Rate Of False-positive Results Research Articles

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

Screening for Lung Cancer: Lexicon for Communicating With Health Care Providers.

The effectiveness of lung cancer screening with low-dose CT (LDCT) has been shown by multiple clinical trials, particularly the National Lung Screening Trial. Accurate communication of LDCT results to health care providers is critical to optimal patient care. The Lung CT Screening Reporting and Data System (Lung-RADS), a structured decision-oriented reporting system designed to minimize the rate of false-positive results and developed by the American College of Radiology, is recommended for use with all LDCT examinations.

Circulating tumour cells as a potential screening tool for lung cancer (the AIR study): protocol of a prospective multicentre cohort study in France

IntroductionLung cancer (LC) is the leading cause of death from cancer. Early diagnosis of LC is of paramount importance in terms of prognosis. The health authorities of most countries do...

Screening for precancerous anal lesions with P16/Ki67 immunostaining in HIV-infected MSM.

BackgroundScreening of anal cancer in HIV-infected MSM with anal cytology results in high rates of false positive results and elevated burden of high-resolution anoscopies. High-risk HPV up-regulates p16 and Ki67 expression in epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology for the diagnosis of precancerous anal lesions.MethodologyCross-sectional multicenter study. Concomitant anal liquid cytology with p16/Ki-67 immunostaining and HRA with biopsy of acetowhite lugol-negative lesions was performed in HIV-infected MSM. We compared the diagnostic performance of an abnormal anal cytology and p16/Ki-67 immunostaining relative to HRA-guided biopsy by logistic regression and comparison of ROC areas.ResultsWe included 328 HIV-infected MSM. HSIL was histologically diagnosed in 72 subjects (25.1%), and 2 (0.6%) were diagnosed with anal cancer. An abnormal cytology showed a sensitivity of 95.6% and a specificity of 58.8% for the diagnosis of biopsy-proven HSIL. P16/Ki67 positivity was associated with the presence of biopsy-proven HSIL (P trend = 0.004) but with low sensitivity (41.2%) and specificity (71%). The combination of standard cytology with P16/Ki67 immunostaining did not increment the predictive value of standard cytology alone (AUC 0.685 vs. 0.673, respectively, P = 0.688).ConclusionIn HIV-infected MSM P16/Ki67 immunostaining does not improve the diagnostic accuracy of anal cytology, which shows a high sensitivity yet poor specificity. Other approaches aimed at improving the diagnostic accuracy of current techniques for the diagnostic of precancerous HSIL are warranted.

Classifying Schizotypy Using an Audiovisual Emotion Perception Test and Scalp Electroencephalography.

Schizotypy refers to the personality trait of experiencing “psychotic” symptoms and can be regarded as a predisposition of schizophrenia-spectrum psychopathology (Raine, 1991). Cumulative evidence has revealed that individuals with schizotypy, as well as schizophrenia patients, have emotional processing deficits. In the present study, we investigated multimodal emotion perception in schizotypy and implemented the machine learning technique to find out whether a schizotypy group (ST) is distinguishable from a control group (NC), using electroencephalogram (EEG) signals. Forty-five subjects (30 ST and 15 NC) were divided into two groups based on their scores on a Schizotypal Personality Questionnaire. All participants performed an audiovisual emotion perception test while EEG was recorded. After the preprocessing stage, the discriminatory features were extracted using a mean subsampling technique. For an accurate estimation of covariance matrices, the shrinkage linear discriminant algorithm was used. The classification attained over 98% accuracy and zero rate of false-positive results. This method may have important clinical implications in discriminating those among the general population who have a subtle risk for schizotypy, requiring intervention in advance.

Diagnostic precision of triage algorithms for mass casualty incidents. English version.

