False-positive Screening Research Articles

Risks of requiring a dedicated molecular specimen for HIV diagnosis and a potential strategy for mitigation.

BackgroundHIV screening (i.e. antigen/antibody) tests are followed by a supplemental (i.e. antibody-only) if the screen is positive. Discrepant results can result from two scenarios: a false-positive screening test or acute HIV infection. These scenarios can be distinguished by a molecular HIV test, but due to contamination concerns, our laboratory recently implemented a policy requiring a second specimen dedicated for molecular HIV testing. Our objective was to (1) characterize the effect of this policy on the time-to-diagnosis for patients with discrepant screening and supplemental test results, and (2) explore “strength of positivity” as an interim predictor of screening test accuracy while awaiting confirmatory test results.MethodsData from our laboratory information system, electronic health record, and instrument logs were used to collate data for all HIV testing performed at Barnes-Jewish Hospital (BJH) between January 1, 2014 and October 18, 2017.ResultsRequiring a dedicated specimen for molecular testing significantly increased the time-to-diagnosis for patients with discrepant screening and supplemental HIV tests (p = 0.0084). This policy also contributed to loss-to-followup, with 0/35 discrepant cases lost-to-followup prior to policy implementation compared to 2/10 after implementation. However, by optimizing the signal-to-cutoff (S/CO) ratio of the screening test, we were able to more accurately distinguish false-positives from acute-HIV prior to molecular testing (sensitivity of 100%, specificity of 89%).ConclusionsWe propose utilizing quantitative fourth-generation assay results (S/CO) ratios as a predictor of infection true positivity in situations where the screening assay is reactive but the supplemental test is negative and confirmatory molecular results are not immediately available.

Effect of newborn screening for critical CHD on healthcare utilisation.

To evaluate the impact of state-mandated policies for pulse oximetry screening on healthcare utilisation, with a focus on use of echocardiograms. Healthcare Cost and Utilisation Project, Statewide Inpatient Databases from 2008 to 2014 from six states. We defined pre- and post-mandate cohorts based on dates when pulse oximetry became mandated in each state. Linear segmented regression models for interrupted time series assessed associations between implementation of the screening and changes in rate of newborns with Critical CHD-negative echocardiogram results. We also evaluated the changes in rate of newborns who underwent echocardiogram but were not diagnosed with any health issues that could cause hypoxemia. We identified 5967 critical CHD-negative echocardiograms (2847 and 3120 in the pre- and post-mandate periods, respectively). Our models detected a statistically significant increasing trend in rate of critical CHD-negative echocardiograms in the pre-mandate period (Incidence Rate Ratio: 1.08, p = 0.02), but did not detect any statistical differences in changes between pre- and post-mandate periods (Incidence Rate Ratio: 0.93, p = 0.14). Among non-Whites, an increasing trend of Critical CHD-negative echocardiogram during the pre-mandate period was detected (Incidence Rate Ratio 1.12, p < 0.01) and was attenuated during the post-mandate period (Incidence Rate Ratio 0.89, p = 0.02). Similar results were observed in the sensitivity analyses among both Whites and non-Whites. Results suggest that mandatory state screening policies are associated with reductions in false-positive screening rates for hypoxemic conditions, with reductions primarily attributed to trends among non-Whites.

Breast cancer survivors' risk of interval cancers and false positive results in organized mammography screening.

BackgroundBreast cancer survivors are increasing followed for new breast cancers / recurrences by mammography screening only. We aimed at assessing how often breast cancer survivors get a false positive or false negative result at mammography screening.MethodsAll mammography screenings performed between 2007 and 2017 in the Danish national mammography screening programme were included. Screenings in women with a breast cancer diagnosis prior to invitation were included in the “breast cancer survivors” group, while remaining screenings were included in the “no previous breast cancer” group. We compared the proportion of false positive screenings and the proportion of breast cancers detected at screening among breast cancer survivors and women without previous breast cancer. The analyses were further stratified according to whether the women had a diagnostic breast imaging in the 21 months prior to the screening.ResultsAt initial screenings, breast cancer survivors had a significant lower false positive risk than other women, while the risk was similar at subsequent screenings. Breast cancer survivors had a significant lower proportion of breast cancers detected at screening compared to other women. This was true both for women who had a diagnostic breast imaging in the 21 months prior to screening and those who did not.ConclusionThis study shows that breast cancers survivors have a smaller amount of their new breast cancers detected at mammography screening, when compare to the amount of new breast cancers detected at mammography screening among women without previous breast cancer. The lower sensitivity does not seem to be due to different behavior among breast cancer survivors.

