Screening Cutoff Research Articles

Optimization of cloned enzyme donor immunoassay cut-offs for drugs of abuse in whole blood of drivers involved in road accidents

IntroductionImmunoassay (IA) tests should be able to detect low concentrations of illegal drugs when used for the screening of drugs in drivers. False negatives should be avoided, and false positives should be reduced as far as possible. In this study, semi-quantitative results for blood samples containing illicit drugs (cannabinoids, cocaine, amphetamines/methamphetamines, opiates and methadone) obtained with cloned enzyme donor immunoassay (CEDIA), were compared with results of confirmatory analysis performed through gas chromatography-mass spectrometry (GC–MS). Screening cut-off points for each class of drugs were retrospectively optimized. MethodsWhole blood samples from drivers involved in road accidents in the period from January 2013-December 2017 were analyzed with CEDIA (4200 samples). Confirmatory analyses were performed through (GC–MS) on: (i) all samples with screening concentrations above 1ng/ml for at least one drug (positive screening results); (ii) 800 samples with screening concentration lower than 1ng/ml (negative screening results). Recommended per se limits in relation to driving under the influence of drugs were set as fixed values. Sensitivity, specificity, positive and negative predictive values were evaluated by contingency tables and compared to ROC-analysis in order to obtain ideal screening cut-offs. ResultsCEDIA results were available for 4200 blood samples and 1172 positive screening results were found. Among these, 1008 confirmation analysis were obtained through GC–MS. Optimized screening cut-offs obtained through ROC analysis were as follows: 8.0ng/ml for THC; 5.5ng/ml for THC-COOH; 21.1ng/ml for cocaine; 6.9ng/ml for benzoylecgonine; 33.1ng/ml for opiates; 61.6ng/ml for amphetamines; 5.0ng/ml for methadone. Using these cut-offs, sensitivity was above 97% for THC-COOH, cocaine, benzoylecgonine, amphetamines, opiates and methadone, and 92% for THC; specificity was above 90% for cocaine, benzoylecgonine, amphetamines, opiates and methadone, 80% for THC and 89% for THC-COOH; negative predictive value was above 99% for all drugs and metabolites. ConclusionPrevious studies have shown that CEDIA tests are useful for preliminary screening of serum and urine. Its implementation in whole blood is of primary importance for the assessment of impaired driving, since the per se limits of many European countries refer to whole blood, and preparation of the serum and/or the collection of urine is not always possible in the hospital emergency department, where blood samples are withdrawn. Our study shows that CEDIA tests on whole blood permit the definition of cut-off values with optimal sensitivity and negative predictive values for all analytes (near to 100%), including very good specificity.

Assessing High-Throughput Descriptors for Prediction of Transparent Conductors

The growth of materials databases has yielded significant quantities of data to mine for new energy materials using high-throughput screening methodologies. One application of interest to energy and optoelectronics is the prediction of new high performing p-type transparent conductors (TCs). However, screening methods for such materials have never been validated over the breadth of computed materials properties. In this study, we compile an experimental data set of 74 bulk crystal structures corresponding to known state-of-the-art n-type and p-type TCs and compute a series of corresponding computational descriptor properties. Our goals are to (1) compare computational descriptors to experimentally demonstrated properties of real materials in the data set, (2) determine the ability of ground state, density functional theory (DFT)-based computational screening methodologies to identify these experimentally realized TCs, and (3) use this understanding to estimate reasonable screening cutoffs for four commonl...

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland.

