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Background: False-positive results on screening mammography may affect women's willingness to return for future screening., Objective: To evaluate the association between screening mammography results and the probability of subsequent screening., Design: Cohort study., Setting: 177 facilities participating in the Breast Cancer Surveillance Consortium (BCSC)., Patients: 3 529 825 screening mammograms (3 184 482 true negatives and 345 343 false positives) performed from 2005 to 2017 among 1 053 672 women aged 40 to 73 years without a breast cancer diagnosis., Measurements: Mammography results (true-negative result or false-positive recall with a recommendation for immediate additional imaging only, short-interval follow-up, or biopsy) from 1 or 2 screening mammograms. Absolute differences in the probability of returning for screening within 9 to 30 months of false-positive versus true-negative screening results were estimated, adjusting for race, ethnicity, age, time since last mammogram, BCSC registry, and clustering within women and facilities., Results: Women were more likely to return after a true-negative result (76.9% [95% CI, 75.1% to 78.6%]) than after a false-positive recall for additional imaging only (adjusted absolute difference, -1.9 percentage points [CI, -3.1 to -0.7 percentage points]), short-interval follow-up (-15.9 percentage points [CI, -19.7 to -12.0 percentage points]), or biopsy (-10.0 percentage points [CI, -14.2 to -5.9 percentage points]). Asian and Hispanic/Latinx women had the largest decreases in the probability of returning after a false positive with a recommendation for short-interval follow-up (-20 to -25 percentage points) or biopsy (-13 to -14 percentage points) versus a true negative. Among women with 2 screening mammograms within 5 years, a false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result., Limitation: Women could receive care at non-BCSC facilities., Conclusion: Women were less likely to return to screening after false-positive mammography results, especially with recommendations for short-interval follow-up or biopsy, raising concerns about continued participation in routine screening among these women at increased breast cancer risk., Primary Funding Source: National Cancer Institute., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0123.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known., Objective: To estimate outcomes of various mammography screening strategies., Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses., Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment., Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women., Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women., Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Background: Screening for fentanyl has been adopted by many clinical laboratories to detect illicit drug use and monitor medication adherence. However, compared to other urine drug testing, fentanyl screening assays are relatively new and therefore their clinical performances are largely unknown. This study extensively evaluated the clinical performance, positive cutoff, and interference profile of SEFRIA fentanyl immunoassay in real patient settings., Methods: The FDA-cleared cutoff of 1.0 was verified with 21 urine samples with low or undetectable levels of fentanyl. After assay implementation, all screened-positive samples were confirmed by liquid chromatography-tandem mass spectrometry. A new cutoff was derived from the numeric values of the false positive (FP) screening results. The FP rates before and after implementing the new cutoff were compared. Interferences were identified by an untargeted drug analysis and confirmed by spiking experiments., Results: A total of 3951 screening results were reviewed in the first two months of the assay utilization, 410 were screened-positive, and 157 (38 %) were FP. After a new cutoff of 1.3 was implemented, the FP rate was reduced to 17 % based on 11119 screening results. Trazodone, labetalol, and haloperidol were identified as major interferents, accounting for 56 % of the FP results using the cutoff of 1.3., Conclusion: By applying the new cutoff and including an interference comment to positive screening results, the FP rate was reduced from initial 38 % to 7.5 % (17 % times 56 %)., Competing Interests: Declaration of Competing Interest No conflict of interest declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose To evaluate the ability of a semiautonomous artificial intelligence (AI) model to identify screening mammograms not suspicious for breast cancer and reduce the number of false-positive examinations. Materials and Methods The deep learning algorithm was trained using 123 248 two-dimensional digital mammograms (6161 cancers) and a retrospective study was performed on three nonoverlapping datasets of 14 831 screening mammography examinations (1026 cancers) from two U.S. institutions and one U.K. institution (2008-2017). The stand-alone performance of humans and AI was compared. Human plus AI performance was simulated to examine reductions in the cancer detection rate, number of examinations, false-positive callbacks, and benign biopsies. Metrics were adjusted to mimic the natural distribution of a screening population, and bootstrapped CIs and P values were calculated. Results Retrospective evaluation on all datasets showed minimal changes to the cancer detection rate with use of the AI device (noninferiority margin of 0.25 cancers per 1000 examinations: U.S. dataset 1, P = .02; U.S. dataset 2, P < .001; U.K. dataset, P < .001). On U.S. dataset 1 (11 592 mammograms; 101 cancers; 3810 female patients; mean age, 57.3 years ± 10.0 [SD]), the device reduced screening examinations requiring radiologist interpretation by 41.6% (95% CI: 40.6%, 42.4%; P < .001), diagnostic examinations callbacks by 31.1% (95% CI: 28.7%, 33.4%; P < .001), and benign needle biopsies by 7.4% (95% CI: 4.1%, 12.4%; P < .001). U.S. dataset 2 (1362 mammograms; 330 cancers; 1293 female patients; mean age, 55.4 years ± 10.5) was reduced by 19.5% (95% CI: 16.9%, 22.1%; P < .001), 11.9% (95% CI: 8.6%, 15.7%; P < .001), and 6.5% (95% CI: 0.0%, 19.0%; P = .08), respectively. The U.K. dataset (1877 mammograms; 595 cancers; 1491 female patients; mean age, 63.5 years ± 7.1) was reduced by 36.8% (95% CI: 34.4%, 39.7%; P < .001), 17.1% (95% CI: 5.9%, 30.1%: P < .001), and 5.9% (95% CI: 2.9%, 11.5%; P < .001), respectively. Conclusion This work demonstrates the potential of a semiautonomous breast cancer screening system to reduce false positives, unnecessary procedures, patient anxiety, and medical expenses. Keywords: Artificial Intelligence, Semiautonomous Deep Learning, Breast Cancer, Screening Mammography Supplemental material is available for this article. Published under a CC BY 4.0 license.

