At-risk Populations Research Articles

Pregabalin misuse: a case report

ABSTRACT Background Pregabalin is a widely used medication primarily prescribed for the management of neuropathic pain and common psychiatric conditions due to its analgesic and anxiolytic properties. However, it has also been associated with cases of misuse, particularly among individuals with a history of substance use disorders. Case Presentation A case is presented of a 22-year-old male with a history of pregabalin misuse spanning one year, escalating his daily dosage to 2,250 mg/day. The patient experienced episodes of sudden muscle weakness, resulting in unanticipated falls and an inability to maintain grip on objects. These symptoms led him to seek medical attention. After discontinuing pregabalin, the patient did not experience withdrawal symptoms. Conclusion Despite the therapeutic benefits of pregabalin, the potential for its abuse, particularly in at-risk populations, necessitates careful monitoring and prescribing practices.

Remote organ cancer induces kidney injury, inflammation, and fibrosis and adversely alters renal function.

Approximately 30% of the patients with cancer experience kidney complications, which hinder optimal cancer management, imposing a burden on patients' quality of life and the healthcare system. The etiology of kidney complications in patients with cancer is often attributed to oncological therapies. However, the direct impact of cancer on kidney health is underestimated. Our previous study demonstrated that metastatic lung cancer adversely alters the kidney and exacerbates chemotherapy-induced nephrotoxicity, indicating lung cancer-kidney crosstalk. The current study examines whether this phenomenon is specific to the employed cancer model. Female and male mice of various strains were injected with different cell lines of remote organ cancer, and their kidney tissues were analyzed for toxicity and fibrosis. The impact of cancer on the kidney varied by cancer type. Breast cancer and specific subtypes of lung cancer, including KRAS- and epidermal growth factor receptor (EGFR)-mutant cancer, pathologically altered kidney physiology and function in a manner dependent on the metastatic potential of the cell line. This was independent of mouse strain, sex, and cancer cell line origin. Moreover, tumor DNA was not detected in the renal tissue, excluding metastases to the kidney as a causative factor for the observed pathological alterations. Lewis lung carcinoma and B16 melanoma did not cause nephrotoxicity, regardless of the tumor size. Our results confirm cancer-kidney crosstalk in specific cancer types. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.NEW & NOTEWORTHY Patients with cancer frequently experience kidney complications, often attributed to antineoplastic therapies. This emphasis on therapy-induced nephrotoxicity has led to the underestimation of the impact of cancer on the kidney. Our study demonstrates that distant organ cancer is sufficient to induce nephrotoxicity, highlighting the existence of cancer-kidney crosstalk. Our findings underscore a gap in our understanding of renal complications in patients with cancer and provide a rationale for identifying the underlying mechanisms for the development of nephroprotective agents.

Small-molecule activator of SMUG1 enhances repair of pyrimidine lesions in DNA.

A potentially promising approach to targeted cancer prevention in genetically at-risk populations is the pharmacological upregulation of DNA repair pathways. SMUG1 is a base excision repair enzyme that ameliorates adverse genotoxic and mutagenic effects of hydrolytic and oxidative damage to pyrimidines. Here we describe the discovery and initial cellular activity of a small-molecule activator of SMUG1. Screening of a kinase inhibitor library and iterative rounds of structure-activity relationship studies produced compound 40 (SU0547), which activates SMUG1 by as much as 350 ± 60 % in vitro at 100 nM, with an AC50 of 4.3 ± 1.1 µM. To investigate the effect of compound 40 on endogenous SMUG1, we performed in vitro cell-based experiments with 5-hydroxymethyl-2'-deoxyuridine (5-hmdU), a pyrimidine oxidation product that is selectively removed by SMUG1. In several human cell lines, compound 40 at 3-5 µM significantly reduces the cytotoxicity of 5-hmdU and decreases levels of double-strand breaks induced by the damaged nucleoside. We conclude that the SMUG1 activator compound 40 is a useful tool to study the mechanisms of 5-hmdU toxicity and the potentially beneficial effects of suppressing damage to pyrimidines in cellular DNA.

Effects of gut microbiota and metabolites on pancreatitis: a 2-sample Mendelian randomization study.

