High Disease Burden Research Articles

Addressing the rising colorectal cancer burden in the older adult: examining modifiable risk and protective factors for comprehensive prevention strategies

BackgroundColorectal cancer is one of the most prevalent and deadly cancer types worldwide. Emerging evidence suggests that high body mass index (BMI) is a significant risk factor for colorectal cancer, particularly among the older adult population. This comprehensive analysis aims to explore the complex epidemiological patterns of colorectal cancer, with a focus on the association between high BMI and disease burden in the older adult.MethodsThe study leveraged data from the Global Burden of Disease (GBD) 2021 study to examine the temporal trends, regional disparities, and the interplay of age, period, and cohort factors in shaping the global colorectal cancer landscape. Epidemiological techniques, including age-period-cohort modeling and joinpoint regression analysis, were employed to provide insights into the potential drivers of the evolving disease burden while controlling for relevant confounding factors.ResultsThe analysis revealed significant geographical disparities in the burden of colorectal cancer among the older adult population. Countries like Uruguay, Monaco, Croatia, Hungary, and Poland exhibited higher mortality and disability-adjusted life-year (DALY) rates, while regions like Bangladesh, Nepal, and much of Africa had relatively lower disease burden. These regional differences are likely attributable to variations in healthcare systems, access to screening and early detection programs, as well as differences in lifestyle behaviors and risk factor prevalence.ConclusionThe strong association between high BMI and colorectal cancer risk, particularly in the older adult population and among men, emphasizes the importance of comprehensive obesity management strategies as part of comprehensive cancer control efforts. Targeted interventions, such as community-based weight management programs and enhanced screening initiatives in high-risk regions, could help mitigate the disproportionate burden of colorectal cancer observed in countries like Monaco, Croatia, and Hungary. Ongoing research and multifaceted public health interventions are crucial to address the growing global burden of colorectal cancer and mitigate the disproportionate impact on vulnerable populations. Strengthening healthcare systems, improving access to quality cancer care, and promoting lifestyle modifications to reduce obesity and other modifiable risk factors should be prioritized to effectively combat this pressing public health challenge.

Multi-omic spatial effects on high-resolution AI-derived retinal thickness.

Retinal thickness is a marker of retinal health and more broadly, is seen as a promising biomarker for many systemic diseases. Retinal thickness measurements are procured from optical coherence tomography (OCT) as part of routine clinical eyecare. We processed the UK Biobank OCT images using a convolutional neural network to produce fine-scale retinal thickness measurements across > 29,000 points in the macula, the part of the retina responsible for human central vision. The macula is disproportionately affected by high disease burden retinal disorders such as age-related macular degeneration and diabetic retinopathy, which both involve metabolic dysregulation. Analysis of common genomic variants, metabolomic, blood and immune biomarkers, disease PheCodes and genetic scores across a fine-scale macular thickness grid, reveals multiple novel genetic loci including four on the X chromosome; retinal thinning associated with many systemic disorders including multiple sclerosis; and multiple associations to correlated metabolites that cluster spatially in the retina. We highlight parafoveal thickness to be particularly susceptible to systemic insults. These results demonstrate the gains in discovery power and resolution achievable with AI-leveraged analysis. Results are accessible using a bespoke web interface that gives full control to pursue findings.

Characteristics of chicken production systems in rural Burkina Faso: A focus on One Health related practices and food security.

In addition to having cultural importance, village chicken production remains an important source of cash income for most rural households in Burkina Faso. However, strict biosecurity and good management of chicken flocks are required to reduce the risk of exposure of communities to chicken waste at household level. We characterized village production systems in rural Burkina Faso in relation to importance to food security, biosecurity, husbandry and chicken health management. We surveyed 483 chicken-producing households and carried out 20 focus group discussions separately with men and women chicken producers in Boussouma commune, a typical rural setting. Crop farming was reported as the main income-generating activity carried out by chicken producers (79.5%). Seveny six per cent of households sold chicken to local markets. Chicken production and sales were aligned to social/cultural events (religious festivals, weddings, etc…) and school-fee payment period. While men spent more revenues from chicken production on agriculture and household equipment's, women spent more on food, education and medical expenses. The chicken management system is mainly extensive scavenging, with most farmers (81.4%) keeping 5 to 50 birds with little or no supplementary feeding and rudimentary housing. Most producers indicated that Newcastle disease was the main cause of chicken mortality. While men consider high disease burden, lack of finance, and poor chicken housing as the major constraints, women prioritized the lack of adequate chicken housing, lack of feeds and limited access to veterinary services. With locally adapted interventions that build one a One Health approach, village chicken keeping has the potential to secure and greatly improve smallholder livelihoods and household food security, while preserving public health in Burkina Faso.

