Number Of False-positive Tests Research Articles

The Diagnostic Utility of Ultrasound and Electrodiagnostic Studies in The Young and Old

Carpal tunnel syndrome is the most common compressive neuropathy. The diagnostic parameters currently used for the general adult population may not be valid in elderly or younger cohorts. The purpose of this study is to determine the diagnostic accuracy of nerve conduction studies (NCS) and ultrasound (US) in different age groups utilizing the 6-item Carpal tunnel syndrome (CTS) symptoms scale (CTS-6) as the reference standard. A retrospective database of patients who underwent US and NCS as part of the diagnostic work-up for suspected peripheral nerve compression was reviewed. Subjects were separated into three groups based on the median age of carpal tunnel syndrome patients (55 years of age) and two standard deviations (standard deviation 13.5 years) above and below the median. The young group was 28 years of age or less, the middle group was 29-71 years of age, and the old group was 72 years of age or greater. CTS-6 and Boston Carpal Tunnel Syndrome Questionnaire scores were recorded. Using CTS-6 as a reference standard, the sensitivity and specificity were calculated for NCS and US. A total of 295 hands were included in the analysis with 23 hands in the young group and 24 hands in the old group. NCS showed 31% sensitivity and 100% specificity in the young group compared to 54% sensitivity and 90% specificity for US. NCS showed 94% sensitivity and 25% specificity in the old group compared to 81% sensitivity and 38% specificity for US. Overall accuracy for US and NCS was 66% for both tests when looking at all age groups. The accuracy in the young group was 70% for US and 61% for NCS, whereas the accuracy in the old group was 67% for US and 71% for NCS. US has comparable sensitivity and specificity to NCS in patients two or more standard deviations above or below the mean age for presentation of CTS. US may be more accurate in younger patients, although NCS limits the number of false positive tests. There remains a substantial amount of inaccuracy for both tests when using a validated clinical diagnostic tool (CTS-6) as the reference standard. Diagnostic IV.

Newborn screening for congenital adrenal hyperplasia

This presentation discusses newborn screening for congenital adrenal hyperplasia (CAH) which is available in most developed countries. Early detection and hormone replacement prevents the progression of salt-wasting adrenal crises that can become life-threatening in the first two weeks of life. Screening by 17-hydroxyprogesterone immunoassay is sensitive for salt-wasting disease but confounded by poor specificity in premature and ill neonates. The use of liquid chromatography tandem mass spectrometry as a second-tier test offers improvements to screening through improved analytical specificity which reduces the number of false positive tests.

First-Trimester Biochemical Serum Markers in Female Kidney Transplant Recipients-The Impact of Graft Function.

Data on serum biochemistry markers as a component of the first-trimester screening test in pregnant kidney graft recipients are limited. In the absence of a separate validated algorithm, biochemical testing is commonly used in the first-trimester screening in kidney transplant recipients. Therefore, the study aimed to analyze first-trimester serum biochemical markers and the first trimester combined screening results in pregnant kidney graft recipients. A retrospective study was carried out in pregnant women who underwent the first-trimester combined screening test performed per the Fetal Medicine Foundation (FMF) protocol in 2009−2020. The study group included 27 pregnancies in kidney graft transplant recipients, and the control group was 110 patients with normal kidney function, matched according to age, body mass index (BMI), and gestational age. The biochemical serum markers (free beta-human chorionic gonadotropin [beta-hCG] and pregnancy-associated plasma protein A [PAPP-A]) were evaluated using the FMF-approved Roche Elecsys® assay and exhibited as multiples of the median (MoM) values. Data on first-trimester screening test results, perinatal outcomes, and graft function (assessed using serum creatinine concentrations) were analyzed. The analysis of first-trimester screening parameters revealed no difference in nuchal translucency (NT) measurements and uterine artery flow. However, free beta-hCG MoM and PAPP-A values were higher in posttransplant pregnancies than in controls: 3.47 ± 2.08 vs. 1.38 ± 0.85 (p = 0.035) and 1.46 ± 0.81 vs. 0.98 ± 0.57 (p = 0.007), respectively. The false positive rate of trisomy 21 (T21) screening in graft recipients was 25.9% vs. 3% in the controls. The free β-hCG MoM values positively correlated with serum creatinine levels before (r = 0.653; p < 0.001), during (r = 0.619; p = 0.001), and after pregnancy (r = 0.697; p < 0.001). There was a statistically significant negative correlation for PAPP-A MoM values for postpartum serum creatinine concentration (r = −0.424, p = 0.035). Our results show significantly higher serum concentrations of free beta-hCG and PAPP-A in posttransplant pregnancies than in healthy controls, confirmed when exhibited as MoM values and their association with graft function was assessed by serum creatinine concentration. Taking those changes into account would reduce the high number of false positive test results in this group. The validated first-trimester screening algorithm that considers altered kidney function in pregnant kidney graft recipients remains to be developed.

