Multivariable Linear Regression Models Research Articles

Correlates of Sleep Health among Older-Age People with and without HIV in Uganda.

There is a growing population of older people with HIV (PWH) in Uganda. Sleep problems disproportionately affect older people and PWH. This study aimed to estimate correlates of sleep health among older Ugandans (aged ≥ 50 years) with and without HIV, using data from the Quality of Life and Aging with HIV in Rural Uganda Study. We used the Pittsburgh Sleep Quality Index to assess sleep quality, duration, and efficiency. We fitted multivariable linear and logistic regression models to estimate the associations between sleep outcomes and variables selected based on the Senescent Sleep Model: age, HIV serostatus, loneliness, urbanicity, symptoms of depression and anxiety, and perceived stress. Of 556 participants, 271 were PWH and 285 were people without HIV (PWoH). There were no statistically significant differences in sleep outcomes by HIV serostatus. Of the total sample, most reported very good (32.79%) or fairly good sleep quality (49.37%). The mean sleep duration was 6.46h (SD = 1.74). The mean sleep efficiency was 73.98% (SD = 19.52%) with 36.69% having optimal (≥ 85%) sleep efficiency. A positive depression screen was associated with worse sleep quality (adjusted odds ratio [aOR] = 0.21; 95% CI [0.12, 0.36]), shorter sleep duration (b=-0.44; 95% CI [-0.60, -0.28]), and worse sleep efficiency (aOR = 0.51; 95% CI[0.31, 0.83]). Interventions targeting depression may improve sleep among older Ugandans, independent of HIV serostatus. Longitudinal studies are needed to determine the potential bidirectionality of this relationship and elucidate pathways to support sleep health among older Ugandans.

Contribution of inflammation markers and quantitative sensory testing (QST) indices of central sensitisation to rheumatoid arthritis pain.

Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by 'static' (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and 'dynamic' (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman's correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.

The association between circulating saturated fatty acids and thyroid function: results from the NHANES 2011-2012.

Excessive saturated fatty acids (SFAs) are known to be detrimental to human health. Although the majority of research and dietary guidelines have focused on the intake of SFAs, there has been limited attention to the relationship between circulating SFA levels and hormonal regulation, such as that of thyroid hormones. To explore potential associations, we conducted an investigation with 579 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Subgroup analyses and multivariable linear regression models were used to estimate the relationships between eleven distinct SFA concentrations and various thyroid parameters. For 579 adults, subgroup analysis of thyroid stimulating hormone (TSH) revealed significant differences in nine specific SFAs and the total SFA levels (all p < 0.05). Furthermore, multivariable linear regression analysis identified positive correlations between certain SFAs and various parameters, including TSH, total triiodothyronine (TT3), free triiodothyronine (FT3), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroglobulin (Tg), the ratio of FT3 to free thyroxine (FT4) (FT3/FT4), and the thyrotroph T4 resistance index (TT4RI). Conversely, negative correlations were observed between certain SFAs and total thyroxine (TT4), FT4, the ratio of FT3/TT3, and the thyroid feedback quantile-based index (TFQI) (all p < 0.05). These findings collectively suggest associations between SFAs and thyroid parameters, highlighting the need for future studies to elucidate the underlying mechanisms of these interactions.

Similarities of metabolomic disturbances in prematurity-associated obstructive lung disease to chronic obstructive pulmonary disease