Acute pancreatitis (AP) and chronic pancreatitis (CP) have high incidences and poor prognoses. The early screening of at-risk populations still awaits further study. The limitation was mainly based on observational studies, with limited sample size and the presence of confounding factors. This study used a 2-sample Mendelian randomization (MR) analysis based on publicly available data from genome-wide association studies to reveal the causal effect of gut microbiota and metabolites on pancreatitis. This study collected summary statistics on gut microbiota, metabolites, AP, and CP. A 2-sample MR analysis was performed using MR-Egger, inverse variance-weighted, MR Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median. The 2-sample MR showed that only Eubacterium coprostanoligenes was an independent protective factor for AP among all gut microbiota, and the other microbiota were not significant for pancreatitis. Unsaturated fatty acids in metabolites are protective factors for both AP (odds ratio [OR], 0.730; 95% CI, 0.593-0.899; P=.003) and CP (OR, 0.660; 95% CI, 0.457-0.916; P=.013). Furthermore, carnitine was a protective factor CP, and glucose was an independent risk factor for CP. This study provides potential evidence of the causal role of gut microbiota and metabolites on pancreatitis, which may be conducive for designing microbiome and metabolite interventions on AP or CP in the future.

Moving forward together: collaborative strategies in HIV prevention across Africa – a narrative review

HIV remains a major public health challenge across Africa, with the region accounting for nearly 70% of the global HIV burden. Despite significant advances in HIV prevention, treatment, and care, the epidemic continues to disproportionately affect certain populations, exacerbating health disparities and posing a barrier to socioeconomic development. This narrative review explores collaborative strategies in HIV prevention across Africa, focusing on multi-sectoral approaches, community-based interventions, and international partnerships. The review emphasizes the critical role of local communities, healthcare systems, and government organizations in reducing HIV transmission, with a particular focus on the importance of tailored prevention programs for vulnerable populations. Key strategies highlighted in the review include the integration of HIV prevention into broader public health initiatives, such as reproductive health, education, and poverty reduction programs. Community-based interventions, especially those involving community health workers (CHWs) and peer education, have proven effective in reaching at-risk populations. Additionally, international partnerships and funding from organizations like PEPFAR and the Global Fund have been instrumental in scaling up HIV prevention efforts, providing essential resources and technical support. Regional collaborations, such as those between neighboring countries in East and Southern Africa, have also played a vital role in addressing cross-border transmission and providing services to migrant populations.

Identifying At-Risk Populations for Reoperations, Readmissions, and Interventions in MBSAQIP Using a Novel Inpatient Postoperative Care Metric.

Metabolic and bariatric surgery (MBS) is increasingly used for obesity and metabolic disease, with safety profiles showing it is among the safest major operations. The last 20 + years have noted significantly improved safety that has been accompanied by decreasing length of stay and select populations electing for outpatient surgery, leading to continued decreases in cost. Regardless, readmissions and complications still occur, requiring inpatient postoperative care (IP-POC). The current study aimed to identify and characterize at-risk populations for MBS-related IP-POC. The 2015-2021 MBSAQIP (n = 1,346,468 records) was used to extract 973,520 primary cases of laparoscopic sleeve gastrectomy, Roux-en-Y gastric bypass, duodenal switch, and associated IP-POC. Conversions, pediatric cases, and < 30-day follow-up were excluded. IP-POC severity scores were calculated by summing readmissions (1 point), interventions (5 points), and reoperations (15 points). Risk factors associated with IP-POC were identified using zero-inflated Poisson models. GERD, COPD, smoking, and type of MBS procedure were significantly associated with increased IP-POC incidence and severity. Male sex was associated with increased severity but a lower likelihood of IP-POC, while Black and Hispanic race predicted increased IP-POC likelihood but not severity. ROC curve analysis identified IP-POC score thresholds of ≥ 6 and ≥ 10 as significantly associated with MACE (OR 2.4) and 30-day mortality (OR 4.7). The weighted IP-POC model demonstrated associations between preoperative characteristics and increased IP-POC likelihood and severity. These findings add to the current understanding of MBS patient care dynamics, and can be used to improve patient counseling, refine postoperative protocols, and optimize resource allocation.

P-741. Dalbavancin Rationale and Clinical Outcomes in Patients Hospitalized with Serious Bacterial Infections at an Urban Safety Net Hospital: an Observational Cohort

