Differences Research Articles

Abstract TP392: Prior recurrent hypoglycemia exposure potentiates post-ischemic hypoperfusion in male insulin-treated diabetic rats.

Diabetes is a widespread disease, and stroke is one of the serious complications of diabetes. Antidiabetic therapy increases the risk of recurrent hypoglycemia (RH). We have previously shown that RH exposure leads to severe post-ischemic hypoperfusion at least up to 80 minutes after ischemia and increases the extent of ischemic brain injury in insulin-treated diabetic (ITD) rats. However, the total duration for which these perfusion deficits last is unknown. Thus, we evaluated cerebral blood flow up to 7 days post-ischemia in RH-exposed ITD rats using laser speckle imaging. Diabetic male rats were treated for hyperglycemia using insulin pellets, were assigned randomly to either hyperinsulinemic euglycemia (ITD+RH+Glucose control; n=7) or hyperinsulinemic hypoglycemia (ITD+RH; n=7) groups (3 h duration) (Figure B-C) and were subjected to transient global cerebral ischemia overnight after the last episode of hyperinsulinemic euglycemia or hyperinsulinemic hypoglycemia. We evaluated cerebral perfusion at baseline (pre-ischemia), 1 h, 24 h, 3 d, 5 d, and 7 d post-ischemia. The cerebral ischemia in RH-exposed ITD rats resulted in a significant decrease in percentage change in cerebral blood flow as compared to the control rats when quantified 1 hour (23%, p<0.01) and 1 day (17%, p<0.05) after cerebral ischemia. However, the percentage changes in cerebral blood flow in ITD+RH group were not significantly different from that of the control group at 3, 5, and 7 days after ischemia (Figure A, D). The cerebral blood flow post-ischemia at 1-hour (24%) and 1-day (18%) was significantly lower (p<0.001 each) while at 3 (12%, p<0.05), 5 (25%, p<0.05), and 7 days (29%, p<0.01) was significantly higher than that of the baseline values in RH-exposed ITD rats. The cerebral blood flow at 1 hour, 1 day, and 3 days after ischemia in ITD + RH + glucose rats was not significantly different from the baseline values. The cerebral blood flow at 5 (19%, p<0.05) and 7 (42%, p<0.001) days after ischemia in ITD + RH + glucose rats was significantly higher than the baseline values. Our results show that RH exposure induces severe post-ischemic hypoperfusion for at least ≈24 hours after ischemia in young male ITD rats. Next, we aim to study the duration of the effect of RH on post-ischemic hypoperfusion in female ITD rats and to identify the underlying mechanism causing this effect in the animal model of diabetes. Acknowledgment: NIH (NS122808).

Calf circumference may complement the nutritional assessment of children under 10 in the paediatric intensive care unit.

Nutritional intervention during hospitalisation is vital in managing of children and adolescents in intensive care. In this context, body composition measurements, such as mid-upper arm circumference (MUAC), can help improve the accuracy of nutritional assessments. However, using MUAC has some limitations. Calf circumference (CC) is a straightforward, inexpensive, and easily obtainable measurement. However, no reference values currently exist for CC in paediatric patients. To describe the nutritional monitoring of critically ill children and adolescents in the Paediatric Intensive Care Unit (PICU) using CC. Patients aged 6 months to 18 years old who were admitted to the PICUs participated in the study. Two MUAC and CC measurements were performed: one in the first 48h of admission to the PICU and another after 7 days. The percentage change between the two measurements was compared. Information was also evaluated about demographic and outcome data. Analyses were conducted with all patients included in the sample collectively and subdivided by age (<10 years and ≥10 years). Two hundred and eleven patients underwent anthropometric assessment on admission, and the sample for comparative analyses consisted of 103 patients (after discharges and deaths). MUAC and CC significantly decreased in the first week of hospitalisation. A positive weak correlation was found between the percentage change in the MUAC and CC only for individuals under 10 years old and for the total sample, but not for adolescents. The all age group and children under 10 years old showed a greater reduction in CC than in MUAC. The same did not occur for adolescents. Calf circumference may be a promising method for nutritional monitoring of critically ill children in Paediatric Intensive Care Units because it can indicate signs of depletion earlier than mid-upper arm circumference. These results are more meaningful for children than for adolescents.

Disparities in prophylactic tetracycline use among patients with metastatic colorectal cancer undergoing treatment with EGFR inhibitors.

