Individual Risk Research Articles

Trends in simultaneous alcohol and marijuana use among US adult recent drinkers: Differences by sexual identity, 2015–2020

Simultaneous alcohol and marijuana (SAM) use has become increasingly prevalent among young adult populations. Moreover, lesbian, gay, and bisexual populations are at increased risk for substance use initiation. To date, little research has examined trends in SAM use by sexual identity. This study aimed to investigate trends in SAM use among recent drinkers using nationally representative data. Pooled data from the 2015–2019 and 2020 National Survey on Drug Use and Health (NSDUH) were examined among 120,061 individuals (5.75% LGB) 18 years or older who reported using alcohol in the past month. Given the methodological changes in the study design, we analyzed these waves separately. Covariates included age, race, biological sex, sexual identity, rurality, and past month use of tobacco. Weighted logistic regression models and trend analyses were conducted. An estimated 11,952 of the sample reported using marijuana during their last episode of drinking. A significant linear trend (b = 0.12) of increasing SAM use among recent drinkers from 2015 to 2019. When compared to heterosexual individuals, lesbian or gay (aPR: 1.44, 95% CI 1.26, 1.63) and bisexual (aPR: 1.92, 95% CI 1.77, 2.09) individuals were more likely to report SAM use. Among the entire sample, females had a lower risk of SAM use than males (aPR: 0.68, 95% CI 0.65, 0.72). For 2020, a total of 25,679 adults 18 years or older participated in the survey, with 2622 identifying as LGB and 54.1% reporting past month alcohol use. An estimated 1503 individuals reported SAM use. Consistent with our findings, of those reporting past month alcohol use, LGB populations were at higher risk for SAM use, with gay individuals (aPR: 1.59, 95% CI 1.11, 2.30) at increased risk and bisexual individuals having higher risk (aPR: 2.12, 95% CI 1.73, 2.60). SAM use among individuals presents several critical health concerns, especially for at-risk populations. Findings from the present study can inform tailored interventions to reduce minority stress and stigmatized identities are needed.

Phenotype and Clinical OutcomesinDesmin-Related Arrhythmogenic Cardiomyopathy.

Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed invitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n=7) or heart failure death (HFd)/heart transplantation (HTx) (n=4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n=5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n=10). Male sex (P=0.004), nonsustained ventricular tachycardia (P=0.017) and LV ejection fraction≤50% (P=0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. Invitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.

Risk individualisation and moral injury in the treatment of infection as impediments to the tackling of antimicrobial resistance

Antimicrobial resistance (AMR) is subject to extensive risk reduction approaches. A central strategy is reducing the unnecessary use of antimicrobials across agriculture and human and animal health care without jeopardising health outcomes for all species concerned. A prominent framework is antimicrobial stewardship which seeks to balance access to effective infection treatments with ensuring that effective antimicrobials are available for future generations. Balancing these goals has proven challenging and the consumption of antimicrobials and AMR both continue to grow. To shed light on this situation, we examined the risk reasoning that underpins AMR reduction in interviews with 51 practitioners, scientists and policy-makers working on AMR in Australia and the UK. Important themes in our analysis were that action to reduce infection risks clashed with AMR reduction rationalities. Participants were often not able to explain how treating an infection for an individual patient could harmonise with the longer-term goal of AMR reduction. Due to the potential for patient harm, making decisions to use antimicrobials was narrated as individualised and moralised. We argue that more effective AMR reduction depends on addressing this fundamental tension in AMR risk, and its individualising and moralising effects, as the starting point – not the outcome – of policy and practice for AMR reduction.

