Routine Screening Research Articles

7982 Is there a Connection between Alpha Thalassemia and Thyroid Disorders

Abstract Disclosure: W. Akhter: None. V. Taqi: None. J.L. Gilden: None. IntroductionA number of case reports suggest an association between thalassemia and autoimmune diseases through specific mutations and molecular pathways. An example is thyroid disease in thalassemia patients. Due to factors such as age, ethnicity and treatment protocol differences, the frequency of hypothyroidism in thalassemia patients is a wide range of 4 to 29% based on free T4 and TSH levels. Subclinical hypothyroidism is more common in thalassemia patients as compared to overt hypothyroidism. 90% of morbidity and mortality in B-Thalassemia patients is attributed to iron overload, anemia and hypoxia. Understanding this possible mechanism helps guide treatment and monitoring. Case PresentationWe present the case of a 26-year-old African American with Haitian ethnicity female, who upon routine testing was found to have a very high TSH level of 79.084 uIU/ml (nl=0.550-4.780 uIU/ml) for which 125 mcg of Levothyroxine was started, and then she was referred to the endocrine clinic. Past history was notable for sickle cell trait and alpha thalassemia trait. Patient stated that at age 12, she developed fatigue and low energy and was found to have hyperthyroidism which was treated with RAI ablation. After that, no follow up or lab tests were done until recently. The patient denied symptoms of hypo or hyperthyroidism or enlargement of the thyroid gland. She denied any family history of thyroid disorders. After presenting to the endocrine clinic a few days later, she was diagnosed with postprocedural hypothyroidism and the same dose of levothyroxine was continued. Physical exam was unremarkable and no thyromegaly was appreciated on exam. Labs were notable for decreased Hemoglobin of 11.4 g/dL (nl=12-16 g/dL) and CMP was unremarkable except low glucose of 65 mg/dL (nl=70-99 mg/dL). The patient’s most recent labs after 8 weeks of taking Levothyroxine were notable for TSH of 14.65 uIU/ml (nl=0.550-4.780 uIU/ml) and free T4 of 1 ng/dL (nl= 0.89-1.76 ng/dL) and the patient admitted to having still no thyroid symptoms and a little more energy. ConclusionEndocrinopathies are common complications of thalassemia with hypothyroidism being the second most common endocrine disorder in thalassemia patients after hypogonadism, reported in 5.6-17% of patients. In thalassemia patients, endocrine disorders have to be managed as early as possible. Therefore, it is recommended that an endocrine evaluation be carried out in thalassemia patients at a young age.Monitoring for glucose homeostasis, hypothyroidism and hypoparathyroidism is also warranted. Physicians caring for thalassemia patients should perform routine screening for and treat thyroid dysfunction appropriately. Reference: De Sanctis V, Soliman AT, Canatan, et al.. Thyroid Disorders in Homozygous β-Thalassemia: Mediterr J Hematol Infect Dis. 2019 May 1;11(1):e2019029. doi: 10.4084/MJHID.2019.029. PMID: 31205633; PMCID: PMC6548211. Presentation: 6/2/2024

Untargeted Metabolomics for Inborn Errors of Metabolism: Development and Evaluation of a Sustainable Reference Material for Correcting Inter-Batch Variability.

Untargeted metabolomics has shown promise in expanding screening and diagnostic capabilities for inborn errors of metabolism (IEMs). However, inter-batch variability remains a major barrier to its implementation in the clinical laboratory, despite attempts to address this through normalization techniques. We have developed a sustainable, matrix-matched reference material (RM) using the iterative batch averaging method (IBAT) to correct inter-batch variability in liquid chromatography-high-resolution mass spectrometry-based untargeted metabolomics for IEM screening. The RM was created using pooled batches of remnant plasma specimens. The batch size, number of batch iterations per RM, and stability compared to a conventional pool of specimens were determined. The effectiveness of the RM for correcting inter-batch variability in routine screening was evaluated using plasma collected from a cohort of phenylketonuria (PKU) patients. The RM exhibited lower metabolite variability between iterations over time compared to metabolites from individual batches or individual specimens used for its creation. In addition, the mean variation across amino acid (n = 19) concentrations over 12 weeks was lower for the RM (CVtotal = 8.8%; range 4.7%-25.3%) compared to the specimen pool (CVtotal = 24.6%; range 9.0%-108.3%). When utilized in IEM screening, RM normalization minimized unwanted inter-batch variation and enabled the correct classification of 30 PKU patients analyzed 1 month apart from 146 non-PKU controls. Our RM minimizes inter-batch variability in untargeted metabolomics and demonstrated its potential for routine IEM screening in a cohort of PKU patients. It provides a practical and sustainable solution for data normalization in untargeted metabolomics for clinical laboratories.

Prenatal and postnatal antiviral therapies for the prevention and treatment of congenital cytomegalovirus infections.