Lung Cancer Screening with Low-Dose CT: a Meta-Analysis.

Randomized controlled trials have evaluated the efficacy of low-dose CT (LDCT) lung cancer screening on lung cancer (LC) outcomes. Meta-analyze LDCT lung cancer screening trials. We identified studies by searching PubMed, Google Scholar, the Cochrane Registry, ClinicalTrials.gov , and reference lists from retrieved publications. We abstracted data on study design features, stage I LC diagnoses, LC and overall mortality, false positive results, harm from invasive diagnostic procedures, overdiagnosis, and significant incidental findings. We assessed study quality using the Cochrane risk-of-bias tool. We used random-effects models to calculate relative risks and assessed effect modulators with subgroup analyses and meta-regression. We identified 9 studies that enrolled 96,559 subjects. The risk of bias across studies was judged to be low. Overall, LDCT screening significantly increased the detection of stage I LC, RR = 2.93 (95% CI, 2.16-3.98), I2 = 19%, and reduced LC mortality, RR = 0.84 (95% CI, 0.75-0.93), I2 = 0%. The number needed to screen to prevent an LC death was 265. Women had a lower risk of LC death (RR = 0.69, 95% CI, 0.40-1.21) than men (RR = 0.86, 95% CI, 0.66-1.13), p value for interaction = 0.11. LDCT screening did not reduce overall mortality, RR = 0.96 (95% CI, 0.91-1.01), I2 = 0%. The pooled false positive rate was 8% (95% CI, 4-18); subjects with false positive results had < 1 in 1000 risk of major complications following invasive diagnostic procedures. The most valid estimates for overdiagnosis and significant incidental findings were 8.9% and 7.5%, respectively. LDCT screening significantly reduced LC mortality, though not overall mortality, with women appearing to benefit more than men. The estimated risks for false positive results, screening complications, overdiagnosis, and incidental findings were low. Long-term survival data were available only for North American and European studies limiting generalizability.

False-positive reverse transcriptase polymerase chain reaction screening for SARS-CoV-2 in the setting of urgent head and neck surgery and otolaryngologic emergencies during the pandemic: Clinical implications.

BackgroundNo reports describe falsepositive reverse transcriptase polymerase chain reaction (RT‐PCR) for novel coronavirus in preoperative screening.MethodsPreoperative patients had one or two nasopharyngeal swabs, depending on low or high risk of viral transmission. Positive tests were repeated.ResultsForty‐three of 52 patients required two or more preoperative tests. Four (9.3%) had discrepant results (positive/negative). One of these left the coronavirus disease (COVID) unit against medical advice despite an orbital abscess, with unknown true disease status. The remaining 3 of 42 (7.1%) had negative repeat RT‐PCR. Although ultimately considered falsepositives, one was sent to a COVID unit postoperatively and two had urgent surgery delayed. Assuming negative repeat RT‐PCR, clear chest imaging, and lack of subsequent symptoms represent the “gold standard,” RT‐PCR specificity was 0.97.ConclusionsIf false positives are suspected, we recommend computed tomography (CT) of the chest and repeat RT‐PCR. Validated serum immunoglobulin testing may ultimately prove useful.

Oxygen saturation and perfusion index screening in neonates at high altitudes: can PDA be predicted?

