Newborn Pulse Oximetry for Infants Born Out-of-Hospital.

BACKGROUND AND OBJECTIVES: Conventional timing of newborn pulse oximetry screening is not ideal for infants born out-of-hospital. We implemented a newborn pulse oximetry screen to align with typical midwifery care and measure its efficacy at detecting critical congenital heart disease. METHODS: Cohort study of expectant mothers and infants mainly from the Amish and Mennonite (Plain) communities with limited prenatal ultrasound use. Newborns were screened at 1 to 4 hours of life ("early screen") and 24 to 48 hours of life ("late screen"). Newborns were followed up to 6 weeks after delivery to report outcomes. Early screen, late screen, and combined results were analyzed on the basis of strict algorithm interpretation ("algorithm") and the midwife's interpretation in the field ("field") because these did not correspond in all cases. RESULTS: Pulse oximetry screening in 3019 newborns (85% Plain; 50% male; 43% with a prenatal ultrasound) detected critical congenital heart disease in 3 infants. Sensitivity of combined early and late screen was 66.7% (95% confidence interval [CI] 9.4% to 99.2%) for algorithm interpretation and 100% (95% CI 29.2% to 100%) for field interpretation. Positive predictive value was similar for the field interpretation (8.8%; 95% CI 1.9% to 23.7%) and algorithm interpretation (5.4%; 95% CI 0.7% to 18.2%). False-positive rates were ≤1.2% for both algorithm and field interpretations. Other pathologies (noncritical congenital heart disease, pulmonary issues, or infection) were reported in 12 of the false-positive cases. CONCLUSIONS: Newborn pulse oximetry can be adapted to the out-of-hospital setting without compromising sensitivity or prohibitively increasing false-positive rates.

Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin.

Background: Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms. Materials and Methods: Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000. Results: Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8. Conclusions: A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.

Electrophysiological Study-Guided Permanent Pacemaker Implantation in Patients With Conduction Disturbances Following Transcatheter Aortic Valve Implantation.

Conduction disturbances remain common following transcatheter aortic valve implantation (TAVI). Aside from high-degree atrioventricular block (HAVB), their optimal management remains elusive. Invasive electrophysiological studies (EPS) may help stratify patients at low or high risk of HAVB allowing for an early discharge or permanent pacemaker (PPM) implantation among patients with conduction disturbances. We evaluated the safety and diagnostic performances of an EPS-guided PPM implantation strategy among TAVI recipients with conduction disturbances not representing absolute indications for PPM. All patients who underwent TAVI at a single expert center from June 2017 to July 2020 who underwent an EPS during the index hospitalization were included in the present study. False negative outcomes were defined as patients discharged without PPM implantation who required PPM for HAVB within 6 months of the initial EPS. False positive outcomes were defined as patients discharged with a PPM with a ventricular pacing percentage <1% at follow-up. A total of 78 patients were included (median age 83.5, 39% female), among whom 35 patients (45%) received a PPM following EPS. The sensitivity, specificity, positive and negative predictive values of the EPS-guided PPM implantation strategy were 100%, 89.6%, 81.5%, and 100%, respectively. Six patients suffered a mechanical HAVB during EPS and received a PPM. These 6 patients showed PPM dependency at follow-up. In conclusion, an EPS-guided PPM implantation strategy for managing post-TAVI conduction disturbances appears effective to identify patients who can be safely discharged without PPM implantation.

Behavioral Battery for Testing Candidate Analgesics in Mice. I. Validation with Positive and Negative Controls.