Congenital cytomegalovirus infection (cCMV) is the leading infectious cause of sensorineural hearing loss and lifelong neurodevelopmental disabilities. Studies suggest antiviral therapy can prevent fetal infection after maternal primary infection, as well as halt the progression of hearing loss and neurodevelopmental disabilities in newborns with symptomatic cCMV. With growing worldwide momentum on early detection and diagnosis of cCMV, this review describes the exciting recent advances in antiviral therapies in CMV infected pregnant mothers and babies, as well as emerging evidence on anti-CMV vaccines. New opportunities for prenatal and neonatal interventions have driven a rising interest in screening and identification of asymptomatic CMV infection. Routine screening of pregnant women to identify primary infection in first trimester is now advocated in Western Europe but has yet to be examined from a public health perspective in other regions. Evidence is emerging for maternal valaciclovir therapy to prevent fetal infection after a maternal primary CMV infection in the first trimester of pregnancy. For those infants who are born with symptomatic cCMV, a 6-month course of valganciclovir, started within the first 4 weeks of life, and possibly up to 13 weeks of life, is the current recommended therapy. However, there is unclear evidence for the benefit of treatment for asymptomatic cCMV and cCMV with isolated hearing loss. Research to identify more effective antivirals and an effective CMV vaccine continues. More research is needed to determine the region-specific applicability of the new European recommendations for routine CMV screening in pregnancy. Areas of uncertainty in postnatal management include timing of initiation, duration of treatment and identifying pediatric subgroups that benefit from modification of the standard treatment recommendations.

'Whatever the GP says, is what I'll do'-A qualitative study of patient perspectives in accessing primary eye care for type 2 diabetes.

To investigate the perspectives of people accessing a general medical practitioner (GP)-optometry model of collaborative care that was established to increase access to diabetes eye care. Qualitative study of patient barriers and facilitators to accessing primary diabetes eye care located in a metropolitan area in Australia. One-on-one interviews were recorded, transcribed and thematically analysed using a determinant framework on patient-centred access to health care. Twenty-four people with type 2 diabetes, including 15 males and 9 females, who accessed the service between September 2021 and June 2022 agreed to participate. Mean (SD) age of the participants was 52 (12) years and 50% had been diagnosed with diabetes for <2 years. Facilitators to accessing diabetes eye care included a referral from a GP or GP nurse, fee-free consultations, availability of after-hours appointments and short waiting times. Barriers to access included perceived out-of-pocket costs, competing responsibilities and lack of awareness of diabetic retinopathy screening recommendations. Considering diabetic retinopathy may present asymptomatically, primary health practitioners (optometrists and GPs) are well positioned to raise patient awareness of the importance of routine eye examinations. In Australia, access to routine screening could be facilitated by fee-free eye checks and personalised text message reminders implemented at a health system level.

Vulvovaginal candidiasis in pregnant women attending a tertiary care centre in North-Eastern India

BackgroundCandida colonisation in vagina was found to be 20 %, rising to 30 % during pregnancy. According to studies, the prevalence of VVC during pregnancy is higher than healthy women. During pregnancy, candidal colonisation increases, both symptomatic and asymptomatic. However, the difference between strains causing symptomatic infection and those that cause asymptomatic infection is unknown. ObjectiveThis study aimed to compare the virulence factors of Candida VVC isolates from symptomatic and asymptomatic pregnant women. MethodsThe study included 120 pregnant women- 60 symptomatic and 60 asymptomatic, who presented to the Obstetrics and Gynaecology Outpatient Department with vaginitis symptoms. High vaginal swabs from the patient and used for gram stain, direct wet mount, pH detection and fungal culture in SDA with and without antibiotics. Germ tube tests, growth in CMA, and HiCrome Candida Differential Agar were used to identify yeast colonies grown in culture. The isolates were then examined for virulence factors like biofilm formation, phospholipase, coagulase, and hemolysin. Antifungal susceptibility was determined using E-test. ResultsThe current study reveals a high prevalence of Vulvovaginal Candidiasis in pregnant women(35 %). Asymptomatic patients had lower proportion of VVC than symptomatic patients. Non albicans Candida(NAC) outnumbered Candida albicans. Although Candida albicans growth was predominant in asymptomatic patients. Virulence studies revealed that Candida spp. isolated from symptomatic patients expressed a higher proportion of virulence factors. Besides NAC has higher proportion of expressing virulence factors than Candida albicans and has higher propensity to cause infection especially in symptomatic pregnant women. Antifungal susceptibility testing shows Itraconazole to be most sensitive for VVC treatment but Candida albicans was most susceptible to fluconazole while NAC had the least. ConclusionsThe study emphasizes the importance of routine screening of symptomatic pregnant women for VVC, as syndromic treatment will increase antifungal resistance, particularly in NAC.

