Screening Threshold Research Articles

Suitable-Matching Areas’ Selection Method Based on Multi-Level Saliency

Scene-matching navigation is one of the essential technologies for achieving precise navigation in satellite-denied environments. Selecting suitable-matching areas is crucial for planning trajectory and reducing yaw. Most traditional selection methods of suitable-matching areas use hierarchical screening based on multiple feature indicators. However, these methods rarely consider the interrelationship between different feature indicators and use the same set of screening thresholds for different categories of images, which has poor versatility and can easily cause mis-selection and omission. To solve this problem, a suitable-matching areas’ selection method based on multi-level saliency is proposed. The matching performance score is obtained by fusing several segmentation levels’ salient feature extraction results and performing weighted calculations with the sub-image edge density. Compared with the hierarchical screening methods, the matching performance of the candidate areas selected by our algorithm is at least 22.2% higher, and it also has a better matching ability in different scene categories. In addition, the number of missed and wrong selections is significantly reduced. The average matching accuracy of the top three areas selected by our method reached 0.8549, 0.7993, and 0.7803, respectively, under the verification of multiple matching algorithms. Experimental results show this paper’s suitable-matching areas’ selection method is more robust.

Development and quality appraisal of a new English breast screening linked data set as part of the age, test threshold, and frequency of mammography screening (ATHENA-M) study.

To build a data set capturing the whole breast cancer screening journey from individual breast cancer screening records to outcomes and assess data quality. Routine screening records (invitation, attendance, test results) from all 79 English NHS breast screening centres between January 1, 1988 and March 31, 2018 were linked to cancer registry (cancer characteristics and treatment) and national mortality data. Data quality was assessed using comparability, validity, timeliness, and completeness. Screening records were extracted from 76/79 English breast screening centres, 3/79 were not possible due to software issues. Data linkage was successful from 1997 after introduction of a universal identifier for women (NHS number). Prior to 1997 outcome data are incomplete due to linkage issues, reducing validity. Between January 1, 1997 and March 31, 2018, a total of 11 262 730 women were offered screening of whom 9 371 973 attended at least one appointment, with 139 million person-years of follow-up (a median of 12.4 person years for each woman included) with 73 810 breast cancer deaths and 1 111 139 any-cause deaths. Comparability to reference data sets and internal validity were demonstrated. Data completeness was high for core screening variables (>99%) and main cancer outcomes (>95%). The ATHENA-M project has created a large high-quality and representative data set of individual women's screening trajectories and outcomes in England from 1997 to 2018, data before 1997 are lower quality. This is the most complete data set of English breast screening records and outcomes constructed to date, which can be used to evaluate and optimize screening.

A real-world analysis of safety profile of selexipag by using FDA adverse Event Reporting System (FAERS)

ABSTRACT Background The current investigation sought to conduct a real-world analysis of adverse events (AEs) associated with selexipag by utilizing data from the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods The Reporting Odds Ratios (ROR) and the Medicines Healthcare Products Regulatory Agency (MHRA) method were employed to assess the potential associations between selexipag and AEs. Case reports of adverse drug reaction (ADR) related to selexipag were systematically sourced from PubMed, Embase, and Web of Science databases. Results Our analysis identified 281 Preferred Terms (PTs) signals across 20 System Organ Classes (SOCs) were found to meet the screening threshold. The most common AEs were consistent with instructions, randomized controlled trials (RCTs), and case reports. Of significant note, unexpected AEs principally target SOCs of infections and infestations, blood and lymphatic system, renal and urinary disorders, hepatobiliary disorders, including pneumonia, metapneumovirus, decreased hemoglobin. transfusion, iron-deficiency anemia, dialysis hypotension, abnormal creatinine renal clearance, liver function test increased, hepatic function abnormal, hepatic enzyme increased. Within the pediatric population, unexpected signals such as pyrexia, pneumonia, and intussusception necessitate special precautionary measures. Conclusions The findings contribute valuable insights to clinical practice, reinforcing the importance of vigilant monitoring, and can be instrumental in guiding both therapeutic applications and safety assessments of this particular medication.

Establishing thresholds of handgrip strength based on mortality using machine learning in a prospective cohort of Chinese population.