Background: Bacille Calmette-Guérin (BCG) vaccination is known to cause false-positive tuberculin skin test (TST) results from cross-reactions with mycobacterial antigens. However, the duration of BCG vaccination influence on the TST is poorly characterized. The objective of this study was to assess the long-term effect of BCG vaccination on TST reactivity.Methods: Data on TST reactivity were prospectively collected during 1935 to 1947 as part of a clinical trial among Native Americans/Alaskan Natives and were retrospectively collected thereafter between 1948 and 1998. TST induration of ≥ 10 mm was defined as a positive reaction. Kaplan-Meier analysis and multivariate Cox regression were used to compare the time to TST conversion and reversion between the BCG and placebo groups.Results: BCG vaccination after infancy was associated with an increased risk of TST reactivity in the first 15 years after vaccination (adjusted hazard ratio [HR], 2.33). This association remained during the interval 16 to 55 years after vaccination, although the effect was attenuated (adjusted HR, 1.26). Age at vaccination modestly impacted the effect of BCG on TST results in the first 15 years. Positive TST results among the BCG-vaccinated group were more likely to revert to negative results during the first 15 years but not in the latter period.Conclusions: This study provides evidence that BCG vaccination after infancy may influence TST results beyond the 10-year period conventionally accepted by the Centers for Disease Control and Prevention (CDC), extending up to 55 years after vaccination. This suggests that BCG vaccination should be taken into account when interpreting TST results regardless of the time elapsed since vaccination. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This article is a systematic review of the effectiveness of three practices for reducing blood culture contamination rates: venipuncture, phlebotomy teams, and prepackaged preparation/collection (prep) kits. Design and methods: The CDC-funded Laboratory Medicine Best Practices Initiative systematic review methods for quality improvement practices were used. Results: Studies included as evidence were: 9 venipuncture (vs. versus intravenous catheter), 5 phlebotomy team; and 7 prep kit. All studies for venipuncture and phlebotomy teams favored these practices, with meta-analysis mean odds ratios for venipuncture of 2.69 and phlebotomy teams of 2.58. For prep kits 6 studies'' effect sizes were not statistically significantly different from no effect (meta-analysis mean odds ratio 1.12). Conclusions: Venipuncture and the use of phlebotomy teams are effective practices for reducing blood culture contamination rates in diverse hospital settings and are recommended as evidence-based “best practices” with high overall strength of evidence and substantial effect size ratings. No recommendation is made for or against prep kits based on uncertain improvement. [Copyright &y& Elsevier]

At the start of the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) designed, manufactured, and distributed the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel for SARS-CoV-2 detection. The diagnostic panel targeted three viral nucleocapsid gene loci (N1, N2, and N3 primers and probes) to maximize sensitivity and to provide redundancy for virus detection if mutations occurred. After the first distribution of the diagnostic panel, state public health laboratories reported fluorescent signal in the absence of viral template (false-positive reactivity) for the N3 component and to a lesser extent for N1. This report describes the findings of an internal investigation conducted by the CDC to identify the cause(s) of the N1 and N3 false-positive reactivity. For N1, results demonstrate that contamination with a synthetic template, that occurred while the "bulk" manufactured materials were located in a research lab for quality assessment, was the cause of false reactivity in the first lot. Base pairing between the 3' end of the N3 probe and the 3' end of the N3 reverse primer led to amplification of duplex and larger molecules resulting in false reactivity in the N3 assay component. We conclude that flaws in both assay design and handling of the "bulk" material, caused the problems with the first lot of the 2019-nCoV Real-Time RT-PCR Diagnostic Panel. In addition, within this study, we found that the age of the examined diagnostic panel reagents increases the frequency of false positive results for N3. We discuss these findings in the context of improvements to quality control, quality assurance, and assay validation practices that have since been improved at the CDC., Competing Interests: The authors have declared that no competing interests exist.

Background: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people., Objective: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak., Design: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results., Setting: A nursing home with an ongoing SARS-CoV-2 outbreak., Participants: 532 paired specimens collected from 234 available residents and staff., Measurements: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture., Results: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively)., Limitation: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff., Conclusion: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes., Primary Funding Source: None.

Context.—: Coronavirus disease 2019 (COVID-19) test performance depends on predictive values in settings of increasing disease prevalence. Geospatially distributed diagnostics with minimal uncertainty facilitate efficient point-of-need strategies., Objectives.—: To use original mathematics to interpret COVID-19 test metrics; assess US Food and Drug Administration Emergency Use Authorizations and Health Canada targets; compare predictive values for multiplex, antigen, polymerase chain reaction kit, point-of-care antibody, and home tests; enhance test performance; and improve decision-making., Design.—: PubMed/newsprint-generated articles documenting prevalence. Mathematica and open access software helped perform recursive calculations, graph multivariate relationships, and visualize performance by comparing predictive value geometric mean-squared patterns., Results.—: Tiered sensitivity/specificity comprised: T1, 90%, 95%; T2, 95%, 97.5%; and T3, 100%, ≥99%. Tier 1 false negatives exceeded true negatives at >90.5% prevalence; false positives exceeded true positives at <5.3% prevalence. High-sensitivity/specificity tests reduced false negatives and false positives, yielding superior predictive values. Recursive testing improved predictive values. Visual logistics facilitated test comparisons. Antigen test quality fell off as prevalence increased. Multiplex severe acute respiratory syndrome (SARS)-CoV-2)*influenza A/B*respiratory syncytial virus testing performed reasonably well compared with tier 3. Tier 3 performance with a tier 2 confidence band lower limit will generate excellent performance and reliability., Conclusions.—: The overriding principle is to select the best combined performance and reliability pattern for the prevalence bracket. Some public health professionals recommend repetitive testing to compensate for low sensitivity. More logically, improved COVID-19 assays with less uncertainty conserve resources. Multiplex differentiation of COVID-19 from influenza A/B-respiratory syncytial virus represents an effective strategy if seasonal flu surges next year.

Background: Stroke incidence is reportedly increasing in younger populations, although the reasons for this are not clear. We explored possible reasons by quantifying trends in neurologically focused emergency department (ED) visits, classification of stroke vs. TIA, and imaging use., Methods: We performed a retrospective, serial, cross-sectional study using the National Hospital Ambulatory Medical Care Survey to examine time trends in age-stratified primary reasons for visit, stroke/TIA diagnoses, and MRI utilization from 1995 to 2000 and 2005-2015., Results: Five million eight hundred thousand ED visits with a primary diagnosis of stroke (CI 5.3 M-6.4 M) were represented in the data. The incidence of neurologically focused reason for visits (Neuro RFVs) increased over time in both the young and in older adults (young: + 111 Neuro RFVs/100,000 population/year, CI + 94 - + 130; older adults: + 70 Neuro RFVs/100,000 population/year, CI + 34 - + 108). The proportion of combined stroke and TIA diagnoses decreased over time amongst older adults with a Neuro RFV (OR 0.95 per year, p < 0.01, CI 0.94-0.96) but did not change in the young (OR 1.00 per year, p = 0.88, CI 0.95-1.04). Within the stroke/TIA population, no changes in the proportion of stroke or TIA were identified. MRI utilization rates amongst patients with a Neuro RFV increased for both age groups., Conclusions: We found, but did not anticipate, increased incidence of neurologically focused ED visits in both age groups. Given the lower pre-test probability of a stroke in younger adults, this suggests that false positive stroke diagnoses may be increasing and may be increasing more rapidly in the young than in older adults.