A Cohort Study of Free Light Chain Ratio in Combination with Serum Protein Electrophoresis as a First-Line Test in General Practice.

Simple SummaryMultiple Myeloma (MM) can be a diagnostic challenge as it often presents with unspecific symptoms in patients in general practice. Serum-free light chain (sFLC) ratio is suggested to replace urine protein electrophoresis (UPE) in the diagnostic work-up of myeloma. We aimed to investigate the performance of the sFLC ratio in general practice (GP) compared to UPE in a low prevalence cohort of 13,210 patients from general practice. We found that sFLC ratio performs in line with UPE; however, we observed a pronounced number of false-positive tests. Therefore, local instrument-dependent adjustment of reference ranges/decision limits should be considered to avoid an unnecessarily high number of false-positive tests.Multiple Myeloma (MM) often present with unspecific symptoms, which can lead to diagnostic delay. Serum-free light chain (sFLC) ratio is suggested to replace urine protein electrophoresis (UPE) in the diagnostic work-up of myeloma. We aimed to investigate the performance of the sFLC-ratio in general practice (GP) compared to UPE, just as we explored different sFLC-ratio cut-offs’ influence on diagnostic values. In a cohort of 13,210 patients from GP measures of sFLC-ratio, serum protein electrophoresis (SPE), or UPE were compared to diagnoses of incident M-component related diseases acquired from Danish health registers. UPE and sFLC-ratio equally improved diagnostic values when combined with SPE (sensitivity: SPE and UPE: 95.6 (90.6–98.4); SPE and sFLC-ratio: 95.1 (90.2–98.0)). The addition of the sFLC-ratio to SPE resulted in the identification of 13 patients with MGUS, light chain disease and amyloidosis, which was in line with the addition of UPE to SPE. The number of false-positive tests was UPE and SPE: 364 (11%) and sFLC-ratio and SPE: 677(19%). Expanding sFLC-ratio reference range to 0.26–4.32 resulted in a significant reduction in false positives n = 226 (6%) without loss of patients with clinical plasma cell dyscrasias. sFLC-ratio improves the diagnostic value of SPE in GP. However, due to low specificity and a large number of false positives, expanded cut-off values should be considered.

Choosing multichannel objective response detectors for multichannel auditory steady-state responses

The assessment of evoked responses still largely relies on subjective assessment, though a number of objective response detection techniques have been proposed, which are usually based on the statistical analysis of electroencephalogram (EEG) signals. In the current work, we expand on this with an investigation of multichannel objective response detection (MORD) methods, by assessing the performance of six previously published MORD algorithms together with three new methods (named product of Local Spectral F-test, average and the product of Component Synchrony Measure). The MORD techniques were evaluated in both simulated data and in multifrequency Auditory Stead-State Responses (ASSRs) recorded from 11 normal-hearing volunteers. The performances of MORD techniques were evaluated based on detection rates and the number of false positive tests. The results demonstrate that inflated false positive rates can arise when correlation between EEG channels is not taken into account by some of the MORD methods, but the algorithms are fairly robust to low cross-channel correlations. Furthermore, two of the already established MORD techniques showed immunity to cross-channel correlation. The results showed that the sensitivity of response detection increased when more than one channel was used, and an increase of up to 16 % compared to the best single-channel method could be achieved by the newly proposed best MORD methods. MORD methods are thus a promising new tool for ASSR detection.

