High-risk Disease Research Articles

Real-world cost-effectiveness of nirmatrelvir-ritonavir as treatment for SARS-CoV-2 infection in the Belgian setting with omicron variant

BackgroundNirmatrelvir-ritonavir is an oral treatment for SARS-CoV-2 infection in patients who are at high risk of developing severe COVID-19 disease. This antiviral has proven to significantly reduce the risk of hospitalization and death compared to no anti-SARS-CoV-2 treatment in this target population. This paper aims to assess the cost-effectiveness of nirmatrelvir-ritonavir in Belgium using real-world evidence.MethodsA static decision tree model was developed to capture the health progression of patients infected with the SARS-CoV-2 virus. Outcomes were expressed in Quality Adjusted-Life Years (QALYs), hospitalizations, Intensive Care Unit (ICU) admissions, deaths and Long Covid cases, derived from epidemiological data over the first full year of the Omicron variant’s circulation (2022). Costs were calculated for the year 2023 from the healthcare payer’s perspective. Extensive sensitivity analyses were conducted to test the robustness of the cost-effectiveness results.ResultsIn a cohort of 1,000 patients, treatment with nirmatrelvir-ritonavir is projected to save 95 QALYs and €82,658 compared to no anti-SARS-CoV-2 treatment over a lifetime horizon. These savings primarily stem from the reduction in hospitalizations among vulnerable patients who typically require a longer recovery time. The analysis also indicates 5 fewer ICU admissions and 8 fewer premature deaths per 1,000 infected patients.ConclusionIn the context of Omicron SARS-CoV-2 infection, administering nirmatrelvir-ritonavir to patients at high risk of severe disease improves health outcomes and reduces costs. Nirmatrelvir-ritonavir is 100% likely to be cost-effective at a willingness to pay of €2,000 per QALY.

Clinical treatment score Post-5 Years (CTS5) predicts the benefit of postmastectomy radiotherapy in patients with T1-2N1 luminal breast cancer.

To investigate the clinical value of Clinical Treatment Score Post-5 Years (CTS5) to predict the survival benefits of postmastectomy radiotherapy (PMRT) of patients with T1-2N1 luminal breast cancer (BC). Patients who were diagnosed with T1-2N1 luminal BC between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results database. The chi-square test, binomial logistic regression, Kaplan-Meier analysis, and multivariable Cox proportional hazard model were used for statistical analyses. A total of 11190 patients were included with a median follow-up time of 76 months. Regarding the CTS5 classification, 1641 (14.7%), 3915 (35.0%), and 5633 (50.3%) patients had low-risk, intermediate-risk, and high-risk diseases, respectively. Patients with younger age, T2 stage, higher tumor grade, a higher number of positive lymph nodes, infiltrating lobular carcinoma subtype, and receipt of chemotherapy were associated with the receipt of PMRT (all P<0.05). The multivariate analysis showed that the receipt of PMRT was the independent prognostic factor associated with better BCSS (P=0.005) and OS (P<0.001). The sensitivity analysis showed that PMRT did not improve BCSS (low-risk, P=0.932; intermediate-risk, P=0.952) and OS (low-risk, P=0.637; intermediate-risk, P=0.825) compared to those without PMRT in the low-risk and intermediate-risk groups. However, PMRT improved BCSS (P=0.003) and OS (P<0.001) in those with high-risk groups compared to those without PMRT. CTS5 is an innovative model that could predict the survival benefit of PMRT for T1-2N1 luminal BC patients.

Perspectives of Midwives and Nurse Practitioners in Kentucky on Exercise Counseling During Pregnancy: A Qualitative Study.

Healthcare professionals are in an optimal position to deliver exercise information to pregnant women, yet previous research suggests this seldom happens. Midwives and nurse practitioners, who may have more time with pregnant women, are particularly well suited for this role. This qualitative study examined the exercise advice and counseling provided by midwives and nurse practitioners in Kentucky, focusing on the barriers they face. Twenty-one midwives and nurse practitioners were recruited until the sample size reached saturation. A survey with open-ended questions was distributed to potential participants in regional hospitals, universities, and professional associations. The framework method was employed to identify common themes in the responses from participants. Five main themes emerged: nature of advice, discussing exercise benefits, safety concerns, barriers to counseling, and suggestions for improvement. Findings revealed that midwives and nurse practitioners recommend moderate exercise, aiming for 150 min weekly, monitoring heart rate for intensity, continuing prepregnancy exercise routines, starting low-intensity exercise during pregnancy such as walking, slowing down as pregnancy advances, and avoiding heavy lifting and vigorous activities. Many midwives and nurse practitioners in our sample took a reactive approach to exercise counseling, providing exercise advice if pregnant women asked questions or if they were at high risk for hypokinetic diseases. It was also observed that midwives and nurse practitioners discussed the maternal benefits of exercise more than the fetal benefits. Only a few nurse practitioners and midwives were content with their counseling, while the majority did not feel their counseling was effective. Many midwives and nurse practitioners in Kentucky provided comprehensive and accurate physical activity guidelines to pregnant women. However, there is room for them to improve: proactive counseling should include discussions on fetal benefits and using the "talk test" for exercise intensity. Advising patients to slow down as pregnancy progresses should be reconsidered, and evidence-based guidance on specific exercises should be prioritized.

