False-positive Screening Research Articles

Genetic cause and prevalence of hydroxyprolinemia.

Hydroxyprolinemia is an inborn error of amino acid degradation that is considered a non-disease. Known for more than 50years, its genetic cause and prevalence have remained unclear. In MS/MS newborn screening, the mass spectrum of hydroxyproline cannot be differentiated from isoleucine and leucine causing false positive newborn screening test results for maple syrup urine disease (MSUD). We studied two siblings with hydroxyprolinemia via exome sequencing and confirmed the candidate gene in five further individuals with hydroxyprolinemia, who were all characterized biochemically and clinically. The prevalence was calculated based on the number of individuals with hydroxyprolinemia detected via MS/MS newborn screening at our centre from 2003 to 2014. In six cases, we identified homozygous or compound heterozygous mutations in PRODH2 as the underlying genetic cause of hydroxyprolinemia. One individual was heterozygous for a deletion in PRODH2 and had an intermittent biochemical phenotype with partial normalization of hydroxyproline concentrations. In one further individual with persistent hydroxyprolinemia no mutation in PRODH2 was found, raising the possibility of another defect of hydroxyproline degradation yet to be identified as the underlying cause of hydroxyprolinemia. Plasma hydroxyproline concentrations were clearly elevated in all individuals with biallelic mutations in PRODH2. All studied individuals remained asymptomatic, giving further evidence that hydroxyprolinemia is a benign condition. The estimated prevalence of hydroxyprolinemia in Germany is about one in 47,300 newborns. Our results establish mutations in PRODH2 as a cause of human hydroxyprolinemia via impaired dehydrogenation of hydroxyproline to delta1-pyroline-3-hydroxy-5-carboxylic acid, and we suggest PRODH2 be renamed HYPDH. Hydroxyprolinemia is an autosomal-recessively inherited benign condition. It is a frequent cause of false positive screening results for MSUD, the prevalence being about 2.5 times higher than that of MSUD.

A false positive newborn screening result due to a complex allele carrying two frequent CF-causing variants

The detection of two frequent CFTR disease-causing variations in the context of a newborn screening program (NBS) usually leads to the diagnosis of cystic fibrosis (CF) and a relevant genetic counseling in the family. In the present study, CF-causing variants p.Phe508del (F508del) and c.3140-26A>G (3272-26A>G) were identified on a neonate with positive ImmunoReactive Trypsinogen test by the Elucigene™ CF30 kit. The CF diagnosis initially suggested, despite three inconclusive Sweat Chloride Tests (SCT), was finally ruled out after the familial segregation study combined with a negative SCT. Haplotype studies, based on the comparison of 80 p.Phe508del haplotypes, suggested a probable de novo occurrence of c.3140-26A>G on the p.Phe508del ancestral allele in this family.This false positive case emphasizes the importance of SCT in the NBS strategy. Moreover, it raises the need for familial segregation studies in CF and in overall molecular diagnosis strategy of autosomal recessive diseases.

Chorionic Villus Sampling, Early Amniocentesis, and Termination of Pregnancy Without Diagnostic Testing: Comparison of Fetal Risk Following Positive Non-invasive Prenatal Testing.

With the increased accuracy of non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) techniques, the likelihood of false-positive screening results has been reduced for high-risk populations. Following a positive screening test, a diagnostic procedure to confirm the result is strongly recommended, although some patients have terminated pregnancies because of a positive NIPT alone. Chorionic villus sampling (CVS), the diagnostic procedure of choice in the first trimester, is not available in all locations. Amniocentesis before 15 weeks, referred to as early amniocentesis (EA), is associated with a 1% rate of talipes and an increased rate of early pregnancy loss compared with CVS. Our objective was to compare the level of risk for euploid pregnancies following a positive NIPT based on the invasive procedure chosen. Using data from a 2003 meta-analysis, we estimated the rates of adverse pregnancy outcome in euploid pregnancies based on the positive predictive value (PPV) of NIPT and the invasive procedure used-that is, CVS, EA, or termination of pregnancy (TOP). Following NIPT, we found that the rate of adverse fetal outcomes in euploid pregnancies was lower for CVS than for EA at all PPV levels. As the PPV of NIPT increased, the difference in risk between EA and CVS decreased. The risk to euploid pregnancies of TOP was excessive at all PPVs. CVS is the recommended diagnostic test in the first trimester because it is safer than EA for the fetus. However, EA is better than no testing when early TOP is planned. Patients should be strongly counselled against TOP without confirmatory testing.