Exploring Determinants of Mortality among Adult PLHIV under ART at Meru Teaching and Referral Hospital, Kenya

HIV remains a persistent global health challenge, affecting the immune system and leading to significant morbidity and mortality despite advancements in antiretroviral therapy (ART). The study investigated the covariates that correspond to determinants linked to increased mortality among PLHIV (people living with HIV/AIDS) under ART at Meru Teaching and Referral Hospital (MTRH) over a five-year period. This retrospective cohort study utilized secondary data from hospital records between 2018 and 2022, focusing on demographic, socio-economic, and clinical variables. A logistic regression analysis was carried out to identify covariates that correspond to determinants linked to increased mortality among HIV-positive patients. The age range varied significantly, with a smaller percentage falling into younger age groups: 6.7% aged 18-25 years and 10.0% aged 26-35 years. The majority were middle-aged, with 24.9% falling into the 36-45 age group and 31.6% between 46-55 years. Older age groups were also represented, with 17.2% aged 56-65 years and 9.6% above 65 years. In terms of gender, 56.9% of participants were female, while 43.1% were male.Top of Form The study results found a notable gender disparity in mortality risk, with male patients demonstrating higher odds of mortality compared to females (OR = 1.25, p = 0.032). Age emerged as a significant predictor, with each additional year associated with a slight increase in mortality odds (OR = 1.02, p = 0.045). Marital status did not significantly influence mortality risk. Smoking status was identified as a significant predictor, with smokers exhibiting higher mortality risk (OR = 1.40, p = 0.005). Employment status also played a role, with self-employed individuals showing marginally lower mortality risk (OR = 0.90, p = 0.041) and unemployed individuals facing higher risk (OR = 1.50, p = 0.010) all compared to the employed. Educational level showed varying mortality risks, with high school education associated with lower risk (OR = 0.85, p = 0.030) and tertiary education linked to higher risk (OR = 1.60, p = 0.002) both compared to no formal education. CD4 cell count inversely affected mortality risk (OR = 0.99, p < 0.001). Undergoing TB screening was associated with reduced mortality odds (OR = 0.70, p = 0.003). WHO stages of HIV infection significantly influenced mortality odds, with patients in advanced stages (Stage 3: OR = 1.30, p = 0.015; Stage 4: OR = 2.00, p < 0.001) demonstrating higher odds of mortality compared to those in Stage 1.

Overall haemostatic potential assay for prediction of outcomes in venous and arterial thrombosis and thrombo-inflammatory diseases.

Thromboembolic diseases including arterial and venous thrombosis are common causes of morbidity and mortality globally. Thrombosis frequently recurs and can also complicate many inflammatory conditions through the process of 'thrombo-inflammation,' as evidenced during the COVID-19 pandemic. Current candidate biomarkers for thrombosis prediction, such as D-dimer, have poor predictive efficacy. This limits our capacity to tailor anticoagulation duration individually and may expose lower risk individuals to undue bleeding risk. Global coagulation assays, such as the Overall Haemostatic Potential (OHP) assay, that investigate fibrin generation and fibrinolysis, may provide a more accurate and functional assessment of hypercoagulability. We present a review of fibrin's critical role as a central modulator of thrombotic risk. The results of our studies demonstrating the OHP assay as a predictive biomarker in venous thromboembolism, chronic renal disease, diabetes mellitus, post-thrombotic syndrome, and COVID-19 are discussed. As a comprehensive and global measurement of fibrin generation and fibrinolytic capacity, the OHP assay may be a valuable addition to future multi-modal predictive tools in thrombosis.

Immune profiles of MCP-1 with M tb antigens and recombinant cytokines stimulation in tuberculosis

