Background Women with polyendocrine metabolic ovarian syndrome (PMOS; also known as polycystic ovary syndrome [PCOS]) have a high prevalence of cardiovascular disease risk factors during reproductive years. Our aim was to determine whether PMOS status is associated with increased atherosclerotic cardiovascular disease (ASCVD) events, independent of traditional cardiovascular disease risk factors. Methods In this retrospective, longitudinal, US-based cohort study, we used Optum's de-identified Clinformatics Data Mart Database with data from 2000 to 2022. Females aged 18–50 years diagnosed with PMOS (as identified by ICD 9 and 10 coding for PMOS or ICD 9 and 10 coding for a combination of irregular menses and hirsutism) were included. Only individuals with at least 183 days of continuous enrolment before the index date and no previous history of ASCVD were included. Females with PMOS were matched to a reference group identified by ICD codes for routine annual examination visits, in a 1:5 ratio, by age and month of PMOS diagnosis. The main outcome was occurrence of a composite of ASCVD events, defined as coronary artery disease, cerebrovascular disease, or peripheral artery disease. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs. Findings 413 450 females in the PMOS group (mean age 31·1 years [SD 7·1]) were matched to 2 067 250 females in the reference group (31·1 years [7·0]). The PMOS group had a higher prevalence of traditional cardiovascular disease risk factors at baseline than did the reference group. The hazard ratio for ASCVD was higher in the PMOS group compared with the reference group, with an adjusted HR of 4·40 (95% CI 4·23–4·58). Interpretation Our findings that women with PMOS had a higher incidence of ASCVD events than women without PMOS emphasise the need for health-care provider education and PMOS patient awareness of cardiovascular disease risk to improve implementation of early preventive interventions. Funding Patient-Centered Outcomes Research Institute.

PurposeWe aimed to demonstrate distinct body composition (BC) profiles stratified by sex and clarify their joint effects on long-term mortality in a retrospective cohort of inpatients.MethodsVarious BC parameters annotated on computed tomography (CT) images at the third lumbar vertebra were used to define sarcopenia, myosteatosis, low subcutaneous adiposity, and high visceral adiposity. These categories were constructed using sex-specific, outcome-based cutoffs in a prerequisite manner.ResultsAmong 519 patients hospitalized for acute decompensating episodes, the median age was 64.0 years, with a slight female predominance (51.6%). Among the female patients, high visceral adiposity was the most prevalent single BC abnormality (38.4%), while the most common overlapping phenotype was myosteatosis occurring concurrently with high visceral adiposity (9.