Hypothesis: Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of "false positive" prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation., Methods: This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B., Results: A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B., Conclusions: The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.

Context.—: Repair is a challenging diagnosis and a significant source of false-positive (FP) interpretations in cervical cytology. No large-scale study of performance of repair in the liquid-based era has been performed., Objective.—: To evaluate the performance of repair in the College of American Pathologists Pap Education and Proficiency Testing (PT) programs., Design.—: The FP rate for slides classified as repair was evaluated by preparation type, participant type (cytotechnologist, pathologist, or laboratory), and program. The specific misdiagnosis category and individual slide performance were also evaluated. The rate of misclassification of slides as repair by participants for other diagnostic categories in the Pap Education program was assessed., Results.—: The overall FP rate was 1700 of 12 715 (13.4%). There was no significant difference by program or preparation type. Within the Education program there was no difference by participant type, but pathologists' FP rate in the PT program (47 of 514, 9.1%) was significantly better than cytotechnologists in the PT program (51 of 380, 13.4%) and pathologists in the Education program (690 of 4900, 14.1%). High-grade squamous intraepithelial lesions/cancers (HSIL+) accounted for 1380 of 1602 FP interpretations (86%) in Education, but 43 of 98 (43.9%) in PT. Most slides had a low rate of misclassification, but a small number were poor performers. False-negative diagnosis of HSIL+ as repair was less common, ranging from 0.7% to 1.8%., Conclusions.—: Despite initial indications that liquid-based cytology might reduce the rate of misclassification of repair, FP interpretations remain common and are no different by preparation type. Misclassification is most commonly as HSIL or carcinoma, potentially resulting in significant patient harm., Competing Interests: The authors are or were members of the College of American Pathologists Cytopathology Committee. Ms Souers and Ms Goodrich are employees of the College of American Pathologists., (© 2020 College of American Pathologists.)

Background: Patients with both true and false arrhythmia alarms pose a challenge because true alarms might be buried among a large number of false alarms, leading to missed true events., Objective: To determine (1) the frequency of patients with both true and false arrhythmia alarms; (2) patient, clinical, and electrocardiographic characteristics associated with both true and false alarms; and (3) the frequency and types of true and false arrhythmia alarms., Methods: This was a secondary analysis using data from an alarm study conducted at a tertiary academic medical center., Results: Of 461 intensive care unit patients, 211 (46%) had no arrhythmia alarms, 12 (3%) had only true alarms, 167 (36%) had only false alarms, and 71 (15%) had both true and false alarms. Ventricular pacemaker, altered mental status, mechanical ventilation, and cardiac intensive care unit admission were present more often in patients with both true and false alarms than among other patients (P < .001). Intensive care unit stays were longer in patients with only false alarms (mean [SD], 106 [162] hours) and those with both true and false alarms (mean [SD], 208 [333] hours) than in other patients. Accelerated ventricular rhythm was the most common alarm type (37%)., Conclusions: An awareness of factors associated with arrhythmia alarms might aid in developing solutions to decrease alarm fatigue. To improve detection of true alarms, further research is needed to build and test electrocardiographic algorithms that adjust for clinical and electrocardiographic characteristics associated with false alarms., (©2020 American Association of Critical-Care Nurses.)

OBJECTIVE. The objective of our study was to compare diagnostic accuracy and reliability of the 2017 American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and 2015 American Thyroid Association (ATA) classifications for thyroid nodules. MATERIALS AND METHODS. This study was a retrospective cohort study of 1947 consecutive thyroid nodules sampled with fine-needle aspiration (FNA) from 2007 to 2016. Reviewers assigned TI-RADS scores to all nodules while blinded to clinical outcome and histologic diagnosis and compared TI-RADS scores with nodule-specific ATA scores from the same cohort. Five blinded radiologists independently assigned TI-RADS scores to a subset of 151 nodules (interrater agreement). The primary outcome was a comparison of the diagnostic accuracy of the TI-RADS and ATA classifications using ROC curve analysis. The reference standard was cytopathologic diagnosis according to the Bethesda system. Interrater agreement was determined using intraclass correlation (ICC) and kappa statistics. RESULTS. Of 1947 sampled thyroid nodules, 31.8% ( n = 620) met TI-RADS criteria for FNA, 28.0% ( n = 545) met TI-RADS criteria for follow-up, and 40.2% ( n = 782) met TIRADS criteria to be ignored. Applying the 2015 ATA criteria resulted in recommendations of immediate FNA procedures for more nodules than applying the 2017 TI-RADS (ATA vs TIRADS: 62.3% [1213/1947] vs 31.8% [620/1947], p < 0.0001). Diagnostic accuracies (AUCs: TI-RADS score, 0.684 [95% CI, 0.644-0.724]; ATA, 0.686 [95% CI, 0.646-0.725]) and false-negative rates (TI-RADS, 2.2% [43/1947]; ATA, 2.4% [47/1947]) for the two classifications were similar ( p = 0.75). Overall interrater agreement was fair for both (ICCs: TI-RADS, 0.437 [95% CI, 0.357-0.520]; ATA classification, 0.460 [95% CI, 0.391-0.533]). CONCLUSION. The 2017 ACR TI-RADS and 2015 ATA classifications have similar diagnostic accuracies and interrater agreement, but TI-RADS results in fewer nodules being recommended for immediate FNAs and more nodules being recommended for imaging surveillance.

Background Signal generation through data mining algorithms is an innovative and emerging field in pharmacovigilance. Early detection of safety signals is important for public health safety. However, the possibility of generating pseudo signals should not be overlooked. Objective Our study aimed to identify potential signals of aromatase inhibitors associated Osteonecrosis of Jaw and assess the possibilities of the safety signal to be a pseudo signal/false positive in FDA Adverse Event Reporting System (FAERS). Setting Spontaneously reported data in FAERS database. Methods Data for this study were obtained from the public release of data in FAERS. OpenVigil, a pharmacovigilance analytical tool was used to access FAERS data. Reporting Odds Ratio (ROR) was used to assess the relation between the drug and adverse event. A value of ROR-1.96SE  > 1, (SE-standard error) was considered positive. Main outcome measure Signal strength. Results FAERS database had a total of 15,178 reports for Osteonecrosis of Jaw. Amongst which 617 reports were associated with aromatase inhibitors. Signal strength ROR (lower bound of the 95% CI) for letrozole, anastrozole and exemestane associated Osteonecrosis of Jaw without any background correction was 8.34, 6.64 and 15.14 respectively. Upon removing the reports of concomitantly administered drugs (bisphosphonates and denosumab), signal strength drastically decreased to 0.03, 0.36 and 0.47 for letrozole, anastrozole and exemestane respectively. The signal strength of bisphosphonates and denosumab associated Osteonecrosis of Jaw was not changed significantly upon removal of aromatase inhibitors. Conclusion Our study concluded that the signal generated for aromatase inhibitors associated Osteonecrosis of Jaw in FAERS database can be false positive. Careful background corrections with identification of those risk factors are imperative to exclude false positive results.

