Existing Screening Tests Research Articles

S485 Projected Benefit and Cost-Effectiveness of Offering a Choice of Blood-Based Screening Versus Existing Screening Tests for Colorectal Cancer in Two Real-World Settings

S485 Projected Benefit and Cost-Effectiveness of Offering a Choice of Blood-Based Screening Versus Existing Screening Tests for Colorectal Cancer in Two Real-World Settings

The Oropharyngeal Dysphagia Screening Test for Patients and Professionals: Validation in Cognitive Impairment and in Severe Mental Illness.

Dysphagia is a symptom that appears with high prevalence in persons diagnosed with dementia, intellectual disability, or severe mental illness. Risk of aspiration pneumonia or even death is very high in these populations. However, screening for dysphagia risk in these patients is complicated by the fact that most of them suffer from cognitive impairments and behavioral manifestations that hinder the assessment process using the existing screening tests. The aim of this study was to validate the Oropharyngeal Dysphagia Screening Test for Patients and Professionals, in patients with cognitive impairment (dementia/intellectual disability) or with severe mental illness (schizophrenia and other psychotic disorders, bipolar disorder, or major depressive disorder). For this purpose, 148 institutionalized patients were evaluated by professionals responsible for their food intake. The Oropharyngeal Dysphagia Screening Test for Patients and Professionals was used to assess its validity in screening for oropharyngeal dysphagia in patients with cognitive impairments and in patients with severe mental illness. Also, the Eating Assessment Tool-10 and the Swallowing Disturbance Questionnaire were used for convergent reliability procedures. Four comparison groups were established: patients with cognitive impairment with and without oropharyngeal dysphagia, and patients with severe mental illness with and without oropharyngeal dysphagia. Results from the Oropharyngeal Dysphagia Screening Test for Patients and Professionals adequately distinguished between groups with and without dysphagia, in addition to presenting adequate levels of convergent validity and reliability. These results were obtained from other-reports (professionals responsible for patients' food intake), using a simple, quickly applied test that does not require the use of food in patients with an altered cognitive state or with severe mental illness. With this study we expand the validity of the Oropharyngeal Dysphagia Screening Test for Patients and Professionals in populations with severe cognitive deficits and mental illness in which there is a great deficiency of oropharyngeal dysphagia screening instruments.

Automated Assessment of Digital Images of Uterine Cervix Captured Using Transvaginal Device-A Pilot Study.

In low-resource settings, a point-of-care test for cervical cancer screening that can give an immediate result to guide management is urgently needed. A transvaginal digital device, "Smart Scope®" (SS), with an artificial intelligence-enabled auto-image-assessment (SS-AI) feature, was developed. In a single-arm observational study, eligible consenting women underwent a Smart Scope®-aided VIA-VILI test. Images of the cervix were captured using SS and categorized by SS-AI in four groups (green, amber, high-risk amber (HRA), red) based on risk assessment. Green and amber were classified as SS-AI negative while HRA and red were classified as SS-AI positive. The SS-AI-positive women were advised colposcopy and guided biopsy. The cervix images of SS-AI-negative cases were evaluated by an expert colposcopist (SS-M); those suspected of being positive were also recommended colposcopy and guided biopsy. Histopathology was considered a gold standard. Data on 877 SS-AI, 485 colposcopy, and 213 histopathology were available for analysis. The SS-AI showed high sensitivity (90.3%), specificity (75.3%), accuracy (84.04%), and correlation coefficient (0.670, p = 0.0) in comparison with histology at the CINI+ cutoff. In conclusion, the AI-enabled Smart Scope® test is a good alternative to the existing screening tests as it gives a real-time accurate assessment of cervical health and an opportunity for immediate triaging with visual evidence.

Implementation of a multi-cancer early detection (MCED) test using a centralized model within (w/i) a multi-state health system.

