Use Of Screening Research Articles

Utilization of Early Intervention Among Children with Sickle Cell Disease

Background: The most prevalent monogenic disorder among children is sickle cell disease (SCD). SCD is the most common cause of pediatric stroke and is primarily inherited by people that identify as Black or of African descent. 1,2 Children with SCD have an elevated risk for delayed development and poor academic outcomes. 2 Our previous findings identified that 50% of children with SCD have a developmental delay, however, <5% were receiving therapy services. 3-5 Home-based programs have ameliorated cognitive and language delays in children with SCD. 6 In the United States, home-based therapy services (e.g., occupational, physical, and speech therapy) are provided through a federally mandated program called Early Intervention for free or reduced cost for children with developmental delay <3 years of age. 7 Unfortunately, this program is underutilized, especially in underserved and minoritized communities, with as few as 2% of eligible children receiving services. 8,9 Hematologists, who are tasked with providing ongoing medical care for young children with SCD, often lack the resources/tools needed to incorporate developmental screening into standard care. Thus, early indicators of developmental delay remain undetected and untreated, costing children and families precious time to intervene early. 6,10,11 This study aimed to assess the use of early intervention and determinants affecting participation in developmental screening and intervention among caregivers of children 0-4 years of age with SCD. Methods: We recruited caregivers with children under 4 years of age with SCD from clinics in St. Louis, Missouri and Memphis, Tennessee. Semi-structured interviews based on the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) framework were used to describe determinants for referral success and describe the mechanisms (barriers and facilitators) that influence early intervention program utilization. 12 Interviews included open-ended to address topics related to reach, perceived effectiveness, and likelihood of adoption of early intervention if recommended. Additional questions assessed caregiver knowledge of developmental delays in SCD and utilization of screening and intervention. Results: Among 127 caregivers identified as eligible, 47 consented and 20 completed an interview between September 2022 and February 2023. Similar to prior studies, over half of caregivers reported living in a low-income household, over half of children had hemoglobin SS and all participants identified as Black or African American. Interviews lasted between 15-75 minutes (mean = 34). Three themes emerged from the data including 1) Caregivers have not been informed about elevated risk for developmental delay, 2) Caregivers prioritize connecting with their provider and 3) Caregivers had not been adequately informed about early intervention services (Table 1). Conclusions: This study highlights the low utilization of early intervention services for young children with SCD. Caregivers expressed frustration with the lack of awareness regarding the elevated risk for developmental delays and prioritize that information coming from their specialty providers (e.g., sickle cell clinic). Additionally, inadequate information about available services contributes to underutilization. As healthcare providers, we are tasked with increasing awareness about the associated risks of SCD, integrating developmental screening into standard care, and providing caregivers with information that could improve developmental outcomes for children with SCD.

741. Assessing the Concordance of MRSA Carriage Screening with MRSA Infections

Abstract Background There is a lack of research on MRSA surveillance in children. This study focused on children with confirmed MRSA infections to determine the utility of MRSA screens in guiding empiric anti-MRSA treatment for children without history of MRSA infection. We examined the concordance of screens to assess for differences by infection type, and used statistical analysis to determine significant contributors to concordance. Methods Pediatric hospital patients admitted from 2002-2022 were included. Subjects had MRSA infections subsequent to a MRSA surveillance screen performed in the preceding year. Statistical analysis, namely multivariable and binomial regression, identified associations between MRSA screens and infections. Number needed to treat analysis calculated the utility of re-screening. Results Among 246 subjects, 39.0% had concordant screens. 151 (61.4%) screens were obtained in the two weeks preceding infection. Sensitivity for bacteremia was 50.0% (n=42), for ET/respiratory 44.4% (n=81), for SSTI 29.4% (n=102). For children under 6 months of age, sensitivity was 35.9% (n=78). Multivariable analysis significantly associated days since MRSA screening and decreasing likelihood of concordance. Binomial regression modeled the probability of concordance to drop below 50.0% for all infections after four days, after six days for bacteremia specifically, and twelve days for ET/respiratory infections. Probability of Concordance Over Time The probability of MRSA screening concordance over time based upon binomial prediction modeling. Each line represents the probability of concordance on a given day subsequent to MRSA screening. Number Needed to Treat (test) Analysis A theoretical control arm of patients receiving no re-screening is compared to a theoretical treatment arm receiving re-screening. Each column represents the number needed to re-screen (for a given number of days) to predict one MRSA infection. Absolute risk reduction is overlaid. Conclusion The concordance of screens was far lower than NPV found in past studies. Bacteremia concorded at 50.0%, ET/respiratory infections 44.4%, SSTI 29.4%. The number of days elapsed since MRSA screening proved the only significant covariate. When that covariate modeled the probability of screening concordance with infection, 7 days represented when the probability of concordance fell to or dropped below 50.0% for infection types. Only patients with a known MRSA infection were included in our study, and concordance of screens was far lower than NPV found in past studies; previous results may have been impacted by low prevalence to inform high NPV. We suggest that negative MRSA screens should not invalidate reasonable suspicion for MRSA infection in patients with high pre-test probabilities for infection. Re-screening patients may optimize concordance. Disclosures All Authors: No reported disclosures