Urethritis, or inflammation of the urethra, is one of the most common reasons men seek clinical care. Sexually transmitted pathogens including Neisseria gonorrhoeae are responsible for over half of the symptomatic urethritis cases in U.S. men. Recently, clinics in Indianapolis, Columbus, Atlanta, and other U.S. cities began to note increasing numbers of men presenting with urethritis and Gram-negative intracellular diplococci in their urethral smears who test negative for N. gonorrhoeae. Many of these discordant cases, which have periodically reached highs of more than 25% of presumed gonococcal cases in some sexually transmitted infection clinics in the U.S. Midwest, are infected with strains in a novel urethrotropic clade of Neisseria meningitidis ST-11 (US&#95;NmUC). However, no cultivation-independent tests are available for the US&#95;NmUC strains, and prior studies relied on microbial culture and genome sequencing to identify them. Here, we describe a PCR test that can identify the US&#95;NmUC strains and distinguish them from commensal and invasive N. meningitidis strains as well as N. gonorrhoeae. Our SimpleProbe®-based real-time PCR assay targets a conserved nucleotide substitution in a horizontally acquired region of US&#95;NmUC strain genomes. We applied the assay to 241 urine specimens whose microbial compositions had previously been determined by deep shotgun metagenomic sequencing. The assay detected the single US&#95;NmUC positive case in this cohort, with no false positives. Overall, our simple and readily adaptable assay could facilitate investigation of the pathogenesis and epidemiology of the US&#95;NmUC clade., Competing Interests: The authors have declared that no competing interests exist.

Synthesis of 11 steroid hormones in human adrenocortical carcinoma cells (H295R) was measured in a high-throughput steroidogenesis assay (HT-H295R) for 656 chemicals in concentration-response as part of the US Environmental Protection Agency's ToxCast program. This work extends previous analysis of the HT-H295R dataset and model by examining the utility of a novel prioritization metric based on the Mahalanobis distance that reduced these 11-dimensional data to 1-dimension via calculation of a mean Mahalanobis distance (mMd) at each chemical concentration screened for all hormone measures available. Herein, we evaluated the robustness of mMd values, and demonstrate that covariance and variance of the hormones measured appear independent of the chemicals screened and are inherent to the assay; the Type I error rate of the mMd method is less than 1%; and, absolute fold changes (up or down) of 1.5 to 2-fold have sufficient power for statistical significance. As a case study, we examined hormone responses for aromatase inhibitors in the HT-H295R assay and found high concordance with other ToxCast assays for known aromatase inhibitors. Finally, we used mMd and other ToxCast cytotoxicity data to demonstrate prioritization of the most selective and active chemicals as candidates for further in vitro or in silico screening., (Published by Elsevier Inc.)

Lung cancer is the leading cause of cancer-related death around the world, being the top cause of cancer-related deaths among men and the second most common cause of cancer-related deaths among women in Singapore. Currently, no screening programme for lung cancer exists in Singapore. Since there is mounting evidence indicating a different epidemiology of lung cancer in Asian countries, including Singapore, compared to the rest of the world, a unique and adaptive approach must be taken for a screening programme to be successful at reducing mortality while maintaining cost-effectiveness and a favourable risk-benefit ratio. This review article promotes the use of low-dose computed tomography of the chest and explores the radiological challenges and future directions., (Copyright: © Singapore Medical Association.)

Background: Cervical spine injuries (CSI) are rare within the pediatric population. Due to the significant consequences of missed CSI, children are often imaged excessively. In an attempt to decrease imaging of the cervical spine in children, we reviewed abnormal cervical radiographs (XR) to determine if the diagnosis of CSI could be made using a single-lateral cervical radiograph (LAT). Furthermore, we reviewed cervical computed tomography (CT) and magnetic resonance imaging (MRI) to ensure there were no missed CSI., Methods: Electronic medical records of trauma patients treated at a Level I Pediatric Trauma Center with abnormal XR findings followed by confirmatory CT or MRI between 2012 and 2017 were reviewed. All abnormal imaging on XR was compared with the LAT. In addition, all abnormal CTs and MRIs were reviewed to ensure there were no false negative XR., Results: A total of 3,735 XR were performed with 26 abnormal interpretations. All bony CSI were visualized on LAT. Confirmatory imaging found 13 (50%) were false positive and 13 (50%) were true positive. Secondary analysis of CT identified 12 injuries with prior XR; 8 of 12 LAT identifying the injury and 4 of 12 false positive on CT. Secondary analysis of MRI identified nine injuries with prior XR; 5 of 9 LAT identifying the injury. The four false-negative reads on MRI were ligamentous injuries., Conclusion: Radiographs are commonly performed when evaluating CSI. In our population, initial assessment with a single LAT was equivalent to a multiple view XR. On secondary review, the only false-negative LAT reports were due to ligamentous injuries. This data suggests limiting exposure to LAT would accomplish the goal of reducing imaging without missing bony CSI and when ligamentous injury is suspected MRI should be the confirmatory study rather than CT., Level of Evidence: Diagnostic Test, level III.

Objectives: To evaluate the impact of false-positive IgM immunoblots on Lyme disease treatment and case reporting in a large healthcare system., Methods: We obtained the results of all Lyme disease serological tests ordered at U.S. Air Force healthcare facilities in the USA between January 2013 and December 2017. We conducted chart reviews to adjudicate positive IgM immunoblots (from two-tier and independent testing) as true positives or false positives using established criteria, and we assessed whether these cases were reported to the U.S. Department of Defense surveillance system., Results: Of the 18 410 serum tests (17 058 immunoassays and 1352 immunoblots) performed on 15 928 unique individuals, 249/1352 (18.4%) IgM immunoblots were positive. After excluding repeat tests, insufficiently documented cases, and participants with a history of Lyme disease, 212 positive IgM immunoblot cases were assessed. A total of 113/212 (53.3%) were determined to be false positives. Antibiotics were prescribed for Lyme disease for 97/99 (98.0%) participants with a true-positive test and 91/113 (80.5%) participants with a false-positive test. The number of false-positive cases reported to the surveillance system was identical to the number of unreported true-positive cases (n = 44)., Conclusions: Lyme disease serological tests were overused in a large healthcare system, and positive results were frequently misinterpreted, leading to misdiagnosis and widespread antibiotic misuse. Underreporting of true-positive cases was offset by overreporting of false-positive cases, suggesting that the discrepancy between the reported incidence and true incidence of Lyme disease may not be as significant as previously assumed., (Published by Elsevier Ltd.)