Is Pulse Oximetry Useful for Screening Neonates for Critical Congenital Heart Disease at High Altitudes?

Now that pulse oximetry is used widely to screen for critical congenital heart disease, it is time to consider whether this screening method is applicable to those who live at high altitudes. Consideration of basic physical principles and reports from the literature indicate that not only is the 95% cutoff point for arterial oxygen saturation incorrect at high altitudes, but the lower saturations are accompanied by greater variability and therefore there is the possibility of a greater percentage of false-positive screening tests at high altitudes. Because of ethnic differences in response to high altitudes, normative data will have to be collected separately in different countries and perhaps for different ethnic groups.

Screening for Bronchiogenic Carcinoma – Yes or No?

Lung cancer is among the most frequent cancers worldwide with a mean 5-year survival clearly below 20% and smoking being the leading risk factor. In the past, chest radiography and sputum have been investigated as screening tools, but negative results were obtained from randomized trials. In the following, randomized controlled trials were initiated with the „National Lung Screening Trial“ in the U.S. being the first to prove that CT screening is capable to reduce lung cancer mortality in heavy smokers by 20%. Since then, different medical societies in the US recommend annual CT screens for high risk individuals, and in 2015 the US officially introduced a lung cancer screening program with the costs covered. At the same time the discussion in Europe is highly controversial. It is obvious, that lung cancer screening can only be successful if experts from different disciplines collaborate in a comprehensive program with smoking cessation counselling and the complex processes clearly defined, certified and quality assured. This will be key to reduce false positive screen results, complications during further diagnostic work-up and radiation exposure. Also measures to increase pretest probability, e.g. by considering additional risk factors, have to be implemented in risk models in order determine the adequate intervals of CT screening as well as the relevance of the overdiagnosis bias. On top of this the scope of screening should be extended beyond the detection of nodules to a comprehensive risk assessment of smokers, including among others emphysema, airway disease, vascular disease. Cost-effectiveness has to be considered on a national level. Independent, central registration of screening data including image database and biobank, should help to assess and confirm the quality and positive effects of lung cancer screening.

Isolated HBsAg positivity in a Mexican patient with newly diagnosed lupus nephritis

IntroductionHepatitis B surface antigen (HBsAg) is usually regarded as a marker of hepatitis B virus (HBV) infection. The concurrence of lupus nephritis (LN) and HBsAg-positivity is a challenge for the clinician, since immunosuppressant use may be associated with an increase in viral replication and an exacerbation of liver disease. Case presentationHere, we describe the case of a 30-year-old Mexican woman with newly diagnosed focal proliferative LN who also tested repeatedly positive for HBsAg by chemiluminescent microparticle immunoassay (CMIA). She had no clinical features of hepatitis and her liver function tests were within normal limits. Her abdominal ultrasound was also normal. While waiting for further results, she was started on lamivudine (100mg daily). However, total HBV core antibody test was negative. Owing to the infrequency of this serological pattern, an in vitro polymerase chain reaction (PCR) assay was performed and HBV was not detected. Overall, we interpreted these results as a false-positive screening. Methylprednisolone pulse therapy was subsequently given (1g daily for three doses) without hepatic repercussion, neither clinically nor biochemically. ConclusionsIsolated HBsAg positivity may result from multiple causes, one of which is cross-reactivity. To the best of our knowledge, this is the first report of a false-positive reading using CMIA technique in an active lupus patient. It is reasonable to stress that lupus patients with a positive screening for HBV should undergo a confirmatory assay (such as genomic detection), since this diagnosis may have important therapeutic implications.