The relationship of cancer history and chronic disease status to colorectal cancer screening: A cross-sectional analysis of 2020-2021 Behavioral Risk Factor Surveillance System.

We examined whether having a history of cancer and chronic diseases was associated with guideline-concordant colorectal cancer (CRC) screening utilization. Self-reported data from the 2020 and 2021 Behavioral Risk Factor Surveillance System in Oregon and West Virginia were used. Guideline-concordant CRC screening was the outcome of interest. The exposure was having a personal history of cancer, chronic diseases, or both. Multivariable logistic regressions were applied to assess the abovementioned association. Among 10,373 respondents aged 45-75years, 75.5% of those with a history of cancer and chronic diseases had guideline-concordant CRC screening use versus 52.8% of those without any history (p-value < 0.05). In multivariable analysis, having a history of cancer (OR 1.74; 95% CI 1.11-2.71), chronic diseases (OR 1.35; 95% CI 1.14-1.59), and both cancer and chronic diseases (OR 2.14; 95% CI 1.62-2.82) were positively associated with screening uptake compared to respondents without any history. Regardless of disease history, older age was associated with greater CRC screening uptake (p-value < 0.05). Among respondents with chronic diseases only or without any condition, those with a health care provider had 1.7-fold and 2.7-fold increased odds of receiving CRC screening, respectively. However, current smokers were 28% and 34% less likely to be screened for CRC among those with chronic diseases only and without any conditions, respectively. Having a personal history of cancer and chronic diseases appears to be positively associated with guideline-concordant CRC screening use. Effective implementation of patient-centered communication through primary care initiatives may increase adherence to CRC screening recommendations.

Factors Influencing Cervical Cancer Screening in Women Referring to the Therapeutic Centers of Tehran: A Cross-sectional Analysis

Cervical cancer is the second most common cancer in women; screening intervals are the basis of early diagnosis. Moreover, this study was conducted in Tehran, considering the importance of cervical cancer screening for diagnosing this cancer and the lack of sufficient information about the factors related to cervical cancer screening in women. However, this paper studies the extent of screening behaviors and factors influencing it in cervical cancer. This descriptive and analytical paper established the target population of 384 women of different ages who refer to healthcare centers in Tehran. The purpose of data collection was based on the researcher's questionnaire based on the studies and data of the patients registered in Shariati Medical Center in Tehran, whose reliability was confirmed by the test (Cronbach's Alpha= 0.7). Furthermore, data was analyzed by SPSS and Smart PLS. This paper reveals that six factors influence the direct effect of cervical cancer screening. However, the factors include personal hygiene, psychological, pap smear test screening, colposcopy screening, social factors, and Health Care Utilization—the existing observation aimed to assess the influence of risk factors of cervical cancers. Accordingly, most cervical cancers may be diagnosed with previous knowledge of threat factors. Identification of excessive–risk populations and beginning early screening are influential in the early recognition of cervical cancers.

Prenatal aneuploidy screening in a low-risk Hispanic population: price elasticity and cost-effectiveness

Background: In October 2015, the Massachusetts Medicaid program temporarily stopped reimbursing the ICD-10 code used by certain communities for serum aneuploidy screening. This change resulted in a substantial number of patients without aneuploidy screening for approximately three years.Objective: To determine the change in utilization and cost-effectiveness of prenatal aneuploidy serum screening in a low-risk Hispanic Medicaid population in Massachusetts.Study Design: We conducted a retrospective chart review of Spanish-speaking pregnant patients under 35 years of age receiving aneuploidy serum screening at a Massachusetts community health center. The study compared aneuploidy serum screening rates before and after May 2016, when the Massachusetts Medicaid program, MassHealth, temporarily discontinued reimbursement for the screening. Based on these rates, we developed a Markov cohort simulation model to assess the economic value of reimbursed aneuploidy screening versus non-reimbursed or limited screening. Clinical outcomes included trisomy 21, live births, and therapeutic abortions for a trisomy 21 diagnosis. Economic outcomes included discounted quality-adjusted life years and lifetime medical costs, net health benefit, and incremental cost-effectiveness ratios.Results: Before the MassHealth policy change, 69% (55/80) of pregnant individuals selected quad or sequential screens, compared to 9% (10/112) post-policy change. Traditional aneuploidy serum screening in a low-risk (aged <35 years) Hispanic population was considered cost-saving (i.e., resulted in lower incremental costs and higher incremental benefits compared to non-reimbursed or limited screening).Conclusions: From a U.S. healthcare payer perspective, aneuploidy serum screening for Hispanic pregnant individuals under 35 years of age is economically advantageous compared to limited screening.