Abstract Background Dalbavancin is an emerging therapeutic option for gram positive bacterial infections in patients for whom standard IV or PO therapies are less desirable due to housing instability, substance use, or psychiatric conditions. Data on success rates of dalbavancin, rationale for use, and as step down therapy in at-risk populations are limited. In a large urban cohort of hospitalized patients receiving dalbavancin, we assessed rationale for therapy and clinical outcomes following administration. Patient demographic and clinical characteristics and rationale for dalbavancin among inpatients receiving therapy (N=107) *Patients may have more than one A: Substance use included: amphetamines including methamphetamine, cocaine, opioids, and other non-prescribed drugs. B: Housing instability included: any unhoused status including staying on street, in shelter, with friends/family, in vehicle, etc. C: Other infections included: pneumonia, lymphadenitis, septic thrombophlebitis, septic emboli, septic bursitis, mycotic aneurysm, myositis, TMJ septic arthritis, diabetic foot infection, and unknown. D: Source control was considered achieved if bacteremia was cleared, incision and drainage was performed, or hardware/prosthetic line/device was removed. Methods All adult inpatients who received ≥ 1 dalbavancin doses between 12/2021-3/2024 at Zuckerberg San Francisco General Hospital were evaluated. We assessed patients’ demographic features, provider rationale for dalbavancin use, and treatment completion rate. Time-to-event analysis assessed timing of clinical events. Primary outcome was treatment success (lack of recurrence/nonresolution at 90 days post-dalbavancin by in-depth chart review). Secondary outcomes were 90-day hospital re-admission, dalbavancin completion, and adverse effects. Results Overall, 107 patients received dalbavancin, and 48% of treatments were in a context of patient self-discharge from hospital. Co-morbidities were prevalent and included HIV (19%; 11/20 [55%] had viral suppression), substance use (84%), psychiatric conditions (59%), and housing instability (64%). Dalbavancin was used to treat skin/skin structure infections (55/107; 51%), bacteremia (46/107; 43%), bone/joint infection (61/107; 57%), and endocarditis (6/107; 6%). Treatment success was seen in 85% of patients, and 88% with Staphylococcus aureus. Time-to-event analysis shows clinical failures occurred evenly throughout the 90 days post dalbavancin. Ninety-day hospital readmission was 17%. Adverse events were rare (6%). Dalbavancin dose completion for those prescribed &amp;gt; 1 dalbavancin was 77%. Incomplete therapy had a trend towards lower treatment success (5/13, 39%, P=0.09). Conclusion Dalbavancin achieved high treatment success and completion among patients with high prevalence of housing instability, substance use, and medical/psychiatric co-morbidities. Dalbavancin has potential as a patient centered alternative to standard antibiotic therapies in at-risk patients. Disclosures All Authors: No reported disclosures

P-520. Barriers and facilitators towards HIV Pre-Exposure Prophylaxis (PrEP) prescription among healthcare providers in North Louisiana

Abstract Background The HIV/AIDS epidemic remains a major global health challenge. To end the HIV epidemic, it is crucial to ensure that everyone has fair and equal access to HIV treatment and prevention, including PrEP. Identifying and addressing barriers to PrEP prescription to ensure equitable access to prevent new infections is essential to end the HIV epidemic. Therefore, this study aims to identify incentives and barriers towards HIV PrEP prescription among healthcare providers in North Louisiana.Figure 1.How would you rate your knowledge of PrEP?The majority of participants (48%) rated their knowledge about PrEP as fair, good in 20%, and it was reported as poor in 16% of participants. Methods This is an ongoing observational cross-sectional survey study that aims to identify knowledge, attitudes, and intentions toward HIV PrEP among healthcare providers. Participants are faculty, residents, and fellows from the departments of Medicine, Pediatrics, Family Medicine and Obstetrics and Gynecology at an academic center in North Louisiana. A multi-modal recruitment strategy is being used to maximize the number of participants. We have conducted a preliminary descriptive analysis of the responses obtained from the study participants.Figure 2.Have you ever prescribed PrEP to a patient?Among healthcare providers surveyed, the majority (68%) reported that they had never prescribed PrEP to a patient. Results A total of 50 healthcare providers have taken the survey so far. Based on our initial findings, most study participants rated their knowledge of PrEP as either fair (48%) or poor (16%) (Fig.1). Concerning awareness of potential side effects, 44% reported poor knowledge. Most respondents (68%) had never prescribed PrEP (Fig.2). Barriers to PrEP prescription included: lack of PrEP provider training, lack of clinical guidelines for prescription and monitoring, challenges related to clinical and laboratory monitoring requirements, time constraints for patient education, and lack of insurance coverage (Fig.3). Facilitators to PrEP prescription included: access to resources such as PrEP prescription guidelines, implementation of Electronic Medical Records (EMR) order sets, clinical pharmacist support, and having peers who are knowledgeable and supportive of PrEP provision within their practice (Fig.4).Figure 3.Potential barriers to prescribing PrEP.Lack of provider training on PrEP was considered a very likely barrier to prescribing PrEP by 45% of respondents, while more than 50% of participants considered staffing and time constraints likely to be a barrier. Conclusion In order to make a significant contribution to HIV prevention, it is crucial to identify gaps in knowledge, attitudes, and practices among healthcare providers. This study’s ultimate goal is to improve PrEP implementation and dissemination, ultimately reducing new HIV infections among at-risk populations in Louisiana.Figure 4.Facilitators of PrEP prescription.More than 60% of participants considered that having Electronic medical records (EMR) order sets was an extremely likely facilitator, followed by clinical pharmacy support and having knowledgeable and supportive peers of PrEP use. Disclosures All Authors: No reported disclosures