Fully automated coronary artery calcium score and risk categorization from chest CT using deep learning and multiorgan segmentation: A validation study from National Lung Screening Trial (NLST).

The National Lung Screening Trial (NLST) has shown that screening with low dose CT in high-risk population was associated with reduction in lung cancer mortality. These patients are also at high risk of coronary artery disease, and we used deep learning model to automatically detect, quantify and perform risk categorisation of coronary artery calcification score (CACS) from non-ECG gated Chest CT scans. Automated calcium quantification was performed using a neural network based on Mask regions with convolutional neural networks (R-CNN) for multiorgan segmentation. Manual evaluation of calcium was carried out using proprietary software. This study used 80 patients to train the segmentation model and randomly selected 1442 patients were used for the validation of the algorithm. We compared the model generated results with Ground Truth. Automatic cardiac and aortic segmentation model worked well (Mean Dice score: 0.91). Cohen's kappa coefficient between the reference actual and the interclass computed predictive categories on the test set is 0.72 (95% CI: 0.61-0.83). Our method correctly classifies the risk group in 78.8% of the cases and classifies the subjects in the same group. F-score is measured as 0.78; 0.71; 0.81; 0.82; 0.92 in calcium score categories 0(CS:0), I (1-99), II (100-400), III (400-1000), IV (>1000), respectively. 79% of the predictive scores lie in the same categories, 20% of the predictive scores are one category up or down, and only 1.2% patients were more than one category off. For the presence/absence of coronary artery calcifications, our deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating the process could improve diagnostic ability, risk categorization, facilitate primary prevention intervention, improve morbidity and mortality, and decrease healthcare costs.

Features and allele frequency of JAK2 Exon 12-mutated polycythemia vera in comparison with JAK2V617F-mutated disease

Background and AimJAK2 exon 12 mutation status and the clinical characteristics of patients with polycythemia vera (PV) in Asia remain to be defined. MethodWe analyzed the clinical, molecular, and genetic features and outcomes of patients with PV harboring exon 12 mutation and compared them with those with the JAK2V617F mutation in Taiwan. JAK2V617F with allele burden was measured by pyrosequencing and/or RT/qPCR. The allele frequency of exon 12 mutation was analyzed by next-generation sequencing in JAK2V617F-negative patients. ResultsA total of 532 patients diagnosed with PV were enrolled. The JAK2V617F mutation was present in 94.9% and exon 12 mutations in 5.1%. At diagnosis, patients with exon 12 mutation had higher hemoglobin (p = 0.012), and hematocrit levels (p = 0.003), and lower platelet (p <0.001), and leukocyte counts (p <0.001) compared to patients with JAK2V617F mutations. Patients harboring the JAK2V617F mutation had a higher incidence of high allele burden (p <0.001), disease risk (p = 0.014), and bleeding events (p = 0.013) compared to patients with PV with exon 12 mutations. These patients showed similar outcomes (overall survival, leukemia-free, myelofibrosis and thrombosis-free survival) to those with JAK2V617F mutations. An allele frequency ≥52.5% conferred an inferior overall survival compared to ≤52.5% in both exon 12-mutated (p = 0.029) and JAK2V617F patients with PV (p = 0.038). ConclusionTaiwanese patients with PV showed differences in blood count, risk group, and bleeding events between exon 12 and JAK2V617F patients. Higher mutant allele burden had a negative impact on overall survival for both mutation types.

Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging Before Radical Prostatectomy.

Prostate-specific-membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is more accurate than conventional imaging for lymph node (LN) staging in prostate cancer. However, it has limitations in detecting micrometastatic lymph node invasion (LNI). Our aim was to evaluate the accuracy of PSMA PET/CT for overall and size-dependent LNI detection in contemporary patients undergoing radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Within a high-volume center database, we identified 873 patients who underwent PSMA PET/CT for primary staging before RP and PLND between 2016 and 2021. Data for lymph node status on imaging and histology results were analyzed. Of 873 patients, 25% (n=220) had LNI. Median prostate-specific antigen was 8.3ng/ml (interquartile range 4.3-14.3). The majority of patients had high-risk (53%) or intermediate-risk disease (45%). In the overall cohort, the per-patient sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy calculated for LNI detection via PSMA PET/CT were 45.5%, 92.6%, 67.6%, 83.4%, and 80.8%, respectively. The median metastatic LN size in the group of 120 patients with false-negative PET/CT results was 2.5 mm. For metastatic LNs ≥5mm, the sensitivity and NPV increased to 68.8% (+23.3%) and 95.4% (+12.0%), respectively. The main limitation is the lack of central review of PSMA PET/CT scans. PSMA PET/CT is accurate in the staging of pelvic LNs before RP, especially for detection of metastases in LNs with a diameter ≥5mm.

Morbilliform Eruptions: Differentiating Low-Risk Drug Eruptions, Severe Cutaneous Adverse Reactions, Viral Eruptions, and Acute Graft-Versus-Host Disease.