This study evaluated a battery of pain-stimulated, pain-depressed, and pain-independent behaviors for preclinical pharmacological assessment of candidate analgesics in mice. Intraperitoneal injection of dilute lactic acid (IP acid) served as an acute visceral noxious stimulus to produce four pain-related behaviors in male and female ICR mice: stimulation of 1) stretching, 2) facial grimace, 3) depression of rearing, and 4) depression of nesting. Additionally, nesting and locomotion in the absence of the noxious stimulus were used to assess pain-independent drug effects. These six behaviors were used to compare effects of two mechanistically distinct but clinically effective positive controls (ketoprofen and oxycodone) and two negative controls that are not clinically approved as analgesics but produce either general motor depression (diazepam) or motor stimulation (amphetamine). We predicted that analgesics would alleviate all IP acid effects at doses that did not alter pain-independent behaviors, whereas negative controls would not. Consistent with this prediction, ketoprofen (0.1-32 mg/kg) produced the expected analgesic profile, whereas oxycodone (0.32-3.2 mg/kg) alleviated all IP acid effects except depression of rearing at doses lower than those that altered pain-independent behaviors. For the negative controls, diazepam (1-10 mg/kg) failed to block IP acid-induced depression of either rearing or nesting and only decreased IP acid-stimulated behaviors at doses that also decreased pain-independent behaviors. Amphetamine (0.32-3.2 mg/kg) alleviated all IP acid effects but only at doses that also stimulated locomotion. These results support utility of this model as a framework to evaluate candidate-analgesic effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behavioral endpoints. SIGNIFICANCE STATEMENT: Preclinical assays of pain and analgesia often yield false-positive effects with candidate analgesics. This study used two positive-control analgesics (ketoprofen, oxycodone) and two active negative controls (diazepam, amphetamine) to validate a strategy for distinguishing analgesics from nonanalgesics by profiling drug effects in a battery of complementary pain-stimulated, pain-depressed, and pain-independent behaviors in male and female mice.

Recutting Blocks of Prostate Needle Biopsies: How Much Diagnostic Yield Is Gained?

Objectives. The criteria for "active surveillance" depend in part on quantification of tumor extent and grade on prostate biopsies. It is known that false-negative biopsies may occur from incomplete sectioning of cores within the paraffin blocks. Methods. We retrospectively analyzed a prostate biopsy series, which were subjected to a second round of sections, in order to determine the rate of missed cancers. Results. Of 1324 sets of prostate biopsies, 4.5% (60) showed additional involved cores or higher grade tumor on recut sections. In 27 patients (2.0%), the changed diagnosis resulted in a potential mild increase in National Comprehensive Cancer Network (NCCN) risk, from negative to very low (12), very low to low (12), and low to favorable intermediate (3). In 3 patients (0.2%), the changed diagnosis resulted in a significant increase in NCCN risk. Comparison of the initial sets of slides to the recuts demonstrated areas of absent tissue in many of the cases in which tumor segments were missed. In 2/3 cases with the significant grade increase, gaps were present in one that should have alerted the pathologist to incomplete sections, and the tumor was fragmented at the edge of the core appearing incompletely sampled. Conclusions. A significant increase in risk was seen in this study in 0.2% of patients when blocks were recut for further sampling, with minor increases in 2%. While embedding issues only rarely resulted in clinically significant sampling error, the 3 significantly underdiagnosed cases underscore the need for pathologists to be alert to incomplete sections of prostate cores.

Characterization of biotin interference in 21 Vitros 5600 immunoassays and risk mitigation for patient safety at a large academic medical center.

BACKGROUND: Biotin and streptavidin are commonly used reagents in clinical immunoassays. Several cases of biotin interference with immunoassay testing for patients taking biotin supplements have been reported, yet, not all analytes and platforms susceptible to biotin interference have been characterized. The objectives of this study are to characterize biotin interference with 21 immunoassays using the Ortho Clinical Diagnostics Vitros 5600, evaluate a biotin-depletion method, and apply risk mitigation strategies for biotin interference during routine clinical testing at our institution. METHODS: Residual serum without and with increasing concentrations of exogenous biotin were used to evaluate biotin interference with 21 immunoassays using the Vitros 5600. Biotin-depletion was evaluated by comparing measured analyte concentrations in serum with and without exogenous biotin and streptavidin-microparticle pretreatment. Focused education for healthcare professionals about biotin interference was performed in February 2018. Samples with suspected biotin interference were investigated using this biotin-depletion method, and analyte testing by alternate methodology for select samples. RESULTS: Exogenous biotin in serum caused dose-dependent negative biases in 15 immunometric assays, and dose-dependent positive biases in 6 competitive immunoassays. Streptavidin-microparticle pretreatment of serum containing exogenous biotin demonstrated recoveries 100 ±â€¯15% of expected values for all 21 analytes. Physicians identified 21 samples suspicious for biotin interference over 11 months, and streptavidin-microparticle pretreatment verified 11 cases of biotin interference. CONCLUSIONS: Analytical bias caused by biotin interference is dependent on biotin concentration but independent of analyte concentration for immunometric methods using the Vitros 5600, and dependent on both biotin and analyte concentration for competitive immunoassays. Multi-disciplinary education and a lab streptavidin-microparticle pretreatment method help mitigate risk of erroneous results due to biotin interference for patient safety.