Objective: To identify patterns of care for women referred for asymptomatic microhematuria in a single, hospital-based health care system and estimate the cost of unindicated evaluation., Methods: We conducted a retrospective study of 100 women with a diagnosis of asymptomatic microhematuria referred to a tertiary female pelvic medicine and reconstructive surgery practice. Our analysis focused on referral patterns by obstetrician-gynecologists and primary care physicians. Data analyzed included whether asymptomatic microhematuria was documented using urine microscopy (vs urine dipstick) and whether the urine microscopy correctly identified asymptomatic microhematuria with three red blood cells (RBCs)., Results: Forty-six patients were referred who met the American Urological Association's guidelines for asymptomatic microhematuria with a workup estimated at $8,298 per patient. Fifty-four were referred to a female pelvic medicine and reconstructive surgery specialist despite clearly not meeting the American Urological Association's definition of asymptomatic microhematuria. Of these, 33 patients were referred based on dipstick-positive results only, 11 were referred based on microscopic urinalysis demonstrating fewer than three RBCs per high-power field (HPF), and the remaining 10 patients were referred with urine microscopy demonstrating at least 3 RBC/HPF but in the setting of a clearly benign cause, such as infection or menstruation. The total estimated cost of the unnecessary asymptomatic microhematuria workup in patients who did not meet American Urological Association criteria for referral was $1,213 per patient., Conclusion: Fewer than half of the referrals for asymptomatic microhematuria were appropriate, leading to wasted and entirely preventable health care expenditures. This study highlights the need for education of health care providers making these referrals.

Objectives: To compare existing algorithms for classifying screening vs diagnostic colonoscopies and to quantify the increase in screening colonoscopy rates when Medicare began reimbursement in 2001 and when the Affordable Care Act (ACA) eliminated cost-sharing., Data Sources: Twenty percent random sample of fee-for-service (FFS) Medicare claims, 2000-2012., Study Design: Using recent administrative codes as tarnished gold standards, we examined the sensitivity and specificity of five published algorithms for classifying colonoscopies and calculated annual screening colonoscopy rates. We estimated the change in rates after Medicare began reimbursement and used difference-in-differences analysis to estimate the effects of eliminating cost-sharing by comparing states with and without a mandate to cover screening colonoscopy prior to the ACA., Findings: Model-based algorithms have higher sensitivity (0.53-0.99) than expert-based algorithms (0.35-0.39), but lower specificity (0.43-0.65 vs 0.79-0.88). All algorithms detected increases in screening from both Medicare's reimbursement change (range: 24-93/10 000) and the 2011 cost-sharing change (range: 1.1-34/10 000). Difference-in-difference estimates of the ACA's effect varied from 51 to 155 tests per 10 000 depending on the algorithm., Conclusions: Screening colonoscopy rates increased after eliminating cost-sharing in 2011, but the increase's size varied depending on the algorithm used to classify the indication. Improvements are needed in Medicare coding for screening., (© Health Research and Educational Trust.)

Heart failure (HF) is one of the leading causes of hospital admissions in the US. Readmission within 30 days after a HF hospitalization is both a recognized indicator for disease progression and a source of considerable financial burden to the healthcare system. Consequently, the identification of patients at risk for readmission is a key step in improving disease management and patient outcome. In this work, we used a large administrative claims dataset to (1) explore the systematic application of neural network-based models versus logistic regression for predicting 30 days all-cause readmission after discharge from a HF admission, and (2) to examine the additive value of patients' hospitalization timelines on prediction performance. Based on data from 272,778 (49% female) patients with a mean (SD) age of 73 years (14) and 343,328 HF admissions (67% of total admissions), we trained and tested our predictive readmission models following a stratified 5-fold cross-validation scheme. Among the deep learning approaches, a recurrent neural network (RNN) combined with conditional random fields (CRF) model (RNNCRF) achieved the best performance in readmission prediction with 0.642 AUC (95% CI, 0.640-0.645). Other models, such as those based on RNN, convolutional neural networks and CRF alone had lower performance, with a non-timeline based model (MLP) performing worst. A competitive model based on logistic regression with LASSO achieved a performance of 0.643 AUC (95% CI, 0.640-0.646). We conclude that data from patient timelines improve 30 day readmission prediction, that a logistic regression with LASSO has equal performance to the best neural network model and that the use of administrative data result in competitive performance compared to published approaches based on richer clinical datasets.

Background: Recently, a risk index for living donor kidney (LDK) transplantation [living kidney donor profile index (LKDPI)] was proposed to compare LDKs with each other and with deceased donor kidneys (DDKs). Until now, the LKDPI has not been validated externally., Methods: This long-term retrospective analysis included 1305 consecutive adult kidney transplant recipients who were transplanted 2000-16 in our centre. The Kidney Donor Profile Index (KDPI) was calculated in 889 DDKs and the LKDPI in 416 LDKs. Outcome was followed over a median of 6.5 years., Results: The median LKDPI was 17 and the median KDPI was 69, with a high proportion of donor kidneys with a very high KDPI (40% KDPI ≥ 80). Categorization of LDK into LKDPI quartiles (LKDPI -45-3, 3-17, 17-33, 33-90) revealed a significant difference in death-censored graft survival. Comparing corresponding subgroups of the LKDPI and KDPI (LKDPI/KDPI 0-20 or 20-40) showed comparable graft survival. A multivariate analysis adjusting for relevant recipient factors revealed the KDPI [hazard ratio (HR) 1.21; P < 0.001) and LKDPI (HR 1.15; P = 0.049) as significant independent predictors of graft loss. Time-to-event receiver operating characteristic analyses for graft survival demonstrated lower predictive discrimination of the LKDPI [area under the curve (AUC) 0.55] compared with the KDPI (AUC 0.66). The 10-year graft survival of LDK recipients was inferior in the USA compared with our centre (79% versus 84%)., Conclusions: These results provide external validation of the LKDPI to predict death-censored graft survival and confirm comparability of the LKDPI with the KDPI to discriminate post-transplant outcome., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background/objectives: Antibody detection is commonly used for diagnosis of histoplasmosis, and cross-reactions have been recognised due to endemic mycoses but not cryptococcosis. We observed cross-reactions in an anti-Histoplasma antibody enzyme immunoassay (EIA) in the cerebrospinal fluid (CSF) from a patient with cryptococcal meningitis and sought to assess the risk of cross-reactive anti-Histoplasma antibodies in persons with cryptococcal meningitis., Methods: An anti-cryptococcal antibody EIA was developed to measure CSF antibody response in HIV-infected subjects from Kampala, Uganda and previously healthy, HIV-negative subjects at the National Institutes of Health (NIH) with cryptococcal meningitis. Specimens were tested for cross-reactivity in assays for IgG anti-Histoplasma, anti-Blastomyces and anti-Coccidioides antibodies., Results: Among 61 subjects with cryptococcal meningitis (44 Kampala cohort, 17 NIH cohort), elevated CSF anti-cryptococcal antibody levels existed in 38% (23/61). Of the 23 CSF specimens containing elevated anti-cryptococcal antibodies, falsely positive results were detected in antibody EIAs for histoplasmosis (8/23, 35%), coccidioidomycosis (6/23, 26%) and blastomycosis (1/23, 4%). Overall, 2% (2/81) of control CSF specimens had elevated anti-cryptococcal antibody detected, both from Indiana., Conclusions: Cryptococcal meningitis may cause false-positive results in the CSF for antibodies against Histoplasma, Blastomyces and Coccidioides. Fungal antigen testing should be performed to aid in differentiating true- and false-positive antibody results in the CSF., (© 2018 Blackwell Verlag GmbH.)