The relative prognostic importance of handgrip strength (HGS) in comparison with other risk factors for mortality remains to be further clarified, and thresholds used for best identify high-risk individuals in health screening are not yet established. Using machine learning and nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), the study aimed to investigate the prognostic importance of HGS and establish sex-specific thresholds for health screening. A total of 6,762 participants from CHARLS were enrolled. A random forest model was built using 30 variables with all-cause mortality as outcome. SHapley Additive exPlanation values were applied to explain the model. Cox proportional hazard models and Harrell's C index change were used to validate the clinical importance of the thresholds. Among the participants, 3,102 (45.9%) were men, and 622 (9.1%) case of death were documented follow-up period of 6.78 years. The random forest model identified HGS as the fifth important prognostic variable, with thresholds for identifying high-risk individuals were < 32 kg in men and < 19 kg in women. Low HGS were associated with all-cause mortality [HR (95% CI): 1.77 (1.49-2.11), p < 0.001]. The addition of HGS thresholds improved the predictive ability of an established office-based risk score (C-index change: 0.022, p < 0.001). On the basis of our thresholds, low HGS predicted all-cause mortality better than other risk factors and improved prediction of a traditional office-based risk score. These results reinforced the clinical utility of measurement of HGS in health screening.

An optimization framework to guide the choice of thresholds for risk-based cancer screening.

It is uncommon for risk groups defined by statistical or artificial intelligence (AI) models to be chosen by jointly considering model performance and potential interventions available. We develop a framework to rapidly guide choice of risk groups in this manner, and apply it to guide breast cancer screening intervals using an AI model. Linear programming is used to define risk groups that minimize expected advanced cancer incidence subject to resource constraints. In the application risk stratification performance is estimated from a case-control study (2044 cases, 1:1 matching), and other parameters are taken from screening trials and the screening programme in England. Under the model, re-screening in 1 year for the highest 4% AI model risk, in 3 years for the middle 64%, and in 4 years for 32% of the population at lowest risk, was expected to reduce the number of advanced cancers diagnosed by approximately 18 advanced cancers per 1000 diagnosed with triennial screening, for the same average number of screens in the population as triennial screening for all. Sensitivity analyses found the choice of thresholds was robust to model parameters, but the estimated reduction in advanced cancers was not precise and requires further evaluation. Our framework helps define thresholds with the greatest chance of success for reducing the population health burden of cancer when used in risk-adapted screening, which should be further evaluated such as in health-economic modelling based on computer simulation models, and real-world evaluations.

Comorbidities of Sickle Cell Disease with Obstructive Sleep Apnea

BACKGROUND Sickle cell disease (SCD) is a devastating inherited disease process that greatly impairs quality of life and lifespan. It is a common genetic hemoglobinopathy that is vulnerable to hypoxemia due to the sickling property of red blood cells. Desaturation of the hemoglobin S (HbS) molecule leads to the polymerization of HbS, causing the blockage of microvasculature, oxidative stress, and endothelial damage. The clinical sequelae of SCD include vaso-occlusive crisis, hemolytic episodes, and end-organ damage. Obstructive sleep apnea (OSA) is a common but underdiagnosed condition associated with nocturnal hypoxemia due to intermittent upper airway closure. Repetitive episodes of hypoxemia can cause nocturnal sympathetic activation, selectively activate vascular inflammatory pathways leading to endothelial dysfunction, and can impact cardiac output to predispose patients to ischemia. The impact of this pathophysiology on SCD remains unclear and the literature reviews evaluating the relationship of SCD and OSA are scarce. METHODS We performed a retrospective analysis of the Nationwide Inpatient Sample data in adult patients (age greater than 18 years) hospitalized with SCD as the primary diagnosis in 2020 using ICD-10-CM codes. The NIS is the largest all-payer publicly accessible inpatient healthcare database in the United States. We compared the SCD cohort of 164,990 patients to another consisting of SCD with associated secondary diagnosis of OSA, which consisted of 32,998 patients. The Pearson chi-square test and Student's t test were used to assess categorical and continuous variables, respectively. RESULTS Data revealed that patients diagnosed with SCD and OSA had a statistically significant (p &amp;lt; 0.001) greater incidence of comorbidities compared to SCD alone. These included uncomplicated hypertension (29.8 vs 15.5%), complicated hypertension (24.5 vs 10.6%), uncomplicated diabetes mellitus (9.8 vs 3.4%), complicated diabetes mellitus (17.1 vs 5.1%), obesity (38.9 vs 9.2%), peripheral vascular disease (6.0 vs 3.2%), chronic pulmonary disease (39.7 vs 21.1%), chronic kidney disease (10.0 vs 4.1%), coronary artery disease (15.3 vs 5.1%), and heart failure (13.4 vs 5.4%). Illicit drug use was higher (8.4%) in SCD only compared to SCD with OSA (5.1%). CONCLUSION In this study, co-diagnoses of SCD and OSA revealed a greater likelihood of having other comorbidities, typically 2-3 fold. A striking finding is the increased prevalence of complicated hypertension and diabetes mellitus which are known to give way to vasculopathies, a sequela that is unfavorable in patients with SCD. Considering the clinical implications of these comorbidities and concern for overall underdiagnosis of OSA, it may prove beneficial to lower the threshold for OSA screening in patients with SCD who exhibit hypertension, diabetes, obesity, and other disease processes associated with OSA. Furthermore, should OSA screening in patients with SCD prove favorable, a prospective study evaluating outcomes, such as number of hospitalizations due to sickle cell crisis or acute chest syndrome, of patients diagnosed with OSA and subsequently treated with therapeutic measures such as nocturnal continuous positive airway pressure. Likewise, patients with established co-diagnosis of SCD and OSA should have diligent surveillance and treatment of these aforementioned comorbidities.