109 Background: Epidermal growth factor receptor (EGFR) inhibitors have been shown to improve survival in metastatic colorectal cancer and are considered a standard of care option for patients with RAS/RAF wild-type disease. However, anti-EGFR agents are associated with an acneiform rash that can lead to decreased quality of life and early discontinuation of treatment. Prophylactic doxycycline has been shown in a randomized clinical trial to decrease any skin toxicity ≥ grade 2 by 50%. In this study we sought to determine the rate of prophylactic tetracycline use in metastatic colorectal cancer patients receiving anti-EGFR therapy in the United States. Methods: The Flatiron Health Electronic Health Record-derived, de-identified database was used to analyze the records of patients who were at least 18 years old, diagnosed with metastatic colorectal cancer, and received treatment with an anti-EGFR agent (cetuximab or panitumumab). Patients were stratified by receipt of prophylactic tetracycline versus not. This was defined by an order for a tetracycline 28 days before to 1 day after initiation of an anti-EGFR agent. Demographic and clinical characteristics were compared via multivariable logistic regression. The change in percentage of patients who received a prophylactic tetracycline over time was assessed and was compared to the rate of anti-emetic prescription which served as a control to ensure drug administration data was accurately captured. Results: The records of 6,713 patients who met inclusion criteria and received an anti-EGFR agent between 2013 and 2023 were included in our analysis. A logistic regression model assessing the association between patient characteristics and the receipt of a prophylactic tetracycline suggested that older age, race (black/African American or Other), presence of RAS mutation, and higher line of therapy were all significantly associated with not receiving prophylactic tetracyclines. Other patient characteristics including gender, ECOG status, mismatch repair status, and RAF mutation status did not appear to impact the likelihood of receiving a prophylactic tetracycline. The rate of prophylactic tetracycline use increased from 10.9% in 2013 to 22.3% in 2023 while the rate of prophylactic anti-emetic remained stable at around 82%. Conclusions: This real-world analysis suggests the use of preemptive treatment for skin toxicity in patients with metastatic colorectal cancer who are treated with an anti-EGFR in US is suboptimal. Disparities in cancer care are also evidenced by lower use of tetracyclines in elderly and African Americans. Randomized controlled trials support the use of prophylactic tetracycline in these patients; thus, further research into the reason for this practice gap is necessary. Educational efforts should be undertaken to improve tetracycline prescribing rates in this population.

Efficacy and Safety of Admilparant, an LPA1 Antagonist, in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial.

Rationale: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. Objectives: Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF. Methods: This phase 2, randomized, double-blind, placebo-controlled trial included parallel cohorts of patients with IPF (n = 278 randomized, n = 276 treated) or PPF (n = 125 randomized, n = 123 treated) who received 30 mg of admilparant, 60 mg of admilparant, or placebo (1:1:1) twice daily for 26 weeks. Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted. Measurements and Main Results: Rates of change in percentage of predicted FVC over 26 weeks for IPF were -2.7% (placebo), -2.8% (30 mg), and -1.2% (60 mg) and for PPF were -4.3% (placebo), -2.9% (30 mg), and -1.1% (60 mg). Treatment differences between 60-mg admilparant and placebo were 1.4% (95% confidence interval, -0.1 to 3.0) for IPF and 3.2% (95% confidence interval, 0.7 to 5.7) for PPF. Treatment effect was observed with or without background antifibrotics in both cohorts. Diarrhea occurred at similar frequencies in admilparant arms versus placebo. Transient Day 1 postdose blood pressure reductions were observed in all arms in both cohorts but were greater with admilparant. Treatment discontinuations because of adverse events were similar across IPF arms and lower with admilparant (2.5% [30 mg]; 0% [60 mg]) versus placebo (17.1%) for PPF. Conclusions: In this first phase 2 study to evaluate antifibrotic treatment in parallel IPF and PPF cohorts, 60-mg admilparant slowed lung function decline and was safe and well tolerated, supporting further evaluation in phase 3 trials. Clinical trial registered with clinicaltrials.gov identifier (NCT04308681).

The invisible threat: A 30-year review of air pollution's impact on diarrhoea from the global burden of disease study 2021.

Diarrhoea remains a major contributor to global morbidity and mortality among children younger than 5 years. This study aims to provide an updated assessment of diarrhoea deaths and disability-adjusted life years (DALYs) attributable to air pollution from 1990 to 2021. The deaths and DALYs data for diarrhoea attributable to air pollution were derived from the 2021 Global Burden of Diseases Study (GBD). Age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were used to assess trends in deaths related to diarrhoea. In addition, Auto-Regressive Integrated Moving Average (ARIMA) and Ensemble Smoothing (ES) models were used to predict the epidemic trends of diarrhoea from 2022 to 2046, and frontier analysis was conducted to explore the potential reduction in the burden of diarrhoea in different regions. Globally, from 1990 to 2021, there were 45,851 deaths from diarrhoea attributable to air pollution (95 % uncertainty interval [UI], 32,228-56,815) in 1990, and 6559 deaths (95 % UI, 4931 to 9245) in 2021. In total, diarrhoea attributable to air pollution was responsible for 4134,309 DALYs (95 % UI, 1073,440 to 1277,490) in 1990, and 593,960 DALYs (95 % UI, 446,774 to 835,347) in 2021. The decreasing trend of diarrhoea burden is uneven in different countries and regions, with higher diarrhoea deaths and DALYs in low and low-middle SDI regions, while relatively lower in high SDI regions. Predictive analysis suggests that by 2046, deaths and DALYs of air pollution-related diarrhoea, as well as their corresponding ASR, will continue to decrease. Although the global burden of diarrhoea caused by air pollution has decreased in the past 30 years, it remains an important public health issue in low and low-middle SDI regions. The research findings emphasize the importance of public health policies and planning in reducing deaths related to diarrhoea and the disease burden, and point out the need for more targeted prevention strategies in order to reduce the disease burden.

Nationwide analysis of Medicare expenditure and utilization of EGFR inhibitors from 2018-2022.