P-11. Assessing the Epidemiological Impact of an Age-Based Pneumococcal Vaccine Recommendation in France

Abstract Background In France, pneumococcal vaccination recommendations exist for children aged 0-2 years and for adults with certain risk conditions. Despite most countries having age-based recommendations in adults over the age of 60 or 65 years, there is no adult age-based recommendation in France. Since May 2024, PCV20, a 20-valent pneumococcal conjugate vaccine (PCV) has been recommended in adults with risk conditions. V116 is a new adult focused PCV developed to prevent the 21 serotypes that occur most commonly in adults (86%of IPD). Table 1: IPD incidence per 100,000 individuals in the 65+ year old population. Methods We evaluated the impact of introducing an age-based pneumococcal vaccine recommendation in 65+ year-old individuals in France using a compartmental dynamic transmission model which tracked age- and serotype-specific Streptococcus pneumoniae (SP) transmission. The model incorporated the historical introductions of multiple age- and serotype-specific pneumococcal vaccines and accounted for both herd protection from pediatric vaccination and serotype replacement from vaccine introductions while it was calibrated to historical age- and serotype-specific invasive pneumococcal disease (IPD) data spanning 2000-2019. We evaluated the impact of introducing V116 into the at-risk adult population and in individuals aged 65+ years-old. For projections we maintained a 50/50 coverage ratio of PCV13/PCV15 in 95% of children and assumed a vaccine coverage rate (VCR) of 50% or 60% in adults aged 65+ years old. We compared this strategy against the current recommendation of PCV20 in adult risk populations only. Table 2: Cumulative IPD cases in all ages for different projection periods. Results In the first 10 years, the introduction of V116 into an age-based recommendation in France reduced IPD incidence in adults 65+ years old from 29.1 cases/100k to 17.9 or 15.9/100k if VCR of V116 was set to 50% or 60%, respectively. Continued use of PCV20 in adult risk populations led to 24.9 cases/100k (Table 1). This equated to a total IPD case count (all ages) of 57,493 with PCV20, 50,021 with 50% V116 VCR, and 46,355 with 60% V116 VCR (Table 2). Conclusion Introducing an age-based pneumococcal vaccine recommendation in France led to substantial reductions in population level IPD. After 10 years, V116 with a 60% VCR led to ∼11,000 fewer cases than the continued use of PCV20 in risk populations. Disclosures Kevin Bakker, PhD, Merck &amp; Co., Inc.: Grant/Research Support|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Rachel Oidtman, PhD, Merck &amp; Co., Inc.: Full time employee|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Giulio Meleleo, PhD, Merck &amp; Co., Inc.: Vendor Oluwaseun Sharomi, MSc, PhD, Merck &amp; Co., Inc.: Full time employee|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Manon Breau Brunel, n/a, MSD: Grant/Research Support|MSD: Stocks/Bonds (Public Company) Gaelle Farge, n/a, MSD: Grant/Research Support|MSD: Stocks/Bonds (Public Company) Jeremy Carette, n/a, MSD: Advisor/Consultant Robert Nachbar, PhD, Merck &amp; Co., Inc.: US 7,219,020, US 5,292,741|Merck &amp; Co., Inc.: Vendor|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company)

Maternal singing and speech have beneficial effects on preterm infant’s general movements at term equivalent age and at 3 months: an RCT

BackgroundGeneral Movements (GMs) are part of the spontaneous movement repertoire and assessing them helps to determine the integrity of the central nervous system in newborns. The aim of this study was to investigate the effects of maternal singing and speaking in the Neonatal Intensive Care Unit (NICU) on preterm infants’ GMs at term equivalent age and at 3 months.MethodsIn this multi-center randomized clinical trial, 56 stable preterm infants (25–32 weeks) were randomized to either an intervention group – in which mothers were asked to speak and sing to their infants for 20 min, 3 times per week, for 2 weeks – or to a control group. GMs were recorded both before and after the intervention – which took place at term equivalent age – and again at 3 months corrected age. The GMs were blindly coded based on the muted video tracks to produce both a general score and a detailed score.ResultsBefore the intervention, there were no significant differences between the two groups. The intervention wielded a significant effect on the GMs general score (p &amp;lt; 0.05). The effect was also marginally significant for the GMs detailed score (p = 0.06). To avoid influencing outcomes, future research should control for differences in maternal engagement outside of the intervention.ConclusionLive maternal singing and speaking are fundamental human practices that, in this study, enhanced preterm infants’ general movements and potentially supported their neurobehavioral development. Integrating and supporting early vocal interaction into routine NICU care is crucial for at-risk populations.