First-Trimester Preeclampsia-Induced Disturbance in Maternal Blood Serum Proteome: A Pilot Study.

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11-13 weeks of gestation were quantified using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6-40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE.

High-risk HPV mRNA testing on self-samples offered to those who do not attend for organised cervical screening – real world data from the Dumfries and Galloway region in Scotland

BackgroundHPV self sampling can act as a tool to engage women in cervical screening and population based studies can inform optimal implementation of this approach. MethodsSelf sampling kits were mailed to women who had defaulted from routine screening resident in an entire territorial health board in Scotland. Kit return rates and compliance to colposcopy follow up in those who were HPV mRNA positive were assessed. Concordance of the self-sample with samples taken later at colposcopy was measured alongside PPV of an mRNA positive result for CIN2+. ResultsOf 4173 women invited to participate, 20.5 %, returned their kit and a greater return rate with increasing age was observed. HPV mRNA positivity was 12.0 %, and invalidity rate was approximately 3 %. Compliance to colposcopy follow up was 88.3 % and the PPV for an mRNA test for CIN2+ on a self sample was 25.6 %. hr-HPV concordance on the initial swab and the follow up swab and liquid based cytology (LBC) sample taken at colposcopy was 67.1 % and 30 % respectively. ConclusionsHPV self sampling using a “mail to all” approach is feasible in Scotland although only 1 in 5 actively responded to the offer. Future work to monitor screening behaviours in those who were invited but did not engage initially will help quantify any additional benefit(s) incurred.

Routine screening and clinical diagnosis of intestinal helminths in cats and dogs

Anthelmintics remain a fundamental component of both treatment of parasitic disease and preventative health for pets. The focus of intestinal helminth control to reduce disease and zoonotic risk in the UK has been routine treatment rather than testing. As a result, testing is often viewed as unnecessary if routine preventative treatment is occurring. Diagnosing intestinal roundworms in cases of gastrointestinal disease is important because heavy burdens can contribute to the severity of clinical signs and intestinal pathology. However, routine testing alongside prevention for worm infections in cats and dogs is also vital to demonstrate the effectiveness of treatment plans, gather data on parasite distributions and detect anthelmintic resistance.

B-213 Including Turner Syndrome Screening in Newborn Sequencing by Using NGS Read Counts to Infer Sex Chromosomes Copy Number: Leveraging Existing Data to Enhance Early Diagnosis

Abstract Background Turner Syndrome (TS) can lead to heart defects, short stature, and premature ovarian failure. Early diagnosis can improve outcomes, but routine screening is not standard, often delaying diagnosis until symptoms prompt karyotype analysis. Newborn NGS sequencing offers potential for early detection of genetic disorders and targets numerous gene regions on autosomes and sex chromosomes. It could be utilized to deduce sexual chromosomal copy number variations, including not only chrX monosomy but also its partial deletions and structural alterations, and chrY, which increases the risk of gonadoblastoma in TS patients. Thus, this study aims to validate a TS screening approach using NGS read count data from newborn sequencing to develop a strategy for early detection. Methods DNA samples with established chromosomal microarray ChrX and ChrY copy-number assessments were used. The cohort included 13 males (46,XY), 10 females (46,XX), 5 TS cases (45,X), 5 mosaic TS cases (2 with chrY, 3 without), 1 TS case with Isochromosome Xq, 8 Klinefelter Syndrome cases (47,XXY), and one case (48,XXYY). For NGS, a focused newborn sequencing panel targeting 388 genes derived from the larger xGEN Inherited Disease Panel (Integrated DNA Technologies) was employed. The larger panel covers 2,968 chrX regions, 53,455 autosomal regions, and 135 chrY regions. Sample processing utilized the xGEN DNA Library Prep and Hybridization Capture (Integrated DNA Technologies) and sequencing on NextSeq-500 (Illumina). The alignment was conducted with Dragen Enrichment v.3.9.5 and read count analysis with Samtools v.1.19.2. ChrX and ChrY copy numbers were assessed by comparing chrX and chrY read count ratios to autosomal read counts. Hierarchical clustering grouped samples based on ratio similarities, aiding result attribution. To identify structural alterations in each arm of chrX, every tested chrX region was analyzed for read count ratio calculation and subjected to circular binary segmentation using the DNAcopy R package. The observed sex chromosome counts were compared to expected results to validate the approach. Results Observed chrX/autosome and chrY/autosome ratio ranges matched the expected sex chromosome counts: 0.99-1.03 and 0.82-1.02 for 46,XY; 1.92-1.97 and 0.00-0.01 for 46,XX; 1.00-1.02 and 0.00-0.00 for 45,X; 1.15-1.46 and 0.00-0.00 for mosaic TS without chrY; 0.98-1.06 and 0.27-0.32 for mosaic TS with chrY; 2.45 and 0.0 for TS with Isochromosome Xq; 1.82-2.01 and 0.87-0.95 for 47,XXY; and 2.02 and 1.96 for 48,XXYY. Hierarchical cluster analysis grouped these values into three branches: one for 48,XXYY, one for 47,XXY, 46,XX, and Isochromosome Xq, and one for all other TS samples and 46,XY. TS and 47,XXY samples were further divided into subbranches from 46,XX and 46,XY. Circular binary segmentation of chrX read counts provided a visual profile of the copy number for each arm of chrX, explaining structural alterations in out-of-pattern chrX dosages, such as 2.45, 1.15, and 1.46. Conclusions There was complete agreement between the NGS read count-based assessment of sex chromosome copy number and the expected results for 46,XY, 46,XX, 45,X, TS with mosaic and structural variants, 47,XXY, and 48,XXYY samples. This suggests that TS can be effectively screened using newborn sequencing NGS data.