112 Background: EGFR inhibitors are used extensively for treatment of metastatic colorectal cancer ranging from first line drugs in combination with chemotherapy to monotherapy for refractory disease. As we increasingly move towards targeted treatments for cancer, financial implications of these drugs must be taken into consideration. In this study we aim to analyze changes in Medicare spending for Cetuximab and Panitumumab to better understand the financial impact of these therapies. Methods: We obtained data from the publicly available Medicare Part D database from Centers for Medicare and Medicaid Services. Data on total spending, total claims, total beneficiaries, average spending per claim, and average spending per beneficiary was extracted from the database. We adjusted the data for 2018 for 2022 using a standard annual inflation rate. Percentage change was calculated using the adjusted data. Results: For Cetuximab, we saw a sharp increase in total spending by 38.77%, from $4,912,903.87 in 2018 to $6,811,781.05 in 2022. The number of claims rose by 31.96%, while the total number of beneficiaries saw a modest increase of 2.44%. Average spending per claim increased by 16.04%, and average spending per beneficiary grew by 49.44%. Panitumumab showed a similar rise in total spending by 43.23%, from $1,594,347.66 in 2018 to $2,283,142.83 in 2022. Claims increased by 25.42%, and beneficiaries grew by 47.83%. Average spending per claim increased by 25.97%, and average spending per beneficiary saw a substantial rise of 65.75%. Conclusions: Our results indicate a significant increase in the financial burden related to EGFR inhibitors. As we move away from chemotherapy and shift our focus to targeted therapies, it is imperative to explore generic alternatives and direct policy changes to ensure equitable access across various racial and socio-economic groups. These findings highlight the need for further research into healthcare policy reforms to ease the burden on our health system. Drug Year Total Spending ($) Total Claims Total Beneficiaries Avg Spending/Claim ($) Avg Spending/Beneficiary ($) Cetuximab 2018 4,912,903.87 551 123 8,072.80 36,163.51 2022 6,811,781.05 727 126 9,369.71 54,061.75 % Change 0.3877 0.3196 0.0244 0.1604 0.4944 Panitumumab 2018 1,594,347.66 5,955 184 242.72 30,714.91 2022 2,283,142.83 7,470 272 305.81 50,736.51 % Change 0.4323 0.2542 0.4783 0.2597 0.6575

The Burden of Hepatitis B and C in Asia, 1990-2019: An Update Analysis From the Global Burden of Disease Study 2019.

This research was aimed to uncover the hepatitis B virus (HBV) and hepatitis C virus (HCV) related diseases burden in Asia over the past 3 decades, estimating from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Age-standardised rates, case numbers of prevalence, disability-adjusted life-years (DALYs), incidence and deaths with 95% uncertainty intervals (UI) for HBV/HCV-related diseases from 1990 to 2019 were derived from GBD 2019 database, with the estimated annual percentage changes (EAPCs) calculated. Our analysis also encompassed the association between the Sociodemographic Index (SDI) and the burden of HBV/HCV-related diseases, future disease burden predictions in six selected countries and various risk factors. A general downward trend in the age-standardised rates of death, disability-adjusted life years (DALYs), prevalence and incidence for both HBV and HCV-related diseases was observed in Asia during the past 30 years. Despite overall declining trends, some analysed diseases experienced an increase. Compared with females, the disease burden was greater in the male population and peaked in the age of 50-54 for both sexes. It is significant for the HBV-related and HCV-related diseases burden in Afghanistan, Cambodia, Mongolia and Pakistan. Drug use and smoking were prominent contributors to HCV and HBV-related diseases. There was a negative relationship between the burden of HCV and HBV-related diseases and SDI. Although decreases were observed in Asia, the HBV- and HCV-associated diseases burden remained high, highlighting that imperative measures for prevention and treatment should be taken by governments in Asia.

Incidence, mortality, and global burden of retinoblastoma in 204 countries worldwide from 1990 to 2021: Data and systematic analysis from the Global Burden of Disease Study 2021.

Retinoblastoma (Rb), the primary intraocular malignancy in children, poses significant risks, yet its overall burden remains inadequately assessed. This study aims to analyze global Rb trends using Global Burden of Disease, Injuries, and Risk Factors study (GBD) 2021 data. GBD 2021 data was analyzed to assess Rb incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Average annual percentage changes (AAPCs) were calculated across genders, age groups (0-9 years), and geographic regions categorized by socio-demographic index (SDI) quintiles. From 1990 to 2021, the global Rb age-standardized incidence rate (ASIR) increased from 0.08 (per 100,000, range: 0.05 to 0.10) to 0.09 (per 100,000, range: 0.06 to 0.13). ASIR was not significantly correlated with SDI (R = -0.095, P = 0.18), while age-standardized DALYs rate (R = -0.693, P < 0.001) and age-standardized mortality rate (ASMR) (R = -0.71, P < 0.001) were significantly and negatively correlated with SDI. Increases in ASIR were concentrated in Asia, Europe, and northern and southern Africa. The highest standardized DALYs and ASMR were noted in certain countries in Asia, Europe, and South Africa. Among age groups, the highest disease burdens were observed in the "0-6 days" and "2-4 years" groups. There were no significant gender differences in Rb burden globally. Despite global progress, regions with lower SDI face elevated Rb burden and mortality. Females exhibit higher burdens during infancy, necessitating further investigation. Effective Rb management in resource-limited areas requires international collaboration focused on health education, early diagnosis, and prenatal screening for high-risk families.