P-2174. Politics and Money? Mpox Vaccine Coverage in the US: A Study in Healthcare Variation

Abstract Background During the United States (US) mpox outbreak of 2022-2023, the federal government distributed mpox vaccines (JYNNEOS) to individual states for distribution to at-risk persons. For local distribution, there was no immediate federal funding available. The vaccines were not commercially available. Vaccination data was reported to states’ public health and the Centers of Disease Control and Prevention. There was considerable variation in vaccine coverage across different states. Mpox vaccine coverage and associated factors for US states. Methods Using public data, we sought to identify state-level factors associated with full mpox vaccine coverage (two doses), including: political identity, public health spending, public health staffing, diversity index, poverty rate, percentage of population at-risk, and mpox cases. Data sources were: 2020 presidential election result, Association of State and Territorial Health Officials, 2020 US Census, and the CDC. Univariate and multivariable linear regression was performed using all studied variables. P-value of &amp;lt; 0.05 was used to note statistical significance. Factors associated with mpox vaccine coverage: univariate linear regression. Results Nationally, average full mpox vaccine coverage for at-risk persons was 21%. Univariate analysis showed that Republican political status was associated with lower JYNNEOS vaccine coverage. Higher coverage was associated with higher public health spending per capita, increased diversity index, higher proportion of at-risk population, and greater number of absolute mpox cases. Multivariable analysis showed the following: Republican states achieved -5.65% lower vaccine coverage (p=0.036), each $1 increase in public health spending increased vaccine coverage by 0.05% (p=0.000), each additional MSM++ (men who have sex with men [MSM] on HIV pre-exposure prophylaxis plus MSM with HIV) per 1,000 people increased vaccine coverage by 1.5% (p=0.000), and each additional mpox case increased vaccine coverage by 0.003% (p=0.032). Multicollinearity check showed low correlation among tested variables. Factors associated with mpox vaccine coverage: multivariable linear regression. Conclusion Higher mpox vaccine coverage was achieved in US states with Democratic political orientation, higher public health funding, higher proportion of at-risk population, and higher mpox cases. Additional analyses toward equitable vaccine access are needed. Disclosures All Authors: No reported disclosures

Prognostic value of biohumoral markers and echocardiography images in infective endocarditis

Abstract Introduction The incidence of infective endocarditis (IE) has risen due to an increasing at-risk population and improved diagnosis through the widespread use of imaging techniques. With the surge in COVID-19 cases during the pandemic, there have been more frequent reports of patients being diagnosed with IE, likely due to factors such as immunosuppressive therapies and the use of central venous or urinary catheters. Purpose To analyze the prognostic value of biohumoral markers and valvular impairement assessed by echocardiography. Methods We conducted a retrospective observational study involving 29 patients diagnosed with IE who were admitted to our department in 2021. During hospitalization, we monitored and analyzed various biological parameters, including blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatinine and blood cultures. We also interpreted findings from transthoracic and transesophageal echocardiography. Results Most patients were presented with signs of inflammatory syndrome: leukocytosis upon admission in 22 patients (75.8%), elevated CRP in 28 patients (96.5%), ESR in 27 patients (93.1%), and procalcitonin in 6 patients (20.6%). Our analysis also included biomarker parameters with prognostic significance in IE: anemia was present in 22 patients (75.8%), while thrombocytopenia was observed in 11 patients (37.9%). Renal impairment was noted in 11 patients (37.9%). Among the pathogens identified Staphylococcus spp. was detected in 11 patients (37.93%), Streptococcus spp. in 5 patients (17.24%), Enterococcus spp. in 2 patients (6.89%), Acinetobacter spp. in 1 patient (3.44%), and Escherichia coli in 1 patient (3.44%). A notable proportion of cases (31.03% - 9 patients) had negative blood cultures, contrasting with findings from other registries. Vegetations were predominantly localized on the aortic valve in 15 patients (51.72%), followed by the mitral valve in 6 patients (20.68%). Less common locations included prosthetic heart valves in 5 patients (17.24%) and the tricuspid valve in 3 patients (10.34%). Among valvular complications, valve abscesses were most frequently observed in 6 patients (20.6%), followed by valve ruptures in 5 patients (17.2%), and valvular pseudoaneurysms in 2 patients (6.8%). Conclusions CRP was the most sensitive inflammation marker for assessing infection severity, while the most relevant prognostic biomarkers were hemoglobin, platelet count, and serum creatinine. Diagnosing this condition required complex analyses, as a significant percentage of patients presented with negative blood cultures. Staphylococcus spp. was the most identified microorganism. The most frequent infection sites were the native aortic valve, followed by the native mitral valve. The most common local complications included valve abscesses and valve ruptures.