Regarding survival and quality of life recent mass casualty incidents again emphasize the importance of early identification of the correct degree of injury/illness to enable prioritization of treatment amongst patients and their transportation to an appropriate hospital. The present study investigated existing triage algorithms in terms of sensitivity (SE) and specificity (SP) as well as its process duration in arelevant emergency patient cohort. In this study 500 consecutive air rescue missions were evaluated by means of standardized patient records. Classification of patients was accomplished by 19emergency physicians. Every case was independently classified by at least 3physicians without considering any triage algorithm. Existing triage algorithms Primary Ranking for Initial Orientation in Emergency Medical Services (PRIOR), modified Simple Triage and Rapid Treatment (mSTaRT), Field Triage Score (FTS), Amberg-Schwandorf Algorithm for Triage (ASAV), Simple Triage and Rapid Treatment (STaRT), Care Flight, and Triage Sieve were additionally carried out computer based on each case, to enable calculation of quality criteria. The analyzed cohort had an age of (mean± SD) 59± 25years, aNACA score of 3.5± 1.1 and consisted of 57% men. On arrival 8patients were deceased. Consequently, 492 patients were included in the analysis. The distribution of triage categories T1/T2/T3 were 10%/47%/43%, respectively. The highest diagnostic quality was achieved with START, mSTaRT, and ASAV yielding aSE of 78% and aSP ranging from 80-83%. The subgroup of surgical patients reached aSE of 95% and aSP between 85-91%. The newly established algorithm PRIOR exerted aSE of 90% but merely aSP of 54% in the overall cohort thereby consuming the longest time for overall decision. Triage procedures with acceptable diagnostic quality exist to identify the most severely injured. Due to its high rate of false positive results (over-triage) the recently developed PRIOR algorithm will cause overload of available resources for the severely injured within mass casualty incident missions. Non-surgical patients still are poorly identified by the available algorithms.

The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar: an observational study

BackgroundThe use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test’s clinical utility is poorly defined outside sub-Saharan Africa.MethodsThe study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. On enrolment, patients had a LF-LAM test performed according to the manufacturer’s instructions. Clinicians managing the patients were unaware of the LF-LAM result, which was correlated with the patient’s clinical course over the ensuing 6 months.ResultsThe study enrolled 54 inpatients and 463 outpatients between July 1 and December 31, 2015. On enrolment, the patients’ median (interquartile range) CD4 T-cell count was 270 (128–443) cells/mm3. The baseline LF-LAM test was positive in 201/517 (39%). TB was confirmed microbiologically during follow-up in 54/517 (10%), with rifampicin resistance present in 8/54 (15%). In the study’s resource-limited setting, extrapulmonary testing for TB was not possible, but after 6 months, 97/201 (48%) with a positive LF-LAM test on enrolment had neither died, required hospitalisation, received a TB diagnosis or received empirical anti-TB therapy, suggesting a high rate of false-positive results. Of the 97 false-positive tests, 89 (92%) were grade 1 positive, suggesting poor test specificity using this cut-off. Only 21/517 (4%) patients were inpatients with TB symptoms and a CD4 T-cell count of < 100 cells/mm3. Five (24%) of these 21 died, three of whom had a positive LF-LAM test on enrolment. However, all three received anti-TB therapy before death — two after diagnosis with Xpert MTB/RIF testing, while the other received empirical treatment. It is unlikely that knowledge of the baseline LF-LAM result would have averted any of the study’s other 11 deaths; eight had a negative test, and of the three patients with a positive test, two received anti-TB therapy before death, while one died from laboratory-confirmed cryptococcal meningitis. The test was no better than a simple, clinical history excluding TB during follow-up (negative predictive value (95% confidence interval): 94% (91–97) vs. 94% (91–96)).ConclusionsThe LF-LAM test had limited clinical utility in the management of HIV-positive patients in this Asian referral hospital setting.