Efficacy of a Standardized Computer-Based Training Curriculum to Teach Echocardiographic Identification of Rheumatic Heart Disease to Nonexpert Users

The ability to integrate echocardiographic for rheumatic heart disease (RHD) into RHD prevention programs is limited because of lack of financial and expert human resources in endemic areas. Task shifting to nonexperts is promising; but investigations into workforce composition and training schemes are needed. The objective of this study was to test nonexperts' ability to interpret RHD screening echocardiograms after a brief, standardized, computer-based training course. Six nonexperts completed a 3-week curriculum on image interpretation. Participant performance was tested in a school-screening environment in comparison to the reference approach (cardiologists, standard portable echocardiography machines, and 2012 World Heart Federation criteria). All participants successfully completed the curriculum, and feedback was universally positive. Screening was performed in 1,381 children (5 to 18years, 60% female), with 397 (47 borderline RHD, 6 definite RHD, 336 normal, and 8 other) referred for handheld echo. Overall sensitivity of the simplified approach was 83% (95% CI 76% to 89%), with an overall specificity of 85% (95% CI 82% to 87%). The most common reasons for false-negative screens (n= 16) were missed mitral regurgitation (MR; 44%) and MR ≤1.5cm (29%). The most common reasons for false-positive screens (n= 179) included identification of erroneous color jets (25%), incorrect MR measurement (24%), and appropriate application of simplified guidelines (39.4%). In conclusion, a short, independent computer-based curriculum can be successfully used to train a heterogeneous group of nonexperts to interpret RHD screening echocardiograms. This approach helps address prohibitive financial and workforce barriers to widespread RHD screening.

Pulse oximetry screening and home birth

In the US, pulse oximetry screening for detection of critical congenital heart disease has become accepted as an important aspect of newborn screening. Systems to implement pulse oximetry screening are being developed and put in place across the country. In this issue of The Journal, Narayen et al evaluate an approach to pulse oximetry screening developed for the Netherlands, where home birth and very early discharge from the hospital after birth are much more common. To develop an appropriate system for home birth, the authors had to alter the timing of administration of pulse oximetry. They also had to train community midwives and provide each midwife with a handheld pulse oximeter. The results were encouraging in that such screening and follow-up appears feasible. Neonatal pathology other than critical congenital heart disease was detected and the number of false positive screens was low. However, it is important to emphasize that this approach only works with the development of a regional system to support it. These results would not support the use of pulse oximetry in individual home births without the appropriate healthcare system as supporting infrastructure.Article page 188▶ In the US, pulse oximetry screening for detection of critical congenital heart disease has become accepted as an important aspect of newborn screening. Systems to implement pulse oximetry screening are being developed and put in place across the country. In this issue of The Journal, Narayen et al evaluate an approach to pulse oximetry screening developed for the Netherlands, where home birth and very early discharge from the hospital after birth are much more common. To develop an appropriate system for home birth, the authors had to alter the timing of administration of pulse oximetry. They also had to train community midwives and provide each midwife with a handheld pulse oximeter. The results were encouraging in that such screening and follow-up appears feasible. Neonatal pathology other than critical congenital heart disease was detected and the number of false positive screens was low. However, it is important to emphasize that this approach only works with the development of a regional system to support it. These results would not support the use of pulse oximetry in individual home births without the appropriate healthcare system as supporting infrastructure. Article page 188▶ Pulse Oximetry Screening for Critical Congenital Heart Disease after Home Birth and Early DischargeThe Journal of PediatricsVol. 170PreviewTo assess the feasibility of pulse oximetry (PO) screening in settings with home births and very early discharge. We assessed this with an adapted protocol in The Netherlands. Full-Text PDF

Risk of Breast Cancer in Women with False-Positive Results according to Mammographic Features.

Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article.

Abstract P6-02-11: When needles are needed

Abstract Background Women with positive screening mammograms but negative at assessment (false-positive) are referred back to routine screening assuming that they have an average risk of breast cancer. However in a long-term follow-up of women with false-positive screening mammography we found that these women had in fact an excess risk of breast cancer later in life; RR=1.67(von Euler-Chelpin et al, JNCI 2012). This finding has later been supported by Castells et al.(Cancer Epidemiol, 2013). Furthermore, we studied the breast cancer cases in false-positive women and found that 26% of the cases were misclassified and were in fact true positives. However, even correction for misclassification, the false-positive women in our study remained at an excess breast cancer risk. At the same time, it was clear that, in the later periods of our study, when more modern techniques were used, the rate of misclassification decreased (von Euler-Chelpin et al, Cancer Epidemiol., 2014). Over time there have been changes both in the imaging and biopsy techniques. We used data from an organised screening programme in Denmark. Since its start in 1991, needle biopsies have been performed on all palpable solid lesions and on all uncertain, suspicious or malignant findings. In the very beginning fine needle aspiration cytology (FNAC) was used, later to be replaced by needle core biopsies in the majority of cases. Since 2002, suspicious micro-calcifications and impalpable mammographic findings not found by ultrasound have been examined using stereotactic needle core biopsy and later with vacuum-assisted breast biopsy as a replacement for surgical biopsy. To have a needle breast biopsy taken is a psychological burden on the woman. To minimize the harms and maximize the benefits is at the core of developing medical care. We therefore mapped the use of needle biopsies over time in a long-standing, organised screening programme. Method: We used data from the population-based screening mammography program in Copenhagen, Denmark. The programme has a database including personal records on demographic data, date of invitation, data of screening, and test results,1998-2013. Data from the Mammography Register were linked to the Danish Pathology Register (for biopsy procedures). Results: A total of 208 500 screens were included in the study. The rate of recall for assessment ranged between 1.7-3.2% of screened women with a mean of 2.4. The false-positive rate ranged between 1.0-2.5% with a mean of 1.6%. In 1998, 56% of all recalled women had a biopsy taken, which by 2013 had risen to 74% (using two-year smoothing). In proportion of all screens, the biopsy rate was 1.9% in 1998/99 which then fell to 0.7% in 2005/06 and the rose again 2.0% in 2012/13. In 1998, 59% of the biopsies were fine-needle aspiration cytology (FNAC) which by 2013 was only used in 11% of the cases, and replaced by core biopsies, ultrasound or stereotactic guided. Conclusion While the recall rate, as well as the false-positive rate, has been fairly stable during the study period the use of needle core biopsies has had a u-shaped development and has intensified in the later years. Citation Format: von Euler-Chelpin M, Vejborg I, Lænkholm A-V, Guleria S, Peterkin A, Lynge E. When needles are needed. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-02-11.

The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study.

BackgroundThere is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants.MethodsThe cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use.ResultsWe identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life.ConclusionsThe higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.

Pulse Oximetry Screening for Critical Congenital Heart Disease after Home Birth and Early Discharge