P-1486. Comprehensive Approach to Vibrio Vulnificus: Integrating Drug Therapy, Diagnostic Modalities, and Targeted Care for At-Risk Populations

Abstract Background Vibrio vulnificus (VV), is endemic to warm coastal waters where it causes significant foodborne and aquatic illnesses resulting in high mortality and morbidity. There are no FDA-approved treatments or standard management strategies. Here we explore the landscape of VV infections, their characteristics and treatment outcomes.Figure 1:Outcome of Vibrio Vulnificus Infections Methods Cases of VV from 2014 to 2024 were identified from PubMed and Embase databases, employing pertinent keywords, MeSH terms, and Emtree terms. Articles underwent screening using Rayyan.ai using PRISMA protocol. 72 cases that met inclusion criteria were entered to CURE ID and aggregated data was analyzed.Figure 2:Age Distribution of Vibrio Cases Results The outcome distribution of cases are in Figure 1. 46/72 patients recovered while 21 died. Age and gender of patients with VV infections are displayed in Figure 2 and 3 respectively. Most cases occurred in middle aged individuals while there was a male prevalence in cases. Figure 4 displays the countries where most infections occurred. China and the United States had the highest incidence of cases.Figure 3:Sex of Patients Conclusion The high mortality of VV underscores the importance of finding treatment options for this often-forgotten disease. The age and sex distribution in middle aged males is indicative of the correlation between aquatic activity such as fishing and VV. Males who engage in these activities are at highest risk of contracting VV infections. The geographic distribution of cases underscores countries with warm oceans is where most cases occur. In our data we noticed a prevalence of chronic liver diseases amongst VV patience. We aim to explore this correlation and most effective antimicrobials in a full manuscript.Figure 4:Geographic Distribution of Vibrio Vulnificus Disclosures All Authors: No reported disclosures

P-163. Efficacy of Wolbachia-mediated sterility to suppress dengue

Abstract Background Vector control remains the primary means to mitigate the spread of dengue. Matings between male Aedes aegypti mosquitoes infected with the wAlbB strain of Wolbachia and wildtype females yield non-viable eggs (Wolbachia-Aedes). We evaluated the efficacy of Wolbachia-Aedes to suppress dengue incidence. We present data comprising a field trial of 607,872 residents over 5 years. Methods We utilized the synthetic control method and trial emulation approach to evaluate large-scale field trials in Singapore involving the deployment of Wolbachia-Aedes for dengue control via vector population suppression, from epidemiological week (EW) 27, 2018, to EW 26, 2022. We selected two large towns (Yishun and Tampines) to adopt an expanding release strategy and two smaller towns (Bukit Batok and Choa Chu Kang) to adopt a targeted-release approach. All intervention and control locations practised the same baseline dengue control protocol. The main outcome was weekly dengue incidence rate caused by any dengue virus serotype (in the case of the synthetic control method) and risk of being test positive for dengue (when using the trial emulation approach). We used incidence data collected by the Singapore Ministry of Health as well as a nationally representative dengue test positive/negative database to assess the efficacy of the interventions, To compare interventions, we used the synthetic control method or constrained randomization protocols to generate appropriate counterfactuals for the intervention towns selected from a combination of 30 control towns from EW 1, 2014 to EW 26, 2022. Results Our study comprised an at-risk population of 607 872 individuals living in intervention sites and 3 894 544 individuals living in control sites. Interventions demonstrated up to 77⋅28% (121/156, 95% CI 75⋅81–78⋅58) intervention efficacy despite incomplete coverage across all towns. Intervention efficacies increased as release coverage increased across all intervention sites. Secondary analysis showed that these intervention effects were replicated across all age groups and both sexes for intervention sites. Conclusion Wolbachia-mediated incompatible insect technique can strengthen dengue control in tropical cities, where dengue burden is the greatest. Disclosures All Authors: No reported disclosures

P-781. The Impact of Hepatitis B Virus Infection on the Management of Latent Tuberculosis Infection in Northern California, 2010-2022