Patient perspectives on acromegaly disease burden: insights from a community meeting

ObjectiveA profound mismatch between biological and symptom control in acromegaly creates a high disease burden despite achieving optimal biological control. There is a great need to learn more about the perspectives of patients living with acromegaly.MethodsAcromegaly Community hosted a virtual meeting in January 2021 and prepared a detailed report capturing participants’ input on acromegaly symptoms and current and future treatment approaches. The findings of this report are reviewed and summarized in this study.ResultsFatigue/muscle weakness (92%) and joint pain/arthritis (90%) are the two most common and troublesome symptoms reported by meeting participants. Acromegaly negatively impacts all aspects of daily living: social interaction (49%); exercise (42%); sports/recreational activities (39%); household activities (38%); attending school or job (38%); family relationships (33%); and walking (26%). Anxiety/depression is experienced by 75% of respondents. Eighty-three percent of patients underwent pituitary surgery, and over 71% of patients require medical therapy. Patients desire future improvements in medication efficacy, tolerability, and administration; mental health resources for themselves and their families; and other multimodal approaches to address their physical symptoms, specifically hunger, weight gain, muscle weakness, and joint pains.ConclusionAcromegaly patients experience significant physical and psychological burdens despite biochemical control, highlighting the need for comprehensive and patient-centered care. In particular, the impacts on activities of daily living (ADLs) and heavy psychosocial and socioeconomic burdens are striking. We advocate for periodic screening for impacted ADLs, multidisciplinary teams to proactively address these symptoms, and call for further research on under-evaluated aspects of the disease.

A randomized phase 2 study of an individualized neoantigen-targeting immunotherapy in patients with newly diagnosed metastatic microsatellite stable colorectal cancer (MSS-CRC).

LBA13 Background: Neoantigen-targeting immunotherapy aims to provide therapeutic benefit to patients by generating potent neoantigen-specific T cells. GRANITE is an immunotherapy regimen that uses chimpanzee adenovirus and self-amplifying mRNA vaccines encoding patient-specific neoantigens in combination with immune checkpoint inhibitors. Preliminary efficacy was noted in MSS-CRC (Palmer et al Nature Medicine 2022) and this regimen is being assessed in a randomized Phase 2 study in 1L metastatic MSS-CRC (NCT05141721). Methods: Patients (pts) with 20 neoantigens based on the EDGEÔ prediction model were randomized 1:1 to receive the GRANITE regimen in addition to 1L standard of care (SOC) (GRANITE vaccine arm), or 1L SOC alone (control arm). Results: Baseline demographics and disease characteristics were balanced between arms. As of 15 Oct 2024, GRANITE pts had an improvement in PFS relative to control pts (HR=0.73, 90% CI [0.44, 1.21]). In this study, high and low disease burden groups were identified using baseline ctDNA assessed by Gritstone’s validated, highly sensitive, tumor-informed assay. Patients with low disease burden benefited more than those with high disease burden, consistent with emerging data suggesting neoantigen-targeting immunotherapy having greater activity in minimal disease settings (e.g., adjuvant setting). Furthermore, in the low disease burden group at the most recent study visit, more patients were free of progression with very low ctDNA levels (ie, below the limit of quantification of the assay) in the GRANITE arm, 41% (7/17), versus the control arm, 21% (3/14). The greater proportion of GRANITE patients both free of progression and with very low ctDNA, suggests potential further separation of PFS cuves with additional follow up. Neoantigen-specific T cell responses were observed in 100% of patients in the GRANITE arm with evaluable PBMC samples (17/17 assessed by ex vivo and in vitro stimulation ELISpots). Molecular responses based on a reduction in ctDNA at a single timepoint was similar between arms (39% in GRANITE and 40% in control arms). Most common (≥20%) treatment-related adverse events (TRAE) included pyrexia and influenza like illness and no pts discontinued due to a TRAE. Conclusion: This randomized study shows GRANITE may benefit patients, especially those with low burden disease, in this front line setting of metastatic MSS-CRC that has not benefitted from immunotherapy. Updated analysis will be presented. Clinical trial information: NCT05141721 .