Congenital hypothyroidism (CHT) is one of the most common preventable causes of learning disability. Newborn screening with whole-blood thyroid-stimulating hormone measurements was introduced in the Republic of Ireland in 1979 and is coordinated from a single center with an unchanged protocol since its inception. Our objective in this study was to describe the incidence of CHT in the Republic of Ireland over the past 37 years in the context of a complete national population and an unchanged screening protocol. The newborn screening records of all individuals who were diagnosed with CHT between 1979 and 2016 were reviewed. Infants with positive screening results had a whole-blood thyroid-stimulating hormone value of ≥15 mU/L at 72 to 120 hours of life; values of 8 to 15 mU/L required a repeat whole-blood screening test. Of 2 361 174 infants who were screened between July 1979 and December 2016, 1063 (662 girls) were diagnosed with CHT (incidence: 0.45 cases per 1000 live births). The number of detected cases increased from 0.27 cases per 1000 live births treated between 1979 and 1991 to 0.41 cases per 1000 live births treated between 1992 and 2004 to 0.65 cases per 1000 live births treated between 2005 and 2016. The increase in detected cases of CHT was predominantly in the normal or hyperplastic gland category. The incidence of CHT has increased significantly in the Republic of Ireland over the past 37 years despite a consistent screening cutoff. The increased rate was not explained by an increased survival rate of preterm infants or a changing population heterogeneity.

Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?

Newborn screening (NBS) is an invaluable tool for identification of CH; however almost 70% of newborns worldwide do not benefit from NBS at all. In countries with NBS, lowering of TSH cut-offs over the years led to major controversy on the optimal TSH screening cut-off. In this very interesting debate paper, arguments are presented for and against the lowering of TSH cutoffs at NBS. The arguments in support of lowering TSH cutoffs are based on: 1) the higher detection rate and consequent higher treatment rate of children with CH, and 2) the likelihood to improve health and developmental outcomes in early screened and treated infants. Arguments against lower TSH cut-offs are: 1) not all children detected by lower TSH cut-offs with mild CH would profit from treatment, and 2) an important proportion of mild CH detected by low TSH cut-offs were transient on re-evaluation at age 3 years.

Picky eating in Swedish preschoolers of different weight status: application of two new screening cut-offs

BackgroundCharacteristics of picky eaters of different weight status have not been sufficiently investigated. We used two newly developed screening cut-offs for picky eating in the Food fussiness (FF) subscale of the Child Eating Behavior Questionnaire (CEBQ) to investigate the prevalence and characteristics of picky eaters in preschool-aged children with thinness, normal weight, overweight or obesity.MethodsData for 1272 preschoolers (mean age 4.9 years) were analyzed. The parent-reported FF subscale ranges from 1 to 5, and two screening cut-offs were applied to classify children as picky eaters (3.0 and 3.33). Structural Equation Modeling was used to study associations with other factors in the CEBQ, the Child Feeding Questionnaire (CFQ) and the Lifestyle Behavior Checklist (LBC). Scores were compared separately for each weight status group.ResultsNearly half of the children were classified as moderate or severe picky eaters (cut-off 3.0) and 30% as severe (cut-off 3.33). For both cut-offs, prevalence was significantly lower in the obesity group. Still, one-third of children with obesity met the cut-off of 3.0 and 17% met the cut-off of 3.33. While picky eaters displayed similar patterns across weight status groups, some differences emerged. Food responsiveness was lower for picky eaters, but the difference was significant only among children with obesity. Slowness in eating was not as pronounced among picky eaters in the obesity group. In the overweight and obesity groups, parents of picky eaters did not report as high pressure to eat, as compared to the thinness or normal weight groups; in the obesity group, parents of picky eaters also perceived their children’s weight as lower. In all weight status groups, parents of picky eaters were more likely to report their children had too much screen time, complained about physical activity, and expressed negative affect toward food.ConclusionsPicky eating was less common but still prevalent among children with obesity. Future studies should investigate the potential influence of picky eating on childhood overweight and obesity. Moreover, as children with picky eating display higher emotional sensitivity, further research is needed to understand how to create positive eating environments particularly for children with picky eating and obesity.