Automated image transcription for perinatal blood pressure monitoring using mobile health technology.

This paper introduces a novel approach to address the challenges associated with transferring blood pressure (BP) data obtained from oscillometric devices used in self-measured BP monitoring systems to integrate this data into medical health records or a proxy database accessible by clinicians, particularly in low literacy populations. To this end, we developed an automated image transcription technique to effectively transcribe readings from BP devices, ultimately enhancing the accessibility and usability of BP data for monitoring and managing BP during pregnancy and the postpartum period, particularly in low-resource settings and low-literate populations. In the designed study, the photos of the BP devices were captured as part of perinatal mobile health (mHealth) monitoring programs, conducted in four studies across two countries. The Guatemala Set 1 and Guatemala Set 2 datasets include the data captured by a cohort of 49 lay midwives from 1697 and 584 pregnant women carrying singletons in the second and third trimesters in rural Guatemala during routine screening. Additionally, we designed an mHealth system in Georgia for postpartum women to monitor and report their BP at home with 23 and 49 African American participants contributing to the Georgia I3 and Georgia IMPROVE projects, respectively. We developed a deep learning-based model which operates in two steps: LCD localization using the You Only Look Once (YOLO) object detection model and digit recognition using a convolutional neural network-based model capable of recognizing multiple digits. We applied color correction and thresholding techniques to minimize the impact of reflection and artifacts. Three experiments were conducted based on the devices used for training the digit recognition model. Overall, our results demonstrate that the device-specific model with transfer learning and the device independent model outperformed the device-specific model without transfer learning. The mean absolute error (MAE) of image transcription on held-out test datasets using the device-independent digit recognition were 1.2 and 0.8 mmHg for systolic and diastolic BP in the Georgia IMPROVE and 0.9 and 0.5 mmHg in Guatemala Set 2 datasets. The MAE, far below the FDA recommendation of 5 mmHg, makes the proposed automatic image transcription model suitable for general use when used with appropriate low-error BP devices.

Application of a Computational Metabolomics Workflow for the Diagnosis of Inborn Errors of Metabolism in a Laboratory Setting.

Inborn errors of metabolism constitute a set of hereditary diseases that impose severe medical and physical challenges in the affected individual, in particular, for the pediatric patient population. Timely diagnosis is crucial for these patients, as any delay could result in irreversible health damage, underscoring the importance of early initiation of personalized treatment. Current routine diagnostic screening for inborn errors of metabolism relies on various targeted analyses of established biomarkers. However, this approach is time-consuming, focuses on a limited number of tests (based on clinical information) with a relatively small number of biomarkers, and does not facilitate the identification of new markers. In contrast, untargeted metabolomics-based screening offers a more efficient diagnostic solution, by assessing thousands of metabolites across multiple metabolic pathways in a single test. This not only saves time but also conserves resources for clinicians, the diagnostic laboratory, and for patients.This chapter describes the computational workflow of our "Next Generation Metabolic Screening" approach, which is a metabolomics-based method that is currently applied at the Translational Metabolic Laboratory of the Radboud University Medical Center (the Netherlands) for the diagnosis of inborn errors of metabolism.