Pharmacogenomic profiling of variants affecting efficacy and toxicity of anti-infective medicines in a south Asian population from Sri Lanka

BackgroundAnti-infective medicines are crucial for treating infections, but improper dosing can cause toxicity, resistance and treatment failure. Pharmacogenomics can address genetic variations affecting drug efficacy and safety. Despite the high burden of diseases like TB and HIV in Sri Lanka and South Asia, pharmacogenomic data for these populations are limited. This study aims to fill this gap by investigating pharmacogenomic variants in a South Asian population from Sri Lankan.MethodsPharmacogenomic data on anti-infective medicines were obtained from the PharmGKB database, selecting variants with evidence levels 1 A, 1B, 2 A, and 2B. Sri Lankan genetic data were sourced from an anonymized database of 670 Sri Lankans maintained by the Centre for Genetics and Genomics, Faculty of Medicine, University of Colombo. MAFs were compared between Sri Lankan sub-populations and global data from gnomAD, with statistical significance set at p < 0.05.ResultsMAFs of NAT2 gene rs1041983 and rs1799931 variants were, 43.7% (95%CI:41.1–46.4), 7.3% (95%CI:6.0-8.8), respectively. The UGT1A1 rs4148323 variant had a MAF of 3.5% (95%CI:2.6–4.6). In the CYP2B6 gene, 109 individuals were homozygous for the rs3745274 (poor metaboliser) variant, with a MAF of 39.6% (95%CI:37.0-42.3), while the rs34097093 and rs28399499 variants had no individuals homozygous for the variant (MAF: 0.2% [95%CI:0-0.5] (poor/intermediate metaboliser), and 0.1% [95%CI:0-0.4] (poor/intermediate metaboliser), respectively). The MAFs of the CYP2C19 rs12769205 (poor/intermediate metaboliser), rs4244285 (poor/intermediate metaboliser), rs3758581 (poor/intermediate metaboliser), and rs4986893 (poor/intermediate metaboliser) variants were 41.9% (95%CI:39.3–44.6), 41.9% (95%CI:39.2–44.7), 9.7% (95%CI:8.2–11.4), and 0.5% [(95%CI:0.2–1.1), respectively. Most variants showed significant differences compared to global populations, with some exhibiting higher frequencies, particularly when compared to Europeans. CYP2C19 rs12769205 and rs4244285 exhibited higher MAFs in Sri Lankans compared to both other South Asians and Europeans. The NAT2 rs1041983, NAT2 rs1799931, CYP2C19 rs4986893, CYP2C19 rs3758581, and CYP2B6 rs3745274 variants demonstrated significantly higher MAFs than in Europeans but not significantly different from South Asians.ConclusionThis preliminary study identifies variants in NAT2, UGT1A1, CYP2B6, and CYP2C19 genes relevant to the metabolism of anti-TB drugs, antiretrovirals, and voriconazole among Sri Lankans. Several variants, including CYP2C19 rs12769205 and rs4244285, showed higher MAFs, particularly in comparison to European populations, indicating potential differences in drug response. However, the nature of the study limits the ability to explore clinical correlations with the genotypes, therefore further research focusing on clinical correlation and functional validation is required.

Leading the way: How leading Chinese institutions drive MDT excellence in hepatocellular carcinoma.

563 Background: HCC MDTs involve specialists collaborating on patient cases to create personalized treatment plans. Implementing MDTs can be challenging in countries with limited resources and high disease burdens. In China, there were 368,000 new liver cancer cases in 2022 representative of 40% of global cases. Therefore, evaluating MDT practices at leading hospitals in China may offer valuable insights that could help improve HCC MDT practices worldwide. Methods: This study selected hospitals with distinct MDT models: one for all new patients and one for complex cases. Hospitals handling over 1,000 HCC cases annually were chosen. Desk research and virtual interviews with MDT members from three leading Chinese hospitals—The First Affiliated Hospital of USTC, The First Affiliated Hospital of SYSU, and Tongji Hospital—were conducted to analyze their MDTs and determine key best practices. Results: We identified 6 key best practice in HCC MDTs at these leading Chinese hospitals. 1) Quality Control on MDT process: Leading hospitals ensure the MDT’s efficient execution and effective outcomes. E.g., USTC established a quality control team to audit the MDT process. 2) Real-World Evidence: Leading hospitals prioritize the construction of real-world databases linked to MDT-care to inform impact on outcomes. E.g., SYSU's preliminary data shows impact of MDT care on survival rates (From 2006 to 2010, 5,627 patients who underwent radical liver cancer resection with MDT care saw their five-year survival rate reach 60%, a notable improvement over historical averages) 3) Comprehensive Teams: These hospitals typically have robust teams, involving around 10 specialties. E.g., Tongji Hospital’s MDTs involve ~10 specialties for holistic care. 4) Patient Journey Coverage: MDTs manage patients from diagnosis to rehabilitation, providing a holistic approach to patient management. 5) Guideline-based treatment decisions: They follow latest guidelines coupled with access to approved therapies to make treatment decisions 6) Training: Young physicians are invited to actively participate in MDT consultations (e.g., through case preparation and presentation, etc.). Conclusions: Evaluation of MDT practices at leading China institutes highlights key best practices that could be adopted to enhance care quality for patients with HCC. The ongoing efforts and successes of these institutions provide a model for broader adoption and standardization of MDT practices across the country.