Diagnostic quality of triage algorithms for mass casualty incidents

Regarding survival and quality of life, recent mass casualty incidents have once more emphasized the importance of early identification of the correct degree of injury or illness, to enable prioritizing treatment of patients and transportation to an appropriate hospital. The present study investigated international triage algorithms in terms of sensitivity (SE) and specificity (SP) as well as the process duration in arelevant emergency patient cohort. A total of 500 consecutive air rescue missions were evaluated by means of standardized patient records. Interdisciplinary classification of patients was accomplished by 19emergency physicians. Every case was independently classified according to the triage category by at least three physicians without considering any triage algorithm. The available triage algorithms PRIOR (Primary Ranking for Initial Orientation in Emergency Medical Services), mSTaRT (modified Simple Triage and Rapid Treatment), FTS (Field Triage Score), ASAV (Amberg-Schwandorf Algorithm for Triage), STaRT (Simple Triage and Rapid Treatment), CareFlight triage and Triage Sieve were additionally carried out for each patient in a computer-based procedure, to enable calculation of test quality criteria for all procedures. The analyzed cohort had a mean age of 59± 25years (±SD), aNational Advisory Committee for Aeronautics (NACA) score of 3.5± 1.1 and consisted of 57% men. On arrival 8patients were already deceased, consequently 492 patients were included in the analysis. The distributions of triage categoriesI/II/III were 10%/47%/43%, respectively. The highest diagnostic quality was achieved with START, mSTaRT, and ASAV with 78% SE and 80-83% SP. The subgroup of surgical patients achieved 95% SE and 85-91% SP. The newly established algorithm PRIOR exerted an SE of 90% but an SP of only 54% in the overall cohort thereby taking the longest overall time for decisions. Triage procedures with acceptable diagnostic quality exist to identify the most severely injured. Due to its high rate of false positive results (overtriage) in this study, the recently developed PRIOR algorithm could result in exhaustion of available resources for the severely injured and therefore to undertreatment of correctly assigned triage category I cases within mass casualty incidents. Non-surgical patients are still poorly allocated by the available algorithms. Contribution available free of charge by "Free Access".

The morbidly adherent placenta: when and what association of signs can improve MRI diagnosis? Our experience.

We aimed to verify whether combination of specific signs improves magnetic resonance imaging (MRI) accuracy in morbidly adherent placenta (MAP). MRI findings for MAP were retrospectively evaluated in 27 women. Histopathology was the reference standard, showing MAP in eight of 27 cases. Specificity, sensitivity, positive predictive value, and negative predictive value were calculated for all MRI signs. Two skilled radiologists analyzed MRI findings, resolving discrepancies by consensus, using three alternative diagnostic criteria during three consecutive sections. First criterion: at least one of reported MRI signs indicates MAP and the absence of any sign is normal; second criterion: at least one statistically significant sign indicates MAP and no sign or nonsignificant sign is normal; third criterion: at least two statistically significant signs indicate MAP and no sign, nonsignificant sign, or only one significant sign is normal. Using the first criterion yielded an unacceptable rate of false positive results (78.9%). Using the second criterion there were less false positive results (31.5%), and diagnostic accuracy of the second criterion was significantly higher than the first; the third criterion correctly classified 100% of cases. Only specific MRI signs can correctly predict MAP at histopathology, particularly when multiple (at least two) specific signs are observed together.

Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birthweight improve the efficacy of congenital adrenal hyperplasia newborn screening.

The primary concern related to congenital adrenal hyperplasia (CAH) newborn screening (NBS) is the high rate of false-positive results (FPR) associated with prematurity; false-negative results (FNR) can also occur due to precocious sample collection. To determine the neonatal 17-hydroxyprogesterone (N17OHP) normal range in newborns in Sao Paulo using different references according to age and birthweight (BW) and to establish the optimal NBS cut-off levels. Neonatal 17-hydroxyprogesterone levels from 271 810 newborns (NBs) according to sample collection time (G1: 48-<72 h and G2: ≥72 h) and BW (≤1500 g, 1501-2000 g, 2001-2500 and >2500 g) were evaluated. N17OHP was measured by an fluoroimmunoassay, and serum 17OHP was measured by liquid chromatography-mass spectrometry. Affected and asymptomatic NBs with persistently increased 17OHP levels were submitted to CYP21A2-sequencing. Neonatal 17-hydroxyprogesterone levels in G1 were lower than G2 in all BW groups (P < 0·001). The FPR rate in G1/G2 was 0·2% using the 99·8th and 0·5% using the 99·5th percentile. The 99·8th percentile N17OHP value was the best cut-off for distinguishing between unaffected and affected NBs. Forty-four salt wasters, and five simple virilisers were diagnosed; N17OHP levels ranged from 93·3 to 2209·8 nmol/l, and no affected neonates with FNR were identified. The positive predictive value in G1 and G2 using the 99·8th percentile was 5·6% and 14·1%, respectively, and 2·3% and 7%, respectively, using the 99·5th percentile. Molecular tests identified two NBs with the nonclassical form among the 29 FPR. Neonatal 17-hydroxyprogesterone levels adjusted to sample collection age and birthweight reduced the FPR, and the use of N17OHP values based upon the 99·8th percentile improved the NBS efficacy.