Establishing Chronic Toxicity Effect Levels for Zebrafish (Danio rerio) Exposed to Perfluorooctane Sulfonate.

Zebrafish (Danio rerio) are among the aquatic species most sensitive to perfluorooctane sulfonate (PFOS). Environmental regulatory agencies and researchers use effect benchmarks from laboratory zebrafish PFOS toxicity studies in PFOS-spiked water to calculate PFOS aquatic life criteria. Threshold values as low as 0.7 µg/L (identified in an early, limited scope study) have been used in criteria derivation and site-specific aquatic ecological risk assessments. The present study reviews PFOS effects benchmarks for lethality, growth, and reproduction endpoints from more than 20 zebrafish toxicity studies, including a recent multigenerational study conducted by the United States Army Corps of Engineers Engineer Research & Development Center. Our review of 12 key studies examining long-term, chronic exposures (including multigenerational exposures of 300 days or more) indicated that 0.7 µg/L should not be used as a conservative screening threshold given that effects could not be repeated at this concentration by the recent enhanced multigenerational study. Based on this finding and multiple chronic sublethal studies on PFOS in zebrafish, chronic effects on lethality, growth, and reproduction occur at concentrations two orders of magnitude higher than 0.7 µg/L. Overall, the present review indicates a no-effect screening level of 31 µg/L and a low-effect screening level of 96 µg/L should be used to develop PFOS aquatic life criteria and to inform site-specific ecological risk assessments that are charged with evaluating risks to freshwater fish. Environ Toxicol Chem 2024;43:7-18. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study.

Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17β-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5-8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17β-oestradiol (oxidative 17β-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P < 0.05 and log fold change >0.5 were selected as the screening threshold. Formation and inactivation of 17β-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups. Sex hormones are produced and broken down by enzymes that can be found in the endometrium (the inner lining of the womb). This enzyme activity might influence the chances of becoming pregnant. We compared (i) enzyme activity in the endometrium of 15 women who did and 15 women who did not become pregnant in their second in vitro fertilisation attempt, (ii) how enzyme activity can be blocked by an inhibitor, and (iii) differences in gene expression (the process by which instructions in our DNA are converted into a product). Enzyme activity was similar between groups. We found that in women who have never been pregnant in the past, inhibition of enzyme activity was higher and found differences in a gene that has been linked to the implantation of the embryo, but future studies should be performed in larger, well-defined patient groups to confirm these findings.