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.

Digitalization of health care in low- and middle-income countries.

The rising incidence of noncommunicable diseases, combined with the costs of mitigating climate change, sovereign debt and regional conflicts, is undermining global health security and threatening progress towards achieving the sustainable development goals of the United Nations. The negative impact of these polycrises is disproportionately borne by low- and middle-income countries, which have the highest disease burden and lowest health-care spending. Health digitalization is emerging as a promising countermeasure, accelerated by artificial intelligence (AI) software and quantum computing hardware. We provide a multisector critical analysis of the three key enablers - governance, infrastructure and security - of the responsible AI-enabled digitalization for safe, affordable, equitable and sustainable health-care systems in low- and middle-income countries. We consider leading use cases in public-private partnerships, democratized sovereign AI and embedded human security. Our analysis proposes that these use cases demonstrate how digital AI-accelerated global health may be advanced as human-centred managed strategic competition. We conducted our analysis through an inclusive range of theoretical perspectives and practical experience spanning academia, industry and practice across the world. We provide recommendations for the responsible management of the key enablers to accelerate global health for all. We anticipate that this paper will be useful for public health decision-makers, both in low- and middle-income countries leading local health digitalization, and in high-income countries supporting this transaction through their technologies, funding and knowledge exchange.

Safety and immunogenicity in humans of enterotoxigenic Escherichia coli double mutant heat-labile toxin administered intradermally

Enterotoxigenic Escherichia coli (ETEC) diarrhea is associated with a high burden of disease globally, for which no licensed vaccine is available. A Phase 1, double-blind, dose-escalation (0.1-2.0 µg) study was conducted to evaluate the safety and immunogenicity of double mutant heat-labile toxin LTR192G/L211A (dmLT) delivered intradermally (ID) to healthy adults. Subjects received up to three immunizations at three-week intervals. The vaccine was safe, although it induced mild local and some gastrointestinal adverse events, as well as frequent hyperpigmentation at the injection site. High levels of serum IgG and IgA, LT neutralizing antibodies, and IgG and IgA antibodies in lymphocyte supernatant were elicited post-vaccination, most prominently at the largest dose (2.0 μg). Rates of responses were the highest in subjects who received the largest dose (2.0 μg) and multiple immunizations. The ETEC dmLT vaccine was safe and highly immunogenic, inducing long-lasting systemic and mucosal responses when administered by the ID route. Trial registration Clinical Trials NCT02531685.

Cross-Country Inequalities in Disease Burden and Quality of Care of Stroke, 1990-2021: A Systematic Analysis of the Global Burden of Disease Study 2021.

This study aims to assess the disease burden and care quality along with cross-country inequalities for stroke at global, regional, and national levels from 1990 to 2021. Data on stroke were extracted from the Global Burden of Disease (GBD) study 2021 for the globe, five sociodemographic index (SDI) regions, 21 GBD regions, and 204 countries/territories. The disease burden was quantified using the age-standardized disability-adjusted life years rate (ASDR). Quality of care (QoC) was evaluated through the age-standardized QoC index (QCI). To assess cross-country disparities in both disease burden and age-standardized QCI, the slope index of inequality (SII) and the concentration index were utilized. From 1990 to 2021, the global ASDR of stroke decreased from 3078.95 (95% uncertainty interval [UI]: 2893.58, 3237.34) to 1886.20 (95% UI: 1738.99, 2017.90) per 100,000 population, while the age-standardized QCI improved from 50.79 to 64.61. However, the results of inequalities showed worsening inequalities in both ASDR and QCI, with lower SDI countries shouldering a disproportionate burden and higher SDI countries maintaining higher QoC. The SII and concentration index for ASDR indicated a worsening inequality among lower SDI countries, with SII increasing to -2616.44 and the concentration index increasing to -0.1119 in 2021. Meanwhile, the SII and concentration index for age-standardized QCI showed a worsening inequality among higher SDI countries, with SII of 27.48 and concentration index of 0.0922 in 2021. Despite notable global advancements, significant disparities in stroke still exist, particularly in lower SDI regions facing high disease burdens and substandard care.

Cholesterol screening by nativity status in pediatric patients receiving care in United States community-based clinics.