Recommendations for the screening of paediatric latent tuberculosis infection in indigenous communities: a systematic review of screening strategies among high-risk groups in low-incidence countries

BackgroundTuberculosis (TB) continues to be a global public health concern. Due to the presence of multiple risk factors such as poor housing conditions and food insecurity in Canadian Indigenous communities, this population is at particularly high risk of TB infection. Given the challenges of screening for latent TB infection (LTBI) in remote communities, a synthesis of the existing literature regarding current screening strategies among high-risk groups in low-incidence countries is warranted, in order to provide an evidence base for the optimization of paediatric LTBI screening practices in the Canadian Indigenous context.MethodsA literature search of the Embase and Medline databases was conducted, and studies pertaining the evaluation of screening strategies or screening tools for LTBI in paediatric high-risk groups in low-incidence countries were included. Studies focusing on LTBI screening in Indigenous communities were also included, regardless of whether they focused on a paediatric population. Their results were summarized and discussed in the context of their relevance to screening strategies suitable to the Canadian Indigenous setting. Grey literature sources such as government reports or policy briefs were also consulted.ResultsThe initial literature search returned 327 studies, with 266 being excluded after abstract screening, and 36 studies being included in the final review (original research studies: n = 25, review papers or policy recommendations: n = 11). In the examined studies, case identification and cost-effectiveness of universal screening were low in low-incidence countries. Therefore, studies generally recommended targeted screening of high-risk groups in low-incidence countries, however, there remains a lack of consensus regarding cut-offs for the incidence-based screening of high-risk communities, as well as regarding the utility and prioritization of individual risk-factor-based screening of high-risk groups. The utility of the TST compared to IGRAs for LTBI detection in the pediatric population also remains contested.ConclusionsRelevant strategies for targeted screening in the Canadian Indigenous context include community-level incidence-based screening (screening based on geographic location within high-incidence communities), as well as individual risk-factor-based screening, taking into account pertinent risk factors in Indigenous settings, such as poor housing conditions, malnutrition, contact with an active case, or the presence of relevant co-morbidities, such as renal disease.

Diagnosis of primary aldosteronism in the hypertension specialist centers in Italy: a national survey.

Primary aldosteronism (PA) is the most common endocrine cause of resistant hypertension. Individuals with PA are at increased cardiovascular risk, and an appropriate management and treatment would ideally reduce such risk. Screening and diagnosis of PA requires a specific diagnostic test whichis considered time- and cost-consuming and, as a result, is underperformed in clinical practice. An online survey reviewing available diagnostic procedures, laboratory testing, and clinical protocols for screening and confirmation of PA diagnosis was conducted among clinical lead of Reference andExcellence centers of the Italian Hypertension Society. A total of 102 questionnaires were sent and 62 centers participated in the survey. Assessment of the plasma renin (plasma renin activity/direct renin concentration) and plasma aldosterone concentration (PAC) was available in all centers. Captopril challenge test (CCT) and saline infusion test (SIT) were available in 60% and 61% of the centers, respectively. Fludrocortisone suppression test was available in 32% of the units. Adrenal vein sampling was accessible in 32% of the centers. We found discrepancies in cutoff levels of aldosterone-to-renin ratio (ARR) and PAC after SIT. Other discrepancies involved the duration of the wash-out period before ARR testing and dosage of captopril administered during CCT. In conclusion, although all centers are sufficiently equipped to perform PA screening, often patients should be referred to other centers to confirm the diagnosis of PA. A greater uniformity across centers to define precise cutoffs for screening and confirmatory testing for the diagnosis of PA would be of utility.

