Difference In Positive Predictive Value Research Articles

Optimising breast cancer screening reading: blinding the second reader to the first reader\u2019s decisions

ObjectivesIn breast cancer screening, two readers separately examine each woman’s mammograms for signs of cancer. We examined whether preventing the two readers from seeing each other’s decisions (blinding) affects behaviour and outcomes.MethodsThis cohort study used data from the CO-OPS breast-screening trial (1,119,191 women from 43 screening centres in England) where all discrepant readings were arbitrated. Multilevel models were fitted using Markov chain Monte Carlo to measure whether reader 2 conformed to the decisions of reader 1 when they were not blinded, and the effect of blinding on overall rates of recall for further tests and cancer detection. Differences in positive predictive value (PPV) were assessed using Pearson’s chi-squared test.ResultsWhen reader 1 recalls, the probability of reader 2 also recalling was higher when not blinded than when blinded, suggesting readers may be influenced by the other’s decision. Overall, women were less likely to be recalled when reader 2 was blinded (OR 0.923; 95% credible interval 0.864, 0.986), with no clear pattern in cancer detection rate (OR 1.029; 95% credible interval 0.970, 1.089; Bayesian p value 0.832). PPV was 22.1% for blinded versus 20.6% for not blinded (p < 0.001).ConclusionsOur results suggest that when not blinded, reader 2 is influenced by reader 1’s decisions to recall (alliterative bias) which would result in bypassing arbitration and negate some of the benefits of double-reading. We found a relationship between blinding the second reader and slightly higher PPV of breast cancer screening, although this analysis may be confounded by other centre characteristics.Key Points• In Europe, it is recommended that breast screening mammograms are analysed by two readers but there is little evidence on the effect of ‘blinding’ the readers so they cannot see each other’s decisions.• We found evidence that when the second reader is not blinded, they are more likely to agree with a recall decision from the first reader and less likely to make an independent judgement (alliterative error). This may reduce overall accuracy through bypassing arbitration.• This observational study suggests an association between blinding the second reader and higher positive predictive value of screening, but this may be confounded by centre characteristics.

Use of Antiplatelet Agents Decreases the Positive Predictive Value of Fecal Immunochemical Tests for Colorectal Cancer but Does Not Affect Their Sensitivity.

Previous studies have evaluated the effects of antithrombotic agents on the performance of fecal immunochemical tests (FITs) for the detection of colorectal cancer (CRC), but the results were inconsistent and based on small sample sizes. We studied this topic using a large-scale population-based database. Using the Korean National Cancer Screening Program Database, we compared the performance of FITs for CRC detection between users and non-users of antiplatelet agents and warfarin. Non-users were matched according to age and sex. Among 5,426,469 eligible participants, 768,733 used antiplatelet agents (mono/dual/triple therapy, n = 701,683/63,211/3839), and 19,569 used warfarin, while 4,638,167 were non-users. Among antiplatelet agents, aspirin, clopidogrel, and cilostazol ranked first, second, and third, respectively, in terms of prescription rates. Users of antiplatelet agents (3.62% vs. 4.45%; relative risk (RR): 0.83; 95% confidence interval (CI): 0.78–0.88), aspirin (3.66% vs. 4.13%; RR: 0.90; 95% CI: 0.83–0.97), and clopidogrel (3.48% vs. 4.88%; RR: 0.72; 95% CI: 0.61–0.86) had lower positive predictive values (PPVs) for CRC detection than non-users. However, there were no significant differences in PPV between cilostazol vs. non-users and warfarin users vs. non-users. For PPV, the RR (users vs. non-users) for antiplatelet monotherapy was 0.86, while the RRs for dual and triple antiplatelet therapies (excluding cilostazol) were 0.67 and 0.22, respectively. For all antithrombotic agents, the sensitivity for CRC detection was not different between users and non-users. Use of antiplatelet agents, except cilostazol, may increase the false positives without improving the sensitivity of FITs for CRC detection.

Relationship between body mass index and malignancy rates of MRI-guided breast biopsies: impact of clinicodemographic factors.