Is Clinical Exam of the Axilla Sufficient to Select Node-Positive Patients Who Downstage After NAC for SLNB? A Comparison of the Accuracy of Clinical Exam Versus MRI.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) endorses sentinel lymph node biopsy (SLNB) in patients with clinically positive axillary nodes who downstage after neoadjuvant chemotherapy (NAC). In this study, we compared the accuracy of post-NAC MRI to clinical exam alone in predicting pathologic status of sentinel lymph nodes in cN1 patients. METHODS: We identified patients with T0-3, N1 breast cancer who underwent NAC and subsequent SLNB from March 2014 to July 2017. Patients were grouped based on whether a post-NAC MRI was done. MRI accuracy in predicting SLN status was assessed versus clinical exam alone. RESULTS: A total of 450 patients met initial study criteria; 269 were analyzed after excluding patients without biopsy-confirmed nodal disease, palpable disease after NAC, and failed SLN mapping. Median age was 49 years. Post-NAC MRI was done in 68% (182/269). Patients undergoing lumpectomy vs mastectomy more frequently received a post-NAC MRI (88 vs 54%, p < 0.001). All other clinicopathologic parameters were comparable between those who did and did not have a post-NAC MRI. Thirty percent (55/182) had abnormal lymph nodes on MRI. Among these, 58% (32/55) had a positive SLN on final pathology versus 42% (53/127) of patients with no abnormal lymph nodes on MRI and 52% (45/87) of patients who had clinical exam alone (p = 0.09). MRI sensitivity was 38%, specificity was 76%, and overall SLN status prediction accuracy was 58%. CONCLUSIONS: Post-NAC MRI is no more accurate than clinical exam alone in predicting SLN pathology in patients presenting with cN1 disease. Abnormal lymph nodes on MRI should not preclude SLNB.

Estimating sodium intake from spot urine samples at population level: a validation and application study in French adults.

The aim of this study was to assess the validity of the predictive INTERSALT equation using spot urine samples to estimate 24-h urinary Na (24-hUNa) excretion and daily Na intake among the French adult population. Among 193 French adults ('validation sample'), we assessed the validity by comparing predicted 24-hUNa excretion from spot urine and measured 24-hUNa excretion from 24-h urine collections. Spearman correlation coefficients and Bland-Altman plots were used and we calculated calibration coefficients. In a nationally representative sample of 1720 French adults ('application sample'), the calibrated predictive equation was then applied to the spot urine Na values to estimate 24-hUNa excretion and daily Na intake. In that sample, predicted Na intake was compared with that estimated from 24-h dietary recalls. Results were adjusted and corrected using calibration coefficients. In the validation sample, the measured 24-hUNa excretion was on average 14 % higher than the predicted 24-hUNa (+13 % for men and +16 % for women). Correlation between measured and predicted 24-hUNa excretion was moderate (Spearman r 0·42), and the Bland-Altman plots showed underestimation at lower excretion level and overestimation at higher level. In the application study, estimated daily salt intake was 8·0 g/d using dietary recalls, 8·1 g/d using predicted INTERSALT equation and 9·3 g/d after applying calibration coefficients calculated in the validation study. Despite overall underestimation of 24-hUNa excretion by spot urinary Na, the use of predictive INTERSALT equation remains an acceptable alternative in monitoring global Na intake/excreted in the French population but its use is not advised at the individual level.

Syncope, conduction disturbance, and negative electrophysiological test: Predictive factors and risk score to predict pacemaker implantation during follow-up.

BACKGROUND: Patients with syncope and bundle branch block (BBB) are at risk for atrioventricular block (AVB). Electrophysiological study (EPS) can help in identifying patients at higher risk for AVB, but the false-negative rate is remarkable. Few data on the predictors of the need for pacemaker implantation during follow-up have been reported. OBJECTIVE: The purpose of this study was to analyze the rate of patients who need pacemaker implantation after negative EPS and predictive factors. METHODS: A single-center prospective study of 159 consecutive patients (73.9 ± 12.1 years; male 64.9%) with syncope and BBB (January 2012-December 2016) and negative EPS was conducted. An implantable loop recorder was implanted. RESULTS: After 27.9 ± 10.8 months of follow-up, 39 patients (24.8%) underwent pacemaker implantation because of bradyarrhythmia. In the univariate analysis, bifascicular (right BBB + left fascicular block) block, bifascicular block + long PR interval, conduction disturbance different from isolated right BBB, HV ≥60 ms, and HV ≥70 ms after class I drug challenge were predictors of pacemaker implantation. In the multivariate analysis, only bifascicular block (hazard ratio 2.5; 95% confidence interval 1.4-4.8; P = .04) and HV interval ≥60 ms (hazard ratio 3.5; 95% confidence interval 1.8-6.2; P <.001) were statistically significant. A risk score according to the multivariate model identified 3 levels of pacemaker implantation rate (13.5%, 32.7%, and 66.7%; P <.001). No death or severe trauma related to bradyarrhythmia occurred. CONCLUSION: The strategy of an implantable loop recorder in patients with syncope and BBB is safe after negative EPS, but some patients might need pacemaker implantation during follow-up. A risk score based on HV ≥60 ms and bifascicular block can be useful in identifying patients at risk for advanced AVB after negative EPS.