Correction: Cervical cancer screening utilization and predictors among eligible women in Ethiopia: A systematic review and meta-analysis

Correction: Cervical cancer screening utilization and predictors among eligible women in Ethiopia: A systematic review and meta-analysis

Geographic Variation in Late-Stage Cervical Cancer Diagnosis

There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening. To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas. This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at the time of diagnosis. Statistical analysis was performed from April to September 2023. Census tract of residence at diagnosis. Late-stage cervical cancer diagnosis (ie, cases classified by the National Cancer Institute Surveillance, Epidemiology and End Results summary stages 2 to 4 [regional spread] or 7 [distant metastasis]). A Poisson probability-based model of the SaTScan purely spatial scan statistics was applied at the census tract-level to identify geographic clusters of higher (hot spots) or lower (cold spots) proportions than expected of late-stage cervical cancer diagnosis and adjusted for age. Among a total of 6484 female patients with incident cervical cancer cases (mean [SD] age, 48.7 [14.7] years), 2300 (35.5%) were Hispanic, 798 (12.3%) were non-Hispanic Black, 3090 (47.6%) were non-Hispanic White, and 296 (4.6%) were other race or ethnicity. Of the 6484 patients, 2892 with late-stage diagnosis (mean [SD] age, 51.8 [14.4] years were analyzed. Among patients with late-stage diagnosis, 1069 (37.0%) were Hispanic, 417 (14.4%) were non-Hispanic Black, 1307 (45.2%) were non-Hispanic White, and 99 (3.4%) were other race or ethnicity. SaTScan spatial analysis identified 7 statistically significant clusters of late-stage cervical cancer diagnosis in Texas, of which 4 were hot spots and 3 were cold spots. Hot spots included 1128 census tracts, predominantly in the South Texas Plains, Gulf Coast, and Prairies and Lakes (North Texas) regions. Of the 2892 patients with late-stage cervical cancer, 880 (30.4%) were observed within hot spots. Census tract-level comparison of characteristics of clusters suggested that hot spots differed significantly from cold spots and the rest of Texas by proportions of racial and ethnic groups, non-US born persons, and socioeconomic status. In this cross-sectional study examining geospatial clusters of late-stage cervical cancer diagnosis, place-based disparities were found in late-stage cervical cancer diagnosis in Texas. These findings suggest that these communities may benefit from aggressive cervical cancer interventions.

Toxicological profile using mass-spectrometry in sudden cardiac arrest patients

Abstract Background Many drugs are known to increase the risks of ventricular arrythmias and sudden cardiac death, and current guidelines recommends collection of a blood sample at presentation for toxicological testing. To our knowledge, a broad toxicological analysis based on liquid-chromatography combined with high-resolution mass spectrometry (LC-HRMS) has not previously been performed in a resuscitated sudden cardiac arrest (SCA) cohort. Purpose We aimed to determine the qualitative and quantitative drug composition present in a well-defined SCA population by using a forensic toxicology approach for prescribed, non-prescribed, and recreational drugs, and further investigate whether these drugs were in therapeutic or toxic levels. Methods This study comprised a series of SCA patients (age 18-90 years) admitted to a cardiac intensive care unit in 2019-2020 in Denmark. Data from the SCA hospitalization was collected from the medical reports, including clinical characteristics and drugs prior to the blood sample was drawn. Drugs used during resuscitation were identified in each patient and excluded. Mass-spectrometry based toxicological analyses were performed to determine the absence or presence of any drugs and drug quantification. Results Of the 186 prospectively enrolled SCA patients (median age 62 years [IQR 54-72], 83% men), 167 (90%) had a shockable rhythm, and the majority (n=122, 66%) were caused by ischemic heart disease. We identified 92 different drugs (excluding metabolites), where each patient had a median of 2 detected drugs (IQR: 1-4). A total of 34 (18%) patients did not have any drugs detected. The most frequent drugs detected were analgesics or non-steroidal anti-inflammatory drugs (NSAID) (n=68, 37%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (n=45, 24%), and beta-blockers (n=42, 23%). We detected QT-prolonging drugs in two of three patients with long QT-syndrome, and in both cases the QT-prolonging drug were considered the triggering factor of SCA. Moreover, polypharmacy (≥5 drugs) was common (n=37, 20%), excluding caffeine that was detected in 184 patients (99%). The drug combinations were often analgesics/NSAID, or beta-blockers combined with other drugs. A total of 32 (17%) patients had one or more recreational drugs detected, with the most common being opioid agonists in 14 patients. Importantly, none had toxic concentrations of any drugs. Conclusion We found that 82% had at least one drug detected at SCA, and polypharmacy was displayed in a considerable proportion. Potentially abusable drugs were encountered in 17%. We did not identify any occult overdose related cardiac arrests among resuscitated SCA patients, but in some patients, drugs were considered a contributing factor of SCA. When evaluating the utility of toxicological screening, it would in our setting (90% shockable primary rhythm) not be beneficial to screen SCA patients who are not suspected overdosed.

