False-positive Screening Research Articles

Alkaline phosphatase ınterference in an unconjugated estriol assay causing a false positive Down syndrome screening result

Abstract Objective Decreased unconjugated estriol (uE3) concentrations increase calculated risk of Down syndrome. Therefore, falsely low uE3, due to assay interference, have the potential to cause false-positive screening results. Here we present a 35 years old woman with a pregnancy of 17+2 weeks. Materials and methods Second-trimester screening test was performed on the UniCelDxI 800 (Beckman Coulter, Brea, CA, USA) analyzer and her uE3 level was 0.21 ng/mL (0.21 MoM). Risk calculated for DS was 1/8. Measurements were repeated on IMMULITE 2000 XPi (Siemens Healthcare Diagnostics Inc., USA). uE3 result was 0.614 ng/mL (0.97 MoM). The risk for DS was negative with this system. There was no sign of fetal anomaly on three-dimensional ultrasound examination and cell-free fetal DNA screening test. We suspected assay interference for uE3. Results Serial dilutions of serum samples revealed nonlinearity. 36.3% increase was observed with heterophile antibody blocking tubes. The post-polyethylene glycol treatment resulted approximately the same uE3 levels as IMMULITE system. Addition of alkaline phosphatase Scavenger to serum increased the result by 90% showing that falsely low E3 result was due to an interferent reacting on assay medium. Conclusion Laboratories should be aware that falsely low uE3 results due to interference may be obtained.

Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts

BackgroundWe assessed the long-term risk of screen-detected and interval breast cancer in women with a first or second false-positive screening result.MethodsJoint analysis had been performed using individual-level data from three population-based screening programs in Europe (Copenhagen in Denmark, Norway, and Spain). Overall, 75,513 screened women aged 50–69 years from Denmark (1991–2010), 556,640 from Norway (1996–2008), and 517,314 from Spain (1994–2010) were included. We used partly conditional Cox hazards models to assess the association between false-positive results and the risk of subsequent screen-detected and interval cancer.ResultsDuring follow-up, 1,149,467 women underwent 3,510,450 screening exams, and 10,623 screen-detected and 5700 interval cancers were diagnosed. Compared to women with negative tests, those with false-positive results had a two-fold risk of screen-detected (HR = 2.04, 95% CI: 1.93–2.16) and interval cancer (HR = 2.18, 95% CI: 2.02–2.34). Women with a second false-positive result had over a four-fold risk of screen-detected and interval cancer (HR = 4.71, 95% CI: 3.81–5.83 and HR = 4.22, 95% CI: 3.27–5.46, respectively). Women remained at an elevated risk for 12 years after the false-positive result.ConclusionsWomen with prior false-positive results had an increased risk of screen-detected and interval cancer for over a decade. This information should be considered to design personalised screening strategies based on individual risk.

Psychosocial consequences among women with false-positive results after mammography screening in Norway

Background: Mammography screening may cause psychosocial harm for women experiencing a false-positive screening result. Previous studies suggest long-term consequences. The aim of the present study was to assess psychosocial consequences of false-positive findings on screening mammography within a six month follow-up.Methods: A prospective matched cohort survey study using the questionnaire ‘Consequences of Screening for Breast Cancer’ (COS-BC), which was translated from Danish to Norwegian. Psychometric analyses investigated the measurement properties of the Norwegian version. Two screening clinics in Norway distributed the survey to 299 women with an abnormal mammogram and 541 women with a normal screen. Women received the questionnaire when receiving the screening result, and one and six months after screening.Results: At six months, statistically significant differences appeared in two scales: existential values and breast examination. At six-month follow-up, women with false-positive results showed no statistically significant differences from women diagnosed with breast cancer in three outcomes: sense of dejection, anxiety, and keeping my mind off things.Conclusion: Our results indicate that the psychosocial consequences from having false-positive screening mammography results diminish after six months. The results support previous research describing breast-specific outcomes. However, our results indicate that Norwegian women are less frightened than other Scandinavian mammography screening participants.