1526 Background: Cancer is the second leading cause of death globally. Currently, USPSTF recommends screening for only 5 (breast, cervical, colorectal, lung [high-risk], prostate [individualized basis]) cancers, but ~70% of cancer-related deaths are from cancers without recommended screening. Galleri (GRAIL, LLC, Menlo Park, CA), an MCED test, that uses a cell-free DNA-based targeted methylation assay and machine learning classifiers to detect a shared cancer signal and predict the cancer signal origin is available for use as a complement to existing screening tests. We present a model of centralized MCED test implementation w/i a multi-state health system. Methods: From 11/2021-7/2022, clinical and operational leadership w/i the Mercy Health System (headquartered in St. Louis, MO), including 44 acute and specialty hospitals with over 4000 integrated providers and 44000 coworkers in 5 states (MO, KS, AR, OK, IL), created an MCED test implementation plan for their health system. Results: A model with centralized navigation was developed such that patients (pts) and providers contacted a singular team (MCED team) w/i the Mercy Precision Medicine Division using telemedicine to order an MCED test and navigate processes. In the 2 months prior to and after launch (7/12/2022), 12 medical education sessions were held for various groups w/i the health system, including the centralized MCED team, leaders of subspeciality departments, and all primary care providers, to inform on the MCED test implementation plan. In this model, access to MCED testing commences in 2 ways: (1) pts register through an online form or (2) providers w/i the health system submit a referral to the MCED team through the electronic medical record system. Pts are then contacted by a nurse practitioner on the MCED team for pretest counseling w/i 2 business days. If the pt is still interested after counseling, an MCED test is ordered. Pts go to 1 of 11 Mercy labs to have their blood drawn for MCED testing. “Cancer signal detected (CSD)” test results are given to a specialized navigator who helps schedule diagnostic testing and initial appointments with specialists and coordinates follow-up care and treatment (tx) w/i the health system. Early analytics show that from launch to 1/31/2023, there were 3777 total referrals (2931 pt, 846 provider) that led to 925 MCED test orders, of which 6 had a CSD result. Median time from a CSD test result to pt notification was 22.8 hours, to initial diagnostic evaluation was 3.1 days, and to a cancer diagnosis was 8.7 days. Median time from cancer diagnosis to initiation of tx or first postdiagnosis specialist visit was 33 days. Conclusions: This model allowed for efficient time to diagnosis and tx or triage of eligible-risk pts using an MCED test and is an example of how a healthcare system can incorporate and scale the implementation of the MCED test into clinical practice.

The acceptability of cervical electrical impedance spectroscopy within a multi-modal preterm birth screening package: a mixed methods study

BackgroundReducing the rate of preterm birth is a cornerstone of global efforts to address child mortality, however existing screening tests offer imperfect prediction. Cervical electrical impedance spectroscopy (EIS) is a novel technique to quantify the ripening changes which precede labour. Mid-trimester EIS measurements have been shown to accurately predict preterm birth in asymptomatic women. This study aimed to comprehensively evaluate the acceptability of cervical EIS to low and high-risk women as part of a package of screening tests performed during a larger prospective trial.MethodsIn this parallel convergent mixed methods study, 40 women completed questionnaires before and after screening tests (EIS, cervical length measurement and fetal fibronectin quantification). Quantitative outcomes were anxiety levels before and after screening (Spielberger State Trait Anxiety Inventory, STAI-6), pain (Short Form McGill Pain Questionnaire) and ratings of EIS device appearance and test acceptability (visual analogue scales). Twenty-one women (11 high-risk, 10 low-risk) also attended a semi-structured qualitative interview. Interviews were recorded and transcribed, then thematic analysis was performed. A convergence coding matrix was constructed to enable triangulation of quantitative and qualitative results.ResultsHigh risk women demonstrated a significant reduction in anxiety following screening (mean STAI-6 score 34.5 vs. 29.0, p = 0.002). A similar trend was observed among low-risk participants. Ratings of pain, EIS device appearance and procedural acceptability did not differ between groups. Mean pain ratings were low (visual analogue scale 0.97 and 1.01), comparing favourably to published evaluations of conventional screening tests. Qualitative analysis provided insight into both the physical consequences and emotional experiences of screening. Additional determinants of the screening experience included device design, pre-existing perspectives on intimate examination, attitudes to knowledge in pregnancy and interaction with clinical staff. Finally, a range of practical considerations regarding wider use of EIS were identified, with valuable complementary detail regarding acceptability for use in antenatal care.ConclusionsCervical EIS is well tolerated and acceptable to both low and high-risk women when performed as part of a multi-modal screening package. These results provide useful insights to inform the design of future study and screening protocols.