Accumulation of cardiovascular risks begins early in life. Some experts recommend cholesterol screening for children aged nine to 11. Latinos living in the U.S. have a high burden of cardiovascular disease and risk factors, and this is further influenced by birthplace, yet information on early screening for cardiovascular disease in this group is sparse. We used electronic health records from a national network including 771 community-based clinics across 21 states from 2012 to 2020, from 310,297 foreign-born Latino, US-born Latino, Latino with unknown birthplace, and non-Hispanic white patients aged nine to 17years. Logistic regression including demographic and clinical covariates was conducted to estimate prevalence of cholesterol testing, stratified by obesity. Latino children, regardless of nativity status, had higher adjusted prevalence of cholesterol screening compared to non-Hispanic white children for those with and without obesity. The highest prevalence of screening among those with obesity was in foreign-born Latinos (34.8%), and among those who were not obese, US-born Latinos had the highest screening prevalence (16.8%). Cholesterol screening was low overall in these community-based clinic patients but differed by ethnicity and nativity status. There is opportunity for further research on outcomes in Latino children to inform guidelines for early screening for cardiovascular health.

P-242. Disparities and inequities in the burden of pneumococcal disease in US adults

Abstract Background Understanding the impact of social determinants of health on pneumococcal disease (PD) is important. The purpose of this study was to conduct a targeted literature review (TLR) of the clinical and economic burden of PD in US adults with a focus on examining disparities and inequities by race, geography, urbanicity, income, education, and employment. Methods Original research studies reporting burden of PD in US adults published between 2012 and January 2024 were identified through a US focused TLR in Pubmed (vial Medline) and a review of surveillance data from the CDC website. The original search was supplemented with targeted searches via Google Scholar in areas for which data were not identified via Pubmed or the CDC website. Results Of 4,133 identified publications, 16 studies were identified: 10 described disparities by race, 7 by geography, 2 by urbanicity, 3 by income, 1 by education and 1 by employment. Black adults had the highest incidence and longest length of stay due to IPD and bacteremic community acquired pneumonia (CAP) and highest mortality rates from CAP compared to other racial groups across all adult age groups; Black adults living in poverty experienced a 2.1 times higher rate of PD compared to white adults. Pneumococcal disease also varied by geography and urbanicity. Lower urbanicity displayed higher mortality rates for PD. Incidence of all-cause CAP was higher in early retirees 18–64 years old and their adult dependents compared to their employed counterparts and their adult dependents. PD health care expenditures mirror the patterns observed for disease burden. Vaccination rates were lower in Black adults compared to white adults and in adults who resided in rural areas, were less educated and had a lower income. Conclusion This TLR confirms that disparities and inequities in the burden of PD among US adults exist with higher disease burden and lower pneumococcal vaccination in Black adults, those living in rural areas and with lower education and income. There is a paucity of studies examining inequities and social disparities of health in PD. Additional studies are needed to examine disparities and inequities in PD according to race, geography, urbanicity, income, education, and employment. Disclosures Salini Mohanty, DrPH, MPH, Merck &amp; Co., Inc.: Employee|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Kelly D. Johnson, PhD, Merck &amp; Co., Inc.: Employee|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Sheba Nellore, MBA, Merck: Advisor/Consultant Lindsay McNamee, BSc, Merck &amp; Co Inc.: Advisor/Consultant Hanane Khoury, PhD, Merck: Advisor/Consultant Laura De Benedetti, BSc, Merck &amp; Co, Inc: Advisor/Consultant Elmira Flem, MD, PhD, Merck: Stocks/Bonds (Private Company) Kristen A. Feemster, MD, MPH, MSHPR, FAAP, Merck &amp; Co., Inc., Rahway, NJ, USA: Grant/Research Support|Merck &amp; Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Nicole Cossrow, PhD, Merck: Stocks/Bonds (Public Company)

Evolving Epidemiology of Mpox in Africa in 2024.

For decades after the identification of mpox in humans in the Democratic Republic of Congo (DRC) in 1970, the disease was largely confined to the rural areas of Central and West Africa and thus did not garner broad attention. On August 13, 2024, mpox was declared a Public Health Emergency of Continental Security (PHECS) by the Africa Centers for Disease Control and Prevention (Africa CDC), a notice that was followed the next day by a declaration of a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. In this study we analyzed all mpox cases and deaths, based on clinical or laboratory diagnosis, that were reported to the Africa CDC from January 1, 2022, to October 30, 2024, to identify temporal variations, geographic distributions, and epidemiologic trends. From January 1, 2022, to August 18, 2024, a total of 45,652 mpox cases were clinically diagnosed and laboratory-confirmed in 12 African countries. These cases resulted in 1492 deaths (case fatality rate, 3.3%). From 2022 to 2024, weekly laboratory-confirmed mpox cases increased by a factor of 2.8 (from 176 to 489 cases), whereas all weekly reported cases (including those with a clinical diagnosis) increased by a factor of 4.3 (from 669 to 2900 cases). The DRC, which had reported approximately 88% of mpox cases in Africa in 2024, had 19,513 cases before the emergency declaration, with a case fatality rate of 3.1% - a weekly average of 591 cases as compared with 281 in 2023. In 2024, six African countries reported their first imported mpox infections, with Burundi also reporting local transmission. The high mpox disease burden in Africa, especially in the DRC - with a rising number of cases, high case fatality rate, and high degree of spread to other previously mpox-free African countries - is cause for increased international concern. Case detection, contact tracing, public health measures, and affordable vaccines are needed to implement interventions in the DRC to reduce the risk of global spread of the virus.