False positive screen test for mucopolysaccharidoses in healthy female newborns

BackgroundIn total, 930 urine samples obtained on 2nd and 3rd day from birth have been analyzed for the early diagnosis of Mucopolysaccharidoses. MethodsDimethylmethylene blue (DMB) assay and one-dimensional electrophoresis were performed in all urine samples. Agarose gel electrophoresis, before and after treatment with chondroitinase ABC and heparinases, was used for a comprehensive characterization. ResultsOut of 930 urine samples 7 showed anomalous electrophoretic pattern; 5 of them had high GAG levels by DMB test. Atypical samples (n = 7) were analyzed by agarose gel electrophoresis. After enzymatic digestion, some slow bands were still visible. A second urine sample of the above 7 newborns was analyzed at the age of 1 month, demonstrating both a normal pattern and normal GAG levels. Additional urine and vaginal mucus samples from 10 term neonates with vaginal bleeding showed the same electrophoretic pattern observed in the 7 false positive samples. ConclusionsThe altered electrophoretic pattern may be due to the presence of glycoproteins and not to specific GAGs, due to high levels of maternal hormones exposure during pregnancy. To our knowledge, this is the first time maternal estrogen hormones are proposed as a likely cause of false-positive urinary glycosaminoglycan screen test in healthy newborns.

Organs from deceased donors with false-positive HIV screening tests: An unexpected benefit of the HOPE act.

Organs from deceased donors with suspected false-positive HIV screening tests were generally discarded due to the chance that the test was truly positive. However, the HIV Organ Policy Equity (HOPE) Act now facilitates use of such organs for transplantation to HIV-infected (HIV+) individuals. In the HOPE in Action trial, donors without a known HIV infection who unexpectedly tested positive for anti-HIV antibody (Ab) or HIV nucleic acid test (NAT) were classified as suspected false-positive donors. Between March 2016 and March 2018, 10 suspected false-positive donors had organs recovered for transplant for 21 HIV+recipients (14 single-kidney, 1 double-kidney, 5 liver, 1 simultaneous liver-kidney). Median donor age was 24years; cause of death was trauma (n = 5), stroke (n =4), and anoxia (n = 1); three donors were labeled Public Health Service increased infectious risk. Median kidney donor profile index was 30.5 (IQR 22-58). Eight donors were HIV Ab+/NAT-; two were HIV Ab-/NAT+. All 10 suspected false-positive donors were confirmed to be HIV-noninfected. Given the false-positive rates of approved assays used to screen>20000 deceased donors annually, we estimate 50-100 HIV false-positive donors per year. Organ transplantation from suspected HIV false-positive donors is an unexpected benefit of the HOPE Act that provides another novel organ source.

A preliminary study of astigmatism and early childhood development

To determine whether uncorrected astigmatism in toddlers is associated with poorer performance on the Bayley Scales of Infant and Toddler Development, 3rd edition (BSITD-III). Subjects were 12- to 35-month-olds who failed an instrument-based vision screening at a well-child check. A cycloplegic eye examination was conducted. Full-term children with no known medical or developmental conditions were invited to participate in a BSITD-III assessment conducted by an examiner masked to the child's eye examination results. Independent samples t tests were used to compare Cognitive, Language (Receptive and Expressive), and Motor (Fine and Gross) scores for children with moderate/high astigmatism (>2.00 D) versus children with no/low refractive error (ie, children who had a false-positive vision screening). The sample included 13 children in each group. The groups did not differ on sex or mean age. Children with moderate/high astigmatism had significantly poorer mean scores on the Cognitive and Language scales and the Receptive Communication Language subscale compared to children with no/low refractive error. Children with moderate/high astigmatism had poorer mean scores on the Motor scale, Fine and Gross Motor subscales, and the Expressive Communication subscale, but these differences were not statistically significant. The results suggest that uncorrected astigmatism in toddlers may be associated with poorer performance on cognitive and language tasks. Further studies assessing the effects of uncorrected refractive error on developmental task performance and of spectacle correction of refractive error in toddlers on developmental outcomes are needed to support the development of evidence-based spectacle prescribing guidelines.