Therapy for Recurrent High-Grade Epithelial Ovarian Cancer—The Current Status and Future Trends

AbstractOvarian malignancy is the seventh most frequently diagnosed cancer among women. The most common type is epithelial ovarian cancer. Several subtypes with distinct biological and molecular properties exist, and there is inconsistency in availability of and access to different modalities of treatment. The standard first-line management is combining surgery and platinum-based chemotherapy. Most of them are diagnosed at an advanced stage due to which they have poor outcomes. The existing screening tests have a low predictive value. Even with the best available upfront treatment, high rates of recurrences are observed. As a result, there have been major advances in the treatment of recurrences with the development of anti-angiogenic agents and PARP inhibitors. It has led to the improvement in survival and quality of life among the relapsed epithelial ovarian cancers. This review is focused on the management of recurrent epithelial ovarian cancers and future directions based on current evidence. The application of a personalized and structured approach will meaningfully bring changes in the paradigm of care in these groups of patients.

Pain drawing as a screening tool for anxiety, depression and reduced health-related quality of life in back pain patients: A cohort study.

Back pain patients are more likely to suffer from depression, anxiety and reduced quality of life. Pain drawing is a simple, frequently used anamnesis tool that facilitates communication between physicians and patients. This study analysed pain drawings to examine whether pain drawing is suitable as a screening tool for signs of anxiety, depression or reduced quality of life, as the detection of these symptoms is essential for successful treatment. Pain drawings of 219 patients with lower back pain were evaluated retrospectively. Pain drawings are a schematic drawing of a human being. Six variables of the pain drawing were analysed. Subscales of the Hospital Anxiety and Depression Scale (HADS) and the Mental Component Summary (MCS) of the Short Form 12 (SF-12) were used to measure anxiety, depression and quality of life, respectively. Descriptive statistics, uni- and multivariate linear regression analyses and analysis of variance were performed. Logistic regression analyses were conducted for suitable variables. We revealed significant positive correlations between the variables "filled body surface" and "number of pain sites" and the anxiety (HADS-A) and depression subscales (HADS-D) of the HADS (p<0.01). The same predictors had significant negative correlations with the MCS (p<0.01). However, the sensitivity and specificity of the variable "number of pain sites" were too low compared to those for existing screening tests to consider it as a screening tool for anxiety, depression and quality of life (HADS-A: sensitivity: 45.2%, specificity: 83.3%; HADS-D: sensitivity: 61.1%, specificity: 51%; MCS: sensitivity: 21.2%, specificity: 85.7%). There were significant correlations between the amount of filled body surface and the number of pain sites in the pain drawing and anxiety, depression and quality of life. Although useful in routine clinical practice, pain drawing cannot be used as a screening tool based on our results.

Addressing hepatic metastases in ovarian cancer: Recent advances in treatment algorithms and the need for a multidisciplinary approach.

The lifetime risk for ovarian cancer incidence is 1.39% and the lifetime risk of death is 1.04%. Most ovarian cancer patients are diagnosed at advanced stages (III, IV) because there were no specific symptoms or existing screening tests. Liver metastases have been found in up to 50% of patients dying of advanced ovarian cancer. Recent studies indicate the need for a multidisciplinary approach from initial diagnosis to oncologic surgery and chemotherapy treatment, mandating the involvement of gynecologic oncologists, surgical oncologist, medical oncologists, hepatobiliary surgeons, and interventional radiologists.

Robust cost efficacy of a novel, validated screening test at 12–20 ​Weeks gestation for the prediction of preterm birth (PTB) at or before 32 ​Weeks in singletons