Objectives: Studies have shown that having a baseline mammogram, the first screening mammogram, available for comparison at the time of interpreting a subsequent mammogram significantly decreases the potential of a false-positive examination. Our aim was to evaluate knowledge of and perception about the significance of baseline mammograms in those women undergoing screening mammography., Materials and Methods: A cross-sectional prospective survey study was conducted in women without a history of breast cancer presenting for their screening mammogram. Respondents were surveyed anonymously between March and April 2017. The questionnaire was developed by primary care providers and radiologists and pretested for readability and clarity., Results: In all, 401 women (87% white, 93% educated beyond high school) completed surveys in which 77% of women reported having yearly mammograms, 31% reported having a history of an abnormal mammogram, and 45% had not heard the term baseline mammogram. Of those who had heard the term, the most commonly reported source was their primary care provider (31%). Although 74% chose the correct definition of a baseline mammogram, 67% did not think that a baseline mammogram was important for decreasing associated cost, time, and discomfort due to the number of mammograms incorrectly read as abnormal., Conclusion: In a group of educated women who routinely get mammograms, almost one-half had not heard the term baseline mammogram. Furthermore, most women did not think baseline mammography was important for decreasing associated cost, time, and discomfort due to mammograms incorrectly read as abnormal. This study suggests that efforts to improve women's understanding of baseline mammograms and their importance are warranted, with greatest opportunity for health care providers and radiologists., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Previous cost-effectiveness models found ambulatory blood pressure monitoring (ABPM) to be a favorable strategy to diagnose hypertension; however, they mostly focused on older adults with a positive clinic blood pressure (BP) screen. We evaluated the cost-effectiveness of 3 methods of BP measurement for hypertension diagnosis in primary care settings among 14 age- and sex-stratified hypothetical cohorts (adults ≥21 years of age), accounting for the possibility of both false-positive (white-coat hypertension) and false-negative (masked hypertension) clinic measurements. We compared quality-adjusted life-years and lifetime costs ($US 2017 from the US healthcare perspective) associated with clinic BP measurement, home BP monitoring, and ABPM under 2 scenarios: positive and negative initial screen. Model parameters were obtained from published literature, publicly available data sources, and expert input. In the screen-positive scenario, ABPM was the dominant strategy among all age and sex groups. Compared with clinic BP measurement, ABPM was associated with cost-savings ranging from $77 (women 80 years of age) to $5013 (women 21 years of age). In the screen-negative scenario, ABPM was the dominant strategy in all men and women <80 years of age with cost-savings ranging from $128 (women 70 years of age) to $2794 (women 21 years of age). Sensitivity analyses showed that results were sensitive to test specificity and antihypertensive medication costs. ABPM is recommended as the diagnostic strategy of choice for most adults in primary care settings regardless of initial screening results.

Background: Advances in medicine have improved our understanding of sepsis, but it remains a major cause of morbidity and mortality. The detection of pathogens that cause sepsis remains a challenge for clinical microbiology laboratories., Content: Routine blood cultures are time-consuming and are negative in a large proportion of cases, leading to excessive use of broad-spectrum antimicrobials. Molecular testing direct from patient blood without the need for incubation has the potential to fill the gaps in our diagnostic armament and complement blood cultures to provide results in a timely manner. Currently available platforms show promise but have yet to definitively address gaps in sensitivity and specificity., Summary: Significant strides have been made in the detection of pathogens directly from blood. A number of hurdles, however, remain before this technology can be adapted for routine use., (© 2018 American Association for Clinical Chemistry.)

Context.—: Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging., Objective.—: To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program., Design.—: We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance., Results.—: There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL ( P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL)., Conclusions.—: More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.

Background: Beginning in 2017, successfully passing the four-part pre-enlistment Occupational Physical Assessment Test (OPAT) became a requirement for all U.S. Army recruits. To ensure the test accurately identifies individuals who are qualified for their job, it was necessary to examine classification errors., Objective: The objectives were to 1) determine the accuracy of OPAT cut-scores for combat arms Soldiers, and 2) determine which events contribute to the individuals that are misclassified as passing or failing the OPATMETHODS:A total of 741 trainees were tested on the OPAT within two weeks of entering their initial entry training. At the end of their training, trainees were tested on simulations of the most physically demanding tasks of their job., Results: There was a high classification concordance (76.5%) between success on the OPAT and job task simulations. False positives (6.7%) were misclassified because they did not perform as well on the strength-dominant task simulations. While the interval aerobic run was the greatest contributor to false negatives (16.8%), previous studies indicated high performance on this event as a potential key indicator of injury and attrition risk., Conclusions: The findings provide insight on how the accuracy of the OPAT, and similar pre-employment tests, could be improved.