To assess the feasibility of pulse oximetry (PO) screening in settings with home births and very early discharge. We assessed this with an adapted protocol in The Netherlands. PO screening was performed in the Leiden region in hospitals and by community midwives. Measurements were taken ≥ 1 hour after birth and on day 2 or 3 during the midwife visit. Primary outcome was the percentage of screened infants with parental consent. The time point of screening, oxygen saturation, false positive (FP) screenings, critical congenital heart defects (CCHDs), and other detected pathology were registered. In a 1-year period, 3625 eligible infants were born. Parents of 491 infants were not approached for consent, and 44 refused the screening. PO screening was performed in 3059/3090 (99%) infants with obtained consent. Median (IQR) time points of the first and second screening were 1.8 (1.3-2.8) and 37 (27-47) hours after birth. In 394 infants with screening within 1 hour after birth, the median pre- and postductal oxygen saturations were 99% (98%-100%) and 99% (97%-100%). No CCHD was detected. The FP prevalence was 1.0% overall (0.6% in the first hours after birth). After referral, important noncritical cardiac and other noncardiac pathology was found in 62% of the FP screenings. PO screening for CCHD is feasible after home births and very early discharge from hospital. Important neonatal pathology was detected at an early stage, potentially increasing the safety of home births and early discharge policy.

Urine tests for Down's syndrome screening.

Urine tests for Down's syndrome screening.

A Comparative Study of Solubility Based Sickle Cell Screening Versus Genomic Method in Blood Donors

Background:Sickle cell trait (SCT) is more common in minority African-Americans (AA) and Hispanic blood donors. Screening donors for Sickle Hemoglobin (HbS) carrier status (SCT) can be useful, especially in managing the transfusion needs of neonates and patients with sickle cell disease. Currently, the Sickledex test, based on the principle of relative insolubility of HbS in phosphate buffers, is routinely used for HbS donor screening. However, there are several limitations including the inability to perform high-throughput testing by automation as donor centers target larger numbers of minority blood donors. False positives results due to hyperlipidemia, dysglobulinemia and higher peripheral blood hematologic counts have also been reported. Hence alternative methods to identify SCT donors are highly desirable in blood centers. The purpose of this study was to validate testing, and to identify rates of False Positive (FP) and False Negative (FN) sickledex screening in blood donors by verifying the presence or absence of the most common mutation seen with HbS production using molecular methods. The comparison could offer evidence to use molecular methods as a test of record to manage HbS carriers at blood centers.Methods and ResultsBetween Jan 2012 till Dec 2014, 200 sickledex screening tests were done daily, totaling approximately 90,000 donors self-identifying as Caucasians and 60,000 donors identifying as African American or Hispanic tested during the study period. Amongst Caucasians tested, 154 had a positive sickledex screen result. Since the prevalence of SCT is less common in the Caucasian population, we hypothesized several of these Caucasian donors could have a false positive screening test. All 154 sickledex positive Caucasian donor samples were prospectively tested for the HbS mutation detection with molecular methods. BioArray Human Erythrocyte Antigen (HEA) Bead Chip DNA assay with PCR multiplex based technology was used to detect the HbS mutation (β-globin change -173 A>T, more commonly designated 20A>T). Of the 154 sickledex + Caucasians, 108 (70%) donors tested negative (FP Screen) and 46 (30%) tested positive for the HbS mutation. A retrospective review of sickledex results in our electronic database for minority donors (n-3431) who also had HEA BeadChip assay was performed to determine concordance. Of 3431 minority donors tested, only 2 (0.0006%) had a positive sickledex screening and were negative by HEA, with the remaining negative by both the sickledex screen and HEA tests. Among minority donors (n= 254) testing + for HbS by HEA, 3% (8/254) were negative by sickledex screening. To establish concordance of HEA assay with high performance liquid chromatographic (HPLC) assay, two separate cohorts were evaluated. Initially 12 sickle screen and HEA positive donors was subject to HPLC analysis, which confirmed SCT status in all 12 samples. Subsequently sickledex screen positive but HEA negative samples (n= 40), were subject to HPLC. All 40 showed absence of SCT by HPLC. Finally, 58 random sickledex + samples had gene sequencing and HEA performed in parallel. Out of 58 samples, 54 showed a positive HbS mutation by HEA with A>T (SCT) nucleotide change noted with gene sequencing. In the remaining 4 samples, HEA was negative with gene sequencing showing (3 T>T and in 1C>T) change at nucleotide 163 associated with Hemoglobin Okayama.Conclusion:The HEA bead chip assay testing for the HbS mutation showed 100% concordance with HPLC and gene sequencing in samples studied. Molecular methods can process multiple samples in a single setting to detect SCT. FP sickledex screening results in Caucasians needs confirmatory testing for the HbS mutation to avoid unnecessary donor notification and deferral. The association, if any, of false positive sickledex screening in Caucasian donors with the Hgb Okayama mutation is under further investigation. DisclosuresNo relevant conflicts of interest to declare.