Diagnostic accuracy of fourth-generation ARCHITECT HIV Ag/Ab Combo assay and utility of signal-to-cutoff ratio to predict false-positive HIV tests in pregnancy

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. 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. 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 amongwomen 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. 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). 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.

Does School Screening Affect Scoliosis Curve Magnitude at Presentation to a Pediatric Orthopedic Clinic?

BackgroundWith new data supporting the efficacy of bracing, the role of school screening for early detection of moderate scoliosis curves has been revisited. Because of a high rate of false-positive screening and cost concerns, a comprehensive county-wide school screening program was discontinued in 2004. We aim to determine the impact of a comprehensive school screening program on curve magnitude at presentation and initial scoliosis treatment for all local county patients presenting to a pediatric orthopedic clinic from all referral sources. MethodsBetween 1994 and 2014, a total of 761 county patients presented to a pediatric orthopedic clinic for new scoliosis evaluation. Curve magnitude and recommended treatment were recorded. Treatment indications for bracing, surgery, and observation were consistent over the study period. ResultsFrom January 1994 to July 2004 (school screening period), 514 children were seen by a pediatric orthopedic specialist for scoliosis evaluation compared to 247 patients from August 2004 to December 2014 (no school screening). There was a 48% decrease in the number of county children who were evaluated for idiopathic scoliosis by pediatric orthopedics once school screening was discontinued. Mean maximal Cobb angle at presentation increased from 20° (range, 4°–65°) to 23° (range, 7°–57°). At presentation, 5 of 514 (0.97%) patients in the screened group required surgery and 68 of 514 (13.2%) required bracing, compared to 3 of 247 (1.2%) patients in the nonscreened group requiring surgery and 47 of 247 (19%) requiring bracing (p>.05, p=.04, respectively). ConclusionAfter school screening was discontinued, mean curve magnitude and rates of bracing at presentation statistically increased in county patients evaluated for new scoliosis, although the clinical significance is unclear. After school screening was discontinued, there were fewer patient referrals, braces prescribed, and unnecessary evaluations (patients discharged at first visit). This study provides data to evaluate the role of school screening for children with regular access to health care. Level of EvidenceLevel 3.

Pulmonary nodules measurements in CT lung cancer screening.

To decrease the number of false-positive screen results without losing sensitivity for lung cancer diagnosis, accurate lung nodule management is crucial in low-dose CT lung cancer screening.

Factors associated with false positives in MDQ screening for bipolar disorder: Insight into the construct validity of the scale

BackgroundIdentifying bipolar patients in the first phases of the illness is essential to establish adequate treatment. The goal of this study was to examine the discriminant ability of the Mood Disorders Questionnaire (MDQ) in recognizing bipolar patients referred to a tertiary care structure. MethodsBetween 2006 and 2012, we assessed 843 individuals referred to the Mood Disorders Program by family physicians in the community. The Structured Clinical Interview for DSM-IV-TR (SCID) was used to assess diagnoses. A nurse collected the information about lifetime symptoms of (hypo)mania in 759 individuals using the MDQ. Univariate chi-square test and logistic regression were used for the statistical analysis. ResultsOverall, 86% of the sample had a current anxiety or depressive disorder. When compared to the diagnoses formulated through the SCID, the sensitivity of the MDQ was 75.0%, the specificity was 74%, the positive predictive value was 55%, and the negative predictive value was 88%. Among non-bipolar patients, current post-traumatic stress disorder, borderline personality disorder, current or early remission substance use disorder, and the history of childhood abuse were independently associated with false positive screening using the MDQ. LimitationsIndividuals with current substance use disorders were under-represented, whether or not the patients were aware of their diagnosis of bipolar disorder was not recorded, and the history of childhood abuse was collected based on an open interview. ConclusionsThe self-rated measure of the symptoms listed by the MDQ seems to measure a dimension shared by both bipolar disorder and other conditions characterized by affective instability and impulsivity.