Abstract 12687: Evaluating a Coronary Artery Disease Polygenic Risk Score Screening Strategy in a Diverse Patient Cohort at UCLA

Introduction: Recent efforts to predict and mitigate coronary artery disease (CAD) risk have incorporated polygenic risk scores (PGS). Few studies examine the clinical impact of these PGS screening strategies or quantify their performance in clinical terms. Here we estimate the number needed to screen (NNS) of a PGS screening strategy for CAD based using a diverse electronic health record (EHR) linked biobank at UCLA Health. Methods: We leveraged longitudinal EHR data to conduct a synthetic trial. We assumed PGS screening was performed on 6/1/2013 for patients established prior to 1/1/2013 or 6 months into follow time if established later. Patients with preexisting cardiovascular disease or strong statin indications (LDL &gt; 190, diabetes or already on statins) are excluded. Patients with PGS scores in the top 5% of their genetic ancestry groupings (European, East Asian, African, Hispanic) are assumed to have been started on statins for the median 6.9 years of follow up. CAD diagnosis during follow up time was determined by ICD codes. NNS to prevent one CV event is calculated from cohort size and events assuming a statin number needed to treat of 50. Results: Of 33,789 adults, 17,074 were low risk and eligible for PGS screening (35% male with a mean age of 44). NNS to detect one CAD diagnosis was 351, 359, 814, 159 in the European, Hispanic, East Asian and African ancestry groups and NNS to prevent one cardiovascular event was 17,550, 17,950, 40,700, 7,950 respectively. Conclusion: Although PGS accuracy is lower in African ancestry individuals as compared to Europeans, the clinical utility of this PGS-based screening is highest in African ancestries due to increased baseline rates of disease in the African genetic ancestry grouping. Our results demonstrate that PGS accuracy is distinct from clinical utility of PGS-based strategies. Evaluation of screening strategies rather than accuracy alone will be required before PGS screening implementation.

Self-Sampling for Human Papillomavirus Testing: Acceptability in a U.S. Safety Net Health System

Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system. A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences. Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%). Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems.

Clinical Utility of Monoclonal Gammopathy Screening in the Evaluation of Anemia

Background Screening for monoclonal gammopathy (MG) is often performed in the evaluation of anemia. While certain MGs may be associated with anemia, these are rare conditions. Monoclonal gammopathy of undetermined significance (MGUS; prevalence of 8% among age &amp;gt;50 years) is common, but rarely causes anemia in isolation. Therefore, abnormal results from MG screening may be unrelated to patient symptoms and result in both financial and psychological harm. Limited data exist to guide clinicians regarding the utility of MG testing for anemia. Aims This study aims to describe both the clinical utility of MG screening during the evaluation of anemia and the most common etiologies for anemia in patients whose workup included MG screening. Methods We reviewed medical records of patients who received MG screening to evaluate anemia at Mayo Clinic in 2021. Patients with a previously diagnosed MG were excluded. MG testing included serum protein electrophoresis and free light chain assessments. The following data were extracted: hemoglobin, hematocrit, mean corpuscular volume (MCV), calcium, creatinine, eGFR, and the final hematologic diagnosis related to the monoclonal protein. Clinician documentation was evaluated to determine the attributed etiology of anemia. Results Among the 271 patients with anemia who were screened for MG, 33 (12.2%) were found to have a newly diagnosed MG. Only 2 patients screened for MG were ultimately found to have anemia caused by MG. These included a case of multiple myeloma and one patient with cold agglutinin disease and secondary hemolysis. In all patients screened, their anemia was ultimately thought to be due to iron deficiency (31.7%), B12 deficiency (3.0%), anemia of chronic disease (ACD)/inflammatory anemia (14.4%), chronic kidney disease (CKD) (3.7%), hemolysis (1.5%), hypogonadism (1.9%), idiopathic (21.0%), multifactorial: iron deficiency + ACD/inflammatory (3.0%), multifactorial: nutritional; iron deficiency + B12 deficiency (3.0%), multifactorial: ACD + CKD (5.2%), multifactorial: iron deficiency + CKD (1.8%), multifactorial: not otherwise specified (NOS) (6.6%), medications (0.4%), and other (2.6%). Both patients with newly diagnosed MG associated anemia presented with peripheral neuropathy as their primary symptom. Among these 2 patients diagnosed with dysproteinemia associated anemia, only one (0.4%) was placed on therapy for their MG. Summary/Conclusions In the evaluation of anemia, routine MG screening has low clinical utility. Less than 1 in 100 patients were found to have anemia attributable to MG. Furthermore, only 0.4 in 100 patients received MG-directed therapy. Most patients screened with SPEP for undifferentiated anemia were found to have anemia attributable to common causes including iron/nutritional deficiency, inflammatory processes, and CKD. Most patients with undifferentiated anemia would benefit from an anemia evaluation that focuses on the most common causes up front. Given the cost to healthcare and potential psychological harm to the patient of incidental MG diagnosis, further study is warranted to guide clinicians and limit the ordering of MG testing to individuals who are most likely to derive benefit.