Neonatal screening for congenital adrenal hyperplasia in Southern Brazil: a population based study with 108,409 infants

BackgroundCongenital adrenal hyperplasia (CAH) is an autosomal recessive disorder associated with inborn errors of steroid metabolism. 21-hydroxylase enzyme deficiency occurs in 90 to 95% of all cases of CAH, with accumulation of 17 hydroxyprogesterone (17-OHP). Early diagnosis of CAH based on newborn screening is possible before the development of symptoms and allows proper treatment, correct sex assignment, and reduced mortality rates. This study describes the results obtained in the first year of a public CAH screening program in the state of Rio Grande do Sul, Brazil.MethodsWe reviewed the screening database in search of babies with suspected CAH, that is, altered birth-weight adjusted 17-OHP values at screening. The following data were analyzed for this population: screening 17-OHP values, retest 17-OHP values, serum 17-OHP values for those with confirmed CAH on retest, maternal and newborn data, and family history of CAH. For the screening program, 17-OHP levels are determined on dried blood spots obtained in filter paper with GSP solid phase time-resolved immunofluorescence.ResultsOf 108,409 newborns screened, eight were diagnosed with CAH (four males, four females). The incidence of CAH in the state was 1:13,551. Six cases were identified as classic salt-wasting CAH and two were cases of virilizing CAH. The positive predictive value (PPV) of the initial screening (before diagnostic confirmation) was 1.6%. The overall rate of false positive results was 0.47%. The number of false positive results was higher among newborns with birth weight < 2000 g.ConclusionThe present results support the need for CAH screening by the public health care system in the state, and show that the strategy adopted is adequate. PPV and false positive results were similar to those reported for other states of Brazil with similar ethnic backgrounds.

Novel phototoxicity assay using human embryonic stem cell-derived retinal pigment epithelial cells.

Some chemicals are harmful in to light-exposed tissues such as skin and eyes. The 3T3 Neutral Red Uptake Phototoxicity Test has been validated and adopted by the Organization of Economic and Community Development (OECD) as a method of evaluating chemical phototoxicity using mouse 3T3 fibroblasts. However, the high rate of false positive results associated with this test eventually led to increased laboratory animal usage. Although the eye is vulnerable to light damage because of constant exposure to environmental radiation, few approaches are available to predict ocular phototoxicity in humans. Here, we propose a tier one test that identifies the potential ocular phototoxicity of chemical substances. Using a three-dimensional culture technique, human embryonic stem cells (hESCs) were differentiated to retinal pigment epithelial cell (RPE) precursors. The precursors after prolonged treatment with FBS formed a uniform hexagonal lattice of cells with well-developed tight junctions and time-dependent elevation of melanin content and RPE maturation marker levels. Hierarchical clustering of gene transcripts revealed that hESC-derived RPEs were very similar to tissue-derived adult RPEs. Interestingly, there were a high percentage of chemicals eliciting a positive response in 3T3 cells and negative in hESC-derived RPEs under the experimental conditions used in the phototoxicity test. The response to treatment of hESC-derived RPEs with these negative chemicals became positive at a higher dose of UVA irradiation; however, the biological responses to these chemicals differed between the two cells. Taken together, we conclude that hESC-derived RPEs are novel tool for future toxicological and mechanistic studies of ocular phototoxicity in humans.

In Vitro Diagnostic Testing for Antibiotic Allergy.

Allergy to antibiotics is an important worldwide problem, with an estimated prevalence of up to 10% of the population. Reaction patterns for different antibiotics have changed in accordance with consumption trends. Most of the allergic reactions to antibiotics have been reported for betalactams, followed by quinolones and macrolides and, to a lesser extent, to others, such as metronidazole clindamycin and sulfonamides. The diagnostic procedure includes a detailed clinical history, which is not always possible and can be unreliable. This is usually followed by in vivo, skin, and drug provocation tests. These are not recommended for severe, potentially lifethreaten reactions or for drugs that are known to produce a high rate of false positive results. Given the limitations of in vivo tests, in vitro test can be helpful for diagnosis, despite having suboptimal sensitivity. The most highly employed techniques for diagnosing immediate reactions to antibiotics are immunoassays and basophil activation tests, while lymphocyte transformation tests are more commonly used to diagnose non-immediate reactions. In this review, we describe different in vitro techniques employed to diagnose antibiotic allergy.