Identifying Patients for Whom Lung Cancer Screening Is Preference-Sensitive: A Microsimulation Study.

Many health systems are exploring how to implement low-dose computed tomography (LDCT) screening programs that are effective and patient-centered. To examine factors that influence when LDCT screening is preference-sensitive. State-transition microsimulation model. Two large randomized trials, published decision analyses, and the SEER (Surveillance, Epidemiology, and End Results) cancer registry. U.S.-representative sample of simulated patients meeting current U.S. Preventive Services Task Force criteria for screening eligibility. Lifetime. Individual. LDCT screening annually for 3 years. Lifetime quality-adjusted life-year gains and reduction in lung cancer mortality. To examine the effect of preferences on net benefit, disutilities (the "degree of dislike") quantifying the burden of screening and follow-up were varied across a likely range. The effect of varying the rate of false-positive screening results and overdiagnosis associated with screening was also examined. Moderate differences in preferences about the downsides of LDCT screening influenced whether screening was appropriate for eligible persons with annual lung cancer risk less than 0.3% or life expectancy less than 10.5 years. For higher-risk eligible persons with longer life expectancy (roughly 50% of the study population), the benefits of LDCT screening overcame even highly negative views about screening and its downsides. Rates of false-positive findings and overdiagnosed lung cancer were not highly influential. The quantitative thresholds that were identified may vary depending on the structure of the microsimulation model. Identifying circumstances in which LDCT screening is more versus less preference-sensitive may help clinicians personalize their screening discussions, tailoring to both preferences and clinical benefit. None.

False-positive amphetamine results on several drug screening platforms due to mexiletine

ObjectiveFalse-positive urine drug of abuse screening (UDS) results can have serious implications in clinical practice, particularly when confirmation assay results are not immediately available to providers making medical decisions. Often it is not possible to identify the specific medication or other interfering compound that is responsible for the false-positive UDS result. Even when a potential interference is reported in the literature or package insert for one assay, the applicability to other UDS platforms/assays is often unknown. Mexiletine has been suggested as a cause of false-positive amphetamine results, but never confirmed as the causative agent in previous reports. The goal of this study was to confirm this drug as a cross-reacting compound in amphetamine screening tests. MethodsWe evaluated several amphetamine screening assays: the Syva EMIT II Plus and the Roche KIMS automated immunoassays, along with the Noble Split-Specimen and Synchron QuikScreen point-of-care assays. ResultsUrine samples from two patients treated with mexiletine were positive on all amphetamine screens but confirmed negative by mass spectrometry. Drug-free urine spiked with mexiletine caused positive results on all assays, although the EMIT II Plus and KIMS assays cross-reacted at lower mexiletine concentrations than the point-of-care assays. ConclusionThis report confirms that mexiletine can cross-react on several amphetamine screening assays. Assay manufacturers are encouraged to evaluate mexiletine cross-reactivity, and providers and laboratories should be aware of the potential for false-positive amphetamine screening results in patients taking mexiletine.

Implications of false-positive results for future cancer screenings.

False-positive cancer screening results may affect a patient's willingness to obtain future screening. The authors conducted logistic regression analysis of 450,484 person-years of electronic medical records (2006-2015) in 92,405 individuals aged 50 to 75 years. Exposures were false-positive breast, prostate, or colorectal cancer screening test results (repeat breast imaging or negative breast biopsy ≤3 months after screening mammography, repeat prostate-specific antigen [PSA] test ≤3 months after PSA test result ≥4.0 ng/mL or negative prostate biopsy ≤3 months after any PSA result, or negative colonoscopy [without biopsy/polypectomy] ≤6 months after a positive fecal occult blood test). Outcomes were up-to-date status with breast or colorectal cancer screening. Covariates included prior screening history, clinical information (eg, family history, obesity, and smoking status), comorbidity, and demographics. Women were more likely to be up to date with breast cancer screening if they previously had false-positive mammography findings (adjusted odds ratio [AOR], 1.43 [95% confidence interval, 1.34-1.51] without breast biopsy and AOR, 2.02 [95% confidence interval, 1.56-2.62] with breast biopsy; both P<.001). The same women were more likely to be up to date with colorectal cancer screening (AOR range, 1.25-1.47 depending on breast biopsy; both P<.001). Men who previously had false-positive PSA testing were more likely to be up to date with colorectal cancer screening (AOR, 1.22 [P = .039] without prostate imaging/biopsy and AOR, 1.60 [P = .028] with imaging/biopsy). Results were stronger for individuals with more false-positive results (all P≤.005). However, women with previous false-positive colorectal cancer fecal occult blood test screening results were found to be less likely to be up to date with breast cancer screening (AOR, 0.73; P<.001). Patients who previously had a false-positive breast or prostate cancer screening test were more likely to engage in future screening. Cancer 2018;124:2390-8. © 2018 American Cancer Society.