The Utility of Maternal TORCH Screening Due to Obstetrical Indications in Detecting Congenital Infections: A Retrospective Observational Study.

The diagnostic yield of TORCH screening for obstetrical indications is unclear. We evaluated TORCH testing results among women with intrauterine growth restriction (IUGR), polyhydramnios and oligohydramnios; and associations with congenital infections in neonates. This retrospective single-center study included all the women diagnosed with IUGR, polyhydramnios or oligohydramnios who underwent serological TORCH testing during 2010-2019. TORCH screening included Toxoplasma, cytomegalovirus (CMV), rubella IgM and IgG. The data, which were cross-referenced with data of neonates with congenital TORCH infections during the same period, included indications for neonatal testing, sonographic findings and neonatal ophthalmologic and hearing findings. Six women of 771 (0.8%) were diagnosed with primary TORCH infection: 4 (0.5%) with toxoplasmosis, and 2 (0.3%) with CMV. None had a confirmed congenital infection. The rates of positive maternal TORCH screening in IUGR and polyhydramnios were 2.1% and 0.6%, respectively. Maternal TORCH infection was not identified in any woman with oligohydramnios or severe polyhydramnios. None of the neonates with congenital infection were screened for TORCH during pregnancy due to polyhydramnios, oligohydramnios or IUGR. Among the neonates with congenital CMV, the most common indication for performing neonatal CMV polymerase chain reaction was suspected primary maternal infection during pregnancy due to symptomatic CMV. No incidences of congenital rubella were noted in the last decade in our medical center. Our results suggest that routine TORCH screening in pregnancies complicated with IUGR, polyhydramnios or oligohydramnios should be avoided. Suggestive maternal symptoms and specific fetal sonographic features should prompt testing for CMV and Toxoplasma infection.

Platelets Sequester Extracellular DNA, Capturing Tumour-Derived and Free Fetal DNA