Teste da oximetria de pulso em unidade neonatal de referência - avaliação após 3 anos de sua implantação como teste de triagem universal

INTRODUCTION: The present study searched to evaluate the results of pulse oximetry test in the screening of critical congenital heart disease in a public maternity hospital in Brazil, especially regarding the rate of positive and false positive tests. METHODS: A descriptive, retrospective and cross-sectional study was conducted by collecting data from the oximetry test logbook and from an electronic medical record from January to December 2018.The results were compared with the others described in the literature. RESULTS: 1,976 pulse oximetry tests were performed, with 303 alterations initially. 52 newborns had kept the altered test after retest, and 39 newborns were excluded. Among the altered tests, 9 congenital heart defects were found, but no critical congenital heart defects, generating 2.6% of false positive tests. CONCLUSION: The pulse oximetry test as a neonatal screening tool was important for the diagnosis of newborns with congenital heart disease, even though no cases of critical congenital heart defects. The number of false positive tests observed was much higher than reported in the literature, causing indirect costs in length of hospital stay, unnecessary examinations and family anxiety.

The role and diagnostic value of the most common methods for diagnosing Helicobacter pylori infection

The purpose of the study was to identify and evaluate the practical value of the most common diagnostic methods for Helicobacter pylori infection in patients with chronic inflammation of the gastric mucosa.&#x0D; Materials and methods. The study involved 104 people. All the patients examined underwent esophagogastroduodenoscopy with a rapid urease histochemical test for Helicobacter pylori and a standard five-point biopsy of the gastric mucosa for morphological evaluation and bacterioscopy. If the result of the quick urease histochemical test coincided with the data of the biopsy study on Helicobacter pylori, no further examination was carried out. In case of discrepancy the patients additionally underwent the 13C-urease breath test.&#x0D; Results. It was found that the sensitivity of the rapid urease histochemical test in the area of the proposed model, according to our study, was 89.74% and the specificity was 46.15% when validating it using the additional methods. Similar calculations for the diagnostic method of staining by Giemsa showed sensitivity of 100% and specificity of 97.4%. The total number of the infected in the survey was 78 out of 104 people, which amounted to 75%.&#x0D; When analysing the severity of activity, inflammation and atrophic changes in the gastric mucosa, it was found that in the patients with two positive tests, the severity of the processes was significantly higher than in those with one positive test or all the tests were negative (p 0.05). When comparing the same processes in cases where only a quick urease histochemical test was positive and no signs of Helicobacteriosis were detected in any test, no significant differences were detected.&#x0D; Discussion. The rapid urease histochemical test showed good sensitivity of 89.74%, but unsatisfactory specificity of 46.15%, which severely limits its use. An unexpected result for this methodology was a large number of false positive tests, while the European recommendations indicate a more frequent occurrence of false negative results, which can be explained by differences in the production technology of the test systems. High sensitivity and specificity of the Helicobacter pylori test using Giemsa staining strongly depends on observing the methodology and experience of a specialist and cannot be recommended as a standard in the routine medical use.&#x0D; The study confirmed the recommendations for using at least two diagnostic tests to diagnose the infection, while the most common rapid urease histochemical test always needs confirmation. As a result of the analysis, it can be said that esophagastroduodenoscopy with a rapid urease histochemical test for Helicobacter pylori and standard diagnostic biopsy is the optimal method for diagnosing the pathology of the upper sections of the gastrointestinal tract. Moreover, 13C-UDT seems to be almost ideal as a screening technique and for evaluating treatment in cases where endoscopic monitoring is not necessary.

The results of newborn hearing screening by means of transient otoacoustic emissions – has anything changed over 10 years?

ObjectivesUniversal newborn hearing screening (UNHS) has become the standard of care in many countries. The aim of this study was to evaluate the results of UNHS after ten years of the program in Poland and to compare them with the results of 2003. MethodsIn the study, we analyze the results of UNHS in the University Hospital in Poznan, Poland. Between 01.01.2013 and 31.12.2013, 6827 children were examined by means of otoacoustic emissions. ResultsRisk factors (RF) were identified in 772 (11.3%) newborns, which is significantly less than 10 years ago (p < 0.05). The most frequent RF were: ototoxic medications, treatment in neonatal intensive care unit (NICU) and prematurity < 33 weeks of gestation. In 2003, the most frequent were ototoxic medications and prematurity, less frequent was treatment in NICU and more common was low Apgar score.In 51 (6.6%) newborns with RF, the result of OAE was positive either unilaterally or bilaterally. In infants without RF the result was positive unilaterally in 22 (0.4%) and bilaterally in 14 (0.2%) patients. These results are significantly lower than in our former study.The relative risk of positive result was the highest in infants with complex congenital anomalies (RR = 44.99), craniofacial anomalies (RR = 17.46) and mechanical ventilation for > 5 days (RR = 10.69). In our previous study, the highest RR of positive test results was in infants with family history, congenital malformations and low Apgar score.We found that most predictive as to the final diagnosis was bilaterally positive OAE test. In most patients, the second check confirmed the diagnosis, independently of RF.The number of false positive tests at the 1st level of screening is significantly lower now than 10 years ago, probably due to better staff training. ConclusionsLong term monitoring and the appropriate management of hearing deficit in children is essential. UNHS seems to be the most efficient way of finding children who require treatment of hearing impairment. The prevalence of most risk factors of hearing deficit has significantly changed over the years. The number of false positive results has significantly decreased over the years thanks to better staff training.