ObjectivePreterm birth (PTB) at or before 32 weeks complicates up to 2 ​% of United States (US) births and accounts for 80 ​% of perinatal expenditures in the first year of life. Existing screening tests for PTB performed from 12 weeks to 19 weeks 5 days have receiver operated area under the curve (AUC) indices of <80 ​% and at most <70 ​%. We evaluated FutureBIRTH™, a unique maternal screening test comprised of plasma cell-free RNA for the prediction of PTB ≦ 32 weeks due to spontaneous labor (sPTB) with or without preterm premature rupture of the membranes (PPROM) or early-onset pre-eclampsia before 34 weeks (EOP). FutureBIRTH™ is supported by multiple validation studies derived from 12 weeks to 19 weeks 5 days gestation achieving AUCs of 84.2 ​% for sPTB and 94.1 ​% for EOP. MethodsUsing the US rates for EOP (0.5 ​%) and sPTB ​≦ ​32 weeks (1.8 ​%) and adjusting the US pregnancy/neonatal medical costs to US dollars (2017 value), we calculated the cost per 100,000 singletons with or without universal FutureBIRTH™ testing before 19 weeks and 6 days using three detection rates and assuming screen-positive women would be treated with and respond to aspirin (assumed 80 ​% efficacy for EOP) and vaginal progesterone (assumed 38 ​% efficacy for sPTB). We also assessed test performance at disease incidence rates below that of the US (down to 0.46 ​%). For considering screening costs, we assumed test costs of $750, and treatment costs of $1000 for patients over 20 weeks gestational age. ResultsThe identification and treatment of ‘at-risk’ pregnancies by FutureBIRTH™ with existing therapies would reduce direct healthcare costs by up to $95 million per 100,000 births. The projected savings were robust and achievable at each FutureBIRTH™ price despite the conservative costs, efficacy, and detection rate assumptions. The incidence of PTB ≦ 32 weeks would decline by 40 %–50 ​% with a test cost of $750 and an 80 ​% detection rate. ConclusionThe accurate risk assessment provided by universal FutureBIRTH™ screening coupled with existing preventative treatments could lead to a 40 %–50 ​% decrease in PTB ≦ 32 weeks due to sPTB and EOP among ‘at-risk’ pregnancies, covering the cost of screening and treatment while still saving $450-$950 per pregnancy.

Abstract LB013: Clinical validation of a targeted methylation-based multi-cancer early detection test

Abstract Introduction: A multi-cancer early detection (MCED) test as a complement to existing screening tests could increase the number of cancer cases detected in a population, potentially improving patient outcomes and survival as well as decreasing harmful and aggressive treatments. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was designed to develop and validate a blood-based MCED test analyzing plasma cell-free DNA (cfDNA) to detect cancer signals across multiple cancer types and simultaneously predict their signal origin. Here, the results of the third and final pre-specified CCGA validation sub-study for a refined MCED test in a large cohort in preparation for clinical use are reported. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall population N=15,254). In this sub-study (n=5309), key primary objectives were to evaluate test performance for cancer signal detection (specificity, overall sensitivity, sensitivity by clinical stage) and signal origin prediction (accuracy). cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning algorithm. The classifier was trained to target a specificity of 99.4% and locked before analysis of the independent validation set. Overall, 4077 participants comprised the independent validation set with confirmed status (cancer: n=2823; non-cancer: n=1254 with non-cancer status confirmed at year-one follow-up). MCED test results are reported for this confirmed status set. Results: Mean (SD) age in the cancer and non-cancer groups was 62.6 (11.76) and 56.2 (12.63) years, respectively. Specificity for cancer signal detection was 99.5% (1248/1254; 95% confidence interval: 99.0-99.8%). Overall sensitivity for cancer signal detection was 51.5% (1453/2823; 49.6-53.3%); sensitivity increased with stage (Stage I: 16.8% [14.5-19.5%], Stage II: 40.4% [36.8-44.1%], Stage III: 77.0% [73.4-80.3%], Stage IV: 90.1% [87.5-92.2%]). Stage I-III sensitivity was 67.6% (593/877; 64.4-70.6%) in a pre-specified set of 12 high-signal cancers accounting for ~63% of annual US cancer deaths [1] and was 40.7% (863/2118; 38.7-42.9%) in all cancers. Cancer signals were detected across &amp;gt;50 cancer types [2]. Overall accuracy of signal origin prediction in true positives was 88.7% (87.0-90.2%). Conclusions: In this pre-specified, large-scale, clinical validation sub-study of CCGA, the MCED test detected cancer signals across &amp;gt;50 cancer types, which is critical to maximize the number of cancer cases detected in a population. This MCED test performed with high specificity and high accuracy of signal origin prediction. These data lay the foundation for population-scale clinical implementation of this test. 1.US Mortality Data 1969-2016 (www.seer.cancer.gov); based on 2015-2016. 2.Amin et al. CA Cancer J Clin. 2017;67:93e99. Citation Format: Eric A. Klein, Donald Richards, Allen Cohn, Mohan Tummala, Rosanna Lapham, David Cosgrove, Gina Chung, Jessica Clement, Jingjing Gao, Nathan Hunkapiller, Arash Jamshidi, Kathryn Kurtzman, Michael V. Seiden, Charles Swanton, Minetta C. Liu. Clinical validation of a targeted methylation-based multi-cancer early detection test [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB013.