Identifying Patients with GDM at Risk for GCK-MODY

GCK-MODY is characterized by stable, mild hyperglycemia without typical long-term diabetes complications. The prevalence of GCK-MODY is 0.1% in the general population. However patients are frequently misclassified as type 1, type 2, or gestational diabetes. Since all pregnant women undergo glycemic assessment, there is an opportunity to identify women with GCK-MODY within the Obstetrics (OB) clinic. The purpose of this study is to use retrospective data from the electronic medical record (EMR) to identify a combination of anthropometric and glycemic data that can differentiate women with GCK-MODY from those with gestational diabetes in a multiethnic United States population. A screening cohort of 927 study patients was identified through the University of Chicago Clinical Research Data Warehouse (CRDW) using the parameters of age >=18, outpatient visit to the OB clinic from 2009 to present and ICD-9 or ICD-10 diagnosis code of pregnancy and diabetes. A total of 1patients were identified who fulfilled criteria of BMI < 30 kg/m2 and fasting glucose 99-145 mg/dL or HbA1c 5.6-7.6%. Twelve patients were excluded due to confirmed type 1 diabetes (n= 11) and secondary CF-related diabetes (n= 1). The final cohort are predominantly African-American (66%), followed by Asian/Mideast Indian (13%) and white (11%). Diagnoses based on ICD9/10 codes included gestational diabetes (52%), type 2 diabetes (41%), unconfirmed type 1 diabetes (4%), and secondary diabetes (2%). The average BMI using lowest recorded BMI was 25.6 (range 16-29.96 kg/m2). Average hemoglobin A1c was 6.0% and fasting glucose was 100.6 mg/dL. These patients will be contacted for study enrollment and genetic testing to determine the pickup rate of GCK-MODY using the proposed screening cutoffs in this multiethnic population. The initial data indicate that the EMR can be used to identify patients at higher risk for GCK-MODY to undergo genetic testing. Several challenges were encountered including duplicate ICD codes but these did not preclude successful cohort identification. Disclosure L.T. Dickens: None. L.R. Letourneau: Other Relationship; Self; Novo Nordisk Inc.. M. Sanyoura: None. L.H. Philipson: Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; JAEB Center For Health Research, JDRF, Janssen Pharmaceuticals, Inc., Medtronic MiniMed, Inc. S.W. Greeley: Research Support; Self; Novo Nordisk Inc.. R.N. Naylor: None.

Postmenopausal osteoporosis is associated with elevated aldosterone/renin ratio.

Plasma aldosterone/renin ratio (ARR) is a useful method for primary aldosteronism (PA) screening. However some confounders, such as medications and dietary, affect plasma renin and aldosterone levels, resulting in false-negative or -positive plasma ARR. This study investigated the association between postmenopausal osteoporosis (PMO) and plasma ARR. Bone mineral density (BMD) was measured by dual-energy X-ray-absorptiometry (DXA) in 324 normotensive postmenopausal women. Based on clinical characteristics and BMD, 186 and 96 subjects were diagnosed as PMO and osteopenia respectively, and the remaining 42 subjects were grouped as normal BMD. Plasma aldosterone concentration (PAC), plasma renin concentration (PRC), parathyroid hormone (PTH), bone alkaline phosphatase (BALP) and 25-Hydroxyvitamin D(25-(OH)D) were determined. Subjects with PMO showed significantly higher levels of PAC (121.0 ± 78.8 vs. 81.8 ± 71.5 pg/ml, p < 0.01 and 121.0 ± 78.8 vs. 91.7 ± 56.2 pg/ml, p < 0.01) and ARR (32.0 ± 53.6 vs. 9.0 ± 9.3 pg/μU, p < 0.01 and 32.0 ± 53.6 vs. 16.3 ± 32.1 pg/μU, p < 0.01) compared to women with normal BMD and osteopenia, respectively. Using ARR ≥ 37.0 pg/μU as the cutoff for positive screening, more false-positive was found in the PMO group when compared to the normal BMD group (24 vs. 2%) and osteopenia group (24 vs. 7%), respectively. PAC was negatively associated with lumbar spine BMD T-score (r = -0.239, p < 0.001), femur neck BMD T-score (r = -0.234, p < 0.001) and total hip BMD T-score (r = -0.228, p < 0.001). PTH was positively associated with PAC (r = 0.119, p < 0.05) and ARR (r = 0.136, p < 0.05). PAC and ARR are elevated in women with PMO, which might increase the risk of false-positive for case detection of PA.