Morbilliform eruptions, which are a clinical reaction pattern characterized by erythematous macules and papules coalescing into patches that cover most of the skin surface, are one of the most common cutaneous findings in the inpatient setting. In the hospital setting, most causes are benign and due to low-risk drug exanthems; however, morbilliform eruptions may also be a sign of high-risk diseases, including Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, acute generalized exanthematous pustulosis, and graft-versus-host disease. Proper identification of the etiology and risk stratification of a morbilliform eruption is critical to ensure proper management and optimize patient outcomes. In this review, we discuss the key features that differentiate high-risk from low-risk morbilliform eruptions, as well as specific characteristics that differentiate the different high-risk eruptions. Additionally, we offer a clinical algorithm that may be applied in the management of a patient who presents with a morbilliform rash.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer

Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial. To evaluate the addition of immune therapy in the form of atezolizumab to postoperative chemotherapy in patients with the high-risk triple-negative breast cancer subtype. In this open-label international randomized phase 3 trial conducted in more than 330 centers in 31 countries, patients undergoing surgery as initial treatment for stage II or III triple-negative breast cancer were enrolled between August 2, 2018, and November 11, 2022. The last patient follow-up was on August 18, 2023. Patients were randomized (1:1) to receive standard chemotherapy for 20 weeks with (n = 1101) or without (n = 1098) the immune therapy drug atezolizumab for up to 1 year. The primary end point was invasive disease-free survival (time between randomization and invasive breast cancer in the same or opposite breast, recurrence elsewhere in the body, or death from any cause). The median age of enrolled patients was 53 years and most self-reported as being of Asian or White race and neither Latino nor Hispanic ethnicity. The study independent data monitoring committee halted enrollment at 2199 of 2300 planned patients. All patients stopped atezolizumab following a planned early interim and futility analysis. The trial continued to a premature final analysis. With invasive disease-free survival events in 141 patients (12.8%) treated with atezolizumab-chemotherapy and 125 (11.4%) with chemotherapy alone (median follow-up, 32 months), the final stratified invasive disease-free survival hazard ratio was 1.11 (95% CI, 0.87-1.42; P = .38). Compared with chemotherapy alone, the regimen of atezolizumab plus chemotherapy was associated with more treatment-related grade 3 or 4 adverse events (54% vs 44%) but similar incidences of fatal adverse events (0.8% vs 0.6%) and adverse events leading to chemotherapy discontinuation. Chemotherapy exposure was similar in the 2 treatment groups. The addition of the immune therapy drug atezolizumab to chemotherapy after surgery did not provide benefit among patients with triple-negative breast cancer who are at high risk of recurrent disease. ClinicalTrials.gov Identifier: NCT03498716.

P-596. Immunobridging Demonstrating Effectiveness of the Bivalent Respiratory Syncytial Virus (RSV) Prefusion F Subunit Vaccine in Adults 18-59 Years of Age at High Risk of Severe RSV Disease in a Phase 3 Trial: The C3671023 MONeT Study Results

Abstract Background C3671023 Substudy A (NCT05842967) is a phase 3, randomized, double-blinded, placebo-controlled study to assess the safety and immunogenicity of Pfizer’s RSVpreF in adults 18-59 years of age at high risk of severe RSV disease due to chronic medical conditions, including pulmonary, cardiovascular, hepatic, renal, and metabolic (including diabetes mellitus) disorders. Primary objectives were to assess safety and to demonstrate a non-inferior immune response in adults 18-59 years of age at high risk of severe RSV disease compared to adults age ≥ 60 from the pivotal phase 3 C3671013 study which demonstrated efficacy against RSV Lower Respiratory Tract Illness (LRTI).Table 1:Number of Participants Reporting at Least 1 Adverse Event (Excluding Prespecified Events) for Each Analysis Interval After Vaccination with RSVpreF Methods Participants were randomized 2:1 to receive 1 dose of RSVpreF or placebo (453 RSVpreF: 225 placebo). Sera collected before and at 1 month after vaccination were tested concurrently with sera collected from ∼400 RSVpreF recipients from the C3671013 study. Reactogenicity events were collected for 7 days following vaccination. Adverse events (AEs) were collected through 1 month following vaccination; adverse events of special interest (AESIs), newly diagnosed chronic medical conditions (NDCMCs), and serious AEs were collected throughout the study. Non-inferiority (NI) would be declared if the lower bounds of the 95% confidence interval (CI) of adjusted Geometric Mean Ratio (GMR) of neutralizing titers (NTs) were &amp;gt; 0.667 and lower bounds of the 95% CI of seroresponse rate differences were &amp;gt; -10% for RSV A and RSV B.Table 2:Comparison of Model-Adjusted RSV Neutralizing - GMTs at 1 Month After Vaccination with RSVpreF- 18 Through 59 Years at High Risk (C3671023) versus 60 Years and Older (C3671013) Results Proportions of participants with local reactions were higher in the RSVpreF group; systemic events were generally similar in both groups (Figure 1). Proportions of participants reporting any AEs were similar between RSVpreF and placebo through 1 month following vaccination and throughout the study (Table 1). RSV A and RSV B NTs 1 month after RSVpreF vaccination in adults 18-59 years of age at high risk were non-inferior to adults ≥ 60 years of age (Table 2). NI was met for seroresponse rates (Table 3).Table 3:Comparison of RSV Neutralizing Titer Seroresponse Rates 1 Month After Vaccination with RSVpreF- 18 Through 59 Years at High Risk (C3671023) versus 60 Years and Older (C3671013) Conclusion RSVpreF was well-tolerated with no safety concerns and demonstrated immunobridging to efficacy in adults 18-59 years of age at high risk of severe RSV disease compared to adults age ≥ 60. Results support the use of RSVpreF among adults 18-59 years of age with high-risk conditions to prevent RSV LRTI.Figure 1:Local Reactions and Systemic Events Reported, By Maximum Severity, Within 7 Days After Vaccination with RSVpreF Disclosures William Towner, MD, GSK: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Elliot N. DeHaan, MD, Pfizer, Inc.: Salaried employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Qin Jiang, PhD, Pfizer: Salary|Pfizer: Stocks/Bonds (Public Company) Wen Li, PhD, Pfizer: stipend for my employment|Pfizer: Stocks/Bonds (Public Company) Farah Rahman, DO, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Michael Patton, B.Sc., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Hayley Wyper, BBiomedSc, Pfizer: Stocks/Bonds (Public Company) Maria Maddalena Lino, PhD, Pfizer: Stocks/Bonds (Private Company) Uzma N. Sarwar, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Elena Kalinina, PhD, Pfizer, Inc.: Salary|Pfizer, Inc.: Stocks/Bonds (Public Company) David Cooper, PhD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Kena A. Swanson, Ph.D., Pfizer: Employee of Pfizer|Pfizer: Stocks/Bonds (Public Company) Annaliesa S. Anderson, PhD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Alejandra C. Gurtman, M.D., Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Iona Munjal, MD, Pfizer: Salaried employee|Pfizer: Stocks/Bonds (Public Company)