To determine the positive predictive value (PPV) of magnetic resonance imaging (MRI)-guided breast biopsy stratified by body mass index (BMI). Secondary endpoints include evaluation of indications for breast MRI and identification of factors associated with malignant biopsy. We retrospectively analyzed results of MRI-guided breast biopsies in a consecutive cohort of women at a single institution between 2014 and 2019. The PPV was compared between BMI subgroups and the overall group by the one-sample z-test. Factors associated with malignant biopsy were analyzed using multivariate regression analysis. Among 427 MRI-guided breast biopsies, the PPV was significantly higher in patients with a BMI ≥ 35 compared to BMI < 35 (38.6% versus 24.5%, p = 0.043). This remained true in the 180 biopsies from high-risk screening studies, but there was no difference in PPV by BMI in the 205 biopsies performed to evaluate extent of known disease. Among this cohort who underwent MRI-guided breast biopsy, the underlying indication for MRI was less likely to be high-risk screening in those with a higher BMI or Black or Hispanic race (p = 0.015 and p < 0.001, respectively). For high-risk screening studies, only BMI ≥ 35 was associated with malignant biopsies (OR 37.5, p = 0.003). For evaluation of extent of disease studies, only increased lesion size was a significant predictor of malignant result (OR 1.01, p = 0.04). Among women who underwent MRI-guided breast biopsy, elevated BMI was associated with increased PPV and malignant biopsies. Patients with a higher BMI or Black or Hispanic race who had MRI-guided biopsy were less likely to be undergoing high-risk screening and more likely to have breast MRI to evaluate extent of known disease.

Efficacy of non-invasive diagnostic methods in the diagnosis and screening of oral cancer and precancer

IntroductionTraditional meta-analyses on the diagnostic accuracy of oral lesions have been conducted, but they were inherently limited to direct pairwise comparisons between a single method and a single alternative, while multiple diagnostic options and the ranking thereof were methodologically not possible. ObjectiveTo evaluate the diagnostic values of various methods in patients with oral potential malignant disease by performing a network meta-analysis. MethodsTwo authors independently searched the databases (MEDLINE, SCOPUS, the Cochrane Register of Controlled Trials, and Google scholar) up to June 2020 for studies comparing the diagnostic accuracy of various tools (autofluorescence, chemiluminescence, cytology, narrow band imaging, and toluidine blue) with visual examination or other tools. The outcomes of interest for this analysis were sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Both a standard pairwise meta-analysis and network meta-analysis were conducted. ResultsTreatment networks consisting of six interventions were defined for the network meta-analysis. The results of traditional meta-analysis showed that, among six methods, narrow band imaging showed higher sensitivity, specificity, negative predictive value, positive predictive value, and accuracy compared to visual examination. The results of network meta-analysis showed that autofluorescence, chemiluminescence, and narrow band imaging had higher sensitivity compared with visual examination, and that chemiluminescence and narrow band imaging had higher negative predictive value compared with visual examination. However, autofluorescence and chemiluminescence had lower specificity compared with visual examination. There were no significant differences in positive predictive value and accuracy among the six interventions. ConclusionThis study demonstrated that narrow banding imaging has superiority in terms of sensitivity and negative predictive value compared with the other five tested agents.

Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules

Approximately 20% of thyroid nodules display indeterminate cytology. Molecular testing can refine the risk of malignancy and reduce the need for diagnostic hemithyroidectomy. To compare the diagnostic performance between an RNA test (Afirma genomic sequencing classifier) and DNA-RNA test (ThyroSeq v3 multigene genomic classifier). This parallel randomized clinical trial of monthly block randomization included patients in the UCLA Health system who underwent thyroid biopsy from August 2017 to January 2020 with indeterminate cytology (Bethesda System for Reporting Thyroid Cytopathology category III or IV). Molecular testing with the RNA test or DNA-RNA test. Diagnostic test performance of the RNA test compared with the DNA-RNA test. The secondary outcome was comparison of test performance with prior versions of the molecular tests. Of 2368 patients, 397 were eligible for inclusion based on indeterminate cytology, and 346 (median [interquartile range] age, 55 [44-67] years; 266 [76.9%] women) were randomized to 1 of the 2 tests. In the total cohort assessed for eligibility, 3140 thyroid nodules were assessed, and 427 (13.6%) nodules were cytologically indeterminate. The prevalence of malignancy was 20% among indeterminate nodules. The benign call rate was 53% (95% CI, 47%-61%) for the RNA test and 61% (95% CI, 53%-68%) for the DNA-RNA test. The specificities of the RNA test and DNA-RNA test were 80% (95% CI, 72%-86%) and 85% (95% CI, 77%-91%), respectively (P = .33); the positive predictive values (PPV) of the RNA test and DNA-RNA test were 53% (95% CI, 40%-67%) and 63% (95% CI, 48%-77%), respectively (P = .33). The RNA test exhibited a higher PPV compared with the prior test version (Afirma gene expression classifier) (54% [95% CI, 40%-67%] vs 38% [95% CI, 27%-48%]; P = .01). The DNA-RNA test had no statistically significant difference in PPV compared with its prior version (ThyroSeq v2 next-generation sequencing) (63% [95% CI, 48%-77%] vs 58% [95% CI, 43%-73%]; P = .75). Diagnostic thyroidectomy was avoided in 87 (51%) patients tested with the RNA test and 83 (49%) patients tested with the DNA-RNA test. Surveillance ultrasonography was available for 90 nodules, of which 85 (94%) remained stable over a median of 12 months follow-up. Both the RNA test and DNA-RNA test displayed high specificity and allowed 49% of patients with indeterminate nodules to avoid diagnostic surgery. Although previous trials demonstrated that the prior version of the DNA-RNA test was more specific than the prior version of the RNA test, the current molecular test techniques have no statistically significant difference in performance. ClinicalTrials.gov Identifier: NCT02681328.

Impact of mosaicism ratio on positive predictive value of cfDNA screening.

ObjectiveTo examine the relationship between the fraction of cell‐free DNA (cfDNA) affected by aneuploidy compared to the overall fetal fraction of a prenatal screening specimen and its effect on positive predictive value (PPV).MethodCfDNA specimens positive for trisomy 13, 18, and 21 with diagnostic outcomes were analysed over a 22‐month period in one clinical laboratory. For each positive specimen, a “mosaicism ratio” (MR) was calculated by dividing the fraction of cfDNA affected by aneuploidy by the overall fetal fraction of the specimen. PPVs were calculated and analyzed based on various MR ranges.ResultsTrisomy 13 was the aneuploidy most commonly seen in mosaic form, followed by trisomy 18 and trisomy 21. Significant differences in positive predictive values were noted for all three trisomies between samples with an MR in the “mosaic” versus “non‐mosaic” range, as well as between results classified as “low‐mosaic” versus “high‐mosaic.”ConclusionPPVs may be influenced, in part, by the mosaicism ratio associated with a particular result. The data generated from this study may be useful in providing more personalized risk assessments for patients with positive cfDNA screening results.

Evaluation of Clinical Application of Chemiluminescence and Real-time, Fluorescence-based Quantitative PCR in Diagnosis of Epstein-Barr Virus Infection

Objective: To compare the effects of clinical application of chemiluminescence and real-time, fluorescence-based quantitative PCR in the detection Epstein-Barr virus (EBV). Methods: The data of chemiluminescence and real-time fluorescent quantitative PCR from 97 patients who were suspected of being infected with EBV from January 2016 to January 2019 in our hospital were analyzed. The specific stage of EBV infection was analyzed, and the differences in results of the two detection methods were compared. Results: Chemiluminescence method was used to detect EBV infection during the active phase. The sensitivity of the chemiluminescence method was 76.7% (56/73) and the real-time quantitative PCR method was 90.4% (66/73). There was a statistical difference between the two detection methods (P&lt;0.05). Conclusion: There was no statistical difference in positive predictive values between the chemiluminescence method and the real-time, fluorescence-based quantitative PCR method in the detection of EBV infection, but the sensitivity of chemiluminescence method is slightly lower than the real-time quantitative PCR method. It is noteworthy that chemiluminescence method is convenient and fast while the real-time, fluorescence-based quantitative PCR method is more accurate, which can provide a more accurate reference for clinical treatment.