Tuberculosis is caused by Mycobacterium tuberculosis (M tb), which is recognized by macrophages and produces inflammatory cytokines, and chemokines at the site of infection. The present study was proposed to understand the interaction of M tb antigens, cytokines, and chemokines. We have evaluated the chemokine MCP-1 levels and its expression in PBMCs stimulated with M tb antigens Ag85A, ESAT6 and recombinant cytokines rhTNF-α, rhIFN-γ, rhTGF-β, and rhIL-10 in active pulmonary TB (APTB) patients, household contacts (HHC) at 0 months, 6 months and healthy controls (HC). We have observed low levels of MCP-1 with Ag85A, ESAT6, and rhTNF-α stimulations in APTB 0M compared to HHC and HC (p < 0.0067, p < 0.0001, p < 0.01, p < 0.005, p < 0.0065, p < 0.0001) and significantly increased after treatment with rhTNF-α. The MCP-1 levels with rhIFN-γ were high in APTB, HHC at 0 M and significant between APTB 0 M vs. 6 M, HHC vs. HC, and HHC 0M vs. 6M (p < 0.0352, p < 0.0252, p < 0.00062). The rhTGF-β, rhIL-10 induced high MCP-1 levels in APTB, HHC compared to HC (p < 0.0414, p < 0.0312, p < 0.004, p < 0.0001) and significantly decreased after treatment with rhIL-10 (p < 0.0001). The MCP-1 expression was low with all the stimulations in APTB 0M when compared to HC and after treatment. Whereas, HHC shown low MCP-1 expression with rhTNF-α, rhIFN-γ and Ag85A and high with rhTGF-β, rhIL-10 and ESAT6. In conclusion, the study determined the differential expression and production of MCP-1 with M tb antigens and recombinant cytokines. Further, cohort studies are required to study these interaction to identify the high risk individuals, which might help for TB control.

Development of a smartphone screening test for preclinical Alzheimer’s disease and validation across the dementia continuum

BackgroundDementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer’s disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10–20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia.MethodsAim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50–92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30–40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50–100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis.DiscussionThis study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials.Trial registrationClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.

2023 Australian guideline for assessing and managing cardiovascular disease risk.

The 2023 Australian guideline for assessing and managing cardiovascular disease risk provides updated evidence-based recommendations for the clinical assessment and management of cardiovascular disease (CVD) risk for primary prevention. It includes the new Australian CVD risk calculator (Aus CVD Risk Calculator), based on an equation developed from a large New Zealand cohort study, customised and recalibrated for the Australian population. The new guideline replaces the 2012 guideline that recommended CVD risk assessment using the Framingham risk equation. The new guideline recommends CVD risk assessment in people without known CVD: all people aged 45-79 years, people with diabetes from 35 years, and First Nations people from 30 years. The new Aus CVD Risk Calculator should be used to estimate and categorise CVD risk into low (< 5% risk over five years), intermediate (5% to < 10% risk over five years) or high risk (≥ 10% over five years). The following reclassification factors may be applied to recategorise calculated risk to improve accuracy of risk prediction, particularly in individuals close to a risk threshold: Indigenous status/ethnicity, estimated glomerular filtration rate, urine albumin to creatinine ratio measurements, severe mental illness, coronary artery calcium score and family history of premature CVD. A variety of communication formats is available to communicateCVD risk to help enable shared decision making. Healthy lifestylemodification, including smoking cessation, nutrition, physical activity and limiting alcohol, is encouraged for all individuals. Blood pressure-lowering and lipid-modifying pharmacotherapies should be prescribed for high risk and considered for intermediate risk individuals, unless contraindicated or clinically inappropriate. Reassessment of CVD risk should be considered within five years for individuals at low risk and within two years for those with intermediate risk. Reassessment of CVD risk is not recommended for individuals at high risk. CHANGES IN ASSESSMENT AND MANAGEMENT AS A RESULT OF THE GUIDELINE: The updated guideline recommends assessment over a broader age range and uses the Aus CVD Risk Calculator, which replaces the previous Framingham-based equation. It incorporates new variables: social disadvantage, diabetes-specific risk markers, diagnosis of atrial fibrillation and use of blood pressure-lowering and lipid-modifying therapies. Reclassification factors are also a new addition. Updated risk categories and thresholds are based on the new AusCVD Risk Calculator. The proportion of the population in the high risk category (≥ 10% over five years) is likely to be broadly comparable to more than 15% risk from the Framingham-based equation. The full guideline and Aus CVD Risk Calculator can be accessed at www.cvdcheck.org.au.

