because of the low level of mechanical stress on the calcaneus, the results of the QUS could not be correlated with the DEXA results for diagnosing osteoporosis. Therefore, QUS seems to be not a good choice for diagnosis and follow-up.