Prematurity-associated lung disease (PLD) is a long-term consequence of preterm-birth. Since the underlying mechanisms of PLD remain poorly characterised, we compared the urinary metabolome between recently described spirometry phenotypes of PLD. Preterm- and term-born children aged 7–12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) cohort, underwent spirometry and urine collection. The urinary metabolome was analysed by gas chromatography time-of-flight mass spectrometry. Preterm-born children were classified into phenotypes of prematurity-associated obstructive lung disease (POLD, Forced expiratory volume in 1 s (FEV1) < lower limit of normal (LLN), FEV1/Forced Vital Capacity (FVC) < LLN), prematurity-associated preserved ratio impaired spirometry (pPRISm, FEV1 < LLN, FEV1/FVC ≥ LLN) and Preterm/Term controls (FEV1 ≥ LLN). Metabolite set enrichment analysis was used to link significantly altered metabolites between the groups with metabolic pathways. Univariable and multivariable linear regression models examined associations between early and current life factors and significantly altered metabolites of interest. Urine from 197 preterm- and 94 term-born children was analysed. 23 and 25 were classified into POLD and pPRISm groups respectively. Of 242 identified metabolites, 49 metabolites were significantly altered in the POLD group compared with Preterm controls. Decreased capric acid (log2 fold change − 0.23; p = 0.003), caprylic acid (− 0.18; 0.003) and ceratinic acid (− 0.64; 0.014) in the POLD group, when compared to preterm controls, were linked with reduced β-oxidation of very long chain fatty acids (p = 0.004). Reduced alanine (log2 fold change − 0.21; p = 0.046), glutamic acid (− 0.24; 0.023), and pyroglutamic acid (− 0.17; 0.035) were linked with decreased glutathione metabolism (p = 0.008). These metabolites remained significantly associated with POLD in multivariable models adjusting for early/current life factors. The pPRISm urinary metabolome was minimally changed when compared with preterm-born controls. When compared to term-born subjects, alterations in tryptophan metabolism were implicated (p = 0.01). The urinary metabolome in POLD showed significantly altered β-oxidation of fatty acids and glutathione metabolism, implying alterations in cellular metabolism and oxidative stress. Similar findings have been noted in adults with chronic obstructive pulmonary disease. Given the similarity of findings between the POLD group and those reported for COPD, the POLD group should be considered at future risk of developing COPD.

Higher Serum Dipeptidyl Peptidase-4 Activity in Newly Diagnosed Young-Onset Type 2 Diabetes Mellitus.

Background Dipeptidyl peptidase-4 (DPP4) enzyme inhibition is a therapeutic modality for type 2 diabetes mellitus (T2DM). However, its activity is insufficiently explored yet in youth-onset T2DM. Objective The objective of this study is to measure serum DPP4 enzyme activities in youth-onset T2DM and compare them with those in patients with normal glucose tolerance (NGT). Methods This cross-sectional study comprised 29 young participants with newly diagnosed untreated T2DM (age 24.5±4.5 years, range 13-30 years, 51.7% female) and an equal number of young participants with NGT (age 26.5±2.9 years,48.3% female) screened by a two-sample 75gm oral glucose tolerance test. The relevant history of each participant was obtained, and the waist circumference, waist-hip ratio, blood pressure, and body mass index (BMI) were measured according to the standard procedure and recorded in the data collection sheet. Plasma glucose was measured using the glucose oxidase method, and serum DPP4 activity was measured using the colorimetry method. Results Participants with DM exhibited significantly higher serum DPP4 activity than NGT (DM vs. NGT: 481.4±70.4 pmol/min. vs. 420.3±49.2 pmol/min, mean±SD; p<0.001). A multivariate linear regression model adjusted for age, sex, BMI, and hypertension, found DM as an independent predictor for DPP4 activity (β=0.63.5, 95% CI 28.7-98.4, p=0.022). Conclusion DPP4 activity was significantly elevated in young participants with newly diagnosedT2DM. There might be a pathophysiological implication of DPP4 activity in young-onset T2DM.

Mediating role of accelerated aging in the association between depression and mortality risk: findings from NHANES