Screening critical congenital heart disease in neonates with 24-48 h of age could be made by oxygen saturation determination. Perfusion index may be used as an adjunct to pulse oximetry screening to detect non-cyanotic critical congenital heart disease cases such as a left heart outflow obstruction. We evaluate the results of combined screening for oxygen saturation and peripheral perfusion index at high altitudes. The study included 501 neonates older than gestational week 35. The mean oxygen saturation was lower than at sea level, and the screening test was positive in a total of 21 (4.2%) babies. Critical congenital heart diseases were not detected in any patient. A total of 10 (2%) babies were detected with PDA, nine (1.8%) of whom recorded a positive screening test. The prevalence of PDA was significantly higher in the positive screening test group when compared with those who underwent echocardiography due to clinical findings.Conclusion: The median peripheral perfusion index at high altitude was not lower than at sea level, while the mean oxygen saturation, in contrast, was lower than at sea level. The low partial oxygen pressure found at high altitudes leads to a variation in postnatal adaptation and an increased prevalence of PDA. Accordingly, oxygen saturation screening may serve to identify babies with PDA at high altitudes. What is Known: • Oxygen saturation is known to be low at high altitudes, and thus the rates of false positivity are high when screening for critical congenital heart disease. • High altitudes are also associated with an increased prevalence of simple congenital heart disease. What is New: • The peripheral perfusion index at high altitude is not lower than at sea level. • The prevalence of PDA is significantly higher in those with false positive screening results.

Image processing and machine learning techniques used in computer-aided detection system for mammogram screening - a review

This paper aims to review the previously developed Computer-aided detection (CAD) systems for mammogram screening because increasing death rate in women due to breast cancer is a global medical issue and it can be controlled only by early detection with regular screening. Till now mammography is the widely used breast imaging modality. CAD systems have been adopted by the radiologists to increase the accuracy of the breast cancer diagnosis by avoiding human errors and experience related issues. This study reveals that in spite of the higher accuracy obtained by the earlier proposed CAD systems for breast cancer diagnosis, they are not fully automated. Moreover, the false-positive mammogram screening cases are high in number and over-diagnosis of breast cancer exposes a patient towards harmful overtreatment for which a huge amount of money is being wasted. In addition, it is also reported that the mammogram screening result with and without CAD systems does not have noticeable difference, whereas the undetected cancer cases by CAD system are increasing. Thus, future research is required to improve the performance of CAD system for mammogram screening and make it completely automated.

Psychosocial consequences of false positives in the Danish Lung Cancer CT Screening Trial: a nested matched cohort study

ObjectivesLung cancer CT screening can reduce lung cancer mortality, but high false-positive rates may cause adverse psychosocial consequences. The aim was to analyse the psychosocial consequences of false-positive lung cancer...

SUN-524 Patient with Pseudohypoparathyroidism Type 1B, Graves Disease, and False Positive HIV Screen- a Rare Presentation

Background: Pseudohypoparathyroidism 1B (PHP1B) is a disorder that can lead to thyroid stimulating hormone (TSH) resistance and hypothyroidism, although it is rarely associated with thyrotoxicosis.Clinical Case: A 25-year-old female with a history of PHP1B, seizures due to hypocalcemia, and family history of PHP1B in her three sisters and brother presented to our emergency room with a fever of 1030F and generalized malaise. Two months prior, she was seen at an outside hospital with palpitations and bulging of the left eye. There, she was diagnosed with hyperthyroidism, started on methimazole, and asked to continue levetiracetam and calcitriol upon discharge.On our exam, she had tachycardia of 120 beats per minute, left eye proptosis, positive Chvostek sign, and a large goiter with bruit. Reflexes were 3+.Laboratory evaluation revealed corrected serum calcium of 6.1 (8.5-10.5 mg/dL), TSH < 0.01 (0.34-5.60 mU/L), free T4 2.81 (0.60-1.60 ng/dL), free T3 13.0 (2.4-4.2 ng/dL), and iPTH 131 (12-88 pg/mL). ELISA testing for screening of HIV was positive. She was treated with IV calcium gluconate, methimazole, propranolol, and hydrocortisone. Her home doses of calcitriol and calcium were resumed. She was referred for total thyroidectomy as an outpatient once she became euthyroid. The confirmatory Western blot test for HIV was negative. It was determined that presence of thyroid stimulating immunoglobulin resulted in the false positive ELISA test.Discussion: Hyperthyroidism with Graves disease seen in PHP has only very rarely been reported. (1) It has been postulated that abnormal electrolytes and elevated parathyroid hormone from PHP may lead to stimulation of the thyroid gland and perpetuate Graves disease symptoms. (2) Furthermore, the presentation of thyrotoxicosis despite TSH resistance in PHP indicates that there may be other mechanisms for TSH receptor antibodies to take effect in these patients which have not yet been determined. (3) Lastly, autoimmune diseases, including Graves disease, can cause a false-positive HIV ELISA as seen in our patient.Conclusion: Although rare, thyrotoxicosis may present in patients with PHP1B. Additionally, it should be kept in mind that autoimmune diseases such as Graves disease can cause a false positive HIV ELISA, and follow-up Western blot testing should therefore be performed.