Age-Adjusted D-Dimer Cutoffs for DVT and Pulmonary Embolism: A Comparison of Five Assays

Background: Venous thromboembolism (VTE) is a common but underdiagnosed condition constituted primarily by deep venous thrombosis (DVT, 2/3) and pulmonary embolism (PE, 1/3).Diagnosis of VTE is based on the biomarker D-dimer for excluding low probability VTE, and imaging techniques to verify mid/high probability VTE. D-dimer assays generally have excellent sensitivity, but specificity is kept low by the physiology of the measurand. The plasma concentration of D-dimer increases in thrombosis and activated coagulation, but also in several other conditions such as pregnancy, cancer, trauma, inflammation, infection and with age. Many of these conditions are especially prevalent in VTE-patients, because they are also linked to an increased risk of venous thrombosis.Haase et al. showed that the plasma concentration of D-dimer in a healthy population increases with age, 50% of those ≥70 years old had a positive D-dimer (>0.5 mg/L FEU)1. Age-adjusted decision thresholds have subsequentially been recommended and validated, to increase specificity and reduce the rate of false positive D-dimer results in older patients without decreasing sensitivity.Aims: The study compares age-adjusted D-dimer decision thresholds for different assays in Swedish out-patients with suspected DVT or PE.Methods: Patients (n=940) with clinically suspected PE or DVT in a lower limb were recruited from the medical emergency department (ED) of Karolinska University Hospital, and fresh citrated plasma samples were analyzed for D-dimer within 30 minutes. D-dimer concentrations were measured by four immunoturbidimetric assays using the instruments Sysmex CS2100i and Stago CompactMax. VTE was verified by imaging techniques (ultrasonography, computed tomography or ventilation/perfusion lung scintigraphy, as appropriate) and classified into segmental or subsegmental PE and proximal or distal DVT. Non-VTE was identified by imaging techniques or absence of VTE in a three month follow up of medical records.Age adjusted cutoff values were calculated if age was ≥50 years according to Douma et al.2, as age x 0.01 for assays measured in mg/L FEU (Siemens INNOVANCE® D-dimer and STA®-Liatest® D-Di) and as age x 0.005 for Roche Tina-quant D-dimer and as age x 0.004 for MediRox D-dimer.Results: VTE was found in 125 patients (13.3%), PE in 35 (3.7%; 3.0% segmental and 0.7% subsegmental) and DVT in 90 (9.6%; 6.3% proximal and 3.4% distal). The diagnostic performances of the assays are displayed below, see table 1. All assays had excellent areas under the ROC-curve (AUC) and all except MediRox D-dimer fulfilled the FDA requirements of sensitivity > 95% and a NPV > 97%, at the cutoff recommended by the manufacturer. When age adjusted cutoffs were applied, all assays maintained their sensitivities, whereas specificities increased by 6-7%. The rate of false positive results decreased by 6% overall, but 10-20% for patients older than 70, see table 2.Conclusion: D-dimer is still the only biomarker used for suspected VTE, even though low specificity with false positive results presents a significant problem due to an elderly patient population burdened with co-morbidity. The examined age-adjusteddecision thresholds increase specificity for VTE without decreasing sensitivity and can thus be used to improve diagnosis of VTE. With fewer false positives, diagnosis will be faster, cheaper and will result in decreased health risks from intravenous contrast, radiation and unnecessary hospital admissions.