ObjectiveTo investigate the association between depression, accelerated biological aging, and mortality risk, and to assess whether accelerated aging mediates the relationship between major depression and mortality risk.MethodsA prospective cohort of 12,761 participants aged 20 years or older from the 2005–2010 cycle of the National Health and Nutrition Examination Survey (NHANES) was analyzed. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores of ≥ 10 indicating major depression. Accelerated biological aging was measured using phenotypic age acceleration (PhenoAgeAccel). Multivariable linear regression models and subgroup analyses were used to examine the association between depression and accelerated aging, while weighted multivariable Cox proportional hazards regression models and subgroup analyses assessed the impact of major depression on mortality risk. Mediation analysis was performed to assess whether PhenoAgeAccel mediated the relationship between major depression and mortality outcomes.ResultsAmong the 12,761 adults, the weighted mean age was 46.6 years, with 48.8% being male, and 6.9% experiencing major depression. The results showed a positive association between major depression and PhenoAgeAccel (β: 0.61, 95% CI: 0.06–1.16). Over a median follow-up duration of 11.3 years (interquartile range: 9.9–13.1), major depression was associated with increased all-cause mortality (HR: 1.35, 95% CI: 1.13–1.62) and cardiovascular mortality (HR: 1.73, 95% CI: 1.18–2.54). However, the relationship with cancer mortality was not statistically significant after full adjustment for confounding factors. The mediation analysis further revealed that PhenoAgeAccel accounted for 10.32% and 5.12% of the associations between major depression and all-cause mortality, and cardiovascular mortality, respectively.ConclusionDepression is associated with accelerated aging and contributes to increased all-cause and cardiovascular mortality. Accelerated aging partially mediates the association between major depression and mortality risk. Our findings highlight the urgent need to incorporate mental health care into public health strategies to delay population aging and reduce mortality risk.

Relationship between longer sleep and serum neurofilament light chain in american adults: evidence from the 2013–2014 US national health and nutrition examination survey

BackgroundSleep disturbance is linked to neurodegenerative diseases and the related brain pathophysiology. Serum neurofilament light chain (NfL) is a reliable biomarker for neurological disorders. This study examined the association between sleep characteristics and serum NfL levels in American adults.MethodsIn this cross-sectional study, data from the 2013–2014 US National Health and Nutrition Examination Survey were utilized. Participants were categorized into short (≤ 6 h), normal (7–8 h), and long (≥ 9 h) sleep groups based on their self-reported sleep durations. Sleep duration, trouble sleeping, and diagnosed sleep disorders were queried, forming “sleep pattern (healthy, moderate, and poor).” The association between sleep characteristics and serum NfL levels was assessed using multivariate linear regression models. Stratification and sensitivity analyses were conducted to determine the stability of results.ResultsOverall, 1637 participants were included; among them, 48.2% were male and 51.8% were female (mean ± SD, age: 46.9 ± 15.5 years) and 38.8% reported sleeping for ≤ 6 h, 54.4% for 7–8 h, and 6.8% for ≥ 9 h. Participants with longer sleep duration, poor sleep pattern, diagnosed sleep disorders, or trouble sleeping exhibited higher serum NfL levels. A positive correlation was found between extended sleep and elevated serum NfL levels (Adjusted β = 4.82, 95%CI: 2.2, 7.44, P < 0.001), with no significant correlation observed in the short-sleep group or those with poor sleep pattern. Stratified and sensitivity analyses confirmed the robustness of the relationship between longer sleep and elevated serum NfL levels.ConclusionsA long sleep duration is associated with higher serum NfL levels than a normal sleep duration in American adults.

8054 Temporal Trends In Thyroidal Endocrine Disruptor Exposure Among United States Reproductive-Age And Pregnant Women Over 20 Years And Differences By Socioeconomic Status