Attachment security buffers the HPA axis of toddlers growing up in poverty or near poverty: Assessment during pediatric well-child exams with inoculations

Poverty is associated with poor physical and emotional development. Activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is argued to be one of the pathways through which poverty acts on these outcomes. While studies of school-aged children have found some evidence for this, there is little evidence for this hypothesis early in development. This may be, in part, because for very young children, the security of their attachment relationships with parents moderates the impact of poverty on HPA axis functioning. The current study investigated the relations between family income as a percentage of the federal poverty limit (FPL), salivary cortisol and attachment (Attachment Q-sort) during well-child checkups with inoculations in 177 toddlers between 12- and 22-months of age. Approximately half of the toddlers were in families living below 150% FPL, with 47% of these classified as securely attached, compared to 72% of toddlers in families living above 150% FPL. Cortisol levels increased in response to the inoculation and this did not differ by poverty or attachment security. Overall, however, beginning at clinic arrival toddlers in families living below 150% FPL who had an insecure attachment had significantly higher cortisol compared to toddlers living in poverty or near poverty with secure attachments. This finding held when we removed toddlers with high levels of negative life events in their families and primary caregivers who exceeded the screening cutoff for depressive symptoms. Thus, attachment was a significant moderator of the association between poverty and HPA axis activity, with significant implications for screening and referral of caregiving dyads at risk.

Artificial Intelligence Approach for Variant Reporting.

PurposeNext-generation sequencing technologies are actively applied in clinical oncology. Bioinformatics pipeline analysis is an integral part of this process; however, humans cannot yet realize the full potential of the highly complex pipeline output. As a result, the decision to include a variant in the final report during routine clinical sign-out remains challenging.MethodsWe used an artificial intelligence approach to capture the collective clinical sign-out experience of six board-certified molecular pathologists to build and validate a decision support tool for variant reporting. We extracted all reviewed and reported variants from our clinical database and tested several machine learning models. We used 10-fold cross-validation for our variant call prediction model, which derives a contiguous prediction score from 0 to 1 (no to yes) for clinical reporting.ResultsFor each of the 19,594 initial training variants, our pipeline generates approximately 500 features, which results in a matrix of > 9 million data points. From a comparison of naive Bayes, decision trees, random forests, and logistic regression models, we selected models that allow human interpretability of the prediction score. The logistic regression model demonstrated 1% false negativity and 2% false positivity. The final models’ Youden indices were 0.87 and 0.77 for screening and confirmatory cutoffs, respectively. Retraining on a new assay and performance assessment in 16,123 independent variants validated our approach (Youden index, 0.93). We also derived individual pathologist-centric models (virtual consensus conference function), and a visual drill-down functionality allows assessment of how underlying features contributed to a particular score or decision branch for clinical implementation.ConclusionOur decision support tool for variant reporting is a practically relevant artificial intelligence approach to harness the next-generation sequencing bioinformatics pipeline output when the complexity of data interpretation exceeds human capabilities.

Monitoring and Fostering Elementary School Students' Life Satisfaction: A Case Study

ABSTRACTResearch on the importance of complete mental health has led to increased focus on students' subjective well-being (i.e., happiness and life satisfaction) coupled with the traditional attention to psychopathology. Although screeners for psychopathology abound, the present project is novel in applying best practices in universal screening to grade level-wide assessment of children's life satisfaction, followed by implementation of a positive psychology intervention for students identified through the screener. In this case study of 375 third- to fifth-grade students in one elementary school, 93.6% participated in the screening, 11.2% qualified for supplemental services based on screening cutoff scores, and 4.8% took part in the targeted intervention to improve subjective well-being. Repeated measures analysis of mean scores revealed the intervention increased children's life satisfaction, lending support for the value of universal screeners in the process of service delivery. Implications for practice regarding universal screening and intervention for life satisfaction are discussed.

Recommendations for Toxicological Investigation of Drug-Impaired Driving and Motor Vehicle Fatalities-2017 Update.