P-1407. The Growing Trend of Clinical Tick-Borne Diseases in South Carolina

Abstract Background The trend of human tick-borne disease (TBD) incidence has increased exponentially over the past two decades. Limited healthcare access, substandard housing, socioeconomic fragility, and absence of government-backed tick control initiatives significantly contribute to the high disease burdens nationwide. Given the wide prevalence of socioeconomic and health inequalities in the USA, the risk of TBDs often goes undetected in impoverished and minority communities. Alpha-gal syndrome (AGS) is one TBD that is often overrepresented in white, middle-income individuals, and little information on the incidence in populations of Color exists. Therefore, the current study aims to estimate the seroprevalence and exposure-associated risk factors of AGS among vulnerable populations in South Carolina. Methods First, a five-year retrospective clinical chart abstraction of AGS patients within a large healthcare system covering half of South Carolina was completed to characterize the clinical burden and natural history of AGS. Next, banked serum samples and associated surveys from a cross-sectional minority-represented COVID-19 study were analyzed for AGS seropositivity. Results Fifty patients with positive AGS IgE labs were identified via retrospective chart review. Of these, the majority were male (70%), covered by Medicare (84%), and had a history of tick bites or spent extended periods outdoors (46%). The cross-sectional AGS seroprevalence study detected 3.5% seropositivity among 753 serum samples. Risk factors associated with a positive titer included being male (58%), and regularly spending time outdoors (58%). Notably, the seroprevalence cohort consisted of primarily Black residents and individuals who live below the poverty line. Conclusion These findings highlight the growing issue of TBDs, namely AGS, among minority populations in South Carolina, urging healthcare providers to be more informed. Disclosures All Authors: No reported disclosures

P-2313. Multinational, Retrospective Study Assessing Outcomes and Healthcare Resource Utilization in Hematopoietic Stem Cell Transplant Recipients with Cytomegalovirus Infection and Refractory, Resistance, or Intolerance to Anti-Cytomegalovirus Treatments: Analysis of Impact of Viremia Clearance on Outcomes

Abstract Background Cytomegalovirus (CMV) infection is a risk factor for morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. This real-world analysis describes the impact of viremia clearance on outcomes in HSCT recipients with refractory, resistant or intolerant (RRI) CMV infection to anti-CMV agents. Methods This multicenter, retrospective chart review study included adult HSCT recipients with RRI CMV infection. Data between 2014 and 2021 were collected from 14 centers in Europe and the USA. The analysis descriptively compared demographics, patient characteristics, clinical outcomes, and hospitalizations in patients who did versus did not achieve viremia clearance during the first RRI CMV episode. Results Among 247 patients with a first RRI CMV episode, 145 (59%) achieved viremia clearance and 102 (41%) did not. In patients with vs without viremia clearance, respectively, median age was 53 vs 60 years, and 46% vs 58% were male. Of the 145 and 102 first RRI CMV episodes with vs without viremia clearance, respectively, 52% vs 75% were identified as refractory, 61% vs 31% as intolerant, and 3% vs 9% as resistant (categories not mutually exclusive); 9% vs 15% of patients developed tissue invasive disease. CMV recurrence occurred in 35% vs 37% and graft failure in 3% vs 6% of patients with vs without viremia clearance, respectively (Table). Myelosuppression and nephrotoxicity events during CMV episodes were reported in 54% vs 44% and 26% vs 27% of patients with vs without viremia clearance, respectively (Table). CMV-related hospitalizations with/without emergency department visits occurred in 35% of patients with viremia clearance vs 43% of patients without viremia clearance (Table). Notably, the overall mortality within 1 year of RRI identification in patients without viremia clearance was higher than in those with viremia clearance (68% vs 30%, respectively). Conclusion These results highlight the high disease burden in HSCT recipients with RRI CMV infection. In this difficult-to-treat population, the mortality rate was higher in patients without viremia clearance than in patients with viremia clearance. Disclosures Kimberly Davis, RPh, MS, Takeda: Employee|Takeda: Stocks/Bonds (Public Company) Ines Mendonça, MSBiostats, CTI Clinical Trial &amp; Consulting Services: Employee (paid to provide consulting services including medical writing and statistical analysis) Tien Bo, PharmD, Takeda: Employee|Takeda: Stocks/Bonds (Public Company)