Identifying a group of factors predicting cognitive impairment among older adults.

Cognitive impairment has multiple risk factors spanning several domains, but few studies have evaluated risk factor clusters. We aimed to identify naturally occurring clusters of risk factors of poor cognition among middle-aged and older adults and evaluate associations between measures of cognition and these risk factor clusters. We used data from the National Health and Nutrition Examination Survey (NHANES) III (training dataset, n = 4074) and the NHANES 2011-2014 (validation dataset, n = 2510). Risk factors were selected based on the literature. We used both traditional logistic models and support vector machine methods to construct a composite score of risk factor clusters. We evaluated associations between the risk score and cognitive performance using the logistic model by estimating odds ratios (OR) and 95% confidence intervals (CI). Using the training dataset, we developed a composite risk score that predicted undiagnosed cognitive decline based on ten selected predictive risk factors including age, waist circumference, healthy eating index, race, education, income, physical activity, diabetes, hypercholesterolemia, and annual visit to dentist. The risk score was significantly associated with poor cognitive performance both in the training dataset (OR Tertile 3 verse tertile 1 = 8.15, 95% CI: 5.36-12.4) and validation dataset (OR Tertile 3 verse tertile 1 = 4.31, 95% CI: 2.62-7.08). The area under the receiver operating characteristics curve for the predictive model was 0.74 and 0.77 for crude model and model adjusted for age, sex, and race. The model based on selected risk factors may be used to identify high risk individuals with cognitive impairment.

Perioperative Antibiotic Prophylaxis—Indications and Modalities for the Prevention of Postoperative Wound Infection.

Postoperative surgical site infections (SSI) account for almost 25% of all nosocomial infections in Germany and are a source of increased morbidity and mortality. This review is based on pertinent publications retrieved by a selective search in PubMed and on national and international guidelines. The individual risk factors for SSI must be assessed before any surgical procedure. A body-mass index above 30 kg/m2 is associated with an unadjusted risk ratio of 1.35 [1.28; 1.41] for SSI, which rises to 3.29 [2.99; 3.62] if the patient is also immunosuppressed. The risk of SSI is also significantly higher with certain types of procedure. Perioperative antibiotic prophylaxis (PAP) is clearly indicated for operations that carry a high risk of SSI (e.g., colorectal surgery) and for those that involve the implantation of alloplastic material (e.g., hip endoprostheses). PAP can usually be administered with basic antibiotics such as cefazoline. The basic principles of PAP are that it should be given by the anesthesia team in the interval from 60 minutes preoperatively up to shortly before the incision, and that its administration should only be for a short period of time, usually as a single shot. Continuing PAP onward into the postoperative period leads to increased toxicity, bacterial superinfections, and antibiotic resistance. The evidence shows that perioperative antibiotic prophylaxis is a component of a bundle of measures that can help prevent SSI. Strict indications and adherence to the basic principles of PAP are essential for therapeutic success.

Phenotypic and Genotypic Virulence Potentials of Listeria monocytogenes Isolated from Different Food Samples in Yola

Aim: the aim of this work is to determine the Phenotypic and Genotypic Virulence Potentials of Listeria monocytogenes Isolated from Different Food Samples in Yola. Study Design:  the study was a randomized study; the samples (sources of organisms) were collected at random from different market and shops within the study area. Place and Duration of Study: the study was carried out in Yola, the capital of Adamawa State, north eastern Nigeria. Methodology: phenotypic virulence potentials of the isolates was determined by haemolytic activity on 5% sheep blood agar and biofilm formation ability, using Christensen’s tube method and microtiter plate method  for the qualitative and quantitative biofilm formation respectively. Genotypic virulence determination was done by polymerase chain reaction amplification of plcB, hlyA and actA genes. Results: All the isolates (100%) were beta haemolytic on 5% sheep blood agar and all the isolates were biofilm formers but with different degree of biofilm formation abilities. Genotypically all the isolates (100%) indicated the presence of all the three virulence genes amplified. Conclusion: food samples isolates analyzed are potentially virulence pathogenic of L. monocytogenes that can pose food borne listeriosis to high risk individuals in the study area.