This report describes the outcomes of a process undertaken to review and update the National Safety Council's Alcohol, Drugs and Impairment Division's recommendations for the toxicological investigation of suspected alcohol and drug-impaired driving cases and motor vehicle fatalities. The updates to the recommendations are made based on a survey of practices in laboratories in the USA and Canada performing testing in these cases, consideration of existing epidemiological crash and arrest data, current drug use patterns, and practical considerations of widely available technology platforms in laboratories performing this work. The final recommendations updates are derived from a consensus meeting of experts recruited from survey respondents and the membership of the National Safety Council's Alcohol, Drug and Impairment Division. The principal changes in this round of recommendations include removal of butalbital, phenobarbital, and phencyclidine from Tier I (mandatory) to Tier II (optional) due to changes in prevalence. In addition, buprenorphine, fentanyl, tramadol, and their metabolites were moved from Tier II to Tier I due to increased prevalence and concerns about their potential for causing impairment. In addition, screening and confirmatory cutoffs for the oral fluid scope were further refined. Other additions were made to the list of Tier II compounds including fentanyl analogs (e.g., acetylfentanyl, butyrylfentanyl, furanylfentanyl, etc), mitragynine, novel opioids (e.g., MT-45, U-47700), atypical antipsychotics, and novel benzodiazepines (e.g., clonazolam, flubromazolam, etc).

The Diagnostic Sensitivity of the Memorial Delirium Assessment Scale—Spanish Version

BackgroundAlthough Memorial Delirium Assessment Scale (MDAS) is a successful tool for delirium evaluation and monitoring, it is nevertheless important to determine whether cutoff scores vary according to the studied population. The main objective of this study was to evaluate the diagnostic sensitivity of the recently validated Spanish version of the MDAS. The secondary objective was to analyze possible diagnostic differences when used in a hospice or general hospital setting. MethodologyA prospective study was conducted with advanced cancer patients in two settings (hospice and general hospital). A diagnosis of delirium was established according to clinical criteria and the Confusion Assessment Method. Sensitivity (S), specificity (Sp), positive predictive value, and negative predictive value were determined according to the receiver operating characteristics curve. The MDAS values for different centers were studied using nonparametric tests (Mann-Whitney). ResultsA total of 67 patients were included, 28 of whom had been diagnosed with delirium (15/40 hospice and 13/27 general hospital). The mean MDAS scores were 13.6 and 5.5 for the delirium and nondelirium groups, respectively. A cutoff score of 7 gave the optimal screening diagnosis balance (S 92.6%, Sp 71.8%, positive predictive value 70.1%, and negative predictive value 93.3%). Diagnoses of anxiety and depression were not related with delirium (P ≤ 0.44). A diagnosis of dementia was related to delirium (P ≤ 0.052) but did not influence the diagnostic sensitivity of MDAS (P ≤ 0.26). No differences were found between hospice and general hospital settings as regards the diagnostic sensitivity of MDAS. ConclusionA screening cutoff of 7 appears to be optimal for MDAS Spanish version. No differences were found between advanced cancer patients cared for in a hospice or general hospital. However, more research is required to define the MDAS cutoff for patients with advanced cancer and dementia.

High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry.

New technologies are urgently required for reliable drug screening given a worldwide epidemic of prescription drug abuse and its devastating socioeconomic impacts on public health. Primary screening of drugs of abuse (DoA) currently relies on immunoassays that are prone to bias and are not applicable to detect an alarming array of psychoactive stimulants, tranquilizers, and synthetic opioids. These limitations impact patient safety when monitoring for medication compliance, drug substitution, or misuse/abuse and require follow-up confirmatory testing by more specific yet lower throughput instrumental methods. Herein, we introduce a high throughput platform for nontargeted screening of a broad spectrum of DoA and their metabolites based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). We demonstrate that MSI-CE-MS enables serial injections of 10 samples within a single run (<3 min/sample) where multiplexed electrophoretic separations are coupled to high resolution MS with full-scan data acquisition. Unambiguous drug identification was achieved by four or more independent parameters, including comigration with a deuterated internal standard or in silico prediction of electromigration behavior together with accurate mass, most likely molecular formula, as well as MS/MS as required for confirmation testing. Acceptable precision was demonstrated for over 50 DoA at 3 concentration levels over 4 days (median coefficient of variance = 13%, n = 117) with minimal ion suppression, isobaric interferences, and sample carry-over (<1%). This approach offers a rapid yet accurate method for simultaneous detection and identification of DoA at their recommended screening cutoff levels in human urine while allowing for systematic surveillance, specimen verification, and retrospective testing of designer drugs that elude conventional drug tests.