Abstract Background Tuberculosis (TB) and hepatitis B virus (HBV) infection affect similar at-risk populations. However, there is limited data on how co-infection may influence clinicians’ decision to offer TB preventative treatment (TPT) over concern for hepatotoxicity. We compared TPT by HBV status, and determined factors associated with TPT initiation among HBV-infected persons at a community health center in Northern California serving a large non-U.S.-born Asian population. Methods We extracted electronic health record data for all persons aged ≥18 years old with latent TB infection (LTBI), defined by a positive tuberculin skin test or interferon-gamma release assay in the absence of a TB disease diagnosis from 2010-2022. HBV infection was defined by a single positive HBV DNA or HBV surface antigen assay. We conducted multivariate logistic regression to explore the impact of (a) HBV status and (b) clinical and demographic variables on TPT initiation. We also examined how these factors changed when Rifampin (RIF) usage for TPT increased at this community health center after 2014. Results A total of 11,711 persons had LTBI and 5,530 had HBV. Of all persons with LTBI, 833 (9.0%) of those tested for HBV had a co-infection including 41 (4.9%) on HBV antiviral treatment; while 34% of all HBV-infected persons screened for TB had LTBI. Adjusting for demographics and time period, TPT was significantly lower among those with co-infection than those without (43.5% versus 47.4%, adjusted Odds Ratio (aOR) 0.76, 95% Confidence Interval (CI) 0.66 – 0.88, p&amp;lt; 0.01). Among those with co-infection, increasing age (50-64, ≥65 years), and elevated alanine transaminase (ALT) levels were associated with decreased likelihood of TPT (Table 1). Treatment of co-infected individuals was significantly higher after 2014 when RIF prescribing increased (aOR 2.76, 95% CI 1.81-4.2); however, age over 65 was still associated with decreased TPT prescription (aOR 0.36, 95% 0.19 – 0.67, p &amp;lt; 0.01). Conclusion HBV-LTBI co-infection was associated with reduced odds of TPT. Increased use of Rifamycin based regimens and further guidance on TPT and monitoring of older individuals and persons with elevated ALT levels may be needed to improve TB prevention efforts among HBV-LTBI co-infected persons. Disclosures Robert J. Wong, MD, MS, Durect Corporation: Grant/Research Support|Exact Sciences: Grant/Research Support|Gilead Sciences: Grant/Research Support|Thera Technologies: Grant/Research Support

Improved display and detection of small renal stones using photon-counting detector CT compared to conventional energy-integrating detector CT.

To compare same-day photon-counting detector CT (PCD-CT) to conventional energy-integrating detector CT (EID-CT) for detection of small renal stones (≤ 3mm). Patients undergoing clinical dual-energy EID-CT for known or suspected stone disease underwent same-day research PCD-CT. Patients with greater than 10 stones and no visible stones under 3mm were excluded. Three radiologists selected the optimal reconstruction configuration for each CTmodality and created the reference standard for renal stone presence. Two other radiologists, blinded to imaging modality, independently reviewed anonymized images to detect renal stones, rating confidence in potential stones using a Likert scale (1 = Definitely present, 2 = Probably present, 3 = Questionably present, 4 = Not seen). Sensitivity and false positive detections for PCD and EID-CT were calculated. Twenty-one patients underwent clinical EID-CT followed by same-day PCD-CT, with the reference standard identifying 121 renal stones (mean size 2.8 ± 2.6mm). 0.4-mm PCD-CT images were more likely to display a stone as definitely present compared to 1- or 2-mm EID-CT images (p < 0.0001). Overall sensitivity for detection of all stones was greater at PCD-CT (0.75 vs. 0.55, p < 0.05). Pooled sensitivity of stones 3mm was also significantly higher at PCD-CT (0.67 vs. 0.41, p < 0.05), with false positive detections differing between readers and modalities (PCD-CT vs. EID-CT: R1-7 v. 5; R2 - 7 v. 1). Sensitivity for renal stones was significantly higher using high spatial resolution PCD-CT vs. EID-CT, especially for stones 3mm or less in size, which may be important for at-risk patient populations. Prospective evaluation in larger patient populations that will benefit from detection of small stones is warranted.

