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Background and Aims: The multitarget stool DNA (mt-sDNA) assay is a noninvasive average-risk colorectal cancer (CRC) screening test. A new biomarker panel was developed for a next-generation test to improve specificity while maintaining/increasing sensitivity. We aimed first to establish an algorithm and cutoff for the next-generation mt-sDNA test and then to validate it using archived samples from the pivotal DeeP-C study (NCT01397747) of the first-generation test. Methods: Algorithm development and cross-validation included 3011 samples from 2 specimen collection studies (NCT03821948 and NCT03789162). The algorithm and cutoff were locked before validation. Validation test set samples included 57 CRC, 583 advanced precancerous lesions (APLs), and 7022 samples negative for CRC or APLs from the DeeP-C study, which prospectively enrolled average-risk, asymptomatic adults aged 50–84 years before screening colonoscopy. Next-generation biomarkers included methylated DNA markers ceramide synthase 4 gene, leucine-rich repeat-containing protein 4 gene, serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform gene, and zinc finger DHHC-type containing 1 gene (reference marker), and fecal hemoglobin. Primary validation end points were CRC sensitivity and specificity for the absence of advanced neoplasia. Secondary end points included APL sensitivity and specificity for non-neoplastic findings or negative colonoscopy. Results: Cross-validation and best-fit results from algorithm development closely matched, confirming algorithm reliability and reproducibility. For the test set, next-generation mt-sDNA test sensitivity was 93.0% (95% confidence interval [CI], 83.0%–98.1%) for CRC and 48.4% (95% CI, 44.2%–52.5%) for APLs. Specificity was 88.5% (95% CI, 87.7%–89.2%) for the absence of advanced neoplasia and 90.4% (95% CI, 89.5%–91.2%) for the combination of non-neoplastic findings or negative colonoscopy. Conclusion: Based on archived samples, the next-generation mt-sDNA test demonstrated promising CRC screening performance characteristics that will be further assessed in a prospective clinical validation study (BLUE-C; NCT04144738).

Objective: To evaluate the effect of hemorrhoids on noninvasive stool test performance for colorectal cancer (CRC) screening. Patients and Methods: We conducted a retrospective cohort study of test characteristics for the fecal immunochemical test (FIT) and the multitarget stool DNA (mt-sDNA) test, on the basis of hemorrhoid status, recorded at the time of colonoscopy, among patients enrolled in the pivotal prospective study for mt-sDNA that was conducted from June 2011, to May 2013. Test characteristics (sensitivity, specificity, positive, and negative predictive values) for FIT and mt-sDNA (performed < 90 days before colonoscopy) were stratified by the presence of hemorrhoids and compared. Results: Hemorrhoids were found in 51.7% (5163 of 9989) of the study cohort. Across all test characteristics, there were no statistically significant differences for FIT or mt-sDNA when stratified by hemorrhoid status. Analysis revealed mt-sDNA sensitivity of 44% and 41% for advanced precancerous lesions in nonhemorrhoidal and hemorrhoid patients, respectively (P=.41). The FIT sensitivity among the same lesion category was 24.9% in patients without hemorrhoids and 22.8% in those with hemorrhoids (P=.48). The mt-sDNA specificity was 86.4% in patients without hemorrhoids vs 87.7% in those with hemorrhoids (P=.67), although FIT specificity was 95.0% among patients without hemorrhoids vs 94.7% in those with hemorrhoids (P=.44). Conclusion: The presence of asymptomatic hemorrhoids did not adversely affect test performance in this large clinical study. These findings suggest that in the absence of overt gastrointestinal bleeding, FIT and mt-sDNA are options for CRC screening, irrespective of hemorrhoid status. Trial Registration: clinicaltrials.gov Identifier: NCT01397747

Law enforcement agencies manually transcribe thousands of investigative interviews per year in relation to different crimes. In order to automate and improve efficiency in the transcription of such interviews, applied research explores artificial intelligence models, including Automatic Speech Recognition (ASR) and Natural Language Processing. While AI models can improve efficiency in criminal investigations, their successful implementation requires evaluation of legal and technical risks.This paper explores the legal and technical challenges of applying ASR models to investigative interviews in the context of the European Union Artificial Intelligence Act (AIA). The AIA provisions are discussed in the view of domain specific studies for interviews in the Norwegian police, best practices, and empirical analyses in speech recognition in order to provide law enforcement with a practical code of conduct on the techno-legal requirements for the adoption of such models in their work and potential grey areas for further research.