Optimal risk cut-offs for Down syndrome contingent maternal serum screening

Objectives: The objective of this study is to identify the optimal cut-off points of contingent serum screening excluding nuchal translucency (NT) measurement, to categorize the risk level in the first trimester. Methods: A prospective database of women undergoing contingent serum screening, without NT measurement, was reviewed. In conventional categorization, the results of first-trimester screening were categorized into high risk (>1:30) (invasive diagnosis was offered); intermediate risk (1:30–1:1500) (second-trimester screening was needed); and low risk (<1:1500) (no further test). We recategorized the risk levels using various upper and lower cut-offs and compared detection rates, false-positive rates, and rates of intermediate risk. Results: Among 24,874 women, the prevalence of Down syndrome was 1:691. The previously agreed cut-offs had a detection rate of 88.9% and a false-positive rate of 8.5% with high rate of intermediate risk (38.2%). Re-categorization provided the optimal lower and upper cut-offs 1/900 and 1/50, respectively, giving a detection rate of 86.1%, a false-positive rate of 8.1%, and a rate of intermediate risk of 24.8%. Conclusions: This is the first study on contingent serum screening without NT measurement which shows a high detection rate with an acceptable false-positive rate. The optimal cut-offs to categorize the risk levels of the upper and the lower cut-off was 1:30–1:50 and 1:900, respectively.

Impact of Fecal Hb Levels on Advanced Neoplasia Detection and the Diagnostic Miss Rate For Colorectal Cancer Screening in High-Risk vs. Average-Risk Subjects: a Multi-Center Study.

Objectives:The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to identify high-risk subjects for advanced neoplasia. However, the appropriate fecal immunochemical test (FIT) cutoff for high-risk population may be different from that of average-risk population. We aimed to evaluate the FIT performance at different cutoffs in high-risk subjects undergoing colorectal cancer (CRC) screening.Methods:We prospectively enrolled asymptomatic subjects aged 50–75 years. Using the APCS score, subjects were stratified into either the average-risk or high-risk groups. All subjects were tested with one-time quantitative FIT and underwent colonoscopy. We compared the FIT performance for advanced neoplasia between two groups using different cutoffs (5 (FIT5), 10 (FIT10), 20 (FIT20), 30 (FIT30), and 40 (FIT40) μg Hb/g feces).Results:Overall, 1,713 subjects were recruited, and 1,222 (71.3%) and 491 (28.7%) were classified as average-risk and high-risk, respectively. Advanced neoplasia was detected in 90 (7.4%) of the average-risk subjects and 65 (13.2%) of the high-risk subjects. In the high-risk group, by decreasing the cutoff from FIT40 to FIT5, the sensitivity increased by 33.8 percentage points with decreased specificity by 11 percentage points. In the average-risk group, the sensitivity increased by 20 percentage points with decreased specificity by 9.6 percentage points. At the lowest cutoff (FIT5), the number of needed colonoscopies to find one advanced neoplasia was 2.8 and 6.1 for the high-risk and average-risk groups, respectively.Conclusions:Using an appropriate FIT cutoff for CRC screening in high-risk subjects could improve CRC screening performance and reduce the unnecessary colonoscopies. To maintain high sensitivity and specificity for advanced neoplasia, the optimal cutoff FIT in the high-risk subjects should be lower than that in the average-risk subjects.

Posttraumatic Stress Symptoms and Alcohol-Related Outcomes Among Municipal Firefighters.