SAT-561 Effects of Mineralocorticoid Receptor Antagonists on Primary Aldosteronism Screening

Background: Mineralocorticoid receptor antagonists (MRAs) are the mainstay of medical therapy for primary aldosteronism (PA), and MRAs also benefit patients with other forms of resistant hypertension and cardiovascular disorders. MRAs impact the renin-angiotensin-aldosterone system (RAAS), raising concerns regarding the accuracy of PA screening. The rate of false negative and/or false positive screening for PA in patients taking MRAs has not been systematically evaluated. Herein, we assessed the alterations of both renin and aldosterone after MRA initiation in a large cohort of patients with hypertension. Patients and Methods: We conducted a retrospective cohort study of patients with hypertension seen in a tertiary referral center. We employed our center’s database search engine to identify adults with hypertension who were treated with MRAs. Of these, we included patients who had renin and aldosterone measured both before and after MRA treatment. We excluded patients with adrenal cortical cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. PA screening was considered positive when plasma aldosterone concentration (PAC) was 10 ng/dL, plasma renin activity (PRA) was 1.0 ng/mL/h, and the aldosterone-to renin ratio (ARR) was 20. Mann-Whitney test and Wilcoxon signed rank test were employed to compare independent or paired groups, respectively. Results: In total, 109 patients (57 women), mean age 55+/-13 years were included. Of these, 40% had confirmed PA (14% unilateral and 26% bilateral); in 38% PA was excluded; and in the remaining 22%, testing for PA was incomplete. On average, patients were on 3 +/- 1.6 antihypertensive agents; 60% of patients were prescribed beta blockers, 49% K+-wasting diuretics and 35% were on K+ supplements. Both PAC and PRA increased after MRA treatment (from 19.0 [12.6, 26.7] to 26.3 [17.2, 36.2]; and from 0.6 [0.10, 0.80] to 1.00 [0.60, 2.80], respectively, p < 0.0001 for both), while ARR decreased from 42.5 [18.5, 109.8] to 24.0 [10.9, 55.5] (p = 0.003). Of 71 patients with positive PA screening at baseline, 31 (43.7 %) no longer met positive screening criteria during MRA therapy. Conversely, 7 of 38 patients (18 %) with negative screening at baseline met criteria for positive PA screening while on MRA treatment, including 5 patients with a PAC > 20 ng/dL along with suppressed renin. The impact on PA screening accuracy remained similar irrespective of the MRA dose, duration of treatment, changes in concomitant antihypertensive drugs, or hypertension type. Conclusions: Commonly, MRA treatment leads to renin elevation, ARR reduction, and consequential false negative PA screening. In a minority of patients, MRA therapy can be followed by aldosterone elevations asynchronous from renin, possibly via short feedback loops, mimicking PA. Whenever possible, PA testing should be conducted after MRA discontinuation.