Abstract Disclosure: C. Han: None. S. Lee: None. E.N. Pearce: None. Background: Widespread exposure to endocrine disrupting chemicals (EDCs) poses a risk to public health and environmental safety. Women of reproductive age and pregnant women may be uniquely vulnerable to adverse thyroidal effects of EDCs. A better understanding of thyroidal EDCs exposure is needed to inform public health strategies. Objective: To examine temporal trends in EDC exposure and their effects on thyroid function among reproductive-age and pregnant women in the U.S. over the last two decades, with a focus on the impact of socioeconomic status. Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020 in 25,320 reproductive-age women and 2,525 pregnant women to assess the levels of exposure to thyroid-disrupting chemicals, including dioxins, organochlorides, polyfluoroalkyl substances (PFAS) from serum samples, and polyaromatic hydrocarbons, perchlorates, and metabolites from personal care products, phthalates, and plasticizers from urine samples. We used Kruskal-Wallis tests to analyze changes in EDC exposures over the past 20 years and multivariate linear regression models to identify factors influencing these levels. Results: We found a significant decline in exposures to 20 types of dioxins, 7 organochlorides, 6 PFAS, 5 personal care product chemicals, 6 phthalate metabolites, perchlorate, and thiocyanate, but substantial increases in exposure to 2 polyaromatic hydrocarbons among reproductive-age women. Among pregnant women, trends were similar, with declines in exposures to dioxins, organochlorides, PFAS, and phthalate metabolites; whereas exposure to 3 Polyaromatic hydrocarbons, 1 personal care product chemical, nitrates, and thiocyanates increased. Linear regression indicated a significant positive association between socioeconomic status and the levels of dioxin and PFAS in both reproductive-age and pregnant women, and a negative association between socioeconomic status and perchlorate and polyaromatic hydrocarbons in the participants. Conclusion: The past two decades have witnessed a general decline in the levels of most thyroidal EDCs in U.S. reproductive-age and pregnant women; however, some, particularly polyaromatic hydrocarbons, exposures have increased, especially among women with lower socioeconomic status. This has the potential to worsen disparities in health outcomes. These findings highlight the necessity for targeted public health interventions to reduce the impact of EDCs on thyroid health and address socioeconomic health disparities. Presentation: 6/3/2024

Prediction of emergency department presentations for acute coronary syndrome using a machine learning approach

The relationship between weather and acute coronary syndrome (ACS) incidence has been the subject of considerable research, with varying conclusions. Harnessing machine learning techniques, our study explores the relationship between meteorological factors and ACS presentations in the emergency department (ED), offering insights into seasonal variations and inter-day fluctuations to optimize patient care and resource allocation. A retrospective cohort analysis was conducted, encompassing ACS presentations to Dutch EDs from 2010 to 2017. Temporal patterns were analyzed using heat-maps and time series plots. Multivariable linear regression (MLR) and Random Forest (RF) regression models were employed to forecast daily ACS presentations with prediction horizons of one, three, seven, and thirty days. Model performance was assessed using the coefficient of determination (R²), Mean Absolute Error (MAE), and Mean Absolute Percentage Error (MAPE). The study included 214,953 ACS presentations, predominantly unstable angina (UA) (94,272; 44%), non-ST-elevated myocardial infarction (NSTEMI) (78,963; 37%), and ST-elevated myocardial infarction (STEMI) (41,718; 19%). A decline in daily ACS admissions over time was observed, with notable inter-day (estimated median difference: 41 (95%CI = 37–43, p = < 0.001) and seasonal variations (estimated median difference: 9 (95%CI 6–12, p = < 0.001). Both MLR and RF models demonstrated similar predictive capabilities, with MLR slightly outperforming RF. The models showed moderate explanatory power for ACS incidence (adjusted R² = 0.66; MAE (MAPE): 7.8 (11%)), with varying performance across subdiagnoses. Prediction of UA incidence resulted in the best-explained variability (adjusted R² = 0.80; MAE (MAPE): 5.3 (19.1%)), followed by NSTEMI and STEMI diagnoses. All models maintained consistent performance over extended prediction horizons. Our findings indicate that ACS presentation exhibits distinctive seasonal changes and inter-day differences, with marked reductions in incidence during the summer months and a distinct peak prevalence on Mondays. The predictive performance of our model was moderate. Nonetheless, we obtained good explanatory power for UA presentations. Our model emerges as a potentially valuable supplementary tool to enhance ED resource allocation or future predictive models predicting ACS incidence in the ED.

Melanoma-specific mutation hotspots in distal, non-coding, promoter-interacting regions implicate novel candidate driver genes.