633. Incidence and Outcomes of Pediatric Allogeneic Hematopoietic Cell Transplant (allo-HCT) Recipients Under Surveillance and Not Under Surveillance for Human Adenovirus (HAdV) in the Post-HCT Period

Abstract Background Human Adenovirus (HAdV) can cause life-threatening illness in pediatric allo-HCT recipients, but studies to define incidence and outcomes of HAdV in allo-HCT patients are limited. Use of PCR-based HAdV surveillance varies by HCT center, in part because there are no approved HAdV-directed therapies. This study describes the epidemiology of HAdV infection and disease in pediatric allo-HCT patients who did and did not undergo HAdV surveillance. Methods An allo-HCT cohort was assembled from July 2018 to June 2021 at ten US pediatric HCT centers. Patients were followed for 180 days from HCT to document presence of HAdV infection and disease and were considered under surveillance if ≥ 2 HAdV blood tests were run in the first 14 days post-HCT. Published HAdV disease and attributable death definitions were applied to patients with positive HAdV PCR tests from any site and adjudicated by a central review committee. HAdV events were designated asymptomatic infection or possible, probable, or proven disease. HAdV DNAemia and disease incidence, time to event, and mortality and attributable case fatality rates were described. Results The cohort included 831 allo-HCT recipients: 645 under surveillance &amp; 186 not (Table 1). 15.5% of patients under surveillance had DNAemia; median time to DNAemia was 31.0 days from HCT (Table 2). Probable/proven disease was documented in 11.9% and 3.8% of patients under and not under surveillance, with median time to disease 37.0 days and 66.0 days from HCT, respectively (Table 3). Overall mortality rates were 7.6% and 8.6% in patients under and not under surveillance (Table 4). Attributable case fatality rates for those with probable or proven disease were 13.0% and 14.3% in those under and not under surveillance, respectively. Conclusion HAdV infection and disease events were frequent; however, incidence was higher in patients under surveillance, suggesting detection bias. HAdV disease was identified as a frequent cause of death. Attributable case fatality rates were similar regardless of surveillance, suggesting early detection did not improve outcomes. Future analyses of these data will determine patient factors that identify allo-HCT patients at high risk for HAdV infection and disease to target for novel prophylaxis or pre-emptive therapy studies. Disclosures Michael D. Green, MD, MPH, ADMA: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|ITB-MED: Advisor/Consultant|kamada: Honoraria Monica I. Ardura, DO, MSCS, Karius: Advisor/Consultant|Miravista: Grant/Research Support Jeffrey Auletta, MD, Ascella Health: Advisor/Consultant Diego R. Hijano, MD, MSc, FDA: Grant/Research Support|Merck: Grant/Research Support|National Institute of Health: Grant/Research Support William J. Muller, MD, Ansun Biopharma: Grant/Research Support|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|DiaSorin: Advisor/Consultant|DiaSorin: Honoraria|Eli Lilly and Company: Grant/Research Support|Enanta Pharmaceuticals: Advisor/Consultant|Enanta Pharmaceuticals: Grant/Research Support|F. Hoffmann-LaRoche Ltd (Roche): Grant/Research Support|Finley Law Firm, P.C.: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Melinta Therapeutics, Inc.: Grant/Research Support|Merck Sharpe &amp; Dohme: Grant/Research Support|Moderna: Grant/Research Support|Nabriva Therapeutics, plc: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer: Grant/Research Support|ProventionBio: Advisor/Consultant|Sanofi: Advisor/Consultant|Sanofi: Honoraria|Tetraphase Pharmaceuticals, Inc.: Grant/Research Support Michael Grimley, MD, SymBio Pharmaceuticals Limited: Advisor/Consultant Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio Brian T. Fisher, DO, MPH/MSCE, Allovir: Grant/Research Support|Astellas: Data Safety Monitoring Board|Merck: Grant/Research Support|Pfizer: Grant/Research Support

P-2049. Interim Estimates of Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Outcomes Among Medicare Enrollees with End Stage Renal Disease — United States, September – December 2023