Global burden and cross-country inequalities of nutritional deficiencies in adults aged 65 years and older, 1990–2021: population-based study using the GBD 2021

Background/objectivesNutritional deficiencies remain significant public health issues in older populations globally. This study evaluates the burden, trends, and cross-country inequalities of four common nutritional deficiencies (protein-energy malnutrition, iodine deficiency, vitamin A deficiency, and dietary iron deficiency) in older adults from 1990 to 2021.MethodsAge-standardised prevalence, disability-adjusted life years (DALYs), and average annual percentage changes (AAPCs) of these deficiencies in people aged ≥ 65 years at global, regional, and national levels were estimated from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. Cross-country inequalities in disease burden were quantified using the slope index and concentration index, standard health equity methods recommended by the World Health Organization.ResultsGlobally, age-standardised prevalence rates of protein-energy malnutrition increased from 1407.16 per 100 000 population in 1990 to 2015.58 in 2021, with an AAPC of 1.18 (1.08–1.28), showing significant changes in 2015 and 2019, which were turning points in the joinpoint regression. Age-standardised prevalence rates of iodine, vitamin A, and dietary iron deficiencies decreased, with AAPCs of -0.49 (-0.53 to -0.44), -3.24 (-3.27 to -3.20), and − 0.14 (-0.17 to -0.12), respectively. Except for an increase in the DALY rate of vitamin A deficiency (AAPC 0.40), the DALY rates of the other three deficiencies decreased. Inequality in the burden of protein-energy malnutrition and iodine deficiency between high- and low-income countries narrowed, while inequality for vitamin A and dietary iron deficiencies remained stable. Age-standardised DALY rates for all deficiencies decreased as sociodemographic index increased.ConclusionsThe global status of nutritional deficiency among older adults has improved since 1990, but the increasing prevalence of protein-energy malnutrition requires attention. Additionally, cross-country health inequalities persist, necessitating more efficient public health measures.

Prevalence, incidence and trends of keratinocyte carcinoma in Denmark 2007-2021: A population-based register study.

The incidence of keratinocyte carcinoma (KC), i.e., basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is increasing worldwide, placing a significant burden on healthcare resources. This is especially the case for tumors requiring surgical intervention. It remains unclear whether this increase is a result of the population aging or a genuine increase in risk of skin cancer. Understanding age-adjusted incidence trends of KC is crucial for improving future management of the disease. We studied these trends in a large nationwide cohort, focusing on large, invasive, and surgically challenging tumors. Information on all incident cases of BCC and SCC in Denmark was extracted from population-based databases in the calendar years 2007-2021. Age-adjusted incidence rates were calculated, standardized to the 2013 European Standard Population. Average annual percentage changes were estimated using Joinpoint regression models. Incidence trends for larger, more invasive tumors (tumor (T) category of ≥T2), and of those in the head and neck area, were elucidated with descriptive statistics. We found 183,338 patients with a first-time incidence of BCC and 42,233 patients with a first-time incidence of SCC in the period 2007-2021. The incidence rate, adjusted for age, increased from 252 to 338 per 100,000 for BCC and from 49 to 104 per 100,000 for SCC. For SCC, the increase was particularly pronounced in the last two years of the study period. Tumors ≥T2, and those in the head and neck area, increased markedly. KC is the most common type of cancer worldwide, and the age-adjusted incidence rates of BCC and SCC increased significantly from 2007 to 2021, as did tumors with a higher T category and those located in anatomically sensitive areas. Since the primary treatment for many of these tumors is surgical, this raises concern about the strain on future healthcare resources.

Cervical cancer incidence and trends among women aged 15-29 years by county-level economic status and rurality - United States, 2007-2020.

Variations in cervical cancer incidence rates and trends have been reported by sociodemographic characteristics. However, research on economic characteristics is limited especially among younger women in the United States. We analyzed United States Cancer Statistics data to examine age-standardized cervical cancer incidence rates among women aged 15-29 years during 2007-2020. We used an index-based county-level economic classification to rank counties in the top 25 %, middle 25 %-75 %, and bottom 25 %. We assessed differences in incidence using rate ratios and trends using annual percent changes (APCs) from joinpoint regression. Due to impact from the COVID-19 pandemic, trend analysis excluded 2020 data. Analyses were conducted during August-October 2023. During 2007-2020, incidence rates were lower in the top 25 % counties economically than the bottom 25 % or middle 25 %-75 % (1.6 vs 2.1 vs 1.9 per 100,000, respectively). Rates were higher in nonmetropolitan than metropolitan counties across economic groups. Overall, rates declined in all county-level economic strata, especially in the bottom 25 % during 2015-2019 (APC -10.6 %). Rates appeared to decrease in metropolitan counties and women of all races across economic categories. decreases were most evident in the top 25 % of non-Hispanic White women during 2016-2019 and nonmetropolitan counties during 2017-2019. In women aged 15-29 years, declining rates of cervical cancer during 2007-2019 across county-level economic strata may partly reflect effects of human papillomavirus vaccination and cervical cancer screening. Further observed differences by race and rurality may help inform efforts to increase implementation of preventive measures in populations with the highest burden.