Factors associated with a second deferral among donors eligible for re‐entry after a false‐positive screening test for syphilis, HCV, HBV and HIV

Since 25 May 2010, all donors at our blood centre who tested false-positive for HIV, HBV, HCV or syphilis are eligible for re-entry after further testing. Donors who have a second false-positive screening test, either during qualification for or after re-entry, are deferred for life. This study reports on factors associated with the occurrence of such deferrals. Rates of second false-positive results were compared by year of deferral, transmissible disease marker, gender, age, donor status (new or repeat) and testing platform (same or different) both at qualification for re-entry and afterwards. Chi-square tests were used to compare proportions. Cox regression was used for multivariate analyses. Participation rates in the re-entry programme were 42·1%: 25·6% failed to qualify for re-entry [different platform: 2·7%; same platform: 42·9% (P < 0·0001)]. After re-entry, rates of deferral for second false-positive results were 8·4% after 3 years [different platform: 1·8%; same platform: 21·4% (P < 0·0001)]. Deferral rates were higher for HIV and HCV than for HBV at qualification when tested on the same platform. The risk, when analysed by multivariate analyses, of a second deferral for a false-positive result, both at qualification and 3 years after re-entry, was lower for donors deferred on a different platform; this risk was higher for HIV, HCV and syphilis than for HBV and for new donors if tested on the same platform. Re-entry is more often successful when donors are tested on a testing platform different from the one on which they obtained their first false-positive result.

Aspartyl (Asparaginyl) ß hydroxylase (AABH) as a serum bio-marker for prostate cancer to identify prostate cancer, regardless of PSA level.

10 Background: Background: Prostate Specific Antigen (PSA) is a molecular marker of prostate cancer (PC). I most countries, standard of care suggests annual PSA testing in all men over 50 years of age; and for men at high risk, the test is recommended from 40 years of age. Due to low Specificity and low sensitivity of the PSA test, a large number of unnecessary biopsies occur every year. This low specificity can be due to the fact that PSA is found in both benign and malignant lesions of Prostate tissue. To date measurement of the percentage of free PSA, have resulted an small improvements in specificity of PSA testing. Thus, the development of a simple blood test to detect prostate cancer that exhibits higher specificity compared to PSA could have the potential of reducing biopsies performed due to false positive screening results and improve the quality of medical care. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a prostate cancer biomarker. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including Prostate Adenocarcinoma through out the world. AABH have been detected by IHC in more than 97% of tumor specimens tested (n &gt; 200) while absent in normal and non cancer tissue. We have developed a sandwich ELISA test for the detection of AABH in serum samples. Preliminary results showed an accuracy of 91- 94% for detecting cancer patients from non-cancer patients in different types of Cancer. Here we have utilized this assay to detect AABH levels in the sera of patients diagnosed with Prostate cancer (biopsy proven, pre-treatment samples), compared to non-cancer individuals. Results: AABH was detected above a threshold level of 1.2 ng/mL in 91% of the sera of PC patients (n = 60), in all different stages and grades of Prostate Cancer. All non-cancer individuals (n = 30) had AABH values below the threshold. Further study of direct comparison of AABH to PSA levels (n = 4,000) is underway. Conclusions: Our data suggest that measurement of serum AABH levels may help to detect Prostate Cancer in early stage and potentially reduce the number of prostate biopsies performed due to increased high serum PSA.