Diagnostic Accuracy of a Temporomandibular Disorder Pain Screener in Patients Seeking Endodontic Treatment for Tooth Pain

IntroductionThis study assessed the accuracy of a TMD Pain Screener questionnaire in identifying patients with temporomandibular disorder (TMD) pain among those seeking endodontic treatment for tooth pain. It also investigated whether the screener accuracy could be improved by adding questions regarding putative predictors of TMD status. MethodsOne hundred patients seeking endodontic treatment for tooth pain were enrolled. Participants completed the 6-question TMD Pain Screener before treatment. A board-certified orofacial pain specialist/endodontic resident conducted endodontic and TMD examinations using validated Diagnostic Criteria for TMD (DC/TMD). The sensitivity (Se), specificity (Sp), and positive/negative predictive values (PPVs/NPVs) were calculated for the 6-question and 3-question versions of the TMD Pain Screener. Logistic regression and receiver operating characteristic curve (AUROC) analyses were performed to determine the screening accuracy. ResultsAt the screening threshold of ≥3, TMD Pain Screener's sensitivity was 0.85, specificity 0.52, PPV 0.68, and NPV 0.75 for the 6-question version and 0.64, 0.65, 0.69, and 0.61, respectively, for the 3-question version. The AUROC was 0.71 (95% CL: 0.61, 0.82) and 0.60 (95% CL: 0.48, 0.71) for full and short versions, respectively. Adding a rating of current pain intensity of the chief complaint to the screener improved the AUROC to 0.81 (95% CL: 0.72, 0.89) and 0.77 (95% CL: 0.67, 0.86) for full and short versions, respectively, signifying useful overall accuracy. ConclusionsThe 6-question TMD Pain Screener, combined with the patient's rating of current pain intensity of the chief complaint, could be recommended for use in endodontic patients with tooth pain for detecting painful TMD.

Identifying sex-specific anthropometric measures and thresholds for dysglycemia screening in an HIV-endemic rural South African population.

Valid screening and diagnostic algorithms are needed to achieve 2030 targets proposed by the WHO's Global Diabetes Compact. We explored anthropometric thresholds to optimally screen and refer individuals for diabetes testing in rural South Africa. We evaluated screening thresholds for waist circumference (WC), body mass index (BMI), and waist-hip ratio (WHR) to detect dysglycemia based on a glycated hemoglobin (HbA1C) ≥6.5% among adults in a population-based study in South Africa using weighted, non-parametric ROC regression analyses. We then assessed the diagnostic validity of traditional obesity thresholds, explored optimal thresholds for this population, and fit models stratified by sex, age, and HIV status. The prevalence of dysglycemia in the total study population (n = 17,846) was 7.7%. WC had greater discriminatory capacity than WHR to detect dysglycemia in men (p-value<0.001) and women (p<0.001). WC had greater discriminatory capacity than BMI to detect dysglycemia in women (p<0.001). However, BMI and WC performed similarly for men (p = 0.589). Whereas traditional WC thresholds for women (>81cm) performed well (sensitivity 91%, positive predictive value [PPV] 14.9%), substantially lower thresholds were needed to achieve acceptable sensitivity and PPV among men (traditional >94cm, derived >79.5cm). WC outperforms BMI as an anthropometric screening measure for dysglycemia in rural South Africa. Whereas WC guideline thresholds are appropriate for women, male-derived WC cutoffs performed better at lower thresholds. In this rural South African population, thresholds that maximize specificity and PPV for efficient resource allocation may be preferred.

Serum Anti-Mullerian Hormone Levels Might Indicate Premenopausal Endometrial Lesions.

Endometrial proliferative lesions (EPL) usually refer to endometrial hyperplasia (EH) and endometrial cancer (EC). Among patients with premenopausal EPL who wish to preserve their fertility, only those with EH and early-stage EC have the possibility to undergo fertility preservation therapy. However, there is currently a lack of specific and reliable screening criteria and models for identifying these patients. This study utilized a retrospective diagnostic study design. The training set included medical record information that met the criteria between August 2017 and October 2022, while the validation set consisted of medical record information that met the criteria from November 2022 to May 2023. The endometrial pathological test served as the gold standard. The serum anti-Mullerian hormone (AMH) level before endometrial sampling and a regression model were employed to predict EPL. The study included a total of 1209 patients with PCOS (1119 in the control group and 90 in the endometrial proliferative lesion group) and 5366 women without PCOS (5249 in the control group and 117 in the proliferative lesion group). In the case of PCOS patients aged 20-39 years, the most effective screening threshold for AMH was found to be a serum AMH level of ≤5.39 ng/mL. The model used for this group was logit(p) = -2.562 - 0.430 × AMH + 0.127 × BMI + 1.512 × hypertension + 0.956 × diabetes -1.145 × regular menstruation. On the other hand, for non-PCOS women aged 20-39 years, the optimal screening threshold for AMH was determined to be a serum AMH value of ≤2.18 ng/mL. The model used for this group was logit(p) = -3.778 - 0.823 × AMH + 0.176 × BMI + 2.660 × diabetes -1.527 × regular menstruation -1.117 × dysmenorrhea. It is important to note that all of these findings have successfully passed internal verification. For PCOS and non-PCOS women aged 20-39 years, the serum AMH test and related multiple regression models were obtained for the warning of EPL.