Abstract Background Persons with end stage renal disease (ESRD) on maintenance dialysis are at high risk for severe COVID-19 disease. On September 12, 2023, updated 2023-2024 COVID-19 vaccination was recommended in the United States for all persons aged ≥6 months. Due to the innate immune dysfunction and high prevalence of additional underlying conditions, including immunocompromising conditions (ICs), among individuals with ESRD, there is concern about reduced vaccine effectiveness (VE). Understanding the VE of updated doses among persons with ESRD will inform the need for additional doses in this population. Table 1 Characteristics of Medicare fee-for-service beneficiaries aged ≥18 years with end stage renal disease receiving dialysis1, by presence of additional immunocompromising conditions — United States, September 2023–December 2023 Methods A retrospective cohort study was conducted among Medicare fee-for-service beneficiaries aged ≥18 years with ESRD receiving dialysis using Medicare enrollment and claims records. Follow-up began on September 17, 2023, and continued until the earliest occurrence of a censoring event, COVID-19–associated outcome (medically attended COVID-19 or COVID-19-associated hospitalization), or study end. A marginal structural Cox model was used to estimate VE (calculated as [1 – hazard ratio]*100%), interpreted as the benefit of an updated COVID-19 vaccine dose compared with no updated dose, by presence of additional ICs. Table 2 Vaccine effectiveness1 of updated 2023–2024 (monovalent XBB.1.5) COVID-19 vaccination against medically attended COVID-19 and COVID-19-associated hospitalizations among Medicare fee-for-service beneficiaries aged ≥18 years with end stage renal disease receiving dialysis2, by presence of additional immunocompromising conditions and age group — United States, September 2023–December 2023 Results During September 17 – December 30, 2023, 14,921/112,186 (15%) Medicare beneficiaries aged ≥18 years with ESRD without additional ICs and 5,667/33,957 (17%) beneficiaries aged ≥18 years with ESRD and additional ICs received an updated 2023-2024 COVID-19 vaccine dose (Table 1). Among those with ESRD without additional ICs, VE against medically attended COVID-19 was 47% (95% confidence interval [CI]: 36% - 56%) and against COVID-19-associated hospitalization was 49% (95% CI: 34% - 61%). Among those with ESRD and additional ICs, VE against medically attended COVID-19 was 40% (95% CI: 23% - 53%) and against COVID-19-associated hospitalization was 50% (95% CI: 29% - 64%)(Table 2). Conclusion VE among adults with ESRD was similar to published updated 2023-2024 COVID-19 VE estimates among the general adult population. These data support the recommendation that adults with ESRD get an updated COVID-19 vaccine, especially people 65 years or older and people with ICs, who are eligible for additional doses. Disclosures Ryan E. Wiegand, PhD, Merck &amp; Co, Inc.: Stocks/Bonds (Public Company)|Sanofi ADR: Stocks/Bonds (Public Company) Heng-Ming Sung, MPH, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor. Yue Zhang, MS, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor. Bradley Lufkin, MPA, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor. Yoganand Chillarige, MPA, CDC: Author is an employee of Acumen LLC. This study was funded through an inter-agency agreement between CDC and CMS for which Acumen is a contractor.

P-2017. Patient Reported Outcomes of Nirmatrelvir/Ritonavir Treatment for High-risk, Nonhospitalized Adults with Symptomatic COVID-19

Abstract Background Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for coronavirus disease 2019 (COVID-19). We describe patient-reported outcomes (PROs) with NMV/r in nonhospitalized adults with COVID-19 at high risk of severe disease. Percentage of participants in each treatment group in the mITT2 population reporting return to usual health on each study day through Day 28 on the Global Impressions Questionnaire. n=number of patients with event; mITT2=modified intent-to-treat 2; N=number of patients with nonmissing data. CI=confidence interval; HR=hazard ratio Methods In a phase 2/3 double-blind study, high-risk adults with confirmed COVID-19 and ≤ 5 days of symptoms were randomized 1:1 to receive NMV/r or placebo twice daily for 5 days. All PRO analyses included participants randomly assigned to a study intervention who received ≥ 1 dose of the study intervention and had ≥ 1 postbaseline visit through Day 28 (modified intent-to-treat 2 [mITT2] population). Patients recorded responses to three Global Impression Questions (GIQ) daily through Day 28 to assess return to usual health, return to usual activities, and overall severity of COVID-19 related symptoms. COVID-19–specific Work Productivity and Activity Impairment Questionnaire (WPAI-COVID-19), and the EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) were completed at specified visits through Week 24. Percentage of participants in each treatment group in the mITT2 population reporting return to usual activities on each study day through Day 28 on the Global Impressions Questionnaire. n=number of patients with event; N=number of patients with nonmissing data. CI=confidence interval; HR=hazard ratio; mITT2=modified intent-to-treat 2 Results Compared with placebo, patients receiving NMV/r had a significant 3-day reduction in median time to return to usual health (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.2–1.4), 1-day reduction in median time to return to usual activities (HR, 1.2; 95% CI, 1.1–1.4), and significantly shorter time to sustained resolution of any overall symptoms (HR, 1.2; 95% CI, 1.1–1.3) and sustained alleviation of any overall symptoms (HR, 1.2; 95% CI, 1.1–1.3) based on the GIQ. There were no significant differences between treatment groups on the WPAI or EQ-5D-5L. Conclusion High risk patients receiving NMV/r for COVID-19 reported a reduced duration and severity of COVID-19 symptoms based on their global impression of overall symptom burden and quicker return to usual heath and usual activities compared with those receiving placebo. The main limitation of this analysis was the lack of sufficient ePRO data collection of WPAI and EQ-5D-5L questionnaires. As such, no meaningful conclusions could be drawn regarding the impact of NMV/r on work productivity or activity impairment of HRQoL. Disclosures Ashley S. Cha-Silva, PharmD, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Jinma Ren, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Amie Scott, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Joseph C. Cappelleri, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Wajeeha Ansari, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Heidi Leister-Tebbe, BSN, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)