Women in Punjab are in Dire Need of Awareness Initiatives Related to Cervical Cancer and its Screening Tests

Cervical cancer is the third most common cancer and the fourth dominant cause of cancer related death in women throughout the globe. Eighty percent of cases occur in the developing nations1,2. The extent of this cancer is tough to be evaluated in Pakistanbecause of differing insufficient epidemiological figures obtainable in small scale studies, dealing only reported limited number of cases which are not representative of its true burden3,4,5. As stated by World Health Organization, in 2002, the pervasiveness of cervical cancer in Pakistan was 9 in 100,000; in 2008 it jumped up to 19.5/100,000. Claimed by various studies, this cancer is among the list of first ten frequent cancers in Pakistan6,7,8,9. It is one of the most avoidable cancers nowadays and we have all the tools to eradicate it, still the number of lives lost due to cervical cancer is very high in Pakistan as it is an ignored ailment here in terms of screening, prevention and vaccination9. Economically developed countries who invested capitals for organized screening projects have made notable progress in reducing both occurrence and mortality due to this specific cancer10. The out of proportion load of cervical cancer in developing countries is largely attributable to scarcity of functional screening projects11. In our over 500 bedded teaching hospital with a well running gynecology outdoor, we do receive cervical biopsies positive for invasive malignancies but hardly receive any Pap smear tests in laboratory that prompted us to check for cervical cancer screening especially Pap smear test related awareness among our non-medical ladies.As the foundation of cervical cancer eradication is screening and prevention, each country and its regions must device an elimination plan that fits into its own culture and geographic landscape. Keywords: perception and understanding of existing screening tests, preventive measures, cervical cancer

Optimising dengue pre-vaccination screening

Optimising dengue pre-vaccination screening

How confident are medical students about making clinical decisions relying on the evidence? A cross-sectional questionnaire study.

Objective: Giving information and providing advice on diagnostic tests is one of the tasks physicians must carry out personally. To do so, they must evaluate the evidence and integrate their findings into everyday practice. Clinical decisions should be based on evidence. How well current medical education prepares for such evidence-based clinical decision-making is largely unclear. Therefore, it was examined how confident medical students are in clinical decision-making based on evidence using epidemiological data. It was examined whether the decision-making confidence increases the higher the semester. Further questions were whether scientifically active medical students show higher decision-making confidence and whether the representation of figures as pictograms rather than tables positively influences the decision-making confidence.Methods: An online survey of the medical students of the Friedrich-Alexander-University Erlangen-Nürnberg was carried out. Respondents were presented with three clinical decision-making situations in random order for evaluation in the form of screening scenarios. In each case, the decision-making confidence also had to be specified. The scenarios contained only epidemiological data on existing screening tests. For each scenario, the numbers were presented as a table or a pictogram in a random fashion. In order to avoid false confidence resulting from preconceived opinions neither the illnesses nor the screening tests were mentioned by name.Results: Answers from 171 students were evaluated. Decision-making confidence in dealing with the numbers does not increase in higher semesters (rPearson=0.018, p=0.41). Scientific work is not associated with a higher decision-making confidence (t(169)=-1.26, p=0.11, d=-0.19). Presentation as a pictogram leads to a higher decision-making confidence compared to tables (Pictogram: M=2.33, SD=1.07, Table with numbers: M=2.64, SD=1.11, t(511)=3.21, p<0.01, d=0.28).Conclusions: Medical students from higher semesters show no higher decision-making confidence compared to medical students from lower semesters. Curricular events and scientific work, such as a doctoral thesis, do not seem to strengthen the required skills sufficiently. If evidence is presented in the form of pictograms, this seems to improve student confidence in decision-making.

The Colorado Cognitive Assessment (CoCA): Development of an Advanced Neuropsychological Screening Tool.