Screening for Comorbidity of Sleep Disorders in Career Firefighters.

The purpose of this study was to assess the prevalence and sequelae of insomnia, obstructive sleep apnea (OSA), and comorbid OSA and insomnia (COMISA). In the morning, after a shift end, Midwest career firefighters ( N = 89) in a midsized city completed an electronic battery of questionnaire to screen for OSA, daytime sleepiness, insomnia, presleep arousal, nightmares, mental and physical health symptoms, and a one-night sleep diary. Prevalence of firefighters exceeding screening thresholds: OSA: 54%; insomnia: 30%; COMISA: 17%; four or more nightmares per month: 15%. Firefighters who met criteria for COMISA had shorter total sleep time, less restful and worse sleep quality, higher depression and anxiety symptoms, and presleep arousal symptoms than firefighters without self-reported sleep problems. Many firefighters are at elevated risk of individual behavioral sleep disorders, COMISA, and daytime dysfunction.

Reducing the risk of missing soil contamination by integrating multi-investigated methods in a retired chrome salt factory

An effective contamination screening process is essential for mitigating the risk of overlooking pollution during site investigations. While Electrical resistivity tomography (ERT) and portable X-ray Fluorescence (XRF) offer quick assessments of contaminated areas, there is a notable gap in research regarding ERT’s application in the unsaturated soil layer, and portable XRF’s use for screening polluted samples in chromium-contaminated sites. This study gathered soil pollution and electrical resistivity data from a decommissioned chrome salt factory, employing drilling, sampling, XRF, and ERT methods. Predominantly, sulfate and chromium emerged as the pollutants, with concentrations ranging from 19.24 to 12700.00 mg/kg for sulfate, 0.65 to 3000.00 mg/kg for Cr(VI), and 12.00 to 27800.00 mg/kg for total Cr, respectively. Polluted hotspots were identified by lower apparent soil resistivity compared to the background levels at corresponding depth. Notably, a significant inverse correlation was observed between sulfate and Cr(VI) concentration and soil resistivity, particularly with sulfate (R2 =0.48) demonstrated through a power function fit at depths ranging from −4 to 0 m. The XRF analysis for total Cr concentration exhibited a significant correlation (Pearson’s r = 0.67) with chemical analysis, confirming 1000 mg/kg as an effective screening threshold. In light of these findings, this study proposes a scientific procedure that integrates drilling, sampling, ERT, and XRF for soil contamination investigation. This framework aims to support similar site assessments, reducing the risk of overlooking contamination.

SAT281 Screening For Adrenocortical Insufficiency In Patients With X-linked Adrenoleukodystrophy