Detecting Local Zika Virus Transmission in the Continental United States: A Comparison of Surveillance Strategies

Introduction:The 2015-2017 Zika virus (ZIKV) epidemic in the Americas has driven efforts to strengthen surveillance systems and to develop interventions, testing, and travel recommendations. In the continental U.S. and Hawaii, where limited transmission has been observed, detecting local transmission is a key public health objective. We assessed the effectiveness of three general surveillance strategies for this situation: testing all pregnant women twice during pregnancy, testing blood donations, and testing symptomatic people who seek medical care in an emergency department (ED).Methods:We developed a simulation model for each surveillance strategy and simulated different transmission scenarios with varying population sizes and infection rates. We then calculated the probability of detecting transmission, the number of tests needed, and the number of false positive test results.Results:The probability of detecting ZIKV transmission was highest for testing ED patients with Zika symptoms, followed by pregnant women and blood donors, in that order. The magnitude of the difference in probability of detection between strategies depended on the incidence of infection. Testing ED patients required fewer tests and resulted in fewer false positives than surveillance among pregnant women. The optimal strategy identified was to test ED patients with at least two Zika virus disease symptoms. This case definition resulted in a high probability of detection with relatively few tests and false positives.Discussion:In the continental U.S. and Hawaii, where local ZIKV transmission is rare, optimizing the probability of detecting infections while minimizing resource usage is particularly important. Local surveillance strategies will be influenced by existing public health system infrastructure, but should also consider the effectiveness of different approaches. This analysis demonstrated differences across strategies and indicated that testing symptomatic ED patients is generally a more efficient strategy for detecting transmission than routine testing of pregnant women or blood donors.

New screen on the block: non-invasive prenatal testing for fetal chromosomal abnormalities.

Non-invasive prenatal testing (NIPT) is a new screen for fetal chromosomal abnormalities. It is a screening test based on technology that involves the analysis of feto-placental DNA that is present in maternal blood. This DNA is then analysed for abnormalities of specific chromosomes (eg 13, 18, 21, X, Y). NIPT has a much higher screening capability for chromosomal abnormalities than current combined first trimester screening, with ~99% sensitivity for trisomy 21 (Down syndrome) and at least a 10-fold higher positive predictive value. The low false-positive rate (1-3%) is one of the most advertised advantages of NIPT. In practice, this could lead to a significant reduction in the number of false-positive tests and the need for invasive diagnostic procedures. NIPT is now suitable for singleton and twin pregnancies and can be performed from ~10 weeks in a pregnancy. NIPT is not currently publicly funded in most countries. However, the increasing availability of NIPT commercially will likely lead to an increase in demand for this as a screening option. Given the high numbers of women who visit a general practitioner (GP) in their first trimester, GPs are well-placed to also offer NIPT as a screening option. A GP's role in facilitating access to this service will likely be crucial in ensuring equity in access to this technology, and it is important to ensure that they are well supported to do so.

Arf3DS4: An Integrated Framework for Localization and Connectivity Analysis of fMRI Data

In standard fMRI analysis all voxels are tested in a massive univariate approach, that is, each voxel is tested independently. This requires stringent corrections for multiple comparisons to control the number of false positive tests (i.e., marking voxels as active while they are actually not). As a result, fMRI analyses may suffer from low power to detect activation, especially in studies with high levels of noise in the data, for example developmental or single-subject studies. Activated region fitting (ARF) yields a solution by modeling fMRI data by multiple Gaussian shaped regions. ARF only requires a small number of parameters and therefore has increased power to detect activation. If required, the estimated regions can be directly used as regions of interest in a functional connectivity analysis. ARF is implemented in the R package arf3DS4. In this paper ARF and its implementation are described and illustrated with an example.