To develop targeted treatments, it is crucial to identify the full spectrum of genetic drivers in melanoma, including those in non-coding regions. However, recent efforts to explore non-coding regions have primarily focused on gene-adjacent elements such as promoters and non-coding RNAs, leaving intergenic distal regulatory elements largely unexplored. We used Hi-C chromatin contact data from melanoma cells to map distal, non-coding, promoter-interacting regulatory elements genome-wide in melanoma. Using this "promoter-interaction network", alongside whole-genome sequence and gene expression data from the Pan Cancer Analysis of Whole Genomes, we developed multivariate linear regression models to identify distal somatic mutation hotspots that affect promoter activity. We identified eight recurrently mutated hotspots that are novel, melanoma-specific, located in promoter-interacting distal regulatory elements, alter transcription factor binding motifs, and affect the expression of genes (e.g., HSPB7, CLDN1, ADCY9 and FDXR) previously implicated as tumour suppressors/oncogenes in various cancers. Our study suggests additional non-coding drivers beyond the well-characterised TERT promoter in melanoma, offering new insights into the disruption of complex regulatory networks by non-coding mutations that may contribute to melanoma development. Furthermore, our study provides a framework for integrating multiple levels of biological data to uncover cancer-specific non-coding drivers.

Associations Between Every day and Medical Setting-Based Discrimination and Religious and Sociodemographic Characteristics of Muslim Americans: Findings from a National Survey.

We investigated the associations between sociodemographic factors, religiosity traits, and the perception of discrimination among Muslim Americans in both everyday life and medical settings. A self-administered web-based questionnaire, comprising validated measures of discrimination and religiosity, was completed by a convenience sample of English-speaking adult Muslim Americans, recruited through both in-person and online channels. Among the 1281 respondents, less than half were born in the USA (46%), and a significant portion displayed visible religious markers, such as wearing a hijab or having a beard (61%). Only 154 (12%) reported never experiencing everyday discrimination, while 358 (28%) reported not experiencing discrimination in medical settings. In a multivariable linear regression model, greater perceived everyday discrimination (β = 1.053, p < 0.01) was positively associated with greater discrimination in medical settings. Participants more comfortable self-identifying as Muslim in hospital settings (β = -0.395, p < 0.05) were less likely to perceive healthcare discrimination. Those visibly expressing their religiosity (β = 0.779, p < 0.01) and those with greater intrinsic religiosity (β = 0.231, p < 0.05) were more likely to encounter everyday discrimination. Conversely, older participants (β = -0.015, p < 0.05), adult immigrants to the US (β = -0.375, p < 0.05), those in better health (β = -0.157, p < 0.05), and those more comfortable identifying as Muslim (β = -0.305, p < 0.05) had lower perceptions of everyday discrimination. This study underscores the significance of the relationship between religiosity characteristics and experiences of both hospital and everyday discrimination for Muslim Americans.

Exploring the Relationship Between Hospital Patient Safety Culture and Performance on Measures of Hospital-Acquired Conditions

Objective The aim of the study is to examine the relationship between hospital perceptions of patient safety culture and the incidence of hospital-acquired conditions (HACs) included in Medicare’s HAC Reduction Program utilizing updated and standardized metrics. Methods The pooled cross-sectional study design utilized the 2018 and 2021 datasets from (1) the Agency for Healthcare Research and Quality’s Hospital Survey on Patient Safety Culture (HSOPS), (2) the American Hospital Association’s annual survey, and (3) the Center for Medicare and Medicaid’s Hospital Compare dataset. The final analytic sample included 131 acute care, nonfederal, U.S. facilities. Multivariable linear regression models were used to compare the HSOPS domains of patient safety culture to CMS’s HAC metrics. Results Controlling for hospital structural and patient-mix characteristics, hospitals with higher staff-reported ratings of overall patient safety culture (‘overall perceptions of patient safety’ and ‘patient safety grade’) had significantly lower rates of HACs, including total HAC rate, catheter-associated urinary tract infections, and central line-associated blood stream infections (P’s &lt; 0.000–0.044). Higher HSOPS domain scores were variably associated with lower HAC rates, with consistently significant associations found for domains related to nonpunitive, open communication (P’s &lt; 0.05). Conclusions Our relatively robust results suggest that while patient safety culture may not be the only strategy necessary to improve HAC rates, it needs to be aligned with other efforts to improve quality and safety. This underscores the importance of cultivating a culture of psychological safety that promotes open feedback and communication about errors.