Abstract Ultrasound‐based surveillance has suboptimal sensitivity for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis. There are several emerging alternatives, including a novel multitarget HCC blood test (Mt‐HBT). We compared performance of mt‐HBT against ultrasound with or without alpha‐fetoprotein (AFP) for early HCC detection in patients with cirrhosis. Per the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines, two reviewers searched PubMed, Cochrane, Embase, and clinicaltrials.gov databases from January 1990 through December 2020 to identify studies reporting sensitivity and/or specificity of ultrasound and AFP for overall and early stage HCC detection in patients with cirrhosis. Mt‐HBT diagnostic performance was derived from a clinical validation study. A network meta‐analysis model was built for comparative assessment, and pooled estimates of sensitivity at a fixed specificity were estimated based on Bayesian binormal receiver operating characteristic models for each modality. Forty‐one studies (comprising 62,517 patients with cirrhosis) met inclusion criteria. Ultrasound‐alone sensitivity was 51.6% (95% credible interval [CrI], 43.3%–60.5%) for early stage HCC detection, which increased with the addition of AFP to 74.1% (95% CrI, 62.6%–82.4%); however, this was offset by decreased specificity (87.9% vs. 83.9%, respectively). With specificity fixed at 90%, mt‐HBT sensitivity for early stage HCC detection was higher than ultrasound alone (18.2%; 95% CrI, 0.2%–37.7%) and similar to ultrasound with AFP (−3.3%; 95% CrI, −22.3%–17.4%). Pairwise posterior probabilities suggested a preference for mt‐HBT over ultrasound alone in 97.4% of cases but only 36.3% of cases versus ultrasound with AFP. Conclusion: A blood‐based mt‐HBT has higher sensitivity than ultrasound alone for early stage HCC detection but similar sensitivity compared to ultrasound and AFP. Mt‐HBT could be a comparable alternative to existing methods for HCC surveillance in patients who are at risk.

Abstract Background 18 F‐Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. Methods This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. Results Forty‐five (PET+) ITNs were identified: 31 Afirma‐tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma “suspicious” non‐resected ITNs and assuming all Afirma “benign” ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC‐tested ITNs, the BCR was higher in ITNs demonstrating low/very low‐risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring

Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real‐world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression‐free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety‐one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.

Background: Data from the 2009 influenza pandemic suggested asthma might protect from severe disease in hospitalized patients. Asthma does not appear to increase risk for hospitalization or mortality with COVID-19. Objective: This study was undertaken to see if atopy actually protected those hospitalized with COVID-19. Methods: Retrospective chart review on all patients testing positive for SARS-CoV-2 over 2 months at a major adult and pediatric tertiary referral center hospital. Charts were evaluated for history of atopic disease, as were the need for ICU admission, requirement for supplemental oxygen and/or intubation, and in hospital mortality. Results: No significant differences in outcomes for patients (n = 275) based on atopic disease were noted: ICU admission, 43% versus 44.7% (atopic versus no atopic disease, respectively; p = 0.84); supplemental oxygen use, 79.1% versus 73.6% (p = 0.36); intubation rate, 35.8% versus 36.5% (p = 0.92); and mortality rate, 13.4% versus 20.7% (p = 0.19). More patients with atopic disease had COPD listed as a diagnosis in their chart (38.8% versus 17.3%, p 0.2). Conclusion: Severity of COVID-19 in hospitalized patients does not differ based on atopic status. However, adjusting for presence of COPD led to a suggestion of possible reduced severity in patients with atopy but not asthma.

Adiponectin and leptin are hormones known to play roles in maternal metabolism during pregnancy. Levels of these hormones have been demonstrated to vary based on adiposity and race. However, there is a lack of data concerning the relationship between race and the change of adiponectin and leptin throughout pregnancy. The purpose of this study was to examine serum levels of adiponectin, leptin, and leptin-to-adiponectin ratio (LAR) throughout pregnancy and to assess their association with gestational weight gain (GWG) and infant birth weight while considering the effects of race and pre-pregnancy body mass index (BMI). Serum levels of adiponectin, leptin, gestational weight gain, and infant birth weight were measured in 80 pregnant women at early (12.4 ​± ​1.3 weeks gestation), mid (20.6 ​± ​1.3 weeks gestation), late pregnancy (29.2 ​± ​1.4 weeks gestation), and 7–11 weeks postpartum (8.8 ​± ​0.8 weeks). In women overall, serum adiponectin decreased across pregnancy and increased at postpartum (p ​= ​0.17.) At each prenatal timepoint, both black race and obesity were associated with lower adiponectin (ps ​

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.

Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20-27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio.