Abstract Disclosure: J. Berquist: None. R.N. Kiani: None. M.P. Wahl: None. Background: A 41-year-old male initially presented to neurology clinic for complaints of poor balance, lower extremity weakness, and numbness. He previously had exam findings of lower extremity spasticity and hyperreflexia, distal vibratory loss, positive Romberg, and difficulty with Tandem gait. His symptoms had been progressive following an ankle sprain 8 years earlier and he was treated with physical therapy and baclofen. He is highly active otherwise and enjoys rock climbing, which was difficult to do given his symptoms. Clinical Case: Genetic screening was performed to evaluate for hereditary spastic paraparesis, which resulted positive for a mutation in the ABCD1 gene with a p.Lys336Glu mutation of uncertain significance. Interestingly, this ABDC1 variant was not detected in submitted maternal sample, hence patient’s mutation likely occurred de novo. This variant is not established in population databases (gnomAD no frequency) but has been observed in at least one individual with clinical features of adrenomyeloneuropathy. X-linked adrenoleukodystrophy causes impairment of beta oxidation that leads to accumulation of saturated very long chain fatty acids (VFLA) in multiple tissues. There are many clinical phenotypes, but they are hallmarked by neurologic signs and symptoms. Although neurologic symptoms can often develop in childhood, they can be delayed and present in adulthood, as can adrenal insufficiency (AI). However, males are overwhelmingly likely to develop adrenocortical insufficiency compared to females. Our patient presented with a BMI of 22.94, HR 50 bpm, and blood pressure 120/76; reflecting his active lifestyle. Recent electrolytes were within normal limits, AM cortisol was 13.0, and ACTH 544.0 Given the elevated ACTH and known cause of adrenal insufficiency, we proceeded with ACTH stimulation test. Peak cortisol resulted at 13.1 (at 60 minutes) and he was started on replacement glucocorticoid therapy per body-surface area. Upon further literature review, patients can also develop loss of mineralocorticoid production. Renin and aldosterone were ordered and were both within normal limits. Conclusion: Males with adrenoleukodystrophy are at a much higher risk of developing adrenal insufficiency (AI) compared to females. Additionally, AI will often develop later in life, so a low threshold for screening should be present for the endocrinologist. Mineralocorticoid deficiency can also develop, although not as commonly. Loss of adrenal function can lead to patient demise, and therefore adrenal function needs to be closely evaluated in people with leukodystrophy. Presentation: Saturday, June 17, 2023

The use of liquid chromatography-tandem mass spectrometry in newborn screening for congenital adrenal hyperplasia: improvements and future perspectives.

Newborn screening for congenital adrenal hyperplasia using 17-hydroxyprogesterone by immunoassay remains controversial despite screening been available for almost 40 years. Screening is confounded by poor immunoassay specificity, fetal adrenal physiology, stress, and illness which can result in a large number of false positive screening tests. Screening programmes apply higher screening thresholds based on co-variates such as birthweight or gestational age but the false positive rate using immunoassay remains high. Mass spectrometry was first applied to newborn screening for congenital adrenal hyperplasia over 15 years ago. Elevated 17-hydroxprogesterone by immunoassay can be retested with a specific liquid chromatography tandem mass spectrometry assay that may include additional steroid markers. Laboratories register with quality assurance programme providers to ensure accurate steroid measurements. This has led to improvements in screening but there are additional costs and added laboratory workload. The search for novel steroid markers may inform further improvements to screening. Studies have shown that 11-oxygenated androgens are elevated in untreated patients and that the adrenal steroidogenesis backdoor pathway is more active in babies with congenital adrenal hyperplasia. There is continual interest in 21-deoxycortisol, a specific marker of 21-hydroxylase deficiency. The measurement of androgenic steroids and their precursors by liquid chromatography tandem mass spectrometry in bloodspots may inform improvements for screening, diagnosis, and treatment monitoring. In this review, we describe how liquid chromatography tandem mass spectrometry has improved newborn screening for congenital adrenal hyperplasia and explore how future developments may inform further improvements to screening and diagnosis.

A-035 Association between Obesity and Prostate Specific Antigen level in Diabetes Mellitus Type2