Introduction &amp; Hypothesis Platelets are small, multi-functional cells that lack a nucleus but contain RNA and translational machinery for protein synthesis. Platelet RNA mostly derives from parent megakaryocytes, but they also sense and sequester endogenous and pathogen-derived nucleic acids during circulation (D'Ambrosi, 2021; Koupenova, 2019). Nucleated cells release DNA after cell death or aberrant mitosis, resulting in ‘cell-free’ DNA in plasma (cfDNA). Excess cfDNA is deleterious. cfDNA isolated from platelet-poor plasma is emerging as a major liquid biopsy tool in cancer and antenatal screening, but a major limitation is its low abundance, especially in early-stage disease. Given their role in sensing pathogen-derived nucleic acids, we hypothesized that platelets may clear cfDNA from plasma, and that clinically-relevant insights may be derived from the analysis of DNA fragments contained in platelets. Methods Live/fixed imaging using specific DNA probes and fluorescence in-situ hybridization (FISH), droplet digital PCR (ddPCR), NGS and flow cytometry were applied to platelets isolated from Streck, EDTA tubes or apheresis bags from healthy donors, pregnant women, patients with cancer and murine platelets from cancer models. DNA was extracted from platelet pellets or platelet-depleted plasma (cfDNA) using the Qiagen QIAamp Circulating Nucleic Acid Kit. Results Using live cell imaging and flow cytometry, significant DNA content (Draq5+) was detected in ~8% of platelets from healthy donors, including in platelets with low RNA content (SYTO-13-negative). Overall Draq5+ platelets were larger and primed for agonist activation. FISH and ddPCR of platelets from pregnant women carrying male fetuses detected Y-chromosome fragments (n=10), confirming that platelet DNA is not solely derived from parent megakaryocytes but also sequestered during circulation (Fig. 1a). In contrast, Y-chromosome genes were not detected in DNA isolated from mononuclear cells or red blood cells pellets. Acute platelet depletion in an ITP mouse model (n=20) led to a &amp;gt;2-fold increase in cfDNA extracted from platelet-poor plasma, suggesting a role for platelets in plasma DNA clearance. Platelet uptake in vitro was rapid, visible using live cell microscopy within 2 minutes of co-culture with cancer cells labelled with a probe that irreversibly intercalates to nuclear DNA. ddPCR of platelet DNA following co-culture of healthy donor platelets with cancer cell lines detected a range of canonical cancer driver mutations, including in PI3K, BRAF and JAK2. DNase treatment of co-cultured platelets did not reduce mutant allele content, indicating that platelets encapsulate DNA and protect it from degradation. We explored the mechanism of platelet DNA uptake. Platelets internalized DNA contained in extracellular vesicles (EVs). Platelet uptake of “free” DNA was also confirmed, with uptake of synthetic DNA fragments of varying lengths (120 bp to 650 bp). Importantly, platelet DNA detection was enhanced following exocytosis inhibition, confirming that platelet DNA uptake and release is an active process. Whole genome sequencing revealed that platelets contain a repertoire of DNA fragments that map across the nuclear genome, similar to cfDNA, and that the majority of platelet DNA is of nuclear not mitochondrial origin. We also found tumor-derived DNA showing multiple copy number aberrations in a patient with pancreatic carcinoma. In a transgenic mouse model of colorectal cancer, mutant KRASG12D alleles were readily detectable in platelet DNA and, notably, in higher abundance in platelets than platelet-poor plasma (cfDNA) in 11/16 mice (Fig. 1b). Similarly, KRASG12D was detected in platelets of mice with orthotopic pancreatic adenocarcinoma (n=4). Finally, to explore utility in cancer screening, we analysed patients with high-risk, pre-malignant colonic lesions (serrated polyps). Remarkably, the driver mutation BRAFV600E was detected in platelets in 16% patients despite the small-size lesions (5/30, Fig.1b). Conclusions This study establishes a role for platelets in sequestration of cfDNA, an aspect of platelet biology that has not previously been highlighted and is of substantial clinical relevance. Their abundance, ease of isolation, and continuous tissue perfusion make platelets ideal ‘sentinels’ for genetic perturbations including in early stage/pre-malignant disease.

P004 - Utility of metastatic screening with computerized tomography and bone-scan after prostate cancer diagnosis

P004 - Utility of metastatic screening with computerized tomography and bone-scan after prostate cancer diagnosis

Challenges to Implementation of Community Health Worker-Led Chronic Obstructive Pulmonary Disease (COPD) Screening and Referral in Rural Uganda: A Qualitative Study using the Implementation Outcomes Framework.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The burden of COPD is expected to increase in low- and middle-income countries (LMICs). COPD screening and diagnostics tools are often inaccessible in rural settings of LMICs. To contribute to the growing body of evidence on the effectiveness of Community Health Worker (CHW) interventions, this study aims to understand the facilitators and barriers of implementing a CHW-led COPD screening and referral program in rural Uganda. This qualitative study was conducted from September to October 2022 to explore Community Members, CHWs, and Healthcare Providers (HCPs) perceptions on the challenges of CHW-delivered COPD programming in Nakaseke, rural Uganda. In total, we held eight individual in-depth interviews with CHWs, ten in-depth interviews with HCPs and six focus group discussions with 34 Community Members. Research assistants audio-recorded and transcribed interviews verbatim. The implementation outcomes framework guided the thematic analysis. Implementation acceptability was constrained by a lack of COPD awareness, a lack of perceived utility in COPD screening as well as stigma around the diagnostic process. Limited spirometry adoption was also attributed to Community Member accessibility and willingness to participate in the COPD diagnostic referral process. The high patient volume and the complex, time-consuming diagnostic and referral process hindered successful implementation. To enhance program sustainability, all participants suggested increasing CHW support, medication access, decentralizing COPD care and upscaling follow-up of Community Members by CHWs. CHW-led interventions remain a potentially critical tool to alleviate barriers to treatment and self-management in settings where access to care is limited. While community-based interventions can create sustainable infrastructure to improve health outcomes, formative assessments of the potential barriers prior to intervention are required. Evidence-based, localized approaches and sustained funding are imperative to achieve this.