Breast cancer remains the most common nonskin cancer among women and a leading cause of morbidity and mortality. Early detection through screening and advances in treatment have contributed to a 39% mortality reduction in the United States since 1990. The NCCN Guidelines for Breast Cancer Screening and Diagnosis recommend annual mammographic screening for average-risk women beginning at age 40 years. Mammographic screening and subsequent treatment reduces breast cancer mortality based on a wide range of studies. This article highlights NCCN's position on screening mammography and the screening controversy., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Zika virus disease provides the latest example of a critical nexus between public health and clinical practice. Interpreting Zika virus test results is complicated by the absence of a single testing approach with superior validity across contexts and populations. Molecular tests are highly specific, variably sensitive, and have a short window period. Serologic tests identify antibodies against Zika virus and are more likely than molecular tests to cross-react with other related viruses, reducing specificity. The type of test performed and timing relative to possible Zika virus exposure depend on public health guidance, testing algorithms, test availability, and capacity. Guidance from the Centers for Disease Control and Prevention and local health departments have changed throughout the course of the US epidemic based on prevalence, geography, and clinical concerns. Women with a low pretest probability of infection should be counseled against testing. Women with a high pretest probability of Zika virus infection should still receive enhanced prenatal monitoring and newborn evaluation, regardless of the test result. An appropriate interpretation of results depends on what tests are used, patient characteristics, and reasons for testing. Clinicians should take these factors into account in shared decision making discussions with pregnant women about Zika virus testing., Competing Interests: Conflict of interest: none declared., (© Copyright 2018 by the American Board of Family Medicine.)

Background: Although birth defects are the leading cause of infant mortality in the United States, methods for observing human pregnancies with birth defect outcomes are limited., Objective: The primary objectives of this study were (i) to assess whether rare health-related events-in this case, birth defects-are reported on social media, (ii) to design and deploy a natural language processing (NLP) approach for collecting such sparse data from social media, and (iii) to utilize the collected data to discover a cohort of women whose pregnancies with birth defect outcomes could be observed on social media for epidemiological analysis., Methods: To assess whether birth defects are mentioned on social media, we mined 432 million tweets posted by 112,647 users who were automatically identified via their public announcements of pregnancy on Twitter. To retrieve tweets that mention birth defects, we developed a rule-based, bootstrapping approach, which relies on a lexicon, lexical variants generated from the lexicon entries, regular expressions, post-processing, and manual analysis guided by distributional properties. To identify users whose pregnancies with birth defect outcomes could be observed for epidemiological analysis, inclusion criteria were (i) tweets indicating that the user's child has a birth defect, and (ii) accessibility to the user's tweets during pregnancy. We conducted a semi-automatic evaluation to estimate the recall of the tweet-collection approach, and performed a preliminary assessment of the prevalence of selected birth defects among the pregnancy cohort derived from Twitter., Results: We manually annotated 16,822 retrieved tweets, distinguishing tweets indicating that the user's child has a birth defect (true positives) from tweets that merely mention birth defects (false positives). Inter-annotator agreement was substantial: κ = 0.79 (Cohen's kappa). Analyzing the timelines of the 646 users whose tweets were true positives resulted in the discovery of 195 users that met the inclusion criteria. Congenital heart defects are the most common type of birth defect reported on Twitter, consistent with findings in the general population. Based on an evaluation of 4169 tweets retrieved using alternative text mining methods, the recall of the tweet-collection approach was 0.95., Conclusions: Our contributions include (i) evidence that rare health-related events are indeed reported on Twitter, (ii) a generalizable, systematic NLP approach for collecting sparse tweets, (iii) a semi-automatic method to identify undetected tweets (false negatives), and (iv) a collection of publicly available tweets by pregnant users with birth defect outcomes, which could be used for future epidemiological analysis. In future work, the annotated tweets could be used to train machine learning algorithms to automatically identify users reporting birth defect outcomes, enabling the large-scale use of social media mining as a complementary method for such epidemiological research., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: False-positive HIV screening tests in pregnancy may lead to unnecessary interventions in labor. In 2014, the Centers for Disease Control and Prevention released a new algorithm for HIV diagnosis using a fourth-generation screening test, which detects antibodies to HIV as well as p24 antigen and has a shorter window period compared with prior generations. A reactive screen requires a differentiation assay, and supplemental qualitative RNA testing is necessary for nonreactive differentiation assay. One screening test, the ARCHITECT Ag/Ab Combo assay, is described to have 100% sensitivity and >99% specificity in nonpregnant populations; however, its clinical performance in pregnancy has not been well described., Objective: The objective of the study was to determine the performance of the ARCHITECT assay among pregnant women at a large county hospital and to assess whether the relative signal-to-cutoff ratio can be used to differentiate between false-positive vs confirmed HIV infections in women with a nonreactive differentiation assay., Study Design: This is a retrospective review of fourth-generation HIV testing in pregnant women at Parkland Hospital between June 1, 2015, and Jan. 31, 2017. We identified gravidas screened using the ARCHITECT Ag/Ab Combo assay (index test), with reflex to differentiation assay. Women with reactive ARCHITECT and nonreactive differentiation assay were evaluated with a qualitative RNA assay (reference standard). We calculated sensitivity, specificity, predictive value, and false-positive rate of the ARCHITECT screening assay in our population and described characteristics of women with false-positive HIV testing vs confirmed infection. Among women with a nonreactive differentiation assay, we compared interventions among women with and without a qualitative RNA assay result available at delivery and examined relative signal-to-cutoff ratios of the ARCHITECT assay in women with false-positive vs confirmed HIV infection., Results: A total of 21,163 pregnant women were screened using the ARCHITECT assay, and 190 tested positive. Of these, 33 of 190 (17%) women had false-positive HIV screening tests (28 deliveries available for analysis), and 157 of 190 (83%) had confirmed HIV-1 infection (140 available for analysis). Diagnostic accuracy of the ARCHITECT HIV Ag/Ab Combo assay in our prenatal population (with 95% confidence interval) was as follows: sensitivity, 100% (97.7-100%); specificity, 99.8% (99.8-99.9%); positive likelihood ratio, 636 (453-895); negative likelihood ratio, 0.0 (NA); positive predictive value, 83% (77-88%); and false positive rate, 0.16% (0.11-0.22%), with a prevalence of 7 per 1000. Women with false-positive HIV testing were younger and more likely of Hispanic ethnicity. A qualitative RNA assay (reference standard) was performed prenatally in 24 (86%) and quantitative viral load in 22 (92%). Interventions occurred more frequently in women without a qualitative RNA assay result available at delivery, including intrapartum zidovudine (75% vs 4%, P = .002), breastfeeding delay (75% vs 8%, P = .001), and neonatal zidovudine initiation (75% vs 4%, P = .002). The ARCHITECT signal-to-cutoff ratio was significantly lower for women with false-positive HIV tests compared with those with established HIV infection (1.89 [1.27, 2.73] vs 533.65 [391.12, 737.22], respectively, P < .001)., Conclusion: While the performance of the fourth-generation ARCHITECT HIV Ag/Ab Combo assay among pregnant women is comparable with that reported in nonpregnant populations, clinical implications of using a screening test with a positive predictive value of 83% in pregnancy are significant. When the qualitative RNA assay result is unavailable, absence of risk factors in combination with an ARCHITECT HIV Ag/Ab assay S/Co ratio <5 and nonreactive differentiation assay provide sufficient evidence to support deferral of unnecessary intrapartum interventions while awaiting qualitative RNA results., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives Low-dose computed tomography lung cancer screening has been shown to reduce lung cancer mortality but has a high false-positive rate. The precision medicine approach to low-dose computed tomography screening assesses subjects' benefits versus harms based on their personal lung cancer risk, where harms include false-positive screens and resultant invasive procedures. We assess the relationship between lung cancer risk and the rate of false-positive LDCT screens. Methods The National Lung Screening Trial randomized high-risk subjects to three annual screens with low-dose computed tomography or chest radiographs. Following the completion of National Lung Screening Trial, the Lung CT Screening Reporting and Data System (Lung-RADS) classification system was developed and retrospectively applied to National Lung Screening Trial low-dose computed tomography findings. The rate of false-positive screens (by Lung-RADS) and the resultant invasive procedures were examined as a function of lung cancer risk estimated by a model. Results Of 26,722 subjects randomized to the low-dose computed tomography arm, 26,309 received a baseline screen and were included in the analysis. The proportion with any false positive over three screening rounds increased from 12.9% to 25.9% from lowest to highest risk decile, and the proportion with an invasive procedure following a false positive also significantly increased from 0.7% to 2.0% from lowest to highest risk decile. Conclusion These findings indicate a need for personalized low-dose computed tomography lung cancer screening decision aids to accurately convey the benefits to harm trade-off.