168. Safety, Reactogenicity, and Immunogenicity of mRNA-1345, an Investigational Respiratory Syncytial Virus Vaccine, in Participants Aged 2 to &amp;lt; 18 Years at High Risk of Severe Disease

Abstract Background Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract disease in children aged &amp;lt; 5 years and causes substantial burden in those at high risk aged 5-18 years. No active RSV vaccine is currently available for children. Here, we present interim safety and immunogenicity of a single injection of the mRNA-based vaccine, mRNA-1345, in participants aged 2 to &amp;lt; 18 years at high risk for severe RSV disease. Methods This phase 2, randomized, observer-blind study enrolled participants into 2 age cohorts (2 to &amp;lt; 5 years and 5 to &amp;lt; 18 years). Participants aged 2 to &amp;lt; 5 years were healthy or had stable, chronic conditions increasing risk for RSV disease, and were randomized (1:1:1:1) to receive a single mRNA-1345 injection (7.5, 15, or 30 μg) or placebo. Participants aged 5 to &amp;lt; 18 years had chronic conditions that increased disease risk and were randomized (1:1:1) to receive a single mRNA-1345 injection (15, 30, or 50 μg). Safety and reactogenicity were primary objectives. The secondary objective was immunogenicity, measured by serum RSV neutralizing antibodies (nAb) against RSV-A and RSV-B, and RSV prefusion F (preF)-binding antibodies (bAb). Interim results through Day 29 are reported. Results At data cutoff, 162 participants aged 2 to &amp;lt; 5 years (mean 2.9 ± 0.8 years) and 184 participants aged 5 to &amp;lt; 18 years (mean 11.4 ± 3.8 years) had received a vaccination. In both cohorts, solicited adverse reactions were primarily Grade 1-2 in severity; injection site pain, headache, and fatigue were most frequently reported (Figure 1). No deaths occurred and no adverse events (AEs) led to study discontinuation; 1 unrelated serious AE and 1 AE of special interest were reported. At Day 29, a single mRNA-1345 injection increased RSV nAb titers from baseline by 5.9- to 12.7-fold (RSV-A) and 4.3- to 8.9-fold (RSV-B) in those aged 2 to &amp;lt; 5 years, and by 8.2- to 15.8-fold (RSV-A) and 4.7- to 8.0-fold (RSV-B) in those aged 5 to &amp;lt; 18 years (Figure 2). Similarly, vaccination increased RSV preF bAb concentrations at Day 29 for both cohorts (Figure 2). Conclusion A single injection of mRNA-1345 was well tolerated, raised no safety concerns, and increased both nAb and bAb immune responses in participants aged 2 to &amp;lt; 18 years. These findings support further development of mRNA-1345 for the pediatric population. Disclosures Sabine Schnyder Ghamloush, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Hui Qian, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) HuiLing Chen, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Joseph Whitten, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Sonia K. Stoszek, PhD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds (Public Company) Matthew D. Snape, MBBS, MD, FRCPCH, FPM, FMedSci, Moderna, Inc.: Emplolyee|Moderna, Inc.: Stocks/Bonds (Public Company)

Adolescent Obesity and Charlson Comorbidity Index in Young Adults

Background: There is insufficient evidence regarding the independent risk of childhood/adolescent obesity for morbidity and mortality in adulthood. The objective of the present study was to evaluate the association of weight categories during adolescence with high-risk diseases determined by the Charlson Comorbidity Index in young adulthood. We also analyzed the association of weight categories with cumulative mortality at the age of 30. Methods: A retrospective cohort study, based on the central computerized database of a major health service organization, was conducted. The study population consisted of 80,853 adolescents. The study period was from 1 January 2007 to 31 December 2022 and was divided into the exposure period from 1 January 2007 to 31 December 2011 (ages 17–19) and the follow-up period from 1 January 2007 to 31 December 2022 (from the date of the defining BMI measurement up to the age of 30 years). Results: The five diseases with the highest cumulative incidence were chronic pulmonary disease (8.2%), mild liver disease (3.7%), cerebrovascular disease (2.8%), diabetes without end-organ damage (2.0%), and peptic disease (1.6%). When adjusted for socio-demographic variables and adult BMI, the relative risks with 95% confidence intervals for the increase in the Charlson Comorbidity Index were 1.11 (1.05–1.17), 1.17 (1.11–1.24), and 1.22 (1.09–1.35) for the “overweight”, “obesity”, and “class 2 obesity” categories, respectively, while the mortality for these categories were 1.60 (1.11–2.27), 1.71 (1.12–2.57), and 3.18 (1.48–6.35), respectively. Conclusions: Adolescent obesity is an independent risk factor for high-risk diseases and mortality in young adulthood. Interventions aimed at reducing the rate of adolescent overweight and obesity should be implemented as early as possible.