Abstracts of the 29th Annual Pediatric Pharmacy Association (PPA) Meeting April 29 to May 3, 2020

Abstracts of the 29th Annual Pediatric Pharmacy Association (PPA) Meeting April 29 to May 3, 2020

Ethnic variability in newborn metabolic screening markers associated with false-positive outcomes.

Newborn screening (NBS) programmes utilise information on a variety of clinical variables such as gestational age, sex, and birth weight to reduce false‐positive screens for inborn metabolic disorders. Here we study the influence of ethnicity on metabolic marker levels in a diverse newborn population. NBS data from screen‐negative singleton babies (n = 100 000) were analysed, which included blood metabolic markers measured by tandem mass spectrometry and ethnicity status reported by the parents. Metabolic marker levels were compared between major ethnic groups (Asian, Black, Hispanic, White) using effect size analysis, which controlled for group size differences and influence from clinical variables. Marker level differences found between ethnic groups were correlated to NBS data from 2532 false‐positive cases for four metabolic diseases: glutaric acidemia type 1 (GA‐1), methylmalonic acidemia (MMA), ornithine transcarbamylase deficiency (OTCD), and very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD). In the result, 79% of the metabolic markers (34 of 43) had ethnicity‐related differences. Compared to the other groups, Black infants had elevated GA‐1 markers (C5DC, Cohen's d = .37, P < .001), Hispanics had elevated MMA markers (C3, Cohen's d = .13, P < .001, and C3/C2, Cohen's d = .27, P < .001); and Whites had elevated VLCADD markers (C14, Cohen's d = .28, P < .001, and C14:1, Cohen's d = .22, P < .001) and decreased OTCD markers (citrulline, Cohen's d = −.26, P < .001). These findings correlated with the higher false‐positive rates in Black infants for GA‐1, in Hispanics for MMA, and in Whites for OTCD and for VLCADD. Web‐based tools are available to analyse ethnicity‐related changes in newborn metabolism and to support developing methods to identify false‐positives in metabolic screening.

Syphilis screening in pregnant women: Discordant results require careful confirmation

In the past 15 years, many high volume clinical laboratories implemented reverse sequence syphilis screening. Reverse sequence screening uses an automated treponemal immunoassay as the initial screening step, instead of the traditional rapid plasma reagin. Reverse sequence screening is economical for high volume laboratories but has led to diagnostic difficulties when the testing algorithm yields discordant results, particularly for pregnant women. In this volume of The Journal, Williams et al evaluated 35 108 reverse sequence syphilis screening events among pregnant women in Ohio from 2011-2018. Overall, 127 women had discordant screening results, of which 85 (65%) were ultimately found to have a false positive treponemal immunoassay. These results suggest that for pregnant women in this cohort, discordant screening results were often secondary to false positive screening and were not indicative of syphilis infection. Interpretation of reverse sequence syphilis screening results is challenging in pregnant women, as the stakes are high for early diagnosis and treatment to prevent congenital syphilis. From 2013-2017, the CDC reported that the national rate of reported primary and secondary syphilis in women rose by 156%. In 2016, 628 cases of congenital syphilis were reported by CDC, with 41 cases of syphilis-related stillbirth. Congenital syphilis cases were concentrated in 9 regions across the US (Ohio was one of these areas), and the rise in syphilis in women has been linked to the amphetamine and opioid epidemics. Thus, the results reported by Williams et al require careful interpretation in the context of local epidemiology. Nevertheless, this study highlights the challenges of interpreting screening assays that may offer convenience over specificity and underscores the need to perform confirmatory testing for pregnant women with discordant syphilis screening results. Article page 263 ▸

Abstract OT3-03-01: Diagnostic value of Three-dimensional UltRasound in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result: The TURB0 study