Abstract TP142: Trends in Stroke-Related Mortality Among Coronary Atherosclerotic Disease Patients Aged 45 and Older in the United States and Texas: An Analysis Using the CDC WONDER Database

Introduction: Coronary atherosclerotic disease (CAD) carries the highest risk of recurrent stroke, up to 15% annually, and individuals with coronary heart disease are twice as likely to have a stroke. This study aims to analyze annual mortality trends and sociodemographic factors related to stroke in CAD patients in the U.S. and Texas from 1999 to 2020, to inform public health policies. Methods: Using the CDC's WONDER database from 1999 to 2020, focusing on stroke and CAD-related mortality(ICD-10 code I64.0 “Stroke”&amp;Code I25.1 “Atherosclerotic heart disease ”) in adults aged ≥45 years, annual percent changes(APCs) in age-adjusted mortality rates (AAMRs) with 95% confidence intervals across various demographic (sex, race/ethnicity, age) subgroups were calculated. Results: The AAMR for stroke-related mortality in CAD cases reduced in the US from an adjusted rate(AR) 174.5 in 1999 to 105.2 in 2009(APC: 5.48%; 95% CI: -6.09% to -5.24%) after which it reduced further to 69.4 in 2018(APC: -7.87%; 95% CI: -8.77% to -6.53%) then it increased to 75.9 in 2020(APC: 4.38%; 95% CI: 2.63% to 5.88%). In Texas, AAMR for stroke-associated CAD-related mortality overall decreased from AR 189.7 in 1999 to 73.5 in 2020(APC: -4.96%; 95% CI: -5.27% to -4.66%). Males had higher consistently higher AAMRs than females (83 vs. 69.5). The AAMR in the US men decreased from 183.7 in 1999 to 72.9 in 2018(APC: -7.23%; 95% CI: -8.22% to -5.92%), then it increased to 83 in 2020(APC: 6.40%; 95% CI: 4.31% to 8.19%). The AAMR in the US women decreased from 166.3 in 1999 to 65.7 in 2018(APC: -7.89%; 95% CI: -8.79% to -6.63%) after which it increased to 69.5 in 2020(APC: 2.38%; 95% CI: 0.49% to 4.06 %). The non-Hispanic (NH) Black or African American (AA) has the greatest AAMR (122), followed by the NH American Indian or Alaska Native with an AAMR (76.8) and the NH White population with an AAMR (72.9). The low-risk populations were the Hispanic or Latino (58.8) and the NH Asian or Pacific Islander (54.2). AAMR also varied by region (overall AAMR: Midwest: 82.1; South:82; Northeast:67.1; West:66.4)&amp;non-metropolitan areas had higher AAMR (non-core areas:98.5; micropolitan areas:94) than metropolitan areas (large fringe areas:69.3; large central metropolitan areas:66.7). Conclusions: The stroke-related mortality in CAD cases has overall risen in the US compared to Texas over the past two decades, specifically men and (NH) Black or AA, (NH) American Indian or Alaska Native and (NH) White are at high risk.

Regional variation in trajectories of colon cancer mortality, 2012-2021.

41 Background: Colorectal cancer (CRC) is the fourth most common cancer by incidence in the United States in 2024, and the second most common cause of cancer mortality in Texas. Rates of advanced CRC at diagnosis and cancer related mortality are higher in rural areas. Here we explore the variation in mortality trends across the eleven public health regions (PHR) of Texas from 2012 to 2021. Methods: We conducted a population-based cohort study of colon cancer mortality in Texas over the period 2012 through 2021. We queried the National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) for county level colon cancer deaths in Texas over the most recent available decade. Counties were aggregated into the eleven public health regions defined by the Texas Department of State Health Services. We calculated age-adjusted mortality rates (AAMRs) per 100,000 population using the direct standardization method based on the age group weights from the 2000 standard US population. Confidence intervals for AAMR were derived by estimating the standard error as the AAMR divided by square root of number of mortalities. The annual percent changes (APC) in AAMR were tested using negative binomial regression. Subgroup analyses included age group, sex, and race/ethnicity. Results: A total of 33,591 colon cancer mortalities were included in the study. Total colon cancer mortalities rose from 2,973 in 2012 to 3,800 in 2021. The statewide AAMR was initially 12.4 (95% CI 12.0 to 12.9), and did not change over the study period (APC -0.1% [95% CI -0.5% to 0.2%]; p = 0.5155) ending at (AAMR 12.5 [95% CI 12.1 to 12.9]). Divergent trajectories for AAMR across public health regions were observed. The largest decline in AAMR (APC -3.9% [95% CI -6.3 to -1.6]; p = 0.0013) occurred in region 10, where the AAMR fell from 14.2% [95% CI 8.6 to 19.7]) to AAMR 11.0 [95% CI 6.8 to 15.1]. Region 6 also saw a significant decrease (APC -1.1% [95% CI -1.8% to -0.4%]; p = 0.0029) falling from AAMR 12.2 [95% CI 11.3 to 13.2] to AAMR 11.2 [95% CI 10.4 to 11.9]. The largest significant increasing trend (APC +2.3% [95% CI 0.6% to 4.1%]; p = 0.0089) for AAMR was observed for region 9 rising from AAMR 12.4 (95% CI 9.6 to 15.3) to AAMR 15.4 (95% CI 12.3 to 18.4). Conclusions: Our analysis showed a significant and increasing trend in CRC related mortality in PHR 9. This region, colloquially termed West Texas, consists of 30 counties of which over 86% are designated as rural. Rural areas struggle with higher poverty, lower degree of higher education attainment, less access to healthcare and physicians, and a higher frequency of uninsured status. West Texas in particular also has a higher rate of smoking and obesity. However, PHR 10, which shares many similarities with PHR 9 such as rurality (83.3%) and similar socioeconomic and geographic challenges, witnessed the greatest decline in AAMR of the eleven PHR's in the same time frame, suggesting the presence of other factors which may be contributing to this increase.

Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors onLipoprotein(a): A Meta-Analysis and Meta-Regression of Randomized Controlled Trials.

Lipoprotein(a) [Lp(a)] has been independently associated with increased cardiovascular risk. The authors examined the effect of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) on plasma Lp(a) levels across multiple trials. Studies were retrieved comparing the effect of PCSK9i vs placebo on Lp(a) levels. The primary outcome was percent change in Lp(a) levels. Factors associated with the treatment effect were determined by meta-regression analysis. Subgroup analyses were done to explore potential treatment effect differences. PCSK9i reduced Lp(a) levels on average of-27% (95%CI:-29.8% to-24.1%, P<0.001). Factors associated with the treatment effect included mean percent change in low-density lipoprotein cholesterol (P=0.003, beta coefficient 0.34, 95%CI: 0.11-0.57, tau2=94.8, R2=11.82) and apolipoprotein B (P<0.002, beta coefficient 0.4, 95%CI: 0.14-0.64, tau2=93.68, R2=11.86). Subgroup analyses revealed consistent treatment effect amongst comparators vs placebo:-27.69% (95%CI:-30.85% to-24.54%, P<0.001), vs ezetimibe:-24.0% (95%CI:-29.95% to-18.01%, P<0.001), type of PCSK9i, evolocumab:-29.35% (95%CI:-33.56% to-25.14%, P<0.001) vs alirocumab:-24.50% (95%CI:-27.96% to-21.04%, P<0.001), and presence of familial hypercholesterolemia:-25.63% (95%CI:-31.96% to-19.30%, P<0.001 vs no familial hypercholesterolemia:-27.22%; 95%CI:-30.34% to-24.09%, P<0.001). Varying treatment effects were noted in the duration of treatment (12weeks or shorter:-32.43% [95%CI:-36.63% to-28.23% vs >12weeks:-22.31%] [95%CI:-25.13% to-19.49%, P<0.001]), P interaction< 0.01. PCSK9is reduce Lp(a) levels by an average of 27%. Mean percent change in low-density lipoprotein cholesterol and apolipoprotein B were associated with treatment effect.

Global burden, risk factors, and projections of early-onset dementia: Insights from the Global Burden of Disease Study 2021.

Despite increasing global awareness of dementia, reliable estimates of the disease burden associated with Early-Onset Dementia (EOD) remain insufficiently quantified. This study aims to estimate the disease burden of EOD, analyze the burden attributable to risk factors from 1990 to 2021, and project these trends to 2050 at global, regional, and national levels, providing essential data to inform public health policy. By utilising data from the GBD 2021 database, this study analysed metrics such as age-standardized prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (AS-DALYs) for EOD. Joinpoint Regression analysis was used to calculated average annual percent changes (AAPCs) of ASPR, ASMR, and AS-DALYs. Then, the disease burden attributable to high fasting plasma glucose (FPG), high body-mass index (BMI), and tobacco were also reported. Finally, the Bayesian age-period-cohort (BAPC) model was employed to project global ASPR, ASMR and AS-DALYs, as well as ASMR and AS-DALYs attributed to the three risk factors from 2022 to 2050. In 2021, the global case numbers of prevalence, mortality and DALYs for EOD were 7.75 (95 %UI: 5.82, 10.08) million, 73,386 (14,059, 232,169), and 3.77 (1.69, 8.88) million. Despite large increases in case numbers, AAPCs of ASR (0.08 % [0.02, 0.14], 0.07 % [0.05, 0.1], and 0.08 % [0.05, 0.1]) kept stable. Females exhibited higher case numbers and ASR across all disease burden indicators than males. Region- and country-level geographical heterogeneities were evident. Furthermore, global ASMR and AS-DALYs associated with high BMI and high FPG showed a steady increase, while the growth in ASMR and AS-DALYs attributable to tobacco has declined. To 2050, global case numbers of prevalence, mortality and DALYs for EOD will continue to rise, but ASRs won't change considerably. Females are anticipated to remain at a higher risk. The disease burden associated with high BMI and high FPG are expected to persist in their upward trends, whereas that related to tobacco are projected to decline. The increasing burden of EOD underscores the critical need for tailored public health strategies and policies, a unique challenge underrecognized before.

Mortality trends and racial disparities in hepatocellular carcinoma associated with metabolic syndrome in the United States and Texas: A 21-year analysis (1999-2020) using CDC WONDER database.