Brief Report: Single and Repeat Screening with the Modified Checklist for Autism in Toddlers-Revised in Young Children at Higher Likelihood for Autism Spectrum Disorder.

To compare the utility of single versus repeated autism screening in a sample at higher likelihood (HL) for ASD, following both screen positives and all screen negatives to diagnostic outcome. Using a prospective infant sibling design, the current study followed 135 toddlers at HL for ASD and conducted diagnostic evaluations on the full sample at 18, 24, and 36 months. The psychometric properties of the M-CHAT-R using both concurrent and predictive diagnostic evaluations were compared in a group screened once (at 18 months only, n = 60) or twice (at both 18 and 24 months, n = 75). The study also examined consistency in reporting of ASD symptoms across the M-CHAT-R and a developmental concerns interview, comparing the HL group to a group with lower likelihood (LL) for ASD (n = 88). Sensitivity and specificity of the M-CHAT-R were high (75 - 95%), consistent with previous research. Positive predictive value (43 - 76%) was higher in this HL group than in previous community samples. Repeat screening improved sensitivity with little cost to specificity. At both 18 and 24 months, HL parents were more consistent in their reporting on the M-CHAT-R and a concerns interview than LL parents. The M-CHAT-R has strong psychometric properties when used with groups at HL for ASD, suggesting that scores over the screening cutoff of 3 should lead to prompt diagnostic evaluation referrals in children with older siblings on the spectrum.

Screening and Colonoscopy Quality Measures: Ethnic Disparities and Impact on Patients' Outcome.

Recent reports have confirmed the improving trends in colorectal cancer (CRC) incidence and outcomes. Still, disparities in incidence and mortality in CRC continue to persist between major ethnic groups despite the provision of widespread screening and improved care. We aimed to outline, from an endoscopic point of view, ethnic disparities in major endoscopic measures concerned with CRC screening and detection and track their impact on patients' outcomes. We reviewed electronic reports of patients referred for colonoscopy procedures over 20 years. We compared demographic, clinical, and endoscopic findings between major ethnic population groups in Israel. In addition, trends of screening utilization, bowel preparation, and polyp detection rates were tracked, and the incidence of CRC diagnosis was followed. A total of 51307 patients had undergone colonoscopies, of whom 16% were Arabs, and 84% were Jewish. The procedures performed for CRC screening throughout the study period were significantly lower in Arabs (5% vs. 13.1%; P < 0.0001). In parallel, for most of the follow-up period, the Arab patients had higher rates of inadequate bowel preparation (overall: 19.9% vs. 12%; P < 0.001) and a lower polyp detection rate (16.7% vs. 22.5%; P < 0.0001). Expectedly, the incidence of CRC has steadily decreased in the Jewish group, while an adverse pattern of increasing incidence was documented in the Arab patient during the follow-up period. Characterized by lower screening utilization and poor bowel preparation, the incidence of CRC development in Arab patients is increasing, while improving trends of CRC were observed in their Jewish counterparts.

Personalized Multilevel Intervention for Improving Appropriate Use of Colorectal Cancer Screening in Older Adults

Despite guideline recommendations, clinicians do not systematically use prior screening or health history to guide colorectal cancer (CRC) screening decisions in older adults. To evaluate the effect of a personalized multilevel intervention on screening orders in older adults due for average-risk CRC screening. Interventional 2-group parallel unmasked cluster randomized clinical trial conducted from November 2015 to February 2019 at 2 US Department of Veterans Affairs (VA) facilities: 1 academic VA medical center and 1 of its connected outpatient clinics. Randomization at the primary care physician/clinician (PCP) level, stratified by study site and clinical full-time equivalency. Participants were 431 average-risk, screen-due US veterans aged 70 to 75 years attending a primary care visit. Data analysis was performed from August 2018 to August 2023. The intervention group received a multilevel intervention including a decision-aid booklet with detailed information on screening benefits and harms, personalized for each participant based on age, sex, prior screening, and comorbidity. The control group received a multilevel intervention including a screening informational booklet. All participants received PCP education and system-level modifications to support personalized screening. The primary outcome was whether screening was ordered within 2 weeks of clinic visit. Secondary outcomes were concordance between screening orders and screening benefit and screening utilization within 6 months. A total of 436 patients were consented, and 431 were analyzed across 67 PCPs. Patients had a mean (SD) age of 71.5 (1.7) years; 424 were male (98.4%); 374 were White (86.8%); 89 were college graduates (21.5%); and 351 (81.4%) had undergone prior screening. A total of 258 (59.9%) were randomized to intervention, and 173 (40.1%) to control. Screening orders were placed for 162 of 258 intervention patients (62.8%) vs 114 of 173 control patients (65.9%) (adjusted difference, -4.0 percentage points [pp]; 95% CI, -15.4 to 7.4 pp). In a prespecified interaction analysis, the proportion receiving orders was lower in the intervention group than in the control group for those in the lowest benefit quartile (59.4% vs 71.1%). In contrast, the proportion receiving orders was higher in the intervention group than in the control group for those in the highest benefit quartile (67.6% vs 52.2%) (interaction P = .049). Fewer intervention patients (106 of 256 [41.4%]) utilized screening overall at 6 months than controls (96 of 173 [55.9%]) (adjusted difference, -13.4 pp; 95% CI, -25.3 to -1.6 pp). In this cluster randomized clinical trial, patients who were presented with personalized information about screening benefits and harms in the context of a multilevel intervention were more likely to receive screening orders concordant with benefit and were less likely to utilize screening. ClinicalTrials.gov Identifier: NCT02027545.