The Effects of Home High-Flow Nasal Cannula Oxygen Therapy on Clinical Outcomes in Patients with Severe COPD and Frequent Exacerbations

Background: Chronic Obstructive Pulmonary Disease (COPD) is a disease with high morbidity and mortality globally. Exacerbations of COPD are major contributors to disease progression and a decline in health-related quality of life (HRQoL). High-flow nasal cannula (HFNC) oxygen therapy is an innovative therapy that provides humidified and heated blended air and oxygen through a nasal cannula. There is some preliminary evidence supporting the effectiveness of HFNC in managing COPD exacerbations, but there are limited data on its effectiveness when used at home for patients with stable, severe COPD. The aim of the present study is to test the hypothesis that home HFNC can decrease the COPD exacerbations rate and hospital admissions and improve HRQoL measures in severe COPD patients with frequent COPD exacerbations. Methods: In a prospective proof-of-concept interventional multicenter study, 40 GOLD stage III and IV COPD patients with a high disease burden (≥2 exacerbations treated with antibiotics and/or corticosteroids) and ≥1 hospital admission in the last year were included. Patients were given instructions on the usage of HFNC by a ventilation practitioner during a group session. The flow rate was 25–30 L/min and FiO2 was 21–35%. Outcome measures included the COPD exacerbations rate, hospital admissions, in-hospital days, Medical Research Council dyspnea (MRC) score, Clinical COPD Questionnaire (CCQ) score, Hospital Anxiety Depression Scale (HADS) scores and capillary pCO2. Repeated analysis of variance (ANOVA) was used to analyze the data. Significant effects identified in the ANOVA were further examined using Student’s t-tests. Results: After 1 year, 27 patients could be evaluated. The COPD exacerbations rate decreased by 1.40 (mean difference ± SD: 1.40 ± 2.09; p = 0.002), hospital admissions decreased by 0.96 admissions per year (0.96 ± 1.37; p = 0.001), and in-hospital days decreased by 7.22 days (7.22 ± 9.26; p = 0.001). Capillary pCO2 decreased by 0.02 kPa (0.02 ± 0.52; p = 0.85). The CCQ score decreased by 0.06 (0.06 ± 0.96; p = 0.76). The MRC dyspnea score decreased by 0.04 (0.04 ± 0.80; p = 0.81). The HADS anxiety score decreased by 0.63 (0.63 ± 3.12; p = 0.31). And finally, the HADS depression score decreased by 0.32 (0.32 ± 3.48; p = 0.64). There was a significant difference between the normocapnic (capillary pCO2 &lt; 6.0 kPa) group and the hypercapnic group in terms of change in the CCQ score (−0.24 ± 0.55 and 0.49 ± 1.32 decrease, respectively, p = 0.05) and the HADS depression score (−0.76 ± 1.86 and 2.20 ± 4.75 decrease, respectively, p = 0.03) after 1 year of HFNC treatment. Conclusions: One-year-long HFNC therapy significantly decreased the COPD exacerbations rate, hospital admissions, and in-hospital days in severe COPD patients with a high disease burden and frequent COPD exacerbations irrespective of them having hypercapnia and with the HRQoL measures only improving in the hypercapnic group. This may imply that severe COPD patients with a high disease burden and frequent COPD exacerbations, irrespective being hypercapnic, are candidates for treatment with home HFNC oxygen therapy.

Retrospective Cohort Study of Elderly Users of Single- or Multiple-Inhaler Triple Therapy for the Treatment of Asthma in the USA.