Establishing the added benefit of measuring MMP9 in FOB positive patients as a part of the Wolverhampton colorectal cancer screening programme

BackgroundBowel cancer is common and a major cause of death. The NHS is currently rolling out a national bowel cancer screening programme that aims to cover the entire population by 2010. The programme will be based on the Faecal Occult Blood test (FOBt) that reduces mortality from colon cancer by 16%. However, FOB testing has a relatively low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. MMP9 has potential for detecting those at risk of having colorectal cancer. The aim of this study is to assess whether MMP9 estimation enhances the predictive value of a positive FOBt.Methods and designFOBt positive people aged 60–69 years attending the Wolverhampton NHS Bowel Cancer Screening Unit and providing consent for colonoscopy will be recruited. Participants will provide a blood sample prior to colonoscopy and permission for collection of the clinical outcome from screening unit records. Multivariate logistic regression analyses will determine the independent factors (patient and disease related, MMP9) associated with the prediction of neoplasia.DiscussionColorectal cancer is a major cause of morbidity and mortality. Pilot studies have confirmed the feasibility of the national cancer screening programme that is based on FOBt. However, the test has high false positive rates. MMP9 has significant potential as a marker for both adenomas and cancers. This study is to examine whether using MMP9 as an adjunct to FOBt improves the accuracy of screening and reduces the number of false positive tests that cause anxiety and require invasive and potentially harmful investigation.

Reducing ovarian cancer mortality through screening: Is it possible, and can we afford it?

ObjectiveOvarian cancer is a leading cause of cancer-related deaths among women. Given the low prevalence of this disease, the effectiveness of screening strategies has not been established. We wished to estimate the clinical impact and cost-effectiveness of potential screening strategies for ovarian cancer using population-specific data. MethodsA Markov state transition model to simulate the natural history of ovarian cancer in a cohort of women age 20 to 100. Age-specific incidence and mortality rates were obtained from SEER. Base-case characteristics of a potential screening test were sensitivity 85%, specificity 95%, and cost $50. Outcome measures were mortality reduction, lifetime number of false positive screening tests, positive predictive value, years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (ICER, in cost/YLS). ResultsModel-predicted lifetime risk of ovarian cancer (1.38%), lifetime risk of death from ovarian cancer (0.95%), and stage distribution (stage I-19%; stage II-7%; stage III, IV, or unstaged — 74%) closely approximated SEER data. Annual screening resulted in 43% reduction in ovarian cancer mortality, with ICER of $73,469/YLS (base case) and $36,025/YLS (high-risk population) compared to no screening. In the base case, the average lifetime number of false positive tests is 1.06. Cost-effectiveness of screening is most sensitive to test frequency, specificity and cost. ConclusionsAnnual screening for ovarian cancer has the potential to be cost effective, particularly in high-risk populations. Clinically acceptable positive predictive values are achieved if specificity exceeds 99%. Mortality reduction above 50% may not be achievable without screening intervals less than 12 months.

Who receives, benefits from and is harmed by cervical and breast cancer screening among Hong Kong Chinese?

To estimate the proportion of and characterize women who had received cervical and breast screening and to quantify the associated preventable burden of disease and potential iatrogenic harm. A total of 3484 Hong Kong Chinese women were interviewed in person. Screening prevalence and associated predictors, disability-adjusted life-years (DALYs), the numbers of false-positive tests and the resultant confirmatory procedures and related complications were estimated. A total of 6.2% of women (>or=18) reported regular pap but no mammography or clinical breast examination (CBE) as per local evidence-based guidelines, whereas among women aged >or=40 years, 5.2% reported regular screening by all three modalities and 55.3% had never been screened for either cancer. Women who underwent regular health checkups were consistently the most likely to have been screened, as were younger, married and socially advantaged respondents. Triennial pap screening would save 708 DALYs annually, or 528 more DALYs compared with the status quo. However, this would generate 28,600 repeat smears and 390 colposcopies from false-positive screens. Opportunistic mammographic screening averted 100 DALYs currently, but could have potentially reduced a further 546 with biennial screening. Mass screening mammography (CBE) would lead to 33,700 (20,200) false-positives per year requiring 29,900 (8300) repeat mammograms or ultrasonograms, 6800 (3000) biopsies and 620 (270) biopsy-related complications. Screening uptake patterns are suboptimal. By making explicit the possible risks and benefits based on this template, policy makers in developing Asia with a similar female cancer burden may be able to use the information to make evidence-based decisions that are consistent with local circumstances, values and preferences.