Abstract Background Body mass index (BMI) is a simple index commonly used to classify obesity. It is defined as a person’s weight(kg) divided by the square of his height (m). An inverse relationship between obesity and prostate-specific antigen (PSA) has been reported by previous studies with lower PSA levels found in groups with a higher body mass index (BMI). The main objective of this current study is to assess the association between body mass index (BMI) and PSA in male patients with diabetes mellitus. Methods This study uses a case-control experimental procedure to assess adult men between 40–75 years old, attending University of Nigeria Teaching Hospital, Enugu State, Nigeria. Eighty-six (86) of the volunteers recruited for this study were patients diagnosed with type II diabetes, and sixty (60) others were non-diabetic patients used as controls. Consent was sorted from these patients, and a questionnaire was given to the participants in which data about their age, family history of diabetes, and prostate condition was collected. Their hospital folders were used to confirm their diabetic status and prostate gland health. Body Mass Index (BMI) was calculated after measuring weight (kg) and height(m). Blood samples were assayed to determine the fasting blood sugar (FBS) using Glucose Oxidase enzymatic method, and total prostate-specific antigen (tPSA) concentration was determined using Enzyme-Linked Immunosorbent Assay (ELISA). The Body mass index (BMI), as a “gold standard” approach for obesity classification, was used to group the patients as; underweight (below 18.5), normal weight (18.5–24.9), pre-obesity (25.0–29.9), obesity class I (30–34.9), obesity class II (35.0–34.9), and obesity class III (40 and above). The Statistical Package for Social Sciences (SPSS) version 22.0 was used to analyze data generated and compared between groups using student T-test. Statistical difference was at a P value of 0.05 or higher. Results The result of this study demonstrated a significant difference in the BMI of diabetic men (test) and non-diabetic men (control). Moreso, lower tPSA was observed in obese men compared to normal BMI in both test and control. Hemodilution caused by elevated plasma volume, which may reduce serum concentration of soluble tumor markers, may be responsible for lower PSA levels in obese men. Conclusion Obesity may hinder the ability to detect prostate cancer at an earlier stage. Therefore, BMI should be considered while determining a PSA threshold for prostate disorders screening.

Cognitive function in patients with irritable bowel syndrome: impairment is common and only weakly correlated with depression/anxiety and severity of gastrointestinal symptoms

Objective To investigate cognitive function in patients with irritable bowel syndrome (IBS) and its relation to anxiety/depression and severity of gastrointestinal (GI) symptoms. Methods Patients with IBS (n = 65) and healthy controls (HCs, n = 37) performed the ten subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Age-normed index scores of five cognitive domains (Immediate memory, Visuospatial function, Language function, Attention, Recall) and a total (Fullscale) score were derived from the performance. Emotional function was assessed using the Hospital Anxiety and Depression Scale (HADS), and the IBS Symptom Scoring System (IBS-SSS) was used to define the severity of GI symptoms. Results Patients with IBS reported significantly higher scores than the HC group on symptom measures of anxiety and depression, and significantly lower scores on the Immediate memory, Recall, and Fullscale RBANS indexes. Approximately 30% of the IBS patients obtained index scores at least one standard deviation below the population mean, and more than 50% scored above the screening threshold for an anxiety disorder. The severity of GI symptoms was significantly correlated with the severity level of anxiety symptoms (p=.006), but neither the severity level of emotional nor GI symptoms was significantly correlated with the RBANS index scores in the IBS group. Conclusion Cognitive and emotional function were more severely affected in patients with IBS than in HCs. The weak correlation between the two functional areas suggests that both should be assessed as part of a clinical examination of patients with IBS.

Implementation of risk stratification within bowel cancer screening: a community jury study exploring public acceptability and communication needs

BackgroundPopulation-based cancer screening programmes are shifting away from age and/or sex-based screening criteria towards a risk-stratified approach. Any such changes must be acceptable to the public and communicated effectively. We aimed to explore the social and ethical considerations of implementing risk stratification at three different stages of the bowel cancer screening programme and to understand public requirements for communication.MethodsWe conducted two pairs of community juries, addressing risk stratification for screening eligibility or thresholds for referral to colonoscopy and screening interval. Using screening test results (where applicable), and lifestyle and genetic risk scores were suggested as potential stratification strategies. After being informed about the topic through a series of presentations and discussions including screening principles, ethical considerations and how risk stratification could be incorporated, participants deliberated over the research questions. They then reported their final verdicts on the acceptability of risk-stratified screening and what information should be shared about their preferred screening strategy. Transcripts were analysed using codebook thematic analysis.ResultsRisk stratification of bowel cancer screening was acceptable to the informed public. Using data within the current system (age, sex and screening results) was considered an obvious next step and collecting additional data for lifestyle and/or genetic risk assessment was also preferable to age-based screening. Participants acknowledged benefits to individuals and health services, as well as articulating concerns for people with low cancer risk, potential public misconceptions and additional complexity for the system. The need for clear and effective communication about changes to the screening programme and individual risk feedback was highlighted, including making a distinction between information that should be shared with everyone by default and additional details that are available elsewhere.ConclusionsFrom the perspective of public acceptability, risk stratification using current data could be implemented immediately, ahead of more complex strategies. Collecting additional data for lifestyle and/or genetic risk assessment was also considered acceptable but the practicalities of collecting such data and how the programme would be communicated require careful consideration.