Comparing perceptions of individuals who sexually offend against children versus adults.

We examined how the age of the victim influences the public's risk assessment and punishment attitudes for individuals who have sexually offended and whether actuarial feedback influences these ratings. (1) Risk ratings for child victim vignettes would be higher than ratings for adult victim vignettes. This effect would be driven by higher ratings for lower risk individuals. (2) Because of the increased stigma associated with individuals with child victim sexual abuse convictions, participants who rated this subgroup would be less likely than those who rated adult victim vignettes to revise their initial risk ratings. (3) Dispositional placements for the individuals in vignettes with child victims would be more punitive than for those with adult victims, both before and after feedback. Participants (N = 389, 18-77 years, 51.7% male, 73.0% White) read five vignettes of individuals incarcerated for a sexual offense at five different risk levels and with either child or adult victims. They made judgments about recidivism risk and postprison dispositions and then received actuarial feedback and made the ratings again. Risk ratings for child victim vignettes were higher than ratings for adult victim vignettes, particularly for cases of average risk and below (η²p = .17). Participants were equally likely to revise initial risk ratings for child and adult victim vignettes (η²p = .01). Dispositional placements for child victim vignettes were significantly more punitive than for adult victim vignettes both before and after feedback, especially for the lower risk individuals (η²p = .07). Although judgments of risk and disposition toward individuals who sexually offend can be adjusted regardless of victim type, there is a more severe bias against individuals with child victims. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genetics of gambling disorder and related phenotypes: The potential uses of polygenic and multifactorial risk models to enable early detection and improve clinical outcomes.

Gambling Disorder (GD) is an impactful behavioural addiction for which there appear to be underpinning genetic contributors. Twin studies show significant GD heritability results and intergenerational transmission show high rates of transmission. Recent developments in polygenic and multifactorial risk prediction modelling provide promising opportunities to enable early identification and intervention for at risk individuals. People with GD often have significant delays in diagnosis and subsequent help-seeking that can compromise their recovery. In this paper we advocate for more research into the utility of polygenic and multifactorial risk modelling in GD research and treatment programs and rigorous evaluation of its costs and benefits.