Abstract Background: Three-dimensional automated whole-breast ultrasound (3D ABUS) is an emerging imaging technique that enables the standardized acquisition of volumetric images of the whole breast. Although more data become available on the added value of 3D ABUS both in the screening and diagnostic setting, to date this technique is not widely used in the Netherlands. In the Netherlands, women between the ages of 50 and 75 years are invited for breast cancer screening every two years using full-field digital mammography. Approximately 2.4% of screening participants is recalled and referred to a hospital for diagnostic work-up of inconclusive (BI-RADS 0) or suspicious findings (BI-RADS 4/5). While over half of recalls from screening results from a BI-RADS 0 screening mammography, only 11% of these women has breast cancer. However, invasive diagnostic procedures are performed in every one in five women with a false-positive BI-RADS 0 recall. False-positive screening mammography results cause anxiety in the patient, especially when a biopsy is necessary. Furthermore, the diagnostic work-up after referral is costly and exerts pressure on health care facilities. 3D ABUS may be of added diagnostic value in women recalled from screening with a BI-RADS 0 mammography result. 3D ABUS may potentially lower the number of benign biopsies in the diagnostic setting and, in a future perspective, decrease the false-positive recall rate when used as an adjunct screening tool in women with a BI-RADS 0 screening mammography result. Therefore, we aim to investigate the diagnostic accuracy and added value of 3D ABUS in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result. Trial design: Observational multicenter prospective cohort study. The study was approved by the Medical Research Ethical Committee of the University Medical Center Utrecht. Written informed consent is obtained from all participants. In addition to screening mammography, tomosynthesis and hand-held ultrasound, bilateral, supine 3D ABUS imaging is obtained. Different imaging strategies are compared to determine the optimal combination of imaging modalities and the added value of 3D ABUS. Eligibility criteria: Women recalled from Dutch breast cancer screening with a BI-RADS 0 screening mammography result and able to give informed consent are considered eligible. Aim: To investigate the diagnostic accuracy and added value of 3D ABUS in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result. Statistical methods: Sensitivity, specificity, negative predictive value and positive predictive value of 3D ABUS will be calculated with 95% confidence intervals, using histopathology (if available) or follow up to the next screening round approximately two years later as the reference standard. The diagnostic accuracy of different imaging strategies in the diagnostic work-up will be compared with pairwise McNemar tests and area under the receiver operating characteristic curve analyses. A p-value &amp;lt;0.05 will be considered statistically significant. Screening mammography will be assessed in combination with 3D ABUS imaging to calculate the number of false-positive BI-RADS 0 recalls that 3D ABUS may prevent. Subgroup analysis will be performed based on four breast density categories, measured with automated breast density software, to evaluate the added value of 3D ABUS specifically in women with dense breasts. Present accrual: 360 (April 2018 - June 2019). Target accrual: 600 (expected in April 2020) Acknowledgements: The TURB0 study is funded by General Electric. Hologic provided the breast density assessment software for the purpose of this study. Contact information: B.M.denDekker-3@umcutrecht.nl Citation Format: Bianca M den Dekker, Mireille JM Broeders, Helena M Verkooijen, Alexander Venmans, Carla Meeuwis, Wikke Setz-Pels, Ruud M Pijnappel. Diagnostic value of Three-dimensional UltRasound in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result: The TURB0 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-03-01.

Breast cancer risk, worry, and anxiety: Effect on patient perceptions of false-positive screening results

ObjectiveThe impact of mammography screening recall on quality-of-life (QOL) has been studied in women at average risk for breast cancer, but it is unknown whether these effects differ by breast cancer risk level. We used a vignette-based survey to evaluate how women across the spectrum of breast cancer risk perceive the experience of screening recall. MethodsWomen participating in mammography or breast MRI screening were recruited to complete a vignette-based survey. Using a numerical rating scale (0–100), women rated QOL for hypothetical scenarios of screening recall, both before and after benign results were known. Lifetime breast cancer risk was calculated using Gail and BRCAPRO risk models. Risk perception, trait anxiety, and breast cancer worry were assessed using validated instruments. ResultsThe final study cohort included 162 women at low (n = 43, 26%), intermediate (n = 66, 41%), and high-risk (n = 53, 33%). Actual breast cancer risk was not a predictor of QOL for any of the presented scenarios. Across all risk levels, QOL ratings were significantly lower for the period during diagnostic uncertainty compared to after benign results were known (p < 0.05). In multivariable regression analyses, breast cancer worry was a significant predictor of decreased QoL for all screening scenarios while awaiting results, including scenarios with non-invasive imaging alone or with biopsy. High trait anxiety and family history predicted lower QOL scores after receipt of benign test results (p < 0.05). ConclusionsWomen with high trait anxiety and family history may particularly benefit from discussions about the risk of recall when choosing a screening regimen.