Optimizing cardiovascular disease risk screening in a low-resource setting: cost-effectiveness of program modifications in Sri Lanka modelled with nationally representative survey data

BackgroundWhile screening for cardiovascular disease (CVD) risk can help low-resource health systems deliver low-cost, effective prevention, evidence is needed to adapt international screening guidelines for maximal impact in local settings. We aimed to establish how the cost-effectiveness of CVD risk screening in Sri Lanka varies with who is screened, how risk is assessed, and what thresholds are used for prescription of medicines.MethodsWe used data for people aged 35 years and over from a 2018/19 nationally representative survey in Sri Lanka. We modelled the costs and quality adjusted life years (QALYs) for 128 screening program scenarios distinguished by a) age group screened, b) risk tool used, c) definition of high CVD risk, d) blood pressure threshold for treatment of high-risks, and e) prescription of statins to all diabetics. We used the current program as the base case. We used a Markov model of a one-year screening program with a lifetime horizon and a public health system perspective.ResultsScenarios that included the WHO-2019 office-based risk tool dominated most others. Switching to this tool and raising the age threshold for screening from 35 to 40 years gave an incremental cost-effectiveness ratio (ICER) of $113/QALY. Lowering the CVD high-risk threshold from 20 to 10% and prescribing antihypertensives at a lower threshold to diabetics and people at high risk of CVD gave an ICER of $1,159/QALY. The findings were sensitive to allowing for disutility of daily medication.ConclusionsIn Sri Lanka, CVD risk screening scenarios that used the WHO-2019 office-based risk tool, screened people above the age of 40, and lowered risk and blood pressure thresholds would likely be cost-effective, generating an additional QALY at less than half a GDP per capita.

Clinical utility of routine investigations and risk factors of end-organ damage in asymptomatic severe hypertension.

Asymptomatic severe hypertension is defined as systolic blood pressure of ≥ 180mmHg or diastolic blood pressure of ≥ 120mmHg without signs and symptoms of end-organ damage or dysfunction. Literature shows that around 5% of the patients with severe asymptomatic hypertension had acute hypertension-related end-organ damage. This study aimed to determine the clinical utility of routine investigations and risk factors of end-organ damage in patients presented to the emergency department with asymptomatic severe hypertension. This single-center, cross-sectional study was conducted at the emergency department of the Aga Khan University Hospital, Karachi, Pakistan, from January 2018 to December 2020. All adult patients (age ≥ 18years) presented to the emergency department with a systolic blood pressure of ≥ 180 or diastolic blood pressure of ≥ 120mmHg without any signs and symptoms of end-organ damage (e.g., chest pain, unilateral limb or facial weakness, or hemiplegia, altered mental status, shortness of breath, decreased urine output, and sudden-onset of severe headache) were included. Routine investigations were analyzed to detect end-organ damage, including complete blood count, basic metabolic panel, urine detailed report, electrocardiogram, and troponin-I. Multivariable binary logistic regression was applied to identify the risk factors of end-organ damage considering the significant p value of ≤ 0.05. A total of 180 patients were presented to the emergency department with asymptomatic severe hypertension during the study period. Among the total patients, 60 patients (33.3%) had abnormal investigation findings; out of them, new-onset end-organ damage was diagnosed in 15 patients (8.3%). The most common end-organ damage was the kidney (73.3%) followed by the heart (26.6%). The multivariable binary logistic regression showed that age of more than 60years, past medical history of diabetes, ischemic heart disease, and cerebrovascular accident were significantly associated with a higher risk of end-organ damage (p < 0.05). The study identified a higher prevalence of abnormal routine investigations and acute end-organ damage in emergency department patients with asymptomatic severe hypertension compared to high-income countries and suggested a lower threshold for end-organ damage screening in these patients. The current recommendations of foregoing further workup in patients with asymptomatic severe hypertension may need modification for emergency departments in low-middle-income countries if similar associations are replicated in other settings.