Assessing the Retail Food Environment in Madrid: An Evaluation of Administrative Data against Ground Truthing

Previous studies have suggested that European settings face unique food environment issues; however, retail food environments (RFE) outside Anglo-Saxon contexts remain understudied. We assessed the completeness and accuracy of an administrative dataset against ground truthing, using the example of Madrid (Spain). Further, we tested whether its completeness differed by its area-level socioeconomic status (SES) and population density. First, we collected data on the RFE through the ground truthing of 42 census tracts. Second, we retrieved data on the RFE from an administrative dataset covering the entire city (n = 2412 census tracts), and matched outlets using location matching and location/name matching. Third, we validated the administrative dataset against the gold standard of ground truthing. Using location matching, the administrative dataset had a high sensitivity (0.95; [95% CI = 0.89, 0.98]) and positive predictive values (PPV) (0.79; [95% CI = 0.70, 0.85]), while these values were substantially lower using location/name matching (0.55 and 0.45, respectively). Accuracy was slightly higher using location/name matching (k = 0.71 vs 0.62). We found some evidence for systematic differences in PPV by area-level SES using location matching, and in both sensitivity and PPV by population density using location/name matching. Administrative datasets may offer a reliable and cost-effective source to measure retail food access; however, their accuracy needs to be evaluated before using them for research purposes.

Annual mammography at age 45-49years and biennial mammography at age 50-69years: comparing performance measures in an organised screening setting.

To compare the results of 5years of annual mammography screening at age 45-49 with the results of 5years of biennial screening at age 50-54 and 55-69. In an Italian screening programme, data from 1,465,335 mammograms were analysed. Recall rates, invasive assessment rates, surgical biopsy (including excisional biopsy and definitive surgical treatment) rates, and cancer detection rates were calculated for the first screen (first) and, cumulatively, for the second and subsequent screens (second+). The rate ratios between younger women and the two groups of older ones were (in parentheses, original figures per 1000 mammograms if not otherwise specified): recall rate: first 1.11 (103.6 vs. 93.5) and 1.11 (vs. 93.2), second+ 2.10 (208.9 vs. 99.7) and 2.77 (vs. 75.5); invasive assessment rate: first 0.94 (23.0 vs. 24.5) and 0.94 (vs. 24.6), second+ 1.63 (35.8 vs. 22.0) and 1.56 (vs. 23.0); surgical biopsy rate: first 0.68 (5.9 vs. 8.6) and 0.45 (vs. 13.2), second+ 1.35 (11.5 vs. 8.5) and 0.88 (vs. 13.0); total detection rate: first 0.63 (4.3 vs. 6.7) and 0.37 (vs. 11.7), second+ 1.30 (8.9 vs. 6.8) and 0.74 (vs. 12.0); total positive predictive value of surgical biopsy: first 0.93 (72.8% vs. 78.0%) and 0.82 (vs. 88.9%), second+ 0.96 (77.2% vs. 80.5%) and 0.83 (vs. 92.7%). Younger women experienced two to threefold higher cumulative recall rates at second+ screens and limited differences in surgical biopsy rate. Albeit encouraging, these results must be completed with further investigation, especially on interval cancer incidence. • At repeated screens, cumulative recall rate was two- to threefold higher for younger women. • Differences in cumulative surgical referral and surgical biopsy rates were moderate. • Differences in positive predictive value of surgical biopsy were particularly small.

Effects of Oral Anticoagulants and Aspirin on Performance of Fecal Immunochemical Tests in Colorectal Cancer Screening

The fecal immunochemical test (FIT) is the tool most frequently used for colorectal cancer (CRC) screening worldwide. It is unclear how the use of aspirin and oral anticoagulants in the screening population affects the diagnostic performance of FIT. We performed a cross-sectional study in an ongoing CRC screening trial in Norway. Participants aged 50-74 years with a positive result from an FIT (>15 μg hemoglobin/g feces) and subsequent colonoscopy (reference standard) were included. Those who used regular aspirin, warfarin, or direct-acting oral anticoagulants (DOACs) were defined as users. Non-users were matched according to age, sex, screening center, and screening round. The primary outcomes were the positive predictive value (PPV) for CRC and advanced adenoma. Among 4908 eligible participants, 1008 used aspirin, 147 used warfarin, 212 used DOACs, and 3541 were non-users. CRCs were found in 234 individuals and advanced adenomas in 1305 individuals. The PPV for CRC was 3.8% for aspirin users vs 6.4% for matched non-users (P= .006), The PPV for advanced adenoma in aspirin users was 27.2% vs 32.6% for matched non-users (P= .011). For DOAC, the PPV for CRC was 0.9% in users vs 6.8% in matched non-users (P= .001). The PPV for advanced adenoma in DOAC users was 20.5% vs 32.4% in matched non-users (P= .002). There was no significant difference in PPV for CRC or advanced adenoma in warfarin users compared to non-users. In a large screening cohort in Norway, regular use of aspirin and particularly DOACs, were associated with lower PPV of FIT for detection of CRCs and advanced adenomas. ClinicalTrials.gov ID NCT01538550.