The Colorado Cognitive Assessment (CoCA) was designed to improve upon existing screening tests in a number of ways, including enhanced psychometric properties and minimization of bias across diverse groups. This paper describes the initial validation study of the CoCA, which seeks to describe the test; demonstrate its construct validity; measurement invariance to age, education, sex, and mood symptoms; and compare it to the Montreal Cognitive Assessment (MoCA). Participants included 151 older adults (MAge=71.21, SD=8.05) who were administered the CoCA, MoCA, Judgment test from the Neuropsychological Assessment Battery (NAB), 15-item version of the Geriatric Depression Scale (GDS-15), and 10-item version of the Geriatric Anxiety Scale (GAS-10). A single-factor confirmatory factor analysis model of the CoCA fit the data well, CFI=0.955; RMSEA=0.033. The CoCA factor score reliability was .84, compared to .74 for the MoCA. The CoCA had stronger disattenuated correlations with the MoCA (r=.79) and NAB Judgment (r=.47) and weaker correlations with the GDS-15 (r=-.36) and GAS-10 (r=-.15), supporting its construct validity. Finally, when analyzed using multiple-indicators, multiple-causes (MIMIC) modeling, the CoCA showed no evidence of measurement noninvariance, unlike the MoCA. These results provide initial evidence to suggest that the CoCA is a valid cognitive screening tool that offers numerous advantages over the MoCA, including superior psychometric properties and measurement noninvariance. Additional validation and normative studies are warranted.

The Multidimensional Behavioral Health Screen 1.0: A Translational Tool for Primary Medical Care

The Multidimensional Behavioral Health Screen (MBHS) is a brief, 27-item questionnaire designed for screening every patient in primary medical care settings. It measures nine psychopathology constructs that represent the major distinctive core dimensions of the types of behavioral health symptoms most commonly encountered in primary care (anxiety-related, depressive, and attention/cognitive symptoms). The underlying design of the MBHS is based on the major paradigm shift that has occurred in the field of theoretical psychopathology, replacing categorical syndromes, or “disorders,” with hierarchical-dimensional constructs. Existing screening tests such as the PHQ-9 and GAD-7 are based explicitly on the categorical paradigm and thus suffer from the same (numerous) shortcomings as the categorical model itself. The dimensional paradigm supports enhanced measurement precision with very short scales. The goals of the MBHS are threefold: (1) to provide accurate, treatment-relevant behavioral health information to the medical provider; (2) to provide clear referral cut-points; (3) to contribute nine psychometrically sound behavioral health variables to the “healthcare big data cloud” to support future scholarship of discovery. Presented here are the basic psychometric properties of the MBHS, including reliability, convergent and discriminant validity, and classification accuracy, as well as implementation considerations.

Soft glass multi-channel capillaries as a platform for bioimprinting

Multi-channel capillaries (MC) formed from thousands individual microcapillaries with diameters ranging 10–100 μm are of a great interest for their use as platforms for molecular imprinting due to their relatively large surface area, high mechanical stability and possibility of facile integration in sensor systems. The manuscript proposes a new format of immunoassay based on imprinted protein immobilized on a MC inner surface modified with poly-l-lysine. The combination of the environmentally friendly, easy-to-produce and cheap recognition element with the carrier allowing to increase the assay sensitivity makes the described technique a perspective alternative for the existing screening tests. Two bioimprinting approaches were described. The imprinted protein (ovalbumin, OVA) primarily prepared separately and later immobilized on a MC structure was compared to the imprinted OVA directly prepared on the MC surface. Detection of a food contaminant zearalenone was chosen as a proof-of-concept. In a case of the immobilization of the primarily prepared imprinted OVA the reached limit of detection (LOD) was 0.8 ng/mL, and for the in-situ imprinted OVA the LOD was 0.12 ng/mL. The sensitivity of the developed bioimprinted assay was comparable to the commercially available ELISA kits for ZEN detection.The OVA in-situ imprinted on the MC surface was tested for the detection of ZEN in artificially spiked wheat samples. The high recovery values (88–112%) and good repeatability (RSD of 8.5–9.6%) were demonstrated allowing to conclude that the IPs-based MC-ELISA is a promising tool for analysis of the mycotoxin in complex matrices.

Machine learning enables detection of early-stage colorectal cancer by whole-genome sequencing of plasma cell-free DNA