Screening the NCI diversity set V for anti-MRSA activity: cefoxitin synergy and LC-MS/MS confirmation of folate/thymidine biosynthesis inhibition.

New antibacterial agents and agent combinations are urgently needed to combat antimicrobial resistance. A multidimensional chemical library screening strategy was used to identify compounds in the National Cancer Institute (NCI) diversity set V library (1,593 compounds) with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. In this effort, library compounds were screened for anti-MRSA activity in both their original [un-metabolized (UM)] and human liver microsome-metabolized [post-metabolized (PM)] forms and in the absence and presence of sub-minimum inhibitory concentration (MIC) levels of cefoxitin. This strategy allows for the identification of intrinsically active agents, agents with active metabolites, and agents that can act synergistically with cefoxitin. Sixteen UM compounds with MICs ≤ 12.5 µM were identified. No agents with substantially enhanced activity after microsomal metabolism were found. Several agents showed significant apparent synergy with cefoxitin, and checkerboard assays were used to confirm synergy for four of these (celastrol, porfiromycin, 4-quinazolinediamine, and teniposide). A follow-up comparative screen in the absence and presence of 4-µM thymidine was used to identify three agents as likely folate/thymidine biosynthesis inhibitors. A liquid chromatography-mass spectrometry (LC-MS/MS) assay for deoxythymidine triphosphate (dTTP) was used to confirm these three as suppressing dTTP biosynthesis in MRSA. Bactericidal vs bacteriostatic activity was also evaluated. This study further demonstrates the utility of comparative library screening to identify novel bioactive agents with interesting synergies and biological activities. The identification of several folate/thymidine biosynthesis inhibitors from this small screen indicates that this pathway is a viable target for new drug discovery efforts. IMPORTANCE New antibacterial agents are urgently needed to counter increasingly resistant bacteria. One approach to this problem is library screening for new antibacterial agents. Library screening efforts can be improved by increasing the information content of the screening effort. In this study, we screened the National Cancer Institute diversity set V against methicillin-resistant Staphylococcus aureus (MRSA) with several enhancements. One of these is to screen the library before and after microsomal metabolism as means to identify potential active metabolites. A second enhancement is to screen the library in the absence and presence of sub-minimum inhibitory concentration levels of another antibiotic, such as cefoxitin in this study. This identified four agents with synergistic activity with cefoxitin out of 16 agents with good MRSA activity alone. Finally, active agents from this effort were counter-screened in the presence of thymidine, which quickly identified three folate/thymidine biosynthesis inhibitors, and also screened for bactericidal vs bacteriostatic activity.

Feasibility and Utility of Posttraumatic Stress Disorder Screening Among Postpartum Patients at an Urban Safety-Net Institution.

Posttraumatic stress disorder (PTSD) is underdiagnosed peripartum. We administered a primary care screening tool and a pregnancy-related PTSD screening tool to postpartum patients presenting to our urban safety-net institution within 6 months of delivery, between August 2021 and February 2022. Our primary outcome was prevalence of positive PTSD screening results. Most patients (364/376, 96.8%) completed screening. Thirty (8.4%) had a positive score on at least one instrument, and seven of these 30 (23.3%) did not have a positive postpartum depression screening result. Among patients with a positive score, the majority (66.7%) obtained behavioral health follow-up. We found that routine PTSD screening for postpartum patients is feasible and identified patients at risk for PTSD. Obstetric practitioners should consider integrating PTSD screening into routine care.