Abstract 2137: Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis

Abstract Background: While high-resolution imaging and advancements in therapies have significantly improved breast cancer survival rates, 43,170 breast cancer patients will die in the United States in 2023 alone. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and disproportionately affects BRCA1 mutation carriers and young black women. Black/African American (AA) patients have the highest mortality and the shortest survival of any racial/ethnic group in the US. Persistent cancer racial disparities remain due to a variety of risk factors. The SEER/CDC data show an 8% lower breast cancer incidence rate and a 41% higher mortality rate in Black/AA patients compared to their white counterparts. Methods: Chart review was conducted using Sentara MD Office/EPIC and VOA iKnowMedicine portals to update tumor relapse, metastasis, and survival in 577 TNBC patients. Supported by strong evidence in developmental, evolutionary, and cancer biology, we hypothesize that persistent EGFR/K-RAS/SIAH pathway activation is a major driving force of TNBC malignancy, racial disparity, early relapse, and high mortality. We propose to integrate SIAH expression to augment the existing clinicopathological parameters to improve patient risk stratification, therapy quantification, and relapse/survival prediction at the 1st-line neoadjuvant settings. Results: We report that cancer disparity and high mortality rates are even more pronounced in our racially-diverse communities in Hampton Roads Virginia. We discovered that SIAH is a tumor-specific, therapy-responsive, and prognostic biomarker in TNBC. High SIAH expression in residual tumors reflects tumor-driving EGFR/K-RAS/SIAH pathway activation (ON) that will predict cancer disparity, treatment resistance, early relapse, and poor survival. Low SIAH expression in residual tumors reflect EGFR/K-RAS/SIAH pathway inactivation (OFF) that will predict tumor remission and prolonged survival. Conclusion: We detect a major racial disparity of TNBC patients at Sentara-EVMS-VOA. Our local Black/AA TNBC patients have a 1.6-fold higher mortality rate than their White counterparts. Encouraged by our preliminary data, we aim to develop a SIAH-centered biomarker panel by measuring the EGFR/K-RAS/SIAH pathway activation (ON)/inactivation (OFF), and use SIAH as a new prognostic biomarker to risk stratify patients, detect cancer racial disparities, forecast tumor relapse, and predict patient survival at 1st-line neoadjuvant settings. By targeting SIAH, individualized treatments can be created to allow for increased survival rates in at risk individuals with more aggressive TNBCs. Citation Format: Claire B. Piatak, Taylor N. Drake, Ashleigh Hannah, Jonathan Baker, Caroline L. Dasom, Emily L. Breeding, Janet S. Winston, Billur Samli, Rick Jansen, Michael Danso, Richard A. Hoefer, Amy H. Tang. Racial disparities in triple-negative breast cancer (TNBC) mortality rates in Hampton Roads Virginia and the effects of SIAH expression on prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2137.

Abstract 4870: Defining metabolically healthy and unhealthy obesity in relation to cancer risk: A prospective cohort study by using a machine learning approach in comparison with conventional definitions in the UK Biobank

Abstract Background: The definition of metabolically healthy and unhealthy obesity for cancer risk remains uncertain and controversial. This study proposed a novel classifier based on biomarkers selected using machine learning (ML) and compared its risk stratification with the conventional definition. Methods: A prospective cohort study was conducted of 317,569 UK Biobank participants who were free of cancer and with body mass index (BMI) ≥18.5 kg/m2 at baseline. Individuals were classified into metabolically healthy and non-obese (MHNO), metabolically unhealthy and non-obese (MUNO), metabolically healthy and obese (MHO), and metabolically unhealthy and obese (MUO), according to body mass index (BMI) and six metabolic criteria. For the ML approach, LASSO regularization was used to select a subset from seventeen metabolic biomarkers to optimize C index. Clinical cut-off value was applied to this subset to define MHO. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) of total, obesity-related, type two diabetes (T2D)-related, and 23 site-specific cancers according to the conventional and ML definitions. Findings: Of 21 biomarkers, 17 were selected using LASSO. Compared with MHNO, individuals with MHO had higher risk of obesity-related cancer (HRconventional 1.22, 95% CI 1.15-1.29; HRML 1.23, 95% CI 1.16-1.30) and T2D-related cancer (HRconventional 1.25, 95% CI 1.19-1.39; HRML 1.27, 95% CI 1.20-1.34) after adjusting for sociodemographic and lifestyle factors. ML-defined metabolic status better-stratified individuals with normal weight for risk of total cancer (HRconventional1.02, 95% CI 0.99 -1.06; HRML 1.06, 95% CI 1.02 - 1.10) and some site-specific cancers, e.g., hepatocellular carcinoma (HRconventional 0.89, 95% CI, 0.53-1.48; HRML 2.52, 95% CI, 1.85-3.45). Interpretation: Compared with the conventional definition of metabolic health, a broader array of metabolic markers may help better stratify individuals for cancer risk. Keywords: Obesity, cancer, metabolically healthy obesity, hepatocellular carcinoma. Citation Format: Ziyi Zhou, Solange Parra-Soto, Yujia Lu, Zhe Fang, Kai Wang, Alaina Bever, Liyuan Tao, Fanny Petermann-Rocha, Jirapitcha Boonpor, Naveed Sattar, Carlos Celis-Morales, Jill P. Pell, Frederick K. Ho, Mingyang Song. Defining metabolically healthy and unhealthy obesity in relation to cancer risk: A prospective cohort study by using a machine learning approach in comparison with conventional definitions in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4870.