A pilot cross-sectional investigation of symptom clusters and associations with patient-reported outcomes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is associated with long-term disability and poor quality of life (QoL). Cardinal ME/CFS symptoms (including post-exertional malaise, cognitive dysfunction and sleep disturbances) have been observed in Post COVID-19 Condition (PCC). To gain further insight into the potential role of ME/CFS as a post-COVID-19 sequela, this study investigates associations between symptoms and patient-reported outcomes, as well as symptom clusters. Participants included Australian residents aged between 18 and 65 years formally diagnosed with ME/CFS fulfilling the Canadian or International Consensus Criteria or PCC meeting the World Health Organization case definition. Validated, self-administered questionnaires collected participants' sociodemographic and illness characteristics, symptoms, QoL and functional capacity. Associations between symptoms and patient-reported outcomes were investigated with multivariate linear regression models. Hierarchical cluster analysis was performed to identify symptom clusters. Most people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) were female (n = 48/60, 80.0% and n = 19/30, 63.3%, respectively; p = 0.12). PwME/CFS were significantly younger (x̄=41.75, s = 12.91 years) than pwPCC (x̄=48.13, s =10.05 years; p =0.017). Autonomic symptoms (notably dyspnoea) were associated with poorer scores in most patient-reported outcome domains for both cohorts. None of the four symptom clusters identified were unique to ME/CFS or PCC. Clusters were largely delineated by the presence of gastrointestinal and neurosensory symptoms, illness duration, ME/CFS criteria met and total symptoms. Illness duration may explain differences in symptom burden between pwME/CFS and pwPCC. PCC diagnostic criteria must be refined to distinguish pwPCC at risk of long-term ME/CFS-like illness and subsequently deliver necessary care and support.

Who is consuming ultra-processed food in Canada? A cross-sectional analysis of the 2018/2019 International Food Policy Study.

High consumption of ultra-processed foods and drinks (UPF) has been linked to poor diet quality and an increased risk of non-communicable diseases. To inform public policies and interventions aimed at reducing UPF intake in Canada, updated information on UPF intake among different sociodemographic groups is needed. This study, using data from 5,872 adults aged 18 years and older from the International Food Policy Study (2018-2019), aims to estimate the dietary energy contribution of UPF and assess its variation among sociodemographic subgroups. All foods and drinks reported in a single 24-hour dietary recall were classified using the Nova system. We estimated the mean proportion of total daily energy from UPF and subcategories of UPF in the overall sample and among sociodemographic subgroups. Multivariable linear regression models evaluated the association between sociodemographic characteristics with the proportion of total daily energy from UPF. On average, adults consumed 45.2% of their total daily energy from UPF. UPF consumption was slightly higher among males than females (49.4% vs. 47.6%, p=0.039) and younger adults aged 19-30 years compared with older adults aged 51-64 years (50.0% vs. 47.2%, p=0.029), adjusting for a range of sociodemographic factors. Overall, UPF consumption was relatively high among adults in all sociodemographic subgroups, highlighting the need for policies to decrease UPF consumption in the entire population.

Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.

Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC. We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. A total of 417 patients were enrolled-EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.

Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study

BackgroundThe recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring.MethodsBased on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring.ResultsCompared with “low IPAI” group, offspring with “high IPAI” have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted β were − 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and − 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among “high IPAI” group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72).ConclusionsOur results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

B-158 Association between multiple heavy metals exposure and blood lipid levels: evidence from a cross-sectional study of Korean adults

Abstract Background Metals are ubiquitous in our environment and enter human body via various pathways, such as air, soil, food, water, etc. Increasing studies have found that metals are important risk factors in developing dyslipidemia. However, there is no consensus regarding the effects of co-exposure to multiple metals on blood lipid levels. We investigated both the joint and individual effects of this metal mixture exposure on human blood lipid levels. Methods Blood concentrations of four human toxic metals (Pb, Cs, Hg, and Cd) in 2,798 general populations from Korea were simultaneously determined as a measure of exposure. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of four blood metals and metals mixture with lipid profiles, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Results The mean age of the overall study population was 41.2 ± 9.85 years, and 66.9% were men. The prevalence of overweight or obesity, diabetes, and hypertension in the population was 62.5, 6.8, and 13.9%, respectively. In the multivariable linear regression model, the blood Cs was positively associated with TC and LDL-C(p &amp;lt; 0.05, all), and the blood Pb was positively associated with serum TG (p &amp;lt; 0.05, all). Also, the blood Cd was positively associated with serum HDL-C (p &amp;lt; 0.05, all). We did not identify any other obvious interaction between metals on the lipid profiles using a bivariate exposure-response function in BKMR. Conclusions Our finding suggests that combined exposure to this metal mixture may affect human blood lipid levels. Therefore, reducing exposure to heavy metals, such as Cs and Pb, should be a priority for the general population. However, future studies with a larger number of heavy metals are still needed to focus on the detrimental effects of single metals on lipid profiles as well as to identify key components.