Selected Summary

Selected Summary

Early hearing screening: What is the best strategy?

A discussion concerning the relevance of universal newborn hearing screening has been conducted in France since the end of the 1990s. As a contribution to the choice of strategy to be implemented, we evaluated and compared the results of this screening and its impact on the parent-infant relationship as a function of the time at which screening was performed: during the infant's stay in the maternity unit, in the first strategy (strategy 1), or 2 months after birth, in the second strategy (strategy 2). Five thousand seven hundred and ninety infants participated in the study: 3202 were included in the first strategy and 2588 were included in the second strategy. Within this population, 143 mother-infant pairs were submitted to psychological assessment. We compared the number of infants screened, the number of first positive tests, the number of false-positive tests and the number of infants not reviewed after screening. Adverse effects on the parent-infant relationship were evaluated in terms of maternal anxiety and the quality of early interactions. A statistically significant difference in favor of newborn screening was demonstrated for the number of infants screened: 95.72% for the first strategy [95.0%; 96.4%], 64.18% for the second strategy [62.3%; 66.0%]; the number of first positive tests: 1.11% during newborn screening [0.7%; 1.5%], 3.13% in the second strategy [2.3%; 4.0%]; the number of false-positive tests: 0.29% in the first strategy [0.10%; 0.49%] and 2.65% in the second strategy [1.88%; 3.42%]; and the number of infants not reviewed after screening: 8.8% during newborn screening [0.0%; 18.4%] and 38.5% in the second strategy [25.2%; 51.7%]. Analysis of the results of the psychological assessment showed that screening per se did not have any impact on maternal anxiety or on the quality of early interactions, regardless of the screening strategy used. However, the result of the test had a significant impact. Announcement of a positive result increased maternal anxiety and induced a deterioration of the mother's psychological state which affected the quality of early interactions. As the number of positive results is significantly lower in newborn hearing screening, there are consequently fewer psychological side effects with this strategy than with the second strategy. This study demonstrates that universal newborn hearing screening is the most efficient strategy.

Comparison of conventional Papanicolaou smear and SurePath® liquid‐based cytology in the Copenhagen population screening programme for cervical cancer

To compare diagnostic performance of conventional Papanicolaou smear with SurePath liquid-based cytology in a population screening programme. A retrospective comparison was performed on data from two 18-month periods of the screening programme for cervical cancer in the municipality of Copenhagen with conventional Papanicolaou technique (n = 82,116) and liquid-based cytology (n = 84,414). After the conversion to liquid-based cytology the percentage of unsatisfactory samples decreased from 2.3% to 0.3% (P < 0.001), whereas the number of normal cervical samples lacking an endocervical component increased from 8.5% to 8.9% (P < 0.005). The percentage of samples with atypical cells and cells suspicious for malignancy increased from 3% to 4.2% (P < 0.001) and from 1.9% to 2.4% (P < 0.001), respectively. The subsequent histological follow-up showed normal findings decreased from 70.5% to 68.9% and from 28.0% to 26.1%, respectively. However, in relation to the entire screening populations, there was an increase of normal findings from 2.12% to 2.89% after primary atypical diagnosis and from 0.53% to 0.62% after diagnosis of suspicious cells after conversion to the liquid-based technique. This study showed the number of unsatisfactory samples to be significantly reduced with the liquid-based technique. The data suggest that there is an increased detection rate of cervical precancerous lesions with liquid-based cytology, but the number of false positive tests is still high. The specificity of the two tests seems similar, but this cannot be ascertained exactly, because of the fact that follow-up of negative cases is unavailable.

Editor's choice

Editor's choice

Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants.