A-320 Determination of Guanidinoacetate Methyltransferase Enzyme Biomarkers in Newborn Dried Blood Spot by Tandem Mass Spectrometry-A Two Tier Approach

Abstract Background Guanidinoacetate methyltransferase enzyme (GAMT) deficiency is a rare, inherited metabolic disorder that affects the synthesis of creatine. Creatine is an essential metabolite for regenerating energy, particularly in the brain and muscles. Creatine is synthesized from guanidinoacetate (GUAC) by the GAMT enzyme. Mutations in the GAMT gene result in a shortage of the GAMT enzyme that causes a deficiency of creatine and accumulation of GUAC in the body, which is a neurotoxin. Following a recommendation by the Recommended Uniform Screening Panel and in line with California State statute, all California newborns will be screened for GAMT deficiency beginning July 2024. Here, we developed and validated a quantitative two-tier tandem mass spectrometry (MS/MS) assay for the detection of GAMT biomarkers (GUAC, creatine and creatinine) in newborn dried blood spot (DBS). Methods This method punches a 3.2 mm disc of controls and newborn patient DBS into a 96-well plate. 100 μL of extraction solution, containing internal standards of GAMT biomarkers, is added to each well and incubated at 40°C for 45 minutes. The extract is transferred, evaporated, and derivatized into a 3N-butanol-HCl solution at 60°C for 30 minutes. The excess HCl is evaporated to dryness. The conversion of GUAC and creatine to their butyl esters has improved their detection sensitivity by MS/MS. The butyl esters are reconstituted into the mobile phase and shaken for 10 minutes at 27°C. The final 10 μL extract was analyzed by flow injection analysis (FIA)-MS/MS in multiple reaction monitoring (MRM) positive ion mode with a total run time of 1.5 minutes per sample. The presumptive positive samples from initial analysis are prepared following the same method, and a 5 μL extract is resolved through an ultra-performance liquid chromatography (UPLC) column and analyzed by UPLC-MS/MS in MRM positive ion mode with a total run time of 3.5 minutes per sample. The validation was performed by assessing the linearity, accuracy, imprecision, carryover, limit of detection (LOD) and lower limit of quantitation (LLOQ), matrix effect, analytical measurement range (AMR), percent total allowable error (TEa), and reference range. Results This method is linear for GUAC, creatine and creatinine over a measured range of 1.17-40.00, 121.20-857.36 and 41.34-387.46 µmol/L respectively. The R2 values=1.000, 0.997, 0.9998; slope=0.999, 0.9945, 0.9982; intercept=0.0398, 4.881, 1.7027; mean recoveries=99-104%, 100-104%, 100-104%; intra-assay precision (n=20) =4.05-5.95%, 4.62-5.31%, 3.27-5.19%, inter-assay precision (n=40)=3.7-12.6%, 4.3-7.6%, 3.8-7.4%; TEa=6-21%, 7-17%, 6-17%; LOD=0.12, 0.54, 1.11 µmol/L; AMR=0.33-1300, 1.11-2700, 3.50-4500 µmol/L; median patient results observed from 2293 normal patient=1.48, 494.02, 89.97 μmol/L for GUAC, creatine, and creatinine respectively. The tier-1 and tier-2 assay screening cutoff for GUAC at the population 95th percentile is 2.53 and 4.55 μmol/L respectively. Conclusions The tier-1 and tier-2 methods has been developed and validated to determine GAMT biomarkers in newborn DBS, making it suitable for routine screening of ∼2000 newborn specimens per day by tier-1 and followed by more specific tier-2 to separate GAMT biomarkers from potential isobaric interfering compounds. This two-tier approach greatly improved the test performance and significantly reduced false positive rate.

B-076 Detection of KLHL11 Autoantibodies Using a New Cell-based Indirect Immunofluorescence Assay

Abstract Background Autoantibodies against kelch-like protein 11 (KLHL11) were first described in 2019 as markers of paraneoplastic encephalitis. Early diagnosis and treatment are imperative to improve prognosis and outcome of affected patients. Rat brain immunohistochemistry was reported to be not useful in routine screening for KLHL11 antibodies. This study evaluates the performance of a new recombinant cell-based assay for the standardized detection of KLHL11-specific IgG and reports the characteristics of the examined patients. Methods Serum (n=9), CSF (n=5) and/or plasmapheresis (n=1) samples from 10 patients with clinical presentations compatible with anti-KLHL11 encephalitis as well as sera from 100 healthy blood donors were analyzed using a prototype indirect immunofluorescence assay (IFA; EUROIMMUN) based on recombinant HEK293 cells expressing human KLHL11. Results KLHL11 autoantibodies were detected at high titers in all samples (serum &amp;gt;1:1,000; CSF &amp;gt;1:320; plasma &amp;gt;1:100,000) from all (10/10) patients but in none (0/100) of the blood donors, indicating 100% sensitivity and specificity. Anti-KLHL11-positive patients had a median age of 52 years (range 27-71) and 80% were male. The most common reported clinical presentations were cerebellar syndrome (ataxia), brainstem diencephalic encephalitis, rhombencephalitis and limbic encephalitis. Testicular or ovarian tumors were found in 87.5% (7/8) of the cases with available results from malignancy screening. Conclusions The new cell-based IFA enables the sensitive and specific detection of KLHL11 autoantibodies, thus supporting the diagnosis of patients with predominantly paraneoplastic brainstem cerebellar syndrome. Future studies will evaluate assay performance in larger patient cohorts to address the reported association of KLHL11 autoimmunity with a wider spectrum of syndromes and tumors.