Issues Related to Screening and Caring for Newborns With Hearing Impairments

The critical period for auditory development in humans begins at around the 20th gestational week and continues until 3 years of age. Both genetic and environmental factors are known to cause impaired hearing. Without early identification and intervention, hearing-impaired children face a high risk of experiencing significant difficulties with speech and language development, social behavior, and emotional functioning. Two types of commonly used hearing screening technologies include transient evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (aABR). aABR is considered to have high sensitivity and specificity, to have a relatively low referral rate, and to generate a relatively low rate of false-positive results in identifying newborn hearing impairment. The present paper outlines the psychosocial issues that are commonly experienced by parents of hearing-impaired children. Parents and other family members may benefit from medical, financial, social, and education supports in order to facilitate their adjustment to this challenging situation. The relevant literature is reviewed and recommendations for improving care for this population are provided.

Evaluation of genetically modified rice detection methods 2011/884/EU and 2008/289/EC proposed by the European Union

Increases in the number of cases of identified genetically modified (GM) rice contamination can be traced back to the first Rapid Alert System for Food and Feed (RASFF) in 2006. In response to the lack of reliable detection methods, Decision 2011/884/EU proposed that new screening methods replace Decision 2008/289/EC, to identify all possible GM rice products originating in China. However, the synergy brands (SYBR) Green real-time PCR assay proposed by Decision 2011/884/EU has been shown to lack conformity with other TaqMan methods currently in use. To evaluate the specificity and repeatability of the methods recommended in Decision 2011/884/EU and Decision 2008/289/EC, we collected 74 rice products originating from six countries or districts. The 74 rice samples were tested using the Decision 2011/884/EU and Decision 2008/289/EC methods. The parallel use of different instruments and reagents were used for testing in parallel, and the results were analyzed statistically. To avoid the limitations of specific laboratories, eight GM organism detection laboratories in China participated in a collaborative trial. In our tests, 24.3% (18/74) of the samples tested were positive with the SYBR Green real-time PCR assay using the Decision 2011/884/EU method, but were negative with the TaqMan real-time PCR assay using the Decision 2011/884/EU and Decision 2008/289/EC methods. Sequencing the PCR-amplified CryIA(b/c) genes in three samples (6, 30 and 43) showed that the products consisted of primer dimers rather than the targeted sequence. The combined experimental results showed that testing for the nopaline synthase gene (NOS) of Agrobacterium tumefasciens terminator and CryIA(b/c) produced false-positive results when the Decision 2011/884/EU method was used. Because of the high rate of false-positive results, the Decision 2011/884/EU SYBR Green method to detect GM rice requires improvement.

Nasal bone in screening for T21 at 11-13 + 6 weeks of gestation - a multicenter study.

Trisomy 21 is one of the most common chromosomal defects diagnosed prenatally. Screening for Down syndrome is based on maternal age, measurement of crown-rump length, nuchal translucency and fetal heart rate, together with free β-hCG and PAPP-A at 11 to 13 + 6 weeks. Introduction of additional ultrasound marker of trisomy 21 (evaluation of the nasal bone) may result in increased DR and decreased invasive diagnostic testing rates (FPR). Ultrasound scan with NB evaluation was performed in 5814 fetuses during routine screening for chromosomal defects at 11 to 13 + 6 weeks of gestation. DR and FPR coefficients were calculated for 4 levels of risk as cut-off points for screening model 1, based on MA, NT, and first trimester biochemistry, as well as for screening model 2, based on MA, NT, first trimester biochemistry and NB. There were 5708 normal cases, 71 cases of trisomy 21 and 35 cases of other chromosomal defects. NB was absent in 46 (64.8%) cases and present in 25 (35.3%) cases of trisomy 21, comparing to present NB in 5463 (95.7%) and absent in 245 (4.3%) of normal cases. First-semester screening with additional NB assessment significantly increases the detection rate for trisomy 21 and decreases the rate of false-positive results. Adding NB evaluation at the risk level of 1:50 causes only a small increase in detection rate. Invasive procedures should be performed in that group regardless NB assessment.

Frozen section analysis of SLNs in trunk and extremity melanoma has a high false negative rate but can spare some patients a second operation.