Increased Risk of Developing Breast Cancer after a False-Positive Screening Mammogram.

Women with a history of a false-positive mammogram result may be at increased risk of developing subsequent breast cancer. Using 1994 to 2009 Breast Cancer Surveillance Consortium data, we included women ages 40 to 74 years with a screening mammogram that resulted in a false-positive with recommendation for additional imaging, false-positive with recommendation for biopsy, or true-negative with no cancer within one year following the examination. We used partly conditional Cox proportional hazards survival models to assess the association between a false-positive mammogram result and subsequent breast cancer, adjusting for potential confounders. Adjusted survival curves stratified by breast density and false-positive result were used to evaluate changes in risk over time. During 12,022,560 person-years of follow-up, 48,735 cancers were diagnosed. Compared with women with a true-negative examination, women with a false-positive with additional imaging recommendation had increased risk of developing breast cancer [adjusted HR (aHR) = 1.39; 95% confidence interval (CI), 1.35-1.44] as did women with a false-positive with a biopsy recommendation (aHR = 1.76; 95% CI,1.65-1.88). Results stratifying by breast density were similar to overall results except among women with almost entirely fatty breasts in which aHRs were similar for both the false-positive groups. Women with a false-positive result had persistently increased risk of developing breast cancer 10 years after the false-positive examination. Women with a history of a false-positive screening mammogram or biopsy recommendation were at increased risk of developing breast cancer for at least a decade, suggesting that prior false-positive screening may be useful in risk prediction models.

Cross-reactivity between Lyme and syphilis screening assays: Lyme disease does not cause false-positive syphilis screens

Increased rates of Lyme disease and syphilis in the same geographic area prompted an assessment of screening test cross-reactivity. This study supports the previously described cross-reactivity of Lyme screening among syphilis-positive sera and reports evidence against the possibility of false-positive syphilis screening tests resulting from previous Borrelia burgdorferi infection.

Abstract 18811: Improving the Practicality of Echocardiographic Screening for Rheumatic Heart Disease: Performance of Non-expert Users Following Completion of a Standardized Computer-based Training Curriculum

Background: Echocardiography (echo) is the most sensitive tool for rheumatic heart disease (RHD) detection. However, widespread screening programs are non-existent due to lack of financial and expert human resources in endemic areas. Task-shifting to non-experts to perform RHD screening is promising; however, investigations into workforce composition and replicable training schemes are needed. Objective: Test non-experts’ ability to conduct RHD screening following a brief, standardized, computer-based training course. Methods: Six non-experts with a variety of backgrounds (nurses, health technicians, medical students) and echo experience (6 wks-1 yr) completed a 3-module computer-based curriculum focusing on simplified criteria for RHD screening (mitral regurgitation (MR) ≥1.5cm and/or any aortic regurgitation). Following training, two teams of 3 non-experts were placed in school screening environments. Gold-standard diagnoses of RHD (2012, World Heart Federation criteria) were made by cardiologists using standard portable echo equipment. Children diagnosed with RHD and 25% of the general screening population was blindly evaluated by each non-expert using the simplified criteria with handheld echo. Results: Screening was performed in 1,381 children, with 397 (47 borderline RHD, 6 definite RHD, 336 normal &amp; 8 other) referred for handheld echo (209 Team 1 &amp; 188 Team 2). Age ranged from 5-18 years (mean 13.6); 59% were female. Overall sensitivity of the simplified approach was 90.8% (95% CI 85.4-94.6%; range 75-100%), with an overall specificity of 82.4% (95% CI 79.9-84.7%; range 75-89%). The most common reasons for false-negative screens (n=16) were missed MR (44%) and MR ≤1.5cm (29%), and for false-positive screens (n=179) included identification of erroneous color jets (25%), incorrect MR measurement (24%), and appropriate application of simplified guidelines (MR between 1.5 and 2.0 cm, 39.4%). Conclusions: A short, computer-based curriculum can be successfully used to train a heterogeneous group of non-experts to preform large-scale RHD screening. This simplified approach addresses prohibitive financial and workforce barriers to widespread RHD screening and holds the potential to significantly reduce the global burden of RHD.