Neoplasia detection in FIT positive screening colonoscopies compared with an age-controlled symptomatic cohort: a retrospective review

Colonoscopy following a positive FIT test in an average risk population is effective in reducing CRC incidence and mortality. While lower gastrointestinal symptoms remain a common cause for referral for colonoscopy, symptoms are poor predictors of clinically significant disease. The study was performed to compare neoplasia detection FIT +ve individuals and age-matched symptomatic cohorts. A single centre retrospective observational study was performed including all index colonoscopies performed on patients aged 60-70 from January 2015 to September 2021. Diagnostic yield was reported as adenoma detection rate, SSL detection rate, detection of high risk finding or adenocarcinoma. 8,106 colonoscopies were performed on patients aged 60-70 years. 3,695 (45.6%) originated from screening (FIT +ve). With exclusion criteria applied, 2,640 (59.9%) for screening and 1,767 (40.1%) for symptomatic patients were included. Median age in screening was 65 years (IQR 62-67) and 64 years in the symptomatic group (IQR 62-68), with male predominance in both groups (n=1,536, 58.1%, n=944, 53.4%). There were significant differences in both the ADR (56% vs 26.3%, p&amp;lt;0.01) and the SSLDR (10.4% vs. 8.1%, p=0.05) in the screening cohort compared to the symptomatic group. High risk findings (21.3% vs. 7.5%, p&amp;lt;0.01) were significantly more prevalent in the screening group with a considerably higher colorectal cancer (4.7% vs. 0.9%, p=&amp;lt;0.001) detection rate. FIT based triage significantly outperforms symptom based investigation for individuals in the 60-70 age group. Patients should be preferentially referred to organised colorectal cancer screening. FIT can be performed on symptomatic patients, to identify low risk individuals.

Recovery rates and long‐term olfactory dysfunction following COVID‐19 infection

AbstractObjectivesOlfactory dysfunction is one of the most recognized symptoms of COVID‐19, significantly impacting quality of life, particularly in cases where recovery is prolonged. This review aims to explore patterns of olfactory recovery post‐COVID‐19 infection, with particular focus on delayed recovery.Data SourcesPublished literature in the English language, including senior author's own work, online and social media platforms, and patients' anecdotal reports.MethodA comprehensive review of the literature was undertaken by the authors with guidance from the senior author with expertise in the field of olfaction.ResultsBased on self‐report, an estimated 95% of patients recover their olfactory function within 6 months post‐COVID‐19 infection. However, psychophysical testing detects higher rates of persistent olfactory dysfunction. Recovery has been found to continue for at least 2 years postinfection; negative prognostic indicators include severe olfactory loss in the acute phase, female sex, and older age. Variability in quantitative and qualitative disturbance in prolonged cases likely reflects both peripheral and central pathophysiological mechanisms. Limitations of many of the reviewed studies reflect lack of psychophysical testing and baseline olfactory assessment.ConclusionsPost‐COVID‐19 olfactory dysfunction remains a significant health and psychosocial burden. Emerging evidence is improving awareness and knowledge among clinicians to better support patients through their olfactory rehabilitation, with hope of recovery after several months or years. Further research is needed to better understand the underlying pathogenesis of delayed recovery, identify at risk individuals earlier in the disease course, and develop therapeutic targets.

Identification of cost-effective biosecurity measures to reduce Salmonella along the pork production chain.