This study examined levels of posttraumatic stress symptoms (PTSS) and relationships between PTSS and alcohol-related outcomes in a near census of municipal firefighters. The study also assessed substance-use coping and drinking to cope as potential mediators of such outcomes. Firefighters (N = 740) completed measures that assessed PTSS, alcohol risk behaviors, alcohol problems, drinking motives, and coping with stress. Results showed that 32.4% of firefighters reported significant levels of PTSS using National Center for PTSD (2014) screening cutoff scores. Correlational analysis showed that PTSS was related to at-risk drinking (r = .18) and alcohol-related problems (r = .33), as well as use of maladaptive coping strategies (r = .58) and substance use coping (r = .40). Structural analyses comparing multiple alternative models suggested that a model that included substance use coping and drinking to cope as mediators of the association between PTSS and problem drinking provided the best fit to the data. Tests of multigroup invariance confirmed this model. Overall, PTSS were common in this population and they predicted maladaptive coping patterns and alcohol-related consequences. One implication of these findings is that fire departments might consider adding or enhancing screening and treatment options for PTS, alcohol misuse, or both.

Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?

When newborn screening (NBS) for congenital hypothyroidism (CH) using thyroid-stimulating hormone (TSH) as a primary screening test was introduced, typical TSH screening cutoffs were 20-50 U/L of whole blood. Over the years, lowering of TSH cutoffs has contributed to an increased prevalence of detected CH. However, a consensus on the benefit deriving from lowering TSH cutoffs at screening is lacking. The present paper outlines arguments both for and against the lowering of TSH cutoffs at NBS. It includes a review of recently published evidence from Australia, Belgium and Italy. A section focused on economic implications of lowering TSH cutoffs is also provided. One issue that bears further examination is the extent to which mild iodine deficiency at the population level might affect the association of neonatal TSH values with cognitive and developmental outcomes. A debate on TSH cutoffs provides the opportunity to reflect on how to make NBS for CH more effective and to guarantee optimum neurocognitive development and a good quality of life to babies with mild as well as with severe CH. All authors of this debate article agree on the need to establish optimal TSH cutoffs for screening programs in various settings and to ensure the benefits of screening and access to care for newborns worldwide.

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50.

Patients with Fanconi anemia (FA) have an increased risk for head and neck squamous cell carcinoma (HNSCC). The authors sought to determine the prevalence of undiagnosed FA and FA carriers among patients with HNSCC as well as an age cutoff for FA genetic screening. Germline DNA samples from 417 patients with HNSCC aged <50 years were screened for sequence variants by targeted next-generation sequencing of the entire length of 16 FA genes. The sequence revealed 194 FA gene variants in 185 patients (44%). The variant spectrum was comprised of 183 nonsynonymous point mutations, 9 indels, 1 large deletion, and 1 synonymous variant that was predicted to effect splicing. One hundred eight patients (26%) had at least 1 rare variant that was predicted to be damaging, and 57 (14%) had at least 1 rare variant that was predicted to be damaging and had been previously reported. Fifteen patients carried 2 rare variants or an X-linked variant in an FA gene. Overall, an age cutoff for FA screening was not identified among young patients with HNSCC, because there were no significant differences in mutation rates when patients were stratified by age, tumor site, ethnicity, smoking status, or human papillomavirus status. However, an increased burden, or mutation load, of FA gene variants was observed in carriers of the genes FA complementation group D2 (FANCD2), FANCE, and FANCL in the HNSCC patient cohort relative to the 1000 Genomes population. FA germline functional variants offer a novel area of study in HNSCC tumorigenesis. FANCE and FANCL, which are components of the core complex, are known to be responsible for the recruitment and ubiquitination, respectively, of FANCD2, a critical step in the FA DNA repair pathway. In the current cohort, the increased mutation load of FANCD2, FANCE, and FANCL variants among younger patients with HNSCC indicates the importance of the FA pathway in HNSCC. Cancer 2017;123:3943-54. © 2017 American Cancer Society.