Rising to the challenge: The motivation to champion routine intimate partner violence screening in rural emergency departments.

To understand the motivations of champions who worked to bring about system and practice change that supported routine screening for intimate partner violence (IPV) in two rural emergency departments (EDs). Practice changes are required to achieve routine and effective identification and response to IPV. Nurses play a significant role in affecting such practice change. This paper identifies the motivations of champions in the ED setting who successfully brought about such change. The EDs of two Level 5 tertiary hospitals within a rural Local Health District (LHD) of New South Wales, Australia. Twenty-three individuals who identified as champions and worked to introduce routine IPV screening in two rural hospital EDs. Qualitative longitudinal semi-structured interviews employing a process of constant comparison and an interpretive framework to analyse data thematically. Interviews were carried out between June and August 2017 and again between July and August 2019. Over the period of the study, routine screening was established, and screening rates steadily increased from a low baseline to a significantly higher rate. Three aspects of champion motivation emerged from the analysis: formation of an identity as a champion, making a difference to a significant social justice issue and providing quality and community-relevant care. This study is the first study to report on champions and their motivation as they supported IPV practice change in the ED. The findings highlight the capacity for innovation in rural health services, with important implications for other settings looking to translate similar programs. Understanding motivating factors may assist in improved utilisation and support for champions. This is vital if champions are to bring about required practice change within their service and ensure the needs of individuals experiencing IPV are effectively met.

Implementing a financial toxicity screening program.

275 Background: Financial toxicity (FT) is a well-documented negative side effect of cancer treatment. Routine screening can mitigate FT by proactively connecting at-risk patients to resources and counseling. Herein, we describe implementation of a FT screening quality improvement (QI) program. Methods: At a comprehensive cancer center, an interdisciplinary team explored options for implementation, with consideration for screening content, mechanism for delivery, and clinical workflow. Through consensus, the team agreed to use the 12-item COmprehensive Score for Financial Toxicity (COST) tool, a health-related social risk checklist, patient-self report of cost-related medication non-adherence, and a visual analog quality of life scale. Surveys were sent via portal every four months to patients on active treatment. The QI project was implemented on the breast, gastrointestinal, gynecologic, and thoracic services. COST scores ≤20 or any endorsed social risk (e.g., food, transportation) yielded a positive screen, and nurses placed a financial counseling referral, with counseling dispositions tracked. In March 2023, due to an influx of “unproductive” counseling dispositions (e.g., patient could not be contacted, patient no longer wanted help), machine learning models suggested reducing the screening threshold to COST scores ≤16 and limiting the social risk checklist to four items (food, transportation, medication, and housing insecurity). Results: From 06/2022-12/2023, 196,675 financial toxicity surveys were assigned to 78,289 unique patients: 38% (n=75,526) were completed by 45,003 patients. Of these, 56% have completed one survey, 26% have completed two surveys, and 18% have completed three or more. Since implementation, 9612 financial counseling referrals have been placed, yielding assistance with insurance selection and applications for assistance with co-payments, non-medical expenses, and out-of-pocket costs. During the QI project, several real-time workflow changes were made. On day 1, 519/1811 patients screened positive, yielding an overflow of counseling referrals: an additional question to allow patients to opt into referral, rather than generating an automatic referral, was then added: the following week, 136 referrals were generated. In September 2022, this opt-in was modified to allow patients to directly identify the areas in which they were seeking assistance (e.g., insurance counseling, out-of-pocket expenses). In 2024, the screening was reduced to two COST questions that had a 0.92 correlation with the full-tool. Conclusions: Routine FT screening is feasible during active treatment, although attention is needed to clinical workflows to ensure patients have access to the screening, nurses and other clinical staff are involved in the implementation, and referrals to resources are available for patients who screen positive. Future work will address cadence of delivery and outcomes of interventions.

Frailty and health-related life quality in long-term follow up of intensive care patients above 65 years old: Protocol for a Norwegian prospective, observational multicenter study.

Frailty is strongly correlated with mortality in intensive care unit patients, yet routine screening among intensive care patients is rarely performed. The aim of this study is to assess frailty and health-related quality of life (HRQoL) in patients before intensive care admission and to compare this with outcomes after 3 and 12-months. The Clinical Frailty Scale and EQ-5D-5L will be used to assess frailty and HRQoL, respectively. This is an ongoing, prospective observational study including patients from five Norwegian ICU's. Inclusion criteria are patients aged ≥65 years requiring invasive mechanical ventilation for ≥24 h. The Clinical Frailty Scale and EQ-5D-5L are administered at baseline (before critical illness) and at 3- and 12-months post-inclusion. Additional data collected includes patient characteristics, ICU treatment details, illness severity and mortality. The EQ-5D-5L will be compared to Norwegian population norms and assessed for measurement properties. Inclusion started July 2022 and will be stopped at 350 patients. The study will be completed in 2025. The study will assess the feasibility and measurement properties of the Clinical Frailty Scale and EQ-5D-5L in ICU survivors by telephone at long-term follow-up study and will give additional information on the frailty and HRQoL of intensive care survivors. The study is registered in ClinicalTrials.gov NCT06012942. Protocol version 2.7.1, 19.05.2023.