Measurement of 17-Hydroxyprogesterone by LCMSMS Improves Newborn Screening for CAH Due to 21-Hydroxylase Deficiency in New Zealand.

The positive predictive value of newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency was <2% in New Zealand. This is despite a bloodspot second-tier immunoassay method for 17-hydroxyprogesterone measurement with an additional solvent extract step to reduce the number of false positive screening tests. We developed a liquid chromatography tandem mass spectrometry (LCMSMS) method to measure 17-hydroxyprogesterone in bloodspots to replace our current second-tier immunoassay method. The method was assessed using reference material and residual samples with a positive newborn screening result. Correlation with the second-tier immunoassay was determined and the method was implemented. Newborn screening performance was assessed by comparing screening metrics 2 years before and 2 years after LCMSMS implementation. Screening data analysis demonstrated the number of false positive screening tests was reduced from 172 to 40 in the 2 years after LCMSMS implementation. The positive predictive value of screening significantly increased from 1.71% to 11.1% (X2 test, p < 0.0001). LCMSMS analysis of 17OHP as a second-tier test significantly improves screening specificity for CAH due to 21-hydroxylase deficiency in New Zealand.

False positive testing for sickle hemoglobin in a blood donor with mild erythrocytosis and hemoglobin Geldrop St. Anna

Solubility testing for sickle hemoglobin is commonly performed to identify blood suitable for patients with sickle cell disease. A 32-year-old Caucasian male blood donor’s unit screened positive for sickle hemoglobin via solublity testing (Streck). As the donor was considered low risk for being positive for hemoglobin S (HbS), he self-referred to hematology for further evaluation. Testing with hemoglobin electrophoresis revealed the patient to be negative for HbS; however, 42 % fetal hemoglobin (HbF) was noted. Since this was higher than typically seen in hereditary persistence of HbF, deoxyribonucleic acid (DNA) sequencing of hemoglobin (Hb) was ordered through a referral laboratory. Hb gene sequencing revealed the patient to be heterozygous for Hb Geldrop St. Anna, a rare Hb variant. This variant has previously been shown to migrate in the HbF region with alkaline electrophoresis. The workup demonstrated that the oxygen dissociation curve was left-shifted consistent with slightly increased oxygen affinity of this variant. The patient’s hematocrits (Hct) from his past donations were 53 % and 54 % about two years apart and his Hct at his hematology evaluation was 53 %. This report describes the first case of Hb Geldrop St. Anna in the United States and was associated with a false positive HbS screen. This Hb variant is considered to be benign and has an increased oxygen affinity that is associated with mild erythrocytosis. The donor was allowed to continue donating blood products.

Progestogen-only pill associates with false-positive aldosterone/renin ratio screening test.

Aldosterone/renin ratio (ARR) is commonly used to screen for primary hyperaldosteronism (Conn's disease). A number of drugs can alter ARR measurements, thus requiring omission before testing. However, hormonal agents such as the combined oral contraceptive (COCP) or progestogen-only pill (POP) are not listed for omission. A 20-year-old woman was referred to the endocrinology team, following investigations for syncope by her cardiologist, when ARR was found to be elevated. She was taking POP (Cerelle®) while having ARR measured. After omitting POP for four weeks, plasma aldosterone concentration was reduced by 52% (from 560 pmol/L to 271 pmol/L, reference range: 100-450 pmol/L), plasma renin concentration increased by 253% (from 3.6 mU/L to 12.7 mU/L, reference range: 5.4-30 mU/L) and ARR reduced from 156 to 21 (-86.5%) (reference range: <80 suggests Conn's unlikely). To the best of our knowledge, this is the first reported case of POP-related false-positive ARR screening for primary hyperaldosteronism. Omission of POP should, therefore, be considered in women undergoing ARR measurement.