Abstract PD2-16: Risk of breast cancer after a false-positive screening mammogram in relation to mammographic abnormality: A population-based study in British Columbia

Abstract Background Breast cancer screening by mammography has been shown to reduce breast cancer mortality, however false positive recall rates have consistently been identified as a harm of organized screening. The extent to which these recalled women are at increased risk of future breast cancer remains unclear. Methods The British Columbia Cancer Agency Screening Mammography Program (SMP), the first organized breast screening program in Canada offers screening mammography for women aged 40-74 since 1988. All women who had two or more screening mammograms between1988-2013 within the SMP were included in the study. They were followed until a breast cancer diagnosis, last screen date +5 years, or end of follow-up on Dec 31, 2013, whichever came first. The relative risk (RR) of breast cancer for women with a false-positive test compared with women with negative tests was estimated with Poisson regression, adjusted for age, and five calendar periods. Results A total of 772,289 women with 4.82 million screening mammograms and a median follow up of 11.8 years were included. There were 238,860 women with false positive findings and 26,950 cancers of which 16,084 screen detected and 10,866 non screen detected. Women without any false positive mammogram had a cancer incidence rate of 245/100 000 person-years at risk, whereas women with a false-positive test had an absolute rate of 447/100 000 person-years at risk. The adjusted RR [Value (95% CI)] of breast cancer after the first false-positive test was 1.73(1.68-1.77) for all, 1.65(1.61-1.70) for invasive, and 2.13(2.01-2.27) for in situ cancers respectively. The RR remained increased beyond 8 years after the false-positive test. Of the 5157 screen detected cancers after the first false positive test, 3358 (65%) were on the ipsilateral breast while 1799 (35%) were on the contralateral breast. Women with only one, two, three or four+ false positive test(s) had RR of 1.88(1.83-1.93), 1.42(1.35-1.49), 1.17(1.05-1.30), and 1.08(0.87-1.34) respectively for all cancers. Women with breast density &amp;gt;50% at the time of false positive test had a twofold risk of breast cancer with a RR of 2.07(1.99-2.14), while those with breast density &amp;lt;50% had a RR of 1.58(1.54-1.63). When stratified for mammographic features found on the first false positive mammogram, architectural distortion plus mass had the highest RR 4.68(3.16-6.93) for invasive cancers while calcifications alone and calcifications plus asymmetry had highest RR 5.57(4.88-6.36) and 4.07(2.49-6.66) for in situ cancers. Conclusion False positive mammogram correlates with an increased risk of developing breast cancer. 65% of the screen detected breast cancers post false positive mammogram occur in the ipsilateral breast. Mammographic abnormality features of the false positive mammogram are found to be predictors for the type of future breast cancer. Mammographic features at the time of recall predicts risk of subsequent cancer and may warrant increased surveillance. Citation Format: Rajapakshe R, Miao H, Sam J, Farnquist B, Hartman M. Risk of breast cancer after a false-positive screening mammogram in relation to mammographic abnormality: A population-based study in British Columbia [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-16.

Raising Awareness of False Positive Newborn Screening Results Arising from Pivalate-Containing Creams and Antibiotics in Europe When Screening for Isovaleric Acidaemia.

While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.

A Single, Post-ACTH Cortisol Measurement to Screen for Adrenal Insufficiency in the Hospitalized Patient.