The purpose of this study was to evaluate the accuracy of frozen section (FS) analysis of sentinel lymph nodes (SLN) in melanoma. Five hundred seventy-one patients underwent FS analysis of SLN between 1/2000 and12/2010. Surgical and pathological characteristics, recurrence, and survival were analyzed. Comparisons were made using χ2 and Fisher's exact t-test. One hundred thirty-three (23%) patients were SLN positive of which 63 (47.4%) were identified on FS. 16/70 SLN metastases not identified on FS (23%) were seen only on immunohistochemistry. FS analysis detected 84% of SLN metastasis >2 mm. SLN FS false negative rate was 53%, positive predictive value 100%, negative predictive value 88%, and overall accuracy 89%. Among patients with a FS positive SLN, 17/63 (27%) had additional positive nodes on CLND, versus 1 of 70 (1.4%) with a positive SLN identified only on permanent section pathology (P < 0.0001). The nodal recurrence rate following a negative SLN biopsy was 5%. FS analysis for SLNs spared approximately half of patients a second operation. Patients with a positive SLN detected on FS were more likely to have further nodal involvement. In our experience intraoperative pathologic analysis of melanoma SLNs does not impair our ability to detect SLN metastasis or lead to a high rate of false positive results or nodal recurrences. J. Surg. Oncol. 2016;114:879-883. © 2016 2016 Wiley Periodicals, Inc.

Diagnostic accuracy of intracranial translucency in detecting spina bifida: a systematic review and meta-analysis.

To evaluate the diagnostic accuracy of intracranial translucency (IT) in the detection of spina bifida (SB) in the first trimester of pregnancy. We included study assessing the accuracy of sonographic measurements of IT in a mid-sagittal view of the fetal face in prediction of SB in the first trimester of pregnancy. The primary outcome was the accuracy of IT in prediction of spina bifida. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR), and diagnostic odds ratio for the overall predictive accuracy of IT were computed. Nine studies (21 070 fetuses) were included in the analysis. IT was successfully assessed in the majority of fetuses 97.8% (95% CI 97.6-98.0). The diagnostic performance of IT in detecting SB was as follows: sensitivity: 53.5% (95% CI 42.4-64.3), specificity: 99.7% (95% CI 99.6-99.8), positive LR: 62.1 (95% CI 12.2-317), negative LR:0.55 (95% CI 0.45-0.68), and diagnostic odds ratio: 223 (95% CI 25-2039). Intracranial translucency had low diagnostic accuracy in prediction of open spina bifida, thus questioning its role as a screening marker for open SB in an unselected population. When looking at the individual study data, it appears that IT assessment for open SB prediction can be affected by a high rate of false positive results potentially leading to unnecessary parental anxiety. © 2016 John Wiley & Sons, Ltd.

Discrepancy between genotypic and phenotypic extended-spectrum β-lactamase rates in Escherichia coli from intra-abdominal infections in the USA.

Varying rates of false-positive results of phenotypic extended-spectrum β-lactamase (ESBL) tests have been reported for different methods in different settings, species and geographic locations. This report describes discrepancies in Escherichia coli genotypic and phenotypic ESBL rates observed in a surveillance study of 29 US hospitals that participated in the Study for Monitoring Antimicrobial Resistance Trends (SMART). The ESBL phenotype was determined with the Clinical and Laboratory Standards Institute confirmatory broth microdilution test using cefotaxime and ceftazidime with and without clavulanate. Genes encoding ESBLs, carbapenemases and plasmidic AmpC β-lactamases were detected using a combination of microarray and multiplex PCR assays. Among 168 molecularly characterized phenotypically ESBL-positive E. coli isolates from intra-abdominal infections, 4.8 % were genotypically negative from 2009 to 2012 and 29.5 % in 2013. Because of the high rate of false-positive phenotypic ESBL results in 2013, the 5-year phenotypic ESBL trend was skewed and showed a statistically significant increase (P<0.05) in ESBL-positive E. coli in the USA, which was not seen using the genotypic ESBL rates. The majority of false-positive phenotypic profiles had ceftazidime MICs of 2 µg ml-1 and a ≥3 doubling dilution decrease in MIC for only one of the two antimicrobial agents. False-positive ESBL results can adversely impact epidemiological surveillance and patient care (including inappropriate treatment, unnecessary patient isolation and higher costs). Careful evaluation and comparison of phenotypic and genotypic test results can yield the greatest insight, but the most accurate (and faster) detection of ESBL producers is usually based on molecular data.