Following large declines in tuberculosis transmission the United States, large-scale screening programs targeting low-risk healthcare workers are increasingly a source of false-positive results. We report a large cluster of presumed false-positive tuberculin skin test results in healthcare workers following a change to 50-dose vials of Tubersol tuberculin.Infect Control Hosp Epidemiol 2018;39:750-752.

Human genomic information can yield more effective healthcare by guiding medical decisions. Therefore, genomics research is gaining popularity as it can identify potential correlations between a disease and a certain gene, which improves the safety and efficacy of drug treatment and can also develop more effective prevention strategies [1]. To reduce the sampling error and to increase the statistical accuracy of this type of research projects, data from different sources need to be brought together since a single organization does not necessarily possess required amount of data. In this case, data sharing among multiple organizations must satisfy strict policies (for instance, HIPAA and PIPEDA) that have been enforced to regulate privacy-sensitive data sharing. Storage and computation on the shared data can be outsourced to a third party cloud service provider, equipped with enormous storage and computation resources. However, outsourcing data to a third party is associated with a potential risk of privacy violation of the participants, whose genomic sequence or clinical profile is used in these studies. In this article, we propose a method for secure sharing and computation on genomic data in a semi-honest cloud server. In particular, there are two main contributions. Firstly, the proposed method can handle biomedical data containing both genotype and phenotype. Secondly, our proposed index tree scheme reduces the computational overhead significantly for executing secure count query operation. In our proposed method, the confidentiality of shared data is ensured through encryption, while making the entire computation process efficient and scalable for cutting-edge biomedical applications. We evaluated our proposed method in terms of efficiency on a database of Single-Nucleotide Polymorphism (SNP) sequences, and experimental results demonstrate that the execution time for a query of 50 SNPs in a database of 50,000 records is approximately 5 s, where each record contains 500 SNPs. And, it requires 69.7 s to execute the query on the same database that also includes phenotypes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The heterophile antibody (Monospot), initial test of choice for Epstein-Barr virus (EBV)-associated infectious mononucleosis, is both sensitive (70-92%) and specific (96-100%). False positives have been demonstrated in cases of viral hepatitis, human immunodeficiency virus, leukemia, lymphoma, pancreatic cancer, systemic lupus erythematosus, and rubella. We present a case of a 46-yr-old male who developed fever, chills, headaches, myalgia, fatigue, and photophobia 1 d after returning from the Philippines. He demonstrated a mild transaminitis and significant thrombocytopenia (12,000 cells/μL). His initial evaluation revealed a positive heterophile antibody test. Without a classic EBV presentation, a fever in returning traveler evaluation was instituted resulting in a positive dengue test by direct fluorescence IgM (8.82 IU) and IgG (7.13 IU), respectively. Both his EBV DNA polymerase chain reaction and IgM by viral capsid antigen were negative. Dengue, an RNA flavivirus, and the dengue antibody have demonstrated cross-reactivity with other flaviviruses including Japanese encephalitis virus, yellow fever virus, West Nile virus, and St. Louis encephalitis. However, EBV is a double-helix DNA herpesvirus and structurally very different. To our knowledge, this is the first reported case of cross-reactivity between dengue and EBV that describes a potential false positive for the heterophile antibody test.

Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections., (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)

Importance: One of the most important causes of vision abnormalities in children is amblyopia (also known as "lazy eye"). Amblyopia is an alteration in the visual neural pathway in a child's developing brain that can lead to permanent vision loss in the affected eye. Among children younger than 6 years, 1% to 6% have amblyopia or its risk factors (strabismus, anisometropia, or both). Early identification of vision abnormalities could prevent the development of amblyopia., Subpopulation Considerations: Studies show that screening rates among children vary by race/ethnicity and family income. Data based on parent reports from 2009-2010 indicated identical screening rates among black non-Hispanic children and white non-Hispanic children (80.7%); however, Hispanic children were less likely than non-Hispanic children to report vision screening (69.8%). Children whose families earned 200% or more above the federal poverty level were more likely to report vision screening than families with lower incomes., Objective: To update the 2011 US Preventive Services Task Force (USPSTF) recommendation on screening for amblyopia and its risk factors in children., Evidence Review: The USPSTF reviewed the evidence on the accuracy of vision screening tests and the benefits and harms of vision screening and treatment. Surgical interventions were considered to be out of scope for this review., Findings: Treatment of amblyopia is associated with moderate improvements in visual acuity in children aged 3 to 5 years, which are likely to result in permanent improvements in vision throughout life. The USPSTF concluded that the benefits are moderate because untreated amblyopia results in permanent, uncorrectable vision loss, and the benefits of screening and treatment potentially can be experienced over a child's lifetime. The USPSTF found adequate evidence to bound the potential harms of treatment (ie, higher false-positive rates in low-prevalence populations) as small. Therefore, the USPSTF concluded with moderate certainty that the overall net benefit is moderate for children aged 3 to 5 years., Conclusions and Recommendations: The USPSTF recommends vision screening at least once in all children aged 3 to 5 years to detect amblyopia or its risk factors. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of vision screening in children younger than 3 years. (I statement).