Elemental partitioning, morpho-physiological effects, genotoxicity, and health risk assessment associated with tomato (Solanum lycopersicum L.) grown in soil contaminated with mining tailings.

This study explored the distribution of macronutrients (Ca, Mg, Na, K) and lithogenic (Ba, Cr, Ni, Mn, Fe) and mining-related (As, Pb, Cd, Cu, Zn) toxic metalloids and metals (TMMs) in tomato (Solanum lycopersicum L.), and its effects on plant development, productivity, genotoxicity, and human health, using a soil affected by mine tailings (AfS) and an unaffected control soil (CS). The chemistry of soils reflected their mineralogy, and Fe-Ti oxides, sulfides and sulfosalts were found to be the most significant reservoirs of TMMs. AfS had concentrations of mining-related TMMs 15 to 945 times greater than background (continental crust) levels, and 1.98 to 17.8 times above those of CS. Whitin tomato plants, TMMs were mostly concentrated in the roots but only As and Cd had BCF > 1.0 in AfS. Translocation was also limited to As and Cd in plants from AfS, whereas Ba, Ni, Mn, As, Cd, Cu, and Zn were translocated in CS. Tomato plants from AfS exhibited important alterations in morphological and physiological parameters, with a significant reduction in yield (up to 52%) and nutrimental (up to 81%) contribution relative to plants from CS. AfS plants showed higher DNA damage than CS plants, expressed by an increase in the genotoxic parameters of tail length, tail intensity, and tail moment in the alkaline comet assay. In fruit from both soils, As and Cd exceeded the maximum allowable concentrations proposed by FAO/WHO up to 25 and 54 times, respectively. Moreover, the combined ingestion of TMMs likely poses a high risk of both non-carcinogenic and carcinogenic diseases to consumers-particularly to children.

Dynamic Importance of Genomic and Clinical Risk for Coronary Artery Disease Over the Life Course.

Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to understand how the variable importance of genomic and clinical factors across life stages may significantly improve lifelong CAD event prediction. A longitudinal study was performed using data from 2 cohort studies: the FOS (Framingham Offspring Study) with 3588 participants aged 19 to 57 years and the UKB (UK Biobank) with 327 837 participants aged 40 years to 70 years. A total of 134 765 and 3 831 734 person-time years were observed in FOS and UKB, respectively. Hazard ratios for CAD were calculated for polygenic risk score (PRS) and clinical risk factors at each age of enrollment. The relative importance of PRS and pooled cohort equations in predicting CAD events was also evaluated by age groups. The importance of CAD PRS diminished over the life course, with a hazard ratio of 3.58 (95% CI, 1.39-9.19) at the age of 19 years in FOS and a hazard ratio of 1.51 (95% CI, 1.48-1.54) by the age of 70 years in UKB. Clinical risk factors exhibited similar age-dependent trends. PRS significantly outperformed pooled cohort equations in identifying subsequent CAD events in the 40- to 45-year age group, with 3.2-fold more appropriately identified events. Overall, adding PRS improved the area under the receiving operating curve of the pooled cohort equations by an average of +5.1% (95% CI, 4.9%-5.2%) across all age groups; among individuals <55 years, PRS augmented the area under the curve-ROC of the pooled cohort equations by 6.5% (95% CI, 5.5%-7.5%; P<0.001). Genomic and clinical risk factors for CAD display time-varying importance across the lifespan. The study underscores the added value of CAD PRS, particularly among individuals younger than 55 years, for enhancing early risk prediction and prevention strategies. All results are available at https://surbut.github.io/dynamicHRpaper/index.html.

HDR brachytherapy combined with external beam radiotherapy for unfavorable localized prostate cancer: A single center experience from inception to standard of care.

High dose rate (HDR) brachytherapy is increasingly adopted for dose escalation in prostate cancer treatment. We report the clinical efficacy and toxicity of HDR prostate brachytherapy combined with external beam radiotherapy (EBRT) and evaluate the predictability of the biochemical definition of cure of 4-year PSA ≤0.2 ng/mL for failure free survival (FFS). A single centre retrospective study was conducted, including all patients with high-tier intermediate risk and high-risk prostate cancer treated with HDR brachytherapy combined with EBRT from 2011 to 2019. Patient and prostate cancer characteristics, treatment, clinical endpoints, and follow up were collected. Total 319 patients were analyzed. The median age was 68 with median follow up of 77.1 months. Total 142 had high-tier intermediate and 177 had high-risk disease. Brachytherapy doses were initially 20 Gy/2 fractions, and subsequently 15 Gy/1 fraction. All patients received 46 Gy/23 fractions of EBRT. Overall survival at 5 and 9 years was 92.2% and 77.0%, respectively. Failure-free survival (FFS) was 86.0% at 5 years and 76.1% at 9 years. PSA ≤ 0.2 ng/mL at 4 years was seen in 79.3% of patients and was associated with FFS of 94.1% at 9 years. Grade 3 urethral stricture, hematuria, or proctitis occurred in 2.8%, 0%, and 0%, respectively. HDR brachytherapy in addition to EBRT is effective treatment for unfavourable localized prostate cancer with a very acceptable toxicity profile. The biochemical definition of cure of PSA < 0.2 ng/mL at 4 years was predictive for FFS at 9 years.