Neonatal screening for congenital adrenal hyperplasia (CAH) among preterm infants is complicated by the fact that healthy preterm infants have higher levels of 17-hydroxyprogesterone (17-OHP) than term infants, resulting in a higher false-positive rate. Even when gestational age-related cutoff levels after ether extraction were used, the false-positive cases primarily comprised preterm infants. The aim of the study was to optimize the procedure for neonatal screening for CAH in preterm infants. The 17-OHP levels in 6200 preterm infants were correlated to the gestational age. We also calculated the number of recalls for different putative cutoff levels of the 17-OHP by direct assay and after extraction in 1275 preterm infants who represented the most elevated cases in a population of approximately 30 000 preterm infants. The CYP21 genotypes and screening levels were determined in the 12 preterm infants with CAH diagnosed since the start of screening. The effect of possible interfering factors such as gestational age, neonatal stress, and prenatal glucocorticoid treatment for pulmonary maturation was studied. The extraction procedure did not significantly improve the sensitivity or specificity of the screening, whereas it delayed the day of recall from 8 to 13 days (median). We could not demonstrate any systematic influence of the studied stress factors or the prenatal glucocorticoid treatment on the 17-OHP screening levels. In the patients with CAH, the 17-OHP levels correlated better with disease severity than with the degree of prematurity. On the basis of these results, we omitted the extraction step and changed the cutoff levels in the Swedish screening program for preterm infants. We chose to use a cutoff level of 400 nmol/L plasma in infants who were born before week 35 and 150 nmol/L for infants who were born in weeks 35 and 36. For detecting more patients, the cutoff level would have to be much lower, which would result in a number of false-positive tests that we consider to be unacceptably high. It is clear that neonatal screening cannot detect all infants with CAH. Some milder forms of the disease, just like in the past, will have to be diagnosed on the basis of clinical signs and symptoms.

Not one lancet for multiple SPT.

. SKIN prick tests (SPT) are a common diagnostic method used in allergology. The sensitivity and speci®city of this method depend on the allergen extracts and the method used to perform the tests. This study aimed to determine whether one lancet can be used for skin prick testing with several allergens in the same patient, as this method is used by many practitioners in an attempt to reduce costs. Twelve women and 24 men with (23) or without (13) positive SPT to common allergens participated in the study. Standardization of the method was in line with the position papers of the EAACI (1, 2). Tests were performed with single-use lancets, made of metal with a 1mm long point, specially designed for SPT (Pohl), and standard allergen extracts (Der p, Der f, cat, and grass) (Allergopharma). Positive controls were histamine (10 mg/ml) and codeine (10 mg/ml); the negative control was 50% glycerosaline solution. SPT were applied simultaneously by two methods: one lancet and one prick on one forearm (the ``single test'' method), and one lancet and multiple pricks on the other (the ``multiple test'' method). If one lancet was used for more than one prick, it was carefully cleaned with cotton moistened with 75% ethanol. The skin tests were applied to the volar surfaces of both forearms with a distance of 3 cm between the test sites. The methods were randomly assigned to the left and right forearms, respectively. Histamine, codeine, and allergens were applied alternatively with placebo. The tests were read after 10 min for histamine and after 15 min for the other extracts. All wheal sizes were measured as the mean of the longest diameter and the midpoint of the perpendicular diameter. A false-positive reaction was de®ned as a reaction to placebo after a positive reaction to histamine, codeine, and allergen: mean wheal of $1 mm above baseline ± ®rst variable; mean wheal of $3 mm above ± second variable. The statistical analysis was done with the Wilcoxon rank-sum test and the Spearman rank factor. In the ``multiple test'' method, falsepositive tests at the placebo site following allergen administration were recorded in 20 out of 35 pricks performed when all reactions were considered, and in 13 out of 35 pricks when a 3-mm cutoff was considered. This was observed neither in the ``single test'' method nor with histamine or codeine in both methods. The number of false-positive reactions in the ``multiple test'' method was statistically signi®cant and independent of the criteria for false-positive tests (P=0.0001 for wheal of $1 mm; P=0.0015 for wheal of $3 mm). The size of the false-positive lesion after allergen did not depend on the type of allergen but on the intensity of the reaction to the allergen applied before placebo (R=0.672, P=0.00001) (Fig. 1). The use of one lancet (0.1 euro) to perform 20 skin pricks would result in a saving of 1.9 euro. Unfortunately, our study has shown a statistically signi®cant rise in the number of false-positive tests when using one lancet for multiple skin pricks. This is due to trace amounts of allergen remaining on the lancet even after thorough wiping. False-positive results are mainly observed in subjects who have strong reactions to speci®c allergens. Therefore, the above method cannot be used to identify factors responsible for allergy, particularly in patients who have been quali®ed for immunotherapy and in scienti®c studies. For ®nancial reasons, it can be used in screening tests and epidemiologic studies of A signi®cant rise in false positives was found.