Coronary CT in Australia has high positive predictive value unaffected by site volume: An analysis of 510 positive CTCA scans with invasive angiographic correlation

BackgroundIt was hypothesized that the accuracy of coronary CT angiography would be affected by case volume of the referring sites. MethodsThe positive predictive value (PPV) of CTCA performed at a tertiary hospital specialising in cardiothoracic medicine and services with lower case-volumes were calculated. The tertiary hospital used as the high case-volume reference centre was The Prince Charles Hospital, which performed >1500 CTCA scans per annum over the study period. The low case-volume services used in the study were suburban radiology services, each with <500 cases per year. The PPV of positive CTCA at the reference site was compared to the pooled PPV of all other sites as a combined cohort, using invasive angiography as the reference standard. 512 scans were included, n = 199 subjects in the reference centre cohort, and n = 311 subjects in the pooled community radiology practice cohort. ResultsThe positive predictive value (PPV) of the high case-volume group (n = 199) was 0.7538. The PPV of the pooled low case-volume services (n = 589) was 0.7331, p = 0.604, with no statistically significant difference in positive predictive values. ConclusionsThere was no significant difference in PPV between the two groups. This suggests that high-volume and lower-volume sites both have high PPV in Australia, above the published pooled PPV of four large prospective diagnostic accuracy studies (Miller et al., 2008; Budoff et al., 2008; Meijboom et al., 2008; Achenbach, 2007).

Impact of Immediate Interpretation of Screening Tomosynthesis Mammography on Performance Metrics

This study aimed to compare performance metrics for immediate and delayed batch interpretation of screening tomosynthesis mammograms. This HIPAA compliant study was approved by institutional review board with a waiver of consent. A retrospective analysis of screening performance metrics for tomosynthesis mammograms interpreted in 2015 when mammograms were read immediately was compared to historical controls from 2013 to 2014 when mammograms were batch interpreted after the patient had departed. A total of 5518 screening tomosynthesis mammograms (n = 1212 for batch interpretation and n = 4306 for immediate interpretation) were evaluated. The larger sample size for the latter group reflects a group practice shift to performing tomosynthesis for the majority of patients. Age, breast density, comparison examinations, and high-risk status were compared. An asymptotic proportion test and multivariable analysis were used to compare performance metrics. There was no statistically significant difference in recall or cancer detection rates for the batch interpretation group compared to immediate interpretation group with respective recall rate of 6.5% vs 5.3% = +1.2% (95% confidence interval -0.3 to 2.7%; P = .101) and cancer detection rate of 6.6 vs 7.2 per thousand = -0.6 (95% confidence interval -5.9 to 4.6; P = .825). There was no statistically significant difference in positive predictive values (PPVs) including PPV1 (screening recall), PPV2 (biopsy recommendation), or PPV 3 (biopsy performed) with batch interpretation (10.1%, 42.1%, and 40.0%, respectively) and immediate interpretation (13.6%, 39.2%, and 39.7%, respectively). After adjusting for age, breast density, high-risk status, and comparison mammogram, there was no difference in the odds of being recalled or cancer detection between the two groups. There is no statistically significant difference in interpretation performance metrics for screening tomosynthesis mammograms interpreted immediately compared to those interpreted in a delayed fashion.

Evaluation of AGA and Fukuoka Guidelines for EUS and surgical resection of incidental pancreatic cysts.