Using predicate and provenance information from a knowledge graph for drug efficacy screening.

BACKGROUND: Biomedical knowledge graphs have become important tools to computationally analyse the comprehensive body of biomedical knowledge. They represent knowledge as subject-predicate-object triples, in which the predicate indicates the relationship between subject and object. A triple can also contain provenance information, which consists of references to the sources of the triple (e.g. scientific publications or database entries). Knowledge graphs have been used to classify drug-disease pairs for drug efficacy screening, but existing computational methods have often ignored predicate and provenance information. Using this information, we aimed to develop a supervised machine learning classifier and determine the added value of predicate and provenance information for drug efficacy screening. To ensure the biological plausibility of our method we performed our research on the protein level, where drugs are represented by their drug target proteins, and diseases by their disease proteins. RESULTS: Using random forests with repeated 10-fold cross-validation, our method achieved an area under the ROC curve (AUC) of 78.1% and 74.3% for two reference sets. We benchmarked against a state-of-the-art knowledge-graph technique that does not use predicate and provenance information, obtaining AUCs of 65.6% and 64.6%, respectively. Classifiers that only used predicate information performed superior to classifiers that only used provenance information, but using both performed best. CONCLUSION: We conclude that both predicate and provenance information provide added value for drug efficacy screening.

Biofilms busters to improve the detection of Borrelia using PCR.

Lyme disease is an affection caused by a spirochete infection called Borrelia Burgdorferi which may harbor a varied and misleading clinical symptomatology. The serology tests commonly used for diagnosis show a wide sensitivity varying from 34% to 70,5%, leaving many infected patients with false negative tests. Alternative techniques such as polymerase chain reaction (PCR) could be helpful but not conclusive enough. Using biofilm busters, such as stevia and serratiopeptidase, could lead to bacterial blood release, thus increasing the spirochete load, making PCR test more sensitive, thus improving the patient's diagnosis and management.

Multiplex Immunochromatographic Detection of OXA-48, KPC, and NDM Carbapenemases: Impact of Inoculum, Antibiotics, and Agar.

For the rapid detection of carbapenemase-producing Enterobacteriaceae (CPE), immunochromatographic lateral flow tests (ICT) have recently been developed. The aim of this study was to assess the new multiplex ICT Resist-3 O.K.N. and to investigate if it can be performed directly from susceptibility testing plates. Additionally, the impact of the inoculum and carbapenem disks on sensitivity and specificity was evaluated. The new ICT was challenged using 63 carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 51 carbapenemase producers. It was assessed under five different conditions directly from Mueller-Hinton agar (MHA): 1 µl or 10 µl of inoculum harvested in the absence of antibiotic pressure or 1 µl taken from the inhibition zone of either an ertapenem, imipenem, or meropenem disk. The sensitivity of the ICT was 100% for OXA-48-like and KPC carbapenemases and 94.4% for the NDM carbapenemase with the 1-µl inoculum. When harvested adjacent to a carbapenem disk, the sensitivity increased to 100%. Additionally, with zinc-supplemented MHA, both the sensitivity increased and the NDM band became visible faster (mean time, 8 ± 3.9 min for MHA compared to 1.9 ± 1.5 min for MHA plus zinc; P = 0.0016). The specificity of the ICT was 100%. The Resist-3 O.K.N. ICT is a sensitive and rapid test for the detection of three highly prevalent carbapenemases. However, false-negative results for NDM can occur. We recommend an inoculum of 1 µl that is harvested adjacent to an ertapenem or meropenem disk and the use of agars with sufficient zinc content to achieve the best performance.