Hypofractionated image-guided radiotherapy with 70 Gy in 28 fractions for prostate cancer confined to the pelvis: a single institute experience in Taiwan

BackgroundThe incidence of prostate cancer is increasing in Asian countries. Although moderately hypofractionated radiotherapy is not inferior to conventional fractionated radiation according to the updated guidelines, data regarding its efficacy and safety in Taiwan are currently lacking. The aim of this study was to investigate the outcomes of prostate cancer patients treated with hypofractionated image-guided radiotherapy at a single institution in Taiwan.MethodsWe retrospectively included patients with prostate cancer across all risk groups who were treated with hypofractionated image-guided radiotherapy 70 Gy (Gy) in 28 fractions (at 2.5 Gy/fraction) between 2007 and 2022. We analyzed treatment efficacy by assessing overall survival, prostate cancer-specific survival, event-free survival, biochemical failure, locoregional recurrence, and distant metastasis. The safety of the treatment was evaluated through acute and late gastrointestinal (GI) and genitourinary (GU) toxicity grading based on the Radiation Therapy Oncology Group criteria. Event-free survival, overall survival, prostate cancer-specific survival, biochemical failure, locoregional recurrence, and distant metastasis were evaluated using the Kaplan–Meier method.ResultsWe identified 150 consecutive men with prostate cancer: 12.7% were at low risk, 32.7% were at intermediate risk, 44.6% were at high risk, and 10% had N1 disease. The median follow-up time was 68.9 months (range: 2.3–172 months). The 5-year overall survival rate was 91.7% for the entire cohort, with rates of 100%, 94.3%, 93.3% and 71.1% for the low-risk, intermediate-risk, high-risk, and N1-disease groups, respectively (p < 0.001). The 5-year event-free survival rate for all patients was 75.8%. Among the risk groups, the 5-year event-free survival rates were 100%, 86.3%, 68.3% and 52.5% for the low-risk, intermediate-risk, high-risk, and N1 disease groups, respectively (p < 0.001). Grade ≥ 2 late GI toxicity was rare (0.7%), and grade ≥ 2 late GU toxicity was observed in 9.3% of the patients.ConclusionsHypofractionated image-guided radiotherapy, delivering 70 Gy at 2.5 Gy per fraction, is both effective and safe for Taiwanese patients with prostate cancer across all risk groups, consistent with findings from existing large randomized trials. Therefore, as a solution to enhance patient convenience, hypofractionated radiotherapy is a reasonable option for the definitive treatment of prostate cancer.Trial registrationNot applicable.

Research Progress in Saltiness Perception and Salty Substitutes.

Salty taste in foods is a key sensory attribute for appetite enhancement, however, consumption of a high salt diet is associated with a high risk of hypertension, stroke, and heart diseases. To address this issue, the World Health Organization (WHO) has recommended reducing the global per capita salt consumption by 30% by 2025, with adults optimally consuming less than 5 g/day of salt. Therefore, the search for new salty substitutes to reduce salt intake in foods has become a research hotspot. Despite the ongoing endeavors of global research, multiple studies have focused on the application of a single category of salty alternatives or food processing quality (such as preservative effects and process characteristics), and there is still little comprehensive evaluation of these alternatives in terms of nutritional value, health impact, and consumer acceptance in the literature. This review will first outline the urgency of global salt reduction, followed by thorough discussion of salty substitutes and associated mechanisms from the perspective of human salty taste perception. Second, the present review will explore the potential application of salty substitutes and highlight the interaction between taste and odor in foods. Additionally, the potential impacts of salty substitutes on human health will be discussed. The present review will provide a scientific basis for the development of low salt products by food industry.

Regression of carotid atherosclerosis in high-risk individuals with proprotein convertase subtilisin/kexin type 9 inhibitors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a novel approach for reducing cholesterol and, accordingly, the burden of atherosclerosis. However, limited data are available regarding the possible effects of PCSK9 inhibitors on atherosclerotic plaque. To evaluate the efficacy of PCSK9 inhibitors in reducing carotid plaque progression in individuals with high-risk carotid atherosclerotic disease. We used carotid total plaque area (TPA) to assess the burden of atherosclerosis. Ultrasound imaging of the carotid was acquired before and after the initiation of PCSK9 inhibitor therapy. We selected high-risk cases with atherosclerosis with a minimum of three ultrasound examinations, 1 year before, one at the time of initiation of a PCSK9 inhibitor, and 1 year after initiating a PCSK9 inhibitor. Statistical analysis was conducted using the mixed-effects model with Restricted Maximum Likelihood (REML). We reviewed data from 131 patients with a mean follow-up of 6 (±4) years. Patients were high-risk, with the majority having diabetes or hypertension. There was a decrease in TPA, particularly during the first 3 years after initiating PCSK9 inhibitor therapy (p < 0.05). Furthermore, we observed that individuals with higher baseline serum low-density lipoprotein cholesterol (LDL-C) levels experienced a greater decline in TPA (p < 0.05). PCSK9 inhibitors are effective in achieving plaque regression in high-risk patients with atherosclerosis. This is important, as plaque regression is associated with a lower risk of stroke, myocardial infarction, or vascular death.