Objectives Management of asymptomatic pancreatic cysts is challenging. Guidelines by the American Gastroenterological Association (AGA) and International Association of Pancreatology (Fukuoka) seek to identify high-risk patients. We assessed performance of these guidelines in selecting patients for endoscopic ultrasound (EUS) and/or surgery. Methods PART I – We retrospectively studied 143 asymptomatic cysts with magnetic resonance imaging (MRI) followed by EUS. Appropriate selection for EUS was defined as: malignant cytology or surgical pathology, or development of concerning features on MRI as defined by the guidelines. PART II – We retrospectively studied 152 resected cysts to assess the performance of guidelines in selecting cysts for surgery using malignant histology as the outcome. Results PART I – Of 143 EUS, 43 (30.1 %) were male with median age 65.0 years (interquartile range [IQR] 58.0 – 73.0). AGA guideline demonstrated lower sensitivity (17.6 % versus 35.3 %, P = 0.03), higher specificity (94.5 % versus 66.1 %, p < 0.001), and higher accuracy (76.2 % versus 58.7 %, P = 0.002) than Fukuoka. There was no difference in positive predictive value (50.0 % versus 24.5 %, P = 0.15) and negative predictive value (78.6 % versus 76.6 %, p=0.75). PART II – Of 152 resected cysts, 45 (29.8 %) were male with median age 59.0 years (IQR 47.3 – 66.7). There was no difference in performance characteristics of the guidelines in selecting cysts for surgery. AGA and Fukuoka guidelines missed 25.0 % and 18.8 % of malignant cysts, respectively (P = 1.00). Conclusions For referral to EUS, the AGA guideline was highly specific compared to Fukuoka; both suffered from poor sensitivity, although the Fukuoka guideline was relatively more sensitive than AGA. For referral to surgery, both guidelines have modest sensitivity and specificity and miss a similar percentage of malignant lesions.

Beneficial effects of combining computed tomography enteroclysis/enterography with capsule endoscopy for screening tumor lesions in the small intestine.

Aim. To compare the efficacy of using computed tomography enteroclysis/enterography (CTE), capsule endoscopy (CE), and CTE with CE for diagnosing tumor lesions in the small intestine. Materials and Methods. We included 98 patients who underwent CE during the observation period and were subjected to CTE at our hospital from April 2008 to May 2014. Results. CTE had a significantly higher sensitivity than CE (84.6% versus 46.2%, P = 0.039), but there were no significant differences in specificity, positive or negative predictive values, or diagnostic accuracy rates. The sensitivity of CTE/CE was 100%, again significantly higher than that of CE (P = 0.002). The difference in specificity between CTE/CE and CE was not significant, but there were significant differences in positive predictive values (100% for CTE/CE versus 66.7% for CE, P = 0.012), negative predictive values (100% versus 92.1%, P = 0.008), and diagnostic accuracy rate (100% versus 89.8%, P = 0.001). The diagnostic accuracy rate was also significantly higher in CTE/CE versus CTE (100% versus 95.9%, P = 0.043). Conclusion. Our findings suggested that a combination of CTE and CE was useful for screening tumor lesions in the small intestine. This trial is registered with number UMIN000016154.

Response letter to T Fowler and co-authors – estimating the positive predictive value of opportunistic population testing for gonorrhoea as part of the English Chlamydia Screening Programme

Dear Editor, Fowler et al.1 discuss the inclusion of gonorrhoea screening alongside the National Chlamydia Screening Programme (NCSP) in one part of the UK and the calculation of positive predictive values (PPVs) to guide commissioning decisions. This is a timely and welcome contribution given the increased deployment of ‘dual testing’ – where nucleic acid amplification tests (NAAT) simultaneously test for chlamydia and gonorrhoea using the same sample. However, we have concerns about some of the assumptions used when estimating PPVs, particularly the assertion that sensitivity and specificity may vary by prevalence, which is not substantiated in the context of asymptomatic gonorrhoea testing. Although some studies have shown that sensitivity and specificity may vary by prevalence, this relates to differing disease severity and diagnostic definitions.2 In most disease processes, diagnosis becomes more certain as the disease progresses and it is intuitive that diagnostic test performance should improve with progression, the so-called spectrum bias.3 However, opportunistic testing in non-symptomatic individuals is different; this represents a homogenous group. There is no reason to believe that the sensitivity and specificity will systematically vary with the underlying prevalence of an asymptomatic sexually transmitted infection (STI). Furthermore, the absolute difference in diagnosed gonorrhoea prevalence quoted is small; 35 per 100,000 in Greater Manchester versus 28 per 100,000 in England, and any difference in PPV is unlikely to make testing in one area viable and not in another. We agree with the authors’ emphasis on the importance of confirmatory NAAT testing following a reactive screen for gonorrhoea, which supports current national gonorrhoea testing guidance.4 They also suggest restricting gonorrhoea testing in low prevalence areas to those with a positive chlamydia test. However, where dual testing is used in the NCSP, the chlamydia test result would be unknown at the point of gonorrhoea testing, and it is already the case that the NCSP core requirements recommend a full STI screen (including gonorrhoea, syphilis and HIV testing) for all patients diagnosed with chlamydia as part of routine clinical management.5