Improving analysis of cognitive outcomes in cardiovascular trials using different statistical approaches

BackgroundThe Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires are commonly used to measure global cognition in clinical trials. Because these scales are discrete and bounded with ceiling and floor effects and highly skewed, their analysis as continuous outcomes presents challenges. Normality assumptions of linear regression models are usually violated, which may result in failure to detect associations with variables of interest.MethodsAlternative approaches to analyzing the results of these cognitive batteries include transformations (standardization, square root, or log transformation) of the scores in the multivariate linear regression (MLR) model, the use of nonlinear beta-binomial regression (which is not dependent on the assumption of normality), or Tobit regression, which adds a latent variable to account for bounded data. We aim to empirically compare the model performance of all proposed approaches using four large randomized controlled trials (ORIGIN, TRANSCEND, COMPASS, and NAVIGATE-ESUS), and using as metrics the Akaike information criterion (AIC). We also compared the treatment effects for the methods that have the same unit of measure (i.e., untransformed MLR, beta-binomial, and Tobit).ResultsThe beta-binomial consistently demonstrated superior model performance, with the lowest AIC values among nearly all the approaches considered, followed by the MLR with square root and log transformations across all four studies. Notably, in ORIGIN, a substantial AIC reduction was observed when comparing the untransformed MLR to the beta-binomial, whereas other studies had relatively small AIC reductions. The beta-binomial model also resulted in a significant treatment effect in ORIGIN, while the untransformed MLR and Tobit regression showed no significance. The other three studies had similar and insignificant treatment effects among the three approaches.ConclusionWhen analyzing discrete and bounded outcomes, such as cognitive scores, as continuous variables, a beta-binomial regression model improves model performance, avoids spurious significance, and allows for a direct interpretation of the actual cognitive measure.Trials registrationORIGIN (NCT00069784). Registered on October 1, 2003; TRANSCEND (NCT00153101). Registered on September 9, 2005; COMPASS (NCT01776424). Registered on January 24, 2013; NAVIGATE-ESUS (NCT02313909). Registered on December 8, 2014.

Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study

BackgroundObesity poses a significant global health challenge, with profound implications for women’s reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients.MethodsWe conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses.ResultsAnti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20–30 and 30–35 years. Among women aged 20–35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia.ConclusionsAn age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.

Community Benefit and Tax-Exemption Levels at Non-Profit Hospitals Across U.S. States.

To assess the association between state policies and sociodemographic characteristics and state mean fair share spending at non-profit hospitals. Fair share spending is a hospital's charity care and community investment less the estimated value of their tax-exempt status. Hospitals with non-profit status in the United States are exempt from paying taxes. In return, they are expected to provide community benefits by subsidizing medical care for those who cannot pay and investing in the health and social needs of their community. We used a multivariable linear regression model to determine the association of state-level sociodemographics and policies with state-level mean fair share spending in 2019. Fair share spending data was obtained from the Lown Institute. We found no association between the percentage of people living in poverty, in rural areas, or U.S. region and fair share spending. Similarly, there was no association found for state minimum community benefit and reporting requirements. The state percentage of racial/ethnic minorities was associated with higher mean fair share spending [+$1.48 million for every 10% increase (95% CI: 0.01 to 2.96 million)]. Medicaid expansion status was associated with a 6.9-million-dollar decrease (95% CI: -10.4 to -3.3 million). State-level community benefit policies have been ineffective at raising community benefit spending to levels comparable to the value of non-profit hospital tax-exempt status.