525 Background: The prevalence of hepatocellular carcinoma(HCC) and metabolic syndrome (MetS) is increasing globally. This study aims to examine annual trends of mortality in MetS-associated HCC in the United States and its state of Texas, from 1999 to 2020, to evaluate public health initiatives and identify socioeconomic factors. Methods: Mortality trends for adults aged ≥25 years with MetS-associated HCC were analyzed using CDC WONDER database, identifying deaths through ICD-10 codes C22.9 “Liver Malignant neoplasms” and E88.9 “Metabolic Syndrome”. Crude and age-adjusted mortality rates (AAMRs) per 100,000 people were extracted. Annual percent changes (APCs) in AAMRs, with 95% confidence intervals, were determined across various demographic (sex, race/ethnicity, age) and geographic (state, urban-rural, regional) subgroups. Results: Between 1999 and 2020, 271,046 documented deaths were attributed to HCC due to metabolic syndrome. The AAMR for MetS-related HCC mortality increased in the US from an adjusted rate (AR) (3.7) in 1999 to (4.5) in 2009 (APC:2.10%; 95% CI: -0.13% to 3.10%), after which it increased to (7.6) in 2018 (APC:5.83%; 95% CI:4.25% to 6.99%) and increased to 9.9 in 2020 (APC:13.19%; 95% CI:8.78% to 15.7%). In Texas, AAMR for MetS-related HCC mortality increased from AR (4.9) in 1999 to (8.9) in 2015 (APC:3.95%; 95% CI:3.11% to 4.69%) after which it increased to (15.3) in 2020 (APC:10.64%; 95% CI:8.18% to 17.33%). Men had consistently higher AAMRs than women (12.4 vs. 8). The AAMR in U.S. men increased from (5.1) in 1999 to (12.4) in 2020. The AAMR in U.S. women increased from (2.7) in 1999 to (8) in 2020. The non-Hispanic (NH) American Indian or Alaska Native population has the greatest AAMR (13.4), followed by the NH Black or African American(AA) (12.7) and the Hispanic or Latino population with AAMR (10.9). The low-risk population was NH White with AAMR (9.6) and NH Asian or Pacific Islander (6.6). The AAMR also varied by region (South:11.5; Midwest:9.9; West:9.4; Northeast:7.4) and non-metropolitan areas had higher AAMR (small metro:12.1; non-core areas:11; micropolitan areas:11.7) than metropolitan areas (large central metropolitan: 8.8; large fringe areas: 8.7). The states in the upper 90th percentile of MetS-related HCC AAMRs were Texas, Louisiana, Arkansas, Michigan, Nevada exhibited an approximately two-fold increase in AAMRs, compared to states falling in the lower 10th percentile Nebraska, Wisconsin, Washington, Maine. Conclusions: Mortality rates from hepatocellular carcinoma associated with metabolic syndrome have risen in the United States and Texas over the past two decades. However, significant demographic and geographic disparities in MetS-related HCC mortality continue, emphasizing the need for further investigation and the development of targeted treatment strategies.

Trajectory of peripheral inflammation during index ECT in association with clinical outcomes in treatment-resistant depression.

Electroconvulsive therapy (ECT) is a highly efficacious intervention for severe and intractable depression. Evidence suggests ECT provokes an initial acute inflammatory response that subsequently decreases with repeated administration. However, relationships between inflammatory changes and clinical effects are unclear. Improved understanding of these processes may provide critical insight into effective intervention for treatment-resistant depression (TRD). Plasma inflammatory markers were assessed at pre-treatment (T1), after the second ECT session (T2), and after ECT index series completion (post-treatment/T3) in TRD (n=40). Changes were examined over time and in association with post-treatment Responder/Non-responder status (≥50% reduction in global depression severity) and percent change in affective, cognitive and neurovegetative depressive symptom domains. C-reactive protein (CRP) and interleukin-6 (IL-6) increased from pre-treatment to T2, and decreased from T2 to post-treatment. Neither early (%T2-T1) nor total (%T1-T3) change in inflammation predicted clinical outcomes, however, the interaction between early/acute inflammatory response and post-treatment inflammation (relative to baseline) was associated with clinical outcomes. Larger initial increases in IL-6 predicted greater reductions in both affective and cognitive symptoms in subjects with higher post-treatment IL-6; those with lower post-treatment IL-6 trended toward the opposite. The same was found between changes in CRP and neurovegetative symptoms. Though preliminary, these results demonstrate how processes involved in the acute inflammatory response to ECT may differentially influence clinical outcomes depending on overall trajectory of inflammation following ECT. Findings also highlight the importance of examining symptom-specific changes in depression when studying treatment mechanisms, rather than relying solely on global measures of severity.

Trends in costs of routinely recommended vaccines in the United States, 2001-2023.

Economic models assessing vaccinations commonly assume that inflation-adjusted vaccine costs are constant over time. This study assessed this assumption using historical vaccine cost data. Private sector and CDC contracted vaccine cost data (2001-2023) were collected from the CDC Vaccine Price List and converted to US$2023 to adjust for inflation. Trends in inflation-adjusted costs were described, and the annual percent changes in costs were calculated for each vaccine. Changes in cost varied by vaccine. The average inflation-adjusted private sector costs increased by 0.9% (IQR: -0.4%-2.6%) and 1.4% (IQR: -0.4%-3.2%) annually among pediatric and adult vaccines, respectively, while CDC contracted costs increased by 0.9% (IQR: 0.2%-1.2%) and 1.0% (IQR: -0.8%-2.1%) annually among pediatric and adult vaccines, respectively. Inflation-adjusted vaccine costs increased on average since 2001, highlighting limitations of constant cost assumptions. These findings can inform cost-effectiveness analyses of multi-year vaccination programs and policies.

Histopathology-based near-realistic arterial wall reconstruction of a patient-specific cerebral aneurysm for fluid-structure interaction studies.