Characteristics and outcome of enhancing foci followed on breast MRI with management implications

To evaluate the risk of cancer of an enhancing focus identified at breast magnetic resonance imaging (MRI) by determining the positive predictive value (PPV) associated with specific characteristics of an enhancing focus. Retrospective, institutional review board-approved review of the database identified 111 consecutive patients who underwent short-term follow-up of 136 enhancing foci in 2008. Kinetic analysis (delayed enhancement pattern) and other characteristics, such as interval change and T2 signal intensity, were evaluated to calculate the PPV for malignancy. The overall malignancy rate of an enhancing focus was 2.9% [4/136, 95% confidence interval (CI): 0.9-7.6%]. Kinetic analysis showed no statistical difference in PPV between foci with washout enhancement [5.1% (2/39)] versus persistent enhancement [3.2% (2/62); Fisher's exact test, p=0.6180]. PPV of a T2 hypointense focus was 8.7% (4/46); PPV of a new focus was 13.6% (3/22); PPV of an enlarging focus was 6.7%, (1/15). The combination of a focus being new and T2 hypointense had the highest PPV for malignancy (27.2%, 3/11, 95% CI: 9.2-57.1%). Kinetic analysis was not specific for malignancy and should not be used solely to guide management. A new enhancing focus with T2 hypointensity had a high PPV for malignancy and may warrant immediate biopsy.

Comparative study of galectin-3 and B-type natriuretic peptide as biomarkers for the diagnosis of heart failure.

BackgroundHeart failure (HF) is a common disease with complex pathophysiological causes. The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and results from echocardiography and biochemical tests. Galectin-3, a relatively new biomarker in HF, was approved by the US Food and Drug Administration in 2010 as a marker in the stratification of risk for HF. We assessed galectin-3 as a biomarker for HF diagnosis in patients with preserved ejection fraction (pEF) and compared its performance with that of B-type natriuretic peptide (BNP).MethodsThirty-five pEF patients with HF (HFpEF group) and 43 pEF patients without HF (control group) were enrolled. Plasma levels of galectin-3 and BNP in HFpEF and control subjects were determined. Sensitivity, specificity, predictive values, and accuracy of galectin-3 and BNP as markers for HF diagnosis were calculated and compared.ResultsLevels of galectin-3 and BNP were 23.09 ± 6.97 ng/mL and 270.46 ± 330.41 pg/mL in the HFpEF group, and 16.74 ± 2.75 ng/mL and 59.94 ± 29.93 pg/mL in the control group, respectively. Differences in levels of galectin-3 and BNP between the two groups were significant (P < 0.01). As a biomarker for HF diagnosis in study subjects, galectin-3 showed sensitivity and specificity of 94.3% and 65.1%, respectively, at a cutoff value of 17.8 ng/mL. BNP showed sensitivity and specificity of 77.1% and 90.7%, respectively, at a cutoff value of 100 pg/mL. Galectin-3 was a significantly more sensitive (P < 0.05) but less specific (P < 0.01) biomarker compared with BNP. Differences in positive predictive value, negative predictive value, and accuracy between galectin-3 and BNP markers were not significant (P > 0.05). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.891 (0.808–0.974) and 0.896 (0.809–0.984) for galectin-3 and BNP, respectively, with no significant difference between the two values (P > 0.05).ConclusionsThe level of galectin-3 is significantly elevated in patients with HF. Galectin-3 and BNP are useful biomarkers for the diagnosis of HF in patients with pEF.