The continued occurrence of salmonellosis cases in Europe attributed to the consumption of pork products highlights the importance of identifying cost-effective interventions. Certain biosecurity measures (BSMs) may be effective in reducing the prevalence of specific pathogens along the pork production chain and their presence in food products. The objective of this study was to identify pathogen-specific, cost-effective BSMs to reduce Salmonella at different stages of the pork production chain in two European countries - Austria (AT) and the United Kingdom (UK). For this purpose, a cost-benefit analysis was conducted based on the epidemiological output of an established quantitative microbiological risk assessment that simulated the implementation effect of the BSMs based on their risk ratios. For each of the BSMs, the associated costs and benefits were assessed individually and country-specifically. For both AT and UK, nine different BSMs were evaluated assuming a countrywide implementation rate of 100%. The results showed that four BSMs were cost-effective (benefit-cost ratio > 1) for AT and five for the UK. The uncertainty regarding the cost-effectiveness of the BSMs resulted from the variability of individual risk ratios, and the variability of benefits associated with the implementation of the BSMs. The low number of cost-effective BSMs highlights the need for holistic risk-based models and economic assessments. To increase the willingness to implement BSMs and maximize the benefits for stakeholders, who carry the majority of the implementation costs, epidemiological assessments of BSM effectiveness should consider the impact on several relevant pathogens simultaneously.

Negative life events and their association with anxiety in adolescents with subthreshold depression

Subthreshold depression (SD) is a serious mental health problem in adolescents, and there is increasing evidence that depressive symptoms frequently occur alongside anxiety. Despite this, the extent to which negative life events (NLEs) are an associated factor in adolescents with SD comorbid with anxiety remains unclear. A total of 371 Chinese adolescents with SD were recruited (204 girls, 166 boys and missing data), ranging in age from 14 to 19 years (M = 16.34, SD = 0.96). All subjects were rated on the Centre for Epidemiological Studies Depression Scale (CES-D), the Multidimensional Anxiety Scale for Children (MASC), the Individualism-Collectivism Scale (ICS), the Adolescent Life Events Questionnaire (ALEQ), and the Neuroticism Extraversion-Openness Five-Factor Inventory (NEO-FFI-N). The SD adolescents with higher anxiety had higher neuroticism scores, more self-reported negative life events and vertical individual orientation than those with low anxiety, and more of them were female than male (all p < 0.05). Further logistic regression indicated that gender, severity of depressive symptoms, vertical individualism orientation, and neuroticism were significantly associated with anxiety symptoms (p < 0.05). Our cross-sectional study could not explain the causal relationship between the severity of individual anxiety and risk factors in SD adolescents. Our results suggest that SD adolescents with high anxiety are more likely to experience NLEs than SD adolescents with low anxiety. Gender, severity of symptoms, vertical individualism orientation, and neuroticism are independent risk factors for anxiety in SD adolescents.

Oral health with focus on dental fear and dental caries in Swedish preschool child populations attending public dental health care: Trends over 30 years.

To study changes in oral health with focus on reported dental fear prevalence and interrelationships between dental fear and prevalence of dental caries and performed restorative dental treatment in preschool child populations attending regular public dental health care between 1983 and 2013. Every 10 years, random samples of about 100 children aged 3 and 5 years, respectively, took part in cross-sectional studies based on oral examination and a questionnaire. One question, put to the child and answered by the parent, mirrored dental fear: "What do you feel at the prospect of an appointment with a dentist?". Agreement to at least one of three alternatives, ill at ease, frightened and sick, indicated dental fear. Frightened and/or sick mirrored severe dental fear. 79%-94% of the samples answered the question and constituted the study group. Prevalence of caries and number of filled tooth surfaces were recorded. Dental parameters were presented in mean values. During the 30 years, dental fear prevalence was fairly constant. 21% of 3-year-olds and 15% of 5-year-olds reported dental fear in 2013. Positive relationships between dental fear prevalence and caries prevalence and number of filled tooth surfaces were found. Dental caries was reduced during the study time, but to a lesser degree in children with dental fear compared to children without dental fear. Although children were offered public dental health care, the prevalence of dental fear remained high. Children with dental fear are caries risk individuals.