Validating a simplified financial toxicity screening tool for patients with cancer.

318 Background: Medical-related financial hardship (called financial toxicity) can negatively impact patient clinical outcomes and overall well-being. Routine financial toxicity screening is recommended to facilitate referrals to resources for patients experiencing, or at risk for, financial toxicity. The validated Comprehensive Score for Financial Toxicity (COST) tool is widely used in research to measure financial toxicity; however, its 11-question length and lack of standardized screening threshold make it challenging to implement in clinical practice. This analysis sought to develop and validate an abbreviated version of the tool, suitable for routine screening in clinical practice. Methods: The full COST was administered as part of clinical care from June 2022-August 2023. Patients receiving treatment for breast, gynecologic, thoracic, or gastrointestinal cancer at an urban comprehensive cancer center were queried via patient portal or in clinic. Using 38,330 observations, we calculated the correlation of abbreviated tools of varying length with the full COST score (0-44, lower scores=higher FT). We then used a validation dataset of 19,196 observations to assess the positive and negative predictive values (PPV, NPV) of an abbreviated tool against the full COST score, when compared to thresholds for risk previously used in the literature (score ≤15, ≤20). Results: Including two questions (Q3: “I worry about the financial problems I will have in the future as a result of my illness or treatment”; Q6: “I am satisfied with my current financial situation”) yielded r=0.922 correlation with the full COST. For this 2-item tool, PPV ranged from 74-91%, and NPV ranged from 91-98% when compared to the full COST tool. Table 1 shows the PPV and NPV of varying score thresholds for the abbreviated COST against full scores ≤15 and ≤20. Conclusions: Using a large and clinically diverse sample of patients with cancer,we demonstrate the predictive value of an abbreviated COST tool and show its approximate accuracy when compared to the full tool. Simplified, clinically integratedscreening for financial hardship can efficiently ensure appropriate intervention for patients experiencing medical-related financial hardship and can also be a first step toward mitigating hardship among those at risk for developing it. Predictive value of 2-item COST vs. full COST score in the validation set. Full COST score ≤ 15 Yes No 2-question, COST score ≤ 1 Yes 2337 (14%) 253 (1.5%) PPV = 90% No 822 (4.8%) 13844 (80%) 1-NPV = 5.6% Full COST score ≤ 15 Yes No 2-question, COST score ≤ 2 Yes 2924 (17%) 1045 (6.1%) PPV = 74% No 235 (1.4%) 13052 (76%) 1-NPV = 1.8% Full COST score ≤ 20 Yes No 2-question, COST score ≤ 2 Yes 3626 (21%) 343 (2.0%) PPV = 91% No 1199 (6.9%) 12088 (70%) 1-NPV = 9.0% Full COST score ≤ 20 Yes No 2-question, COST score ≤ 3 Yes 4359 (25%) 1272 (7.4%) PPV = 77% No 466 (2.7%) 11159 (65%) 1-NPV = 4.0%

Beyond Physical Injury: Routine Screening for Acute Stress Disorder and Posttraumatic Stress Disorder in Pediatric Trauma Patients – A Longitudinal Cohort Pilot Study

IntroductionEarly identification of children at risk for PTSD is critical for improving mental health outcomes after traumatic injury. Currently, there is no standard PTSD screen for pediatric trauma patients and limited data on long-term quality of life for those who screen positive. MethodsIn 2022, we piloted a comprehensive routine screening program for ASD and PTSD at our Level I PTC. All admitted trauma patients ≥8 years old were eligible for screening. Inpatients were administered the ASC3. Those who screened positive were referred for follow-up and repeat mental health evaluation. PTSD screening (CTSQ, CPSS) and quality-of-life screening (PedsQL™) surveys were administered to eligible discharged trauma patients at 1-month post-injury. Children who screened positive on the CTSQ or CPSS were referred for behavioral health services. Results205 children were screened for ASD using the ASC3. 49/205 children (23.9 %) had a positive screen (score ≥3). 56 children completed PTSD screening at 1-month post-discharge. 14/54 children (25.9 %) screened positive on CTSQ, and 8/50 children (16 %) screened positive on CPSS. There was a significant positive correlation between CTSQ and CPSS scores (r 0.76, ∗P<0.0001). When stratified by screening results, patients who screened positive on CTSQ and CPSS were found to have the most significant correlations with poor School and Emotional Functioning on their quality-of-life inventory. ConclusionEarly screening for ASD may be predictive of later development of PTSD in children. Screening using previously validated tools (ASC3, CTSQ, CPSS) were effective in identifying children with negative emotional functioning lasting beyond the acute phase of physical recovery following injury. CTSQ and CPSS both performed well for screening at one-month post-discharge. Early identification can facilitate timely referral to mental health services to potentially minimize long-term socioemotional impact of PTSD.