Comparison of the accuracy of capillary hemoglobin estimation and venous hemoglobin estimation by two models of HemoCue against automated cell counter hemoglobin measurement.

BACKGROUND:HemoCue point of care devices has been extensively used in screening for anemia in blood banking. HemoCue can estimate hemoglobin (Hb) both from venous as well as capillary blood. However, the suitability of HemoCue Hb estimation in donor selection is unclear.AIMS:The aims of this study were to evaluate variance of difference in Hb measurement in capillary HemoCue estimation as compared to venous HemoCue estimation from automated cell counter and to assess accuracy of two different HemoCue models (201 and 301) against automated cell counter Hb measurements in both capillary as well as venous blood.MATERIALS AND METHODS:HemoCue 201 and 301 were evaluated by a comparison of methods study against Sysmex XP-100 three-part analyzer at a blood bank of a tertiary care hospital in Uttarakhand, India, in 2017. Assessment for anemia of 115 donors was done initially by capillary Hb by a convenience sampling to 2 instruments from 2 different models of HemoCue (total of 4 instruments). Venous blood collected was analyzed by Sysmex XP-100 and all HemoCue analyzers.RESULTS:For capillary method, bias ranged from −0.97 to −0.37 g/dL, upper limit of agreement (LOA) ranged from 0.72 to −1.06 g/dL, and lower LOA ranged from −2.65 to −1.79 g/dL. For venous method, bias ranged from −0.03 to −0.24 g/dL, the upper LOA ranged from 0.81 to −1.07 g/dL, and lower LOA ranged from −1.04 to −0.57 g/dL. Thus, capillary HemoCue estimation exhibited greater bias as well as wider LOA. Variance of the differences from automated counter was significantly lower for venous HemoCue comparison compared to capillary HemoCue estimation (P < 0.001 for each instrument).CONCLUSION:Errors in capillary sampling of blood show the extent to which preanalytical errors can influence results in point-of-care devices. We suggest augmentation of any blood bank-based Hb screening process based just on capillary sampling to be augmented by a properly selected venous sampling to reduce deferral for a false-positive screen of anemia.

Postulating a positive predictive value for HIV, HBV, and HCV screening tests using electrochemiluminescent assay by comparing with ID-NAT results

Background: In India, blood units reactive by the initial screening assays are discarded. A significant number of these are falsely positive, leading to wastage of precious blood. Also of importance is the dilemma created when it comes to donor disclosure. Hence, it is important to evaluate the positive predictive value (PPV) of the initial screening assay to identify false-positive screening results and implement a more balanced algorithm for donor disclosure and counseling. The study was undertaken with an objective of comparing signal-to-cutoff ratio (S/Co) of positive results in HBV, HCV, and HIV screening of electrochemiluminescent (ECI) assay with the results of ID-NAT so as to predict a S/Co ratio of indicative of true positives. Methods: The retrospective study was conducted in the transfusion-transmissible infection Laboratory in a Regional Blood Transfusion Centre in South India. Consecutive blood donors from January 2015 to December 2019 were evaluated simultaneously for HBV, HCV, and HIV by ECI (Vitros 3600, Ortho Clinical Diagnostics) and ID-NAT (Procleix Panther System by Grifols), and the positive results either by one or both were analyzed. Results: A total of 163,596 voluntary donor samples were evaluated. In case of HBV, a S/Co ratio of 1000 predicts a true positive more than 94% of the time. In case of HCV, a S/Co ratio of 8 predicts a true positive more than 95% of the time. Finally, a S/Co ratio of 30 predicts a true positive as well as true negative 100% of the time in case of HIV. Conclusions: It is challenging to propose a standard S/Co ratio because the performance of each assay varies across laboratories. However, the study throws light on the role of the S/Co ratio in reducing the perplexity during donor notification.