Abstract  This article examines the impact of providing personalized familial cancer risk assessments with the Jameslink Cancer Risk Assessment Tool. Users of the Jameslink (N = 166) at eight community health fairs completed a survey including demographic, psychosocial and behavioral variables to better understand responses to the Jameslink. No differences were found between whites and those of other races for variables of interest, indicating suitability of the Jameslink for diverse populations. Those with higher Jameslink-assessed risk had higher perceived risk of cancer. Approximately half (53.8%) reported that they would speak to their physician about their Jameslink-assessed risk. A regression found Jameslink-assessed risk, cancer worry, and perceived risk of cancer predicted intentions to speak to a physician about their risk. In addition, open-ended data provided suggestions to improve the Jameslink. Changes in content and format were suggested; however most were happy with the program and encouraged its promotion. The lack of findings for differences as a function of race bolsters the use of computerized Cancer Risk Assessment Tools in diverse communities. The positive feedback of users and the close association between cancer risk assessment, perceived risk, and intention to speak to a physician are supportive of continued use and development of Cancer Risk Assessment Tools in the community to promote awareness of cancer risk. [ABSTRACT FROM AUTHOR]

Abstract  Family history is one the greatest risk factors for disease and one of the most important informational tools in medical genetics for the purpose of diagnosis, risk assessment, prevention and treatment. However, research is needed on the comparability of different methods of cancer family history assessment and the influence of psychosocial factors in family history reports. The purpose of this study was to determine if individuals had discrepancies between written and interview reports of cancer family history and the role of psychosocial factors in these discrepancies. Oncology patients (n=104) were administered a survey to assess psychosocial factors (i.e., information-seeking, worry, perceived risk, and health literacy) and were asked to provide family history in a written and an interview form. Randomization determined which form individuals received first. No differences in the amount of missing data or the amount of unspecified data were noted between the written and interview method. Psychosocial factors did not differentiate between those who had discrepancies in family history reports and those who did not have discrepancies in family history reports; although there was a trend for those with lower literacy and those who were blunters to be more discrepant on type of cancer diagnosis. In sum, this preliminary study indicates that written and interview methods of family history assessment for first degree relatives may be used interchangeably. The ability to use written methods will facilitate collection of basic family history information in the oncology clinic. [ABSTRACT FROM AUTHOR]

Evidence guiding inpatient management of buprenorphine is lacking-this retrospective cohort study evaluated the clinical impact of hospital continuation versus discontinuation of buprenorphine at an academic medical center. The primary outcome was inpatient oral morphine equivalents (OME). Secondary outcomes included patient pain levels, functional assessment, and hospital length of stay. One hundred thirty-one patients (74 continued buprenorphine, 57 discontinued) were included in the analysis. Median OME were significantly lower among patients continued on buprenorphine versus discontinued (11 mg vs 103 mg, p  < 0.001), as was maximum 24-hour opioid utilization (60 mg vs 240 mg, p  < 0.001) and 24-hour pre-discharge utilization (10 mg vs 128 mg, p  < 0.001). Median pain levels were similar between groups at the time of admission (8 in each group, p  = 0.48), discharge (7 in each group, p  = 0.26), and over the first 7 days of hospitalization (7 vs 8, p  = 0.08). Hospital length of stay was similar between groups (5 days in each group, p  > 0.99). Failure to reinitiate buprenorphine occurred in 31/57 patients (54.4%) in the discontinuation group. Hospital buprenorphine continuation is associated with reduced opioid requirements, while not significantly impacting pain levels, functionality, or length of admission. Failure to reinitiate buprenorphine was common and may have negative implications for addiction treatment.

Purpose: The acuity adjustment metric that correlates most closely with actual medication expense at a large, tertiary care academic medical center was investigated., Methods: This evaluation was conducted at the Ohio State University Wexner Medical Center. All inpatient discharges between July 1, 2012, and March 31, 2013, were included in this study. Patient medical and financial records were used to obtain the diagnosis-related group (DRG) codes and total medication cost for each patient discharge. The primary DRG for each patient was then used to assign the corresponding relative weight (RW) and pharmacy intensity weight (PIW). The correlation between actual and predicted medication expenditure was determined for every DRG for both RW and PIW. Since this compares cost at the DRG level, RW and PIW were used as markers for case-mix index (CMI) and pharmacy intensity score (PIS), respectively., Results: At this single institution, medication cost per discharge was more strongly correlated with PIW (as a marker for PIS) than with RW (as a marker for CMI). Extrapolating these data to hospital-specific values, the results suggest that PIS is more strongly correlated with overall medication expense than CMI and therefore a better adjustment metric for monitoring medication expense over time., Conclusion: A single-institution study demonstrated that PIW was more strongly correlated than RW with actual medication expenditure. PIS may be a more accurate acuity metric than CMI for predicting changes in drug expense over time., (Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)