Escalation to single- or multiple-inhaler triple therapy (SITT; MITT) is a recommended option for patients with asthma who remain uncontrolled by medium-dose inhaled corticosteroid/long-acting β2-agonist; however, characterization of elderly users of triple therapy is limited. This real-world cohort study describes demographics and clinical characteristics of elderly patients with asthma with and without comorbid chronic obstructive pulmonary disease (COPD) who are new users of triple therapy, and asthma treatment patterns preceding triple therapy initiation. This retrospective cohort study used administrative claims data from the Optum Clinformatics Data Mart database. Eligible patients were ≥ 65years of age with asthma or with asthma and comorbid COPD who initiated either triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25μg) or MITT between September 18, 2017 and September 30, 2020. Demographics, clinical characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns were described in the 12-month period before triple therapy initiation (baseline period). In total, 15,557 patients were included. Among FF/UMEC/VI initiators with asthma (N = 635) mean age was 73.3years and 66.6% were female. During the baseline period, > 75% of patients used controller therapy, > 92% used rescue medications, 27.9% experienced ≥ 1 asthma-related exacerbation, with mean annual exacerbation rate of 0.42, and mean all-cause healthcare costs were $23,407. Patients with asthma initiating MITT and patients with asthma and comorbid COPD initiating FF/UMEC/VI or MITT had similar characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns to FF/UMEC/VI initiators with asthma. Triple therapy is often initiated following use of other asthma controller medications in real-world practice. Substantial rescue medication use and high disease and economic burden among this elderly patient population suggest that their asthma was not adequately controlled prior to triple therapy initiation. This retrospective study provides an early profile of elderly patients with asthma in the USA.

A paper-based HPV E7 oncoprotein assay for cervical precancer detection at the point of care

Cervical cancer, while preventable through screening and treatment of cervical precancer, remains a global challenge with a disproportionately high burden of disease in resource-limited settings, especially in low- and middle-income countries (LMICs). Lack of affordable, easy-to-use screening and diagnostic tests contributes to this disparity. Most commercially available tests are not appropriate for use in LMICs due to resource constraints. Specifically, HPV mRNA and oncoprotein tests that have high specificity for cervical precancer and cancer require complex sample preparation protocols and expensive instrumentation. To address these limitations, an HPV E7 oncoprotein assay for HPV16, 18, and 45 was developed that is appropriate for use at the point of care. The assay is paper-based, involves only five simple steps, and does not require instrumentation. A clinically relevant limit of detection was demonstrated with cellular samples. Additionally, clinical performance was demonstrated with a small pilot study (n = 19), in which the HPV E7 paper-based assay was found to have 95% accuracy when compared to histopathologic diagnosis of cervical intraepithelial neoplasia grade 2 or more severe (CIN2+). With further clinical validation, this assay could enable highly specific point-of-care testing for cervical precancer and cancer that is instrumentation-free, affordable, and ideal for use in resource-limited settings.

Global, regional and national burden of neuroblastoma and other peripheral nervous system tumors, 1990 to 2021 and predictions to 2035: visualizing epidemiological characteristics based on GBD 2021.

Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, accounting for >15 % of cancer-related deaths in children. We analyzed the epidemiological statistical indicators of neuroblastoma and other peripheral nervous system tumors patients from 1990 to 2021 in Global Burden of Disease (GBD) 2021 database, aiming to provide valuable insights for public health interventions and clinical practices. Based on the GBD 2021 database, this study analyzed the incidence, mortality, prevalence, and Disability-Adjusted Life-Years (DALYs) of neuroblastoma and other peripheral nervous system tumors from 1990 to 2021, stratified by sociodemographic development index (SDI) and geographic regions. Cross-country inequalities analysis was conducted to quantify the SDI-related inequality of disease burden across countries. In addition, the average annual percentage change (AAPC) and Age-Period-Cohort (APC) model were used to evaluate the trend of disease burden, while the global burden of disease to 2035 was predicted by Bayesian Age-Period-Cohort (BAPC) model. This study reported the disease burden of neuroblastoma and other peripheral nervous system tumors in GBD 2021 database for the first time. Globally, the incidence and mortality of neuroblastoma have increased year by year from 1990 to 2021, especially in regions with low SDI, such as South Asia and sub-Saharan Africa, where the burden of disease has increased significantly. Regions with high SDI, such as North America and Western Europe, have seen a reduction in disease burden due to higher levels of medical care and earlier diagnosis. The age distribution shows that children under 5 years of age are mainly affected, especially in low- and middle-income areas. In addition, the incidence is slightly higher in men than in women. The BAPC model predicts that the global incidence, mortality, and DALYs of neuroblastoma will continue to increase until 2035. Significant regional and population variation in neuroblastoma and other peripheral nervous system tumors worldwide, with a particularly high disease burden in low SDI areas with limited medical resources. This trend highlights the urgent need for global public health interventions and resource allocation, particularly in low-income countries. Future research should focus on improving early diagnosis, risk stratification and target therapy in order to reduce the global burden of disease and improve patients' prognosis. This study was supported by National Natural Science Foundation of China (No. 82293662, No 82172357 and No 81930066), Key project of Shanghai "Science and Technology Innovation Action Plan (22JC1402304) and Research fund of Shanghai Municipal Health Bureau (No. 2019cxjq03).