Preschool children's vision screening in New Zealand: a retrospective evaluation of referral accuracy

ObjectivesTo assess the accuracy of preschool vision screening in a large, ethnically diverse, urban population in South Auckland, New Zealand.DesignRetrospective longitudinal study.MethodsB4 School Check vision screening records (n=5572) were compared...

A retrospective analysis of false-positive infectious screening results in blood donors.

False-positive infectious transfusion screening results remain a challenge with continued loss of both donors and blood products. We sought to identify associations between donor demographic characteristics (age, race, sex, education, first-time donor status) and testing false positive for viruses during routine blood donation screening. In addition the study assessed the prevalence of high-risk behaviors in false-positive donors. Blood Systems, Inc. donors with allogeneic donations between January 1, 2011, and December 31, 2012, were compared in a case-control study. Those with a false-positive donation for one of four viruses (human immunodeficiency virus [HIV], human T-lymphotropic virus [HTLV], hepatitis B virus [HBV], and hepatitis C virus [HCV]) were included as cases. Those with negative test results were controls. For a subset of cases, infectious risk factors were evaluated. Black race and Hispanic ethnicity were associated with HCV and HTLV false-positive results. Male sex and lower education were associated with HCV false positivity, and age 25 to 44 was associated with HTLV false positivity. First-time donors were more likely to be HCV false positive although less likely to be HBV and HTLV false positive. No significant associations between donor demographics and HIV false positivity were observed. A questionnaire for false-positive donors showed low levels of high-risk behaviors. Demographic associations with HCV and HTLV false-positive results overlap with those of true infection. While true infection is unlikely given current testing algorithms and risk factor evaluation, the findings suggest nonrandom association. Further investigation into biologic mechanisms is warranted.

The 10 Pillars of Lung Cancer Screening: Rationale and Logistics of a Lung Cancer Screening Program.

On the basis of the National Lung Screening Trial data released in 2011, the U.S. Preventive Services Task Force made lung cancer screening (LCS) with low-dose computed tomography (CT) a public health recommendation in 2013. The Centers for Medicare and Medicaid Services (CMS) currently reimburse LCS for asymptomatic individuals aged 55-77 years who have a tobacco smoking history of at least 30 pack-years and who are either currently smoking or had quit less than 15 years earlier. Commercial insurers reimburse the cost of LCS for individuals aged 55-80 years with the same smoking history. Effective care for the millions of Americans who qualify for LCS requires an organized step-wise approach. The 10-pillar model reflects the elements required to support a successful LCS program: eligibility, education, examination ordering, image acquisition, image review, communication, referral network, quality improvement, reimbursement, and research frontiers. Examination ordering can be coupled with decision support to ensure that only eligible individuals undergo LCS. Communication of results revolves around the Lung Imaging Reporting and Data System (Lung-RADS) from the American College of Radiology. Lung-RADS is a structured decision-oriented reporting system designed to minimize the rate of false-positive screening examination results. With nodule size and morphology as discriminators, Lung-RADS links nodule management pathways to the variety of nodules present on LCS CT studies. Tracking of patient outcomes is facilitated by a CMS-approved national registry maintained by the American College of Radiology. Online supplemental material is available for this article.