Evaluation of electrical nerve stimulation for epidural catheter positioning in the dog

ObjectiveTo evaluate the accuracy of epidural catheter placement at different levels of the spinal cord guided solely by electrical nerve stimulation and resultant segmental muscle contraction. Study designProspective, experiment. AnimalsSix male and two female Beagles, age (1 ± 0.17 years) and weight (12.9 ± 1.1 kg). MethodsAnimals were anesthetized with propofol and maintained with isoflurane. An insulated epidural needle was used to reach the lumbosacral epidural space. A Tsui epidural catheter was inserted and connected to a nerve stimulator (1.0 mA, 0.1 ms, 2 Hz) to assess positioning of the tip at specific spinal cord segments. The catheter was advanced to three different levels of the spinal cord: lumbar (L2–L5), thoracic (T5–T10) and cervical (C4–C6). Subcutaneous needles were previously placed at these spinal levels and the catheter was advanced to match the needle location, guided only by corresponding muscle contractions. Catheter position was verified by fluoroscopy. If catheter tip and needle were at the same vertebral body a score of zero was assigned. When catheter tip was cranial or caudal to the needle, positive or negative numbers, respectively, corresponding to the number of vertebrae between them, were assigned. The mean and standard deviation of the number of vertebrae between catheter tip and needle were calculated to assess accuracy. Results are given as mean ± SD. ResultsThe catheter position in relation to the needle was within 0.3 ± 2.0 vertebral bodies. Positive predictive values (PPV) were 57%, 83% and 71% for lumbar, thoracic and cervical regions respectively. Overall PPV was 70%. No significant difference in PPV among regions was found. Conclusion and clinical relevancePlacement of an epidural catheter at specific spinal levels using electrical nerve stimulation was feasible without radiographic assistance in dogs. Two vertebral bodies difference from the target site may be clinically acceptable when performing segmental epidural regional anesthesia.

P5.089 Confirmation of High Specificity of an Automated ELISA Test For Serological Diagnosis of Syphilis - Results from Confirmatory Testing After Syphilis Screening and Sensitivity Analysis in the Absence of a Gold Standard

Background In clinical microbiology laboratories, serological diagnostic assays are usually implemented after evaluation using a selected sample collection. We have previously evaluated the performance of the Bioelisa Syphilis 3.0 compared with the Treponema pallidum Particle Agglutination (TPPA) in a selected collection of serum samples (syphilis positivity rate 44%) and found a sensitivity and specificity of both 100%. In the current study we have compared the specificity of Bioelisa Syphilis 3.0 after clinical implementation as a syphilis screening test with the specificity found in the previous evaluation to assess whether the high specificity would stand up in clinical practise. Methods We included 14,622 sera (positivity rate 0.9%) sent to the laboratory for syphilis serology in the period between October 2007 and February 2010. Results We confirm the initially reported specificity and further narrow down its confidence interval (specificity 99.5%, 95% CI 99.4–99.6%), and show that this high specificity is valid across diverse patient categories. Here we demonstrate that differences in positive predictive values between patient categories reflect the prevalence of syphilis in these categories, and are not due to differences in specificity. In addition, in a sensitivity analysis we show that these conclusions are robust for several assumptions. Conclusion Our analysis shows that the high specificity found in the initial study, stands up after implementation in a population with a low syphilis prevalence (0.9%). Using a selected serum sample collection is therefore a valid manner in the evaluation of syphilis serological diagnostic assays. Confirmatory syphilis testing remains mandatory in low prevalence populations, even when the screening test has a very high specificity.

Is a fluorescence navigation system with indocyanine green effective enough to detect liver malignancies?

Although several reports have shown the efficacy of a fluorescence navigation system (FNS) with indocyanine green (ICG) to detect liver malignancies during hepatectomy, the real accuracy of this procedure is not yet clear. This study aimed to analyze the actual efficacy of ICG-FNS in cirrhotic and non-cirrhotic livers. Ten cirrhotic whole livers explanted from liver transplant recipients and 23 non-cirrhotic livers from patients who underwent hepatectomy for various kinds of liver tumors were investigated with ICG-FNS. All surgical specimens were analyzed macroscopically and pathologically. In the patients with a cirrhotic liver, most nodules illuminated by ICG-FNS were diagnosed as regenerative nodules pathologically. The positive predictive value was 5.4%. There was a significant difference in positive predictive value to detect malignant liver tumors between cirrhotic liver and non-cirrhotic liver (5.4% vs 100%, P < 0.0001). In the non-cirrhotic livers, 11 of 33 (32.4%) tumors were not recognized by ICG-FNS through the liver surface before resection. There was a significant difference in the depth from the liver surface to tumor between illuminated nodules and non-illuminated nodules (1.5 mm vs 11.6 mm, P < 0.01). It is necessary to know the limitation of ICG-FNS when detecting liver malignancies in both cirrhotic and non-cirrhotic livers.