Performance replication of the Hospital Mental Health Risk Screen in ethnoracially diverse U.S. patients admitted through emergency care.

Patients admitted to hospitals after emergency care for injury or acute illness are at risk for later mental health problems. The American College of Surgeons Committee on Trauma Standards for care of injured patients call for mental health risk screening, and the Hospital Mental Health Risk Screen (HMHRS) accurately identified at-risk patients in a developmental study that included patients from five ethnoracial groups. Replication of these findings is essential, because initial positive results for predictive screens can fail to replicate if the items were strongly related to outcomes in the development sample but not in a new sample from the population the screen was intended for. Replication of the predictive performance of the 10-item HMHRS was studied prospectively in ethnoracially diverse patients admitted after emergency care for acute illness or injury in three hospitals across the U.S. Risk screen scores and follow-up mental health outcomes were obtained for 452 of 631 patients enrolled (72%). A cut score of 10 on the HMHRS correctly identified 79% of the patients who reported elevated levels of depression, anxiety, and PTSD symptoms two months post-admission (sensitivity) and 72% of the patients whose symptoms were not elevated (specificity). HMHRS scores also predicted well for patients with acute illness, for patients with injuries, and for patients who reported an Asian American/Pacific Islander, Black, Latinx, Multirace, or White identity. Predictive performance of the HMHRS was strong overall and within all five ethnoracial subgroups. Routine screening could reduce suffering and health care costs, increase health and mental health equity, and foster preventive care research and implementation. The performance of the HMHRS should be studied in other countries and in other populations of recent trauma survivors, such as survivors of disaster or mass violence.

Association between mammographic screening history and stage at diagnosis among women with screen-detected breast cancer.

145 Background: Although screening mammography is an effective means of detecting breast cancer at earlier stages, some women are still diagnosed with later stage disease despite screening mammography. We hypothesized that screening history prior to diagnosis may impact stage at diagnosis and breast cancer mortality among women with screen-detected breast cancer. Methods: Retrospective cohort study of women aged 70+ in the SEER-Medicare database, diagnosed with ER+/HER2- breast cancer from 2010-2017, and enrolled in fee-for service Medicare Parts A and B from 5-years prior to diagnosis through 1 year after. We used validated claims-based algorithms to identify cancers that were detected by screening mammogram. We quantified 5-year screening history by number of prior screens. Stage at diagnosis was dichotomized into very early (T1N0) vs. later stage (T2+ or N+) disease. Multivariable logistic regression was used to assess the association between screening history and stage at diagnosis and Cox proportional hazards used to examine breast cancer mortality. Models were adjusted for demographic and clinical covariates associated with later stage disease in bivariate analyses. Results: We included 13,029 women with screen-detected breast cancer; 3,813 (29.27%) women had later stage disease at diagnosis, and 10,095 (77.48%) had at least one prior negative screening mammogram within the past five years. During this time, 2,359 (18.11%) women had only one prior mammogram, 3,132 (24.03%) had two, and 4,604 (35.34%) had three or four. Having at least one prior mammogram was associated with 56% lower odds of being diagnosed with later stage disease (OR: 0.44, 95% CI=0.40-0.48). Sociodemographic factors associated with increased odds of later stage disease included living in an area with greater poverty (20-100% vs. 0-5% of residents, OR: 1.19, 1.00-1.40), non-Hispanic Black race (OR: 1.18, 1.00-1.38), and Medicare/Medicaid dual eligibility (OR: 1.20, 1.06-1.36). Factors associated with later stage disease included living in an area with a more people with a high-school education (30-40% vs. 0-30% of residents, OR: 0.87, 0.77-0.97). At total of 696 deaths from breast cancer were observed, including 273 deaths among 2,935 women with no prior screening (9.3%) and 423 deaths among 10,097 women who had undergone screening within the past five years (4.2%, P &lt; 0.001). Receiving at least one negative screening prior to diagnosis was associated with decreased breast cancer-specific Mortality in adjusted analysis (HR: 0.48, 0.40-0.57). Conclusions: The use of prior routine screening mammography was associated with lower risk of being diagnosed with later stage disease and dying from breast cancer in elderly women with screen-detected breast cancer. Future research is warranted regarding the impact of routine vs. sporadic screening on potential morbidity and mortality in this age group.