Minerals and Human Health: From Deficiency to Toxicity

Minerals are essential nutrients that play critical roles in human health by regulating various physiological functions. Examples include bone development, enzyme function, nerve signaling, and the immune response. Both the deficiencies and toxicities of minerals can have significant health implications. Deficiencies in macrominerals such as calcium, magnesium, and phosphate can lead to osteoporosis (associated with falls and fractures), cardiovascular events, and neuromuscular dysfunction. Trace mineral deficiencies, such as iron and zinc. Selenium deficiency impairs oxygen transport, immune function, and antioxidant defenses, contributing to anemia, delaying wound healing, and increasing susceptibility to infectious diseases. Conversely, excessive intake of minerals can have severe health consequences. Hypercalcemia can cause kidney stones and cardiac arrhythmias as well as soft-tissue calcification, whereas excessive iron deposition can lead to oxidative stress and organ/tissue damage. Maintaining adequate mineral levels through a balanced diet, guided supplementation, and monitoring at-risk populations is essential for good health and preventing disorders related to deficiencies and toxicities. Public health interventions and education about dietary sources of minerals are critical for minimizing health risks and ensuring optimal well-being across populations. While a comprehensive analysis of all macro and micronutrients is beyond the scope of this article, we have chosen to focus on calcium, magnesium, and phosphate. We summarize the consequences of deficiency and the adverse events associated with the overconsumption of other minerals.

Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance

Factor H (FH) is a crucial complement regulator that prevents complement-mediated injury to healthy cells and tissues. This regulatory function can be disrupted by Factor H autoantibodies (FHAA), which then leads to diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 Glomerulopathy (C3G). In pediatric aHUS, the FHAA incidence is ~10-15%, although in the Indian population, it rises to ~50%. The specific regions of FH targeted by FHAAs correlate with the pathogenic mechanism of the associated disease. In aHUS, FHAAs target the C-terminus, thereby impacting FH ability to recognize cell surfaces. In C3G, in contrast, FHAAs often target the N-terminus, generating an acquired functional FH deficiency. Detection and monitoring FHAAs are decisive for effectively treating patients. Current FHAA analysis normally identify free FHAAs that bind surface-bound FH using ELISA techniques. These methods require well-equipped laboratories and qualified staff, and do not measure FH-FHAA complexes, which can make it difficult to correlate titers with clinical outcomes. The visually-based immunochromatographic test (ICT) described herein allows for quick detection and quantification of IgG and IgM FH-FHAA complexes in human EDTA-plasma or serum. This ICT offers improved detection of FHAAs compared to ELISA as demonstrated by cases where the ICT identifies FH-FHAA complexes in samples that tested negative with the free FHAA ELISA. Importantly, the ICT indirectly informs on the amount of FH that is complexed with FHAAs, thus assessing the significance of the FHAA in disrupting the regulatory function of FH. Overall, this novel assay offers a simple, fast, cost-effective, and, likely, more clinically relevant alternative for diagnosing FHAAs in at-risk populations.

Prevalence of chronic kidney disease in Saudi Arabia: an epidemiological population-based study

BackgroundChronic kidney disease (CKD) is a prevalent global health issue affecting millions of patients worldwide, impacting quality of life, impeding physical and psychological well-being, causing financial stress, and increasing mortality rates. This study aimed to highlight the prevalence of CKD and its associated risk factors across Saudi Arabia. Method: This is a cross-sectional study conducted from 2015 to 2022, using data from 42 branches of a major network of diagnostic laboratories in Saudi Arabia, covering the country's 13 administrative areas.ResultsThe mean age was 40.35 ± 14.5 years. The highest proportion of participants resided in the Makkah region at 35.77%, followed by the Riyadh region at 25.75%. The overall prevalence of CKD was 4.76%, with most having CKD in stage 3 (3.5%). The prevalence of CKD was higher among males compared to females (5.83% vs. 3.88%) and increased significantly with age, being 0.45% among participants aged 18–29 years and reaching 50.94% among participants aged 90 years or older. Predictors of CKD included increasing age, male sex, administrative area (Makkah 1.40 [95% CI:1.26–1.55], Jazan 1.34 [95% CI:1.18–1.52], Najran 0.47 [95% CI, 0.39–0.57], Alqasim 0.73 [95% CI, 0.64–0.82]), and a high hemoglobin A1C. CKD in Saudi Arabia is influenced by various demographic and geographic determinants contributing to its prevalence and associated burden on the population.ConclusionThese findings emphasize the need for targeted screening and prevention strategies, especially for at-risk populations. Continued surveillance, early detection, and effective management are crucial to reducing CKD's burden and improving kidney health outcomes in Saudi Arabia. Further research is essential to better understand the disease's regional and demographic drivers.

Sexual practices and risk behaviours towards human immunodeficiency virus (HIV) infection among Ecuadorian university students: a cross-sectional study

ObjectiveTo describe the sexual practices and behaviour towards HIV infection among Ecuadorian university students.MethodsThis was a cross-sectional, descriptive study carried out between February 2019 and August 2020 among university students...