Cosyntropin stimulation testing (CST) is used to screen patients for adrenal insufficiency (AI). Traditionally, CST includes baseline cortisol concentration, the administration of cosyntropin, and cortisol concentration at 30 and 60 minutes poststimulation. There is debate surrounding the utility of testing and cut-off points for concentrations at each time point. To determine if a single cortisol measurement at 30 or 60 minutes could replace the traditional approach. looked retrospectively at inpatients who underwent standard, high-dose CST (n = 702) and evaluated the number of patients who would screen positive for AI by using a single time point (30 or 60 minutes) compared with the traditional CST. A tertiary-care, academic medical center. Hospital inpatients present between January 2012 and September 2013. Of tests, 84.3% were normal, which was defined as at least 1 cortisol concentration of 18 mcg/dL or higher at any time after stimulation. The average 60-minute concentration was higher than the average 30-minute concentration (P < .001). A single 60-minute concentration is 100% concordant with the full CST in the intensive care unit (ICU) subgroup and 99.6% concordant in floor patients. A single 30-minute concentration is significantly less concordant, 91.9% and 86.9%, in the ICU and floor subgroups, respectively. Overall, a single 60-minute cortisol concentration to screen for AI was 99.7% concordant with the traditional CST, and the positive percent agreement was 98%. Fewer false-positive screens would occur with a single 60-minute cortisol concentration compared with a single 30-minute concentration (P < .001). High-dose CST screening may safely be interpreted with single 60-minute poststimulation cortisol serum concentrations.

A novel method for quantitation of acylglycines in human dried blood spots by UPLC-tandem mass spectrometry

BackgroundSeveral acylcarnitines used as primary markers on dried blood filter papers (DBS) for newborn screening lack specificity and contribute to a higher false positive rate. The analysis of urine acylglycines is useful in the diagnosis of inborn errors of metabolism (IEM) including medium chain acyl-CoA dehydrogenase deficiency (MCADD), isovaleric acidemia, and beta-ketothiolase deficiency (BKTD). Currently, no method for analyzing acylglycines from DBS has been published. MethodsAcylglycines were extracted from two 3.2 mm DBS punches and butylated using Butanol-HCl. Ultra Performance Liquid Chromatography (UPLC-MS/MS) with run time of 10 min permits resolution and quantitation of 15 acylglycines; including several isobaric. Method development was completed. Reference intervals (n = 573) were established for four birth weight groups. Furthermore, samples from patients with a confirmed IEM (n = 11), and false positive screens (n = 78) were analyzed to validate the interpretation obtained from the newly established reference intervals. ResultsCalibration curves were linear from 0.005 to 25.0 μM. Ion suppression was evaluated as minimal (2 to 10%). Samples from known patients were used to validate the reference intervals. For C5OH-related disorders, tiglylglycine (TG), TG/acetylglycine (AG) ratio, 3methylcrotonylglycine (3MCG) and 3MCG/AG ratio increased specificity. Propionylglycine (PG) and PG/acetylglycine ratio were two discriminatory markers in the investigation of C3-related disorders. Hexanoylglycine (HG), octanoylglycine (OG), suberylglycine (SG), and the ratios HG/AG, OC/AG and SG/AG were excellent markers of MCADD deficiency. ConclusionThis method shows potential application as a second tier screen in order to reduce the false positive rate for a number of IEM targeted by newborn screening.

The impact of altitude on screening for critical congenital heart disease.

The objectives were to determine the frequency with which pulse oximetry identifies critical congenital heart defects in asymptomatic full-term and late preterm newborns using the AAP expert panel algorithm in a variety of different hospital settings and to evaluate the impact of altitude on the rate of positive screens. We conducted a prospective clinical study of implementation of a newborn pulse oximetry screening for congenital heart disease in 34 independent hospitals. Infants were eligible for enrollment if their gestational age was 35-44 weeks. Of the 34 sites which enrolled infants into our study, 24 were located at or below 2000 feet; 5 were located between 4700 and 6000 feet and 5 were located above 6000 feet in altitude. We screened 6109 infants; 65 (1.1%) had a positive screen. There were no differences in median gestational age, birth weight, mode of delivery or race/ethnicity for infants with a positive screen compared to infants with a negative screen. Infants with positive screens were more often male and more often born at sites located at high altitudes. The frequency of a positive screen increased from 0.2% for infants born at sites at or less than 2000 feet to 6% for sites located above 6000 feet. We stopped enrollment at the site located at 8163 feet after enrolling 65 infants because 23 (35%) were positive. Screening infants for critical cardiac defects at altitude is complicated by the increased false positive screens.