Cerebral aneurysms occur as balloon-like outpouchings in an artery, which commonly develop at the weak curved regions and bifurcations. When aneurysms are detected, understanding the risk of rupture is of immense clinical value for better patient management. Towards this, Fluid-Structure Interaction (FSI) studies can improve our understanding of the mechanics behind aneurysm initiation, progression, and rupture. Performing retrospective hemodynamic analysis using an accurate computational model that is closer to the actual biological milieu could yield clinically useful rupture risk predictions. Currently, the geometric model for the FSI studies rely on imaging the flow-domain using Computed Tomographic Angiography (CTA) or Digital Subtraction angiography (DSA), which limits accurate discerning of the vessel wall thickness. Histopathological information has always been ignored in accurately reconstructing the geometric model for the aneurysm. The present study combines both the shape information of the 3D lumen model (as it existed in vivo), which is accurately rendered through the CTA, in conjunction with the wall thickness information extracted from histo-pathological 2D images of the aneurysm. Furthermore, fluid-structure interaction (FSI) simulations are performed to understand the influence of patient-specific wall contribution towards rupture. A 3D geometric model of the blood-flow domain of an anterior communicating artery (ACoA) aneurysm is extracted from the CTA of a patient that was surgically clipped. After safely clipping the aneurysm, the fundus of the aneurysm beyond the clip was cut and extracted. This was carefully preserved and sliced to obtain the wall thickness variation of the hoop at various axial sections. This study proposes a novel methodology of combining multi-modal image data to geometrically render the 3D model of the Cerebral aneurysm. The wall thickness extracted from the histological 2D cross-sectional images of the aneurysm is encapsulated around the 3D lumen model obtained from CT Angiographic data. To this end, a wall thickness transfer algorithm is developed to accurately reconstruct the patient-specific aneurysm wall thickness variation for the FSI simulations. The wall thickness transfer algorithm accurately combines both the blood flow domain from the CT angiography and the histopathological images involving the wall thickness heterogeneity for the aneurysm. The patient-specific wall thickness variation, as it existed in vivo, has a mean wall thickness of 0.553 mm with a standard deviation of 0.256 mm. Detailed FSI simulations were performed to study the role of the patient-specific wall thickness (PWT) model vis-a-vis the uniform wall thickness (UWT) model. It was observed that the maximum wall stress for the UWT model was 13.6 kPa, while it was substantially higher for the PWT model (48.4 kPa). The maximum wall displacement for the UWT model was 58.5μm, while it was 162μm for the PWT model. Similarly, the mean wall stress for the UWT model was 2.13 kPa, while for the PWT model, it was 8.43 kPa. The mean wall displacement for the PWT model was substantially higher than the UWT model (52.58μm against 16.47μm). The rendered patient-specific aneurysm wall model with its thickness variation, as it existed in vivo was obtained. Comparing fluid-structure interaction (FSI) simulation results, between the patient-specific wall-lumen combined model against the uniform wall thickness model have clearly shown that there were significant differences (p< 0.05) in the distribution of the hemodynamic parameters. The percentage difference in mean wall displacement and associated wall stress was 69% and 75%, respectively. Corresponding numbers for maximum wall displacement and maximum wall stress are 64% and 72%, respectively. Patient-specific fluid-structure interaction simulations show that, the present approach is highly valuable, as it improves our understanding towards rupture potential analysis for the cerebral aneurysms.

Associations between Per- and Polyfluoroalkyl Substances (PFAS) and Female Sexual Function in a Preconception Cohort

Female sexual function is important for sexual well-being, general health, fertility, and relationship satisfaction. Distressing impairments in sexual function, clinically recognized as female sexual dysfunction (FSD), can manifest as issues with interest/desire, arousal, orgasm, and pain during vaginal penetration. Some evidence suggests that exposure to endocrine-disrupting chemicals may adversely affect female sexual function, but associations for per- and polyfluoroalkyl substances (PFAS) have not been previously evaluated. We investigated associations between serum PFAS concentrations and female sexual function among U.S. pregnancy planners. We used cross-sectional data from participants from Pregnancy Study Online (PRESTO), a prospective preconception cohort study. Participants reported sexual function at baseline on two validated measures: a modified version of the Female Sexual Function Index-6 (FSFI-6) and Female Sexual Distress Scale (FSDS). We quantified PFAS serum concentrations in samples collected in the preconception period (i.e., at baseline) using solid phase extraction-high performance liquid chromatography-isotope-dilution-mass spectrometry. Participants reported sociodemographic information on structured baseline questionnaires. We included 78 participants with complete PFAS and sexual function data and fit multivariable linear regression models to estimate mean differences in FSFI-6 scores (β) or percent differences (%) in FSDS scores per interquartile range (IQR) increase in PFAS concentrations, adjusting for age, annual household income, years of education, parity, and body mass index. We further investigated effect measure modification by parity (parous vs. nulliparous) in stratified models. An IQR increase in perfluorohexanesulfonic acid was associated with a 1.0-point decrease (95% CI=-1.8, -0.1) in reported FSFI-6 scores, reflecting poorer sexual function. PFAS were consistently associated with lower FSFI-6 scores among parous participants. PFAS were also associated, though imprecisely, with greater sexual distress. Some PFAS were associated with poorer sexual function among parous U.S. pregnancy planners, but future studies are needed to clarify the extent to which PFAS influences female sexual health.