BackgroundBlood-based methods using cell-free DNA (cfDNA) are under development as an alternative to existing screening tests. However, early-stage detection of cancer using tumor-derived cfDNA has proven challenging because of the small proportion of cfDNA derived from tumor tissue in early-stage disease. A machine learning approach to discover signatures in cfDNA, potentially reflective of both tumor and non-tumor contributions, may represent a promising direction for the early detection of cancer.MethodsWhole-genome sequencing was performed on cfDNA extracted from plasma samples (N = 546 colorectal cancer and 271 non-cancer controls). Reads aligning to protein-coding gene bodies were extracted, and read counts were normalized. cfDNA tumor fraction was estimated using IchorCNA. Machine learning models were trained using k-fold cross-validation and confounder-based cross-validations to assess generalization performance.ResultsIn a colorectal cancer cohort heavily weighted towards early-stage cancer (80% stage I/II), we achieved a mean AUC of 0.92 (95% CI 0.91–0.93) with a mean sensitivity of 85% (95% CI 83–86%) at 85% specificity. Sensitivity generally increased with tumor stage and increasing tumor fraction. Stratification by age, sequencing batch, and institution demonstrated the impact of these confounders and provided a more accurate assessment of generalization performance.ConclusionsA machine learning approach using cfDNA achieved high sensitivity and specificity in a large, predominantly early-stage, colorectal cancer cohort. The possibility of systematic technical and institution-specific biases warrants similar confounder analyses in other studies. Prospective validation of this machine learning method and evaluation of a multi-analyte approach are underway.

Stable Safe Screening and Structured Dictionaries for Faster $\ell _{1}$ Regularization

In this paper, we propose a way to combine two acceleration techniques for the $\ell\_{1}$-regularized least squares problem: safe screening tests, which allow to eliminate useless dictionary atoms; and the use of fast structured approximations of the dictionary matrix. To do so, we introduce a new family of screening tests, termed stable screening, which can cope with approximation errors on the dictionary atoms while keeping the safety of the test (i.e. zero risk of rejecting atoms belonging to the solution support). Some of the main existing screening tests are extended to this new framework. The proposed algorithm consists in using a coarser (but faster) approximation of the dictionary at the initial iterations and then switching to better approximations until eventually adopting the original dictionary. A systematic switching criterion based on the duality gap saturation and the screening ratio is derived.Simulation results show significant reductions in both computational complexity and execution times for a wide range of tested scenarios.

Noninvasive screening test for detecting early stage lymphedema using follow-up computed tomography imaging after cancer treatment and results of treatment with lymphaticovenular anastomosis.

Although early detection is valuable for secondary lymphedema treatment, existing screening tests are not popular. This study aimed to propose a novel method of screening lymphedema patients based on the thickness of the subcutaneous fat measured with perioperative computed tomography (CT) and present the results from evaluation of patients who underwent those examinations was performed. The medical records of 96 gynecological cancer patients and 189 breast cancer patients, whose lymphatic function was assessed with indocyanine green lymphography, were reviewed. In gynecological cancer patients, the perioperative temporal subcutaneous fat thickness index (T-SFTI) was calculated from presurgical and follow-up CT data, and in breast cancer patients, the postoperative crosswise subcutaneous fat thickness index (C-SFTI) was calculated. In lower extremity lymphedema patients, the effect of lymphaticovenular anastomosis (LVA) was also evaluated using T-SFTI. Perioperative T-SFTI was assessed in 180 lower extremities, and it was significantly higher in 46 lymphatic dysfunction limbs (1.21 ± 0.08) than in 134 normal lymphatic function limbs (1.03 ± 0.08), (P < .01). Postoperative C-SFTI was assessed in 53 upper extremity, and it was significantly higher in 11 lymphatic dysfunction limbs (1.31 ± 0.21) than in 42 normal lymphatic function limbs (1.01 ± 0.06), (P < .01). In lower extremity lymphedema patients, T-SFTI improved significantly after planned conservative treatments and LVA (P = .04). Assessment of subcutaneous fat thickness using CT is useful for screening early stage lymphedema. If the efficacy of this method is validated, patients worldwide may be assessed using the same criterion.

Disparities in Cervical Cancer Incidence and Mortality: Can Epigenetics Contribute to Eliminating Disparities?

Screening for uterine cervical intraepithelial neoplasia (CIN) followed by aggressive treatment has reduced invasive cervical cancer (ICC) incidence and mortality. However, ICC cases and carcinoma in situ (CIS) continue to be diagnosed annually in the United States, with minorities bearing the brunt of this burden. Because ICC peak incidence and mortality are 10-15 years earlier than other solid cancers, the number of potential years of life lost to this cancer is substantial. Screening for early signs of CIN is still the mainstay of many cervical cancer control programs. However, the accuracy of existing screening tests remains suboptimal. Changes in epigenetic patterns that occur as a result of human papillomavirus infection contribute to CIN progression to cancer, and can be harnessed to improve existing screening tests. However, this requires a concerted effort to identify the epigenomic landscape that is reliably altered by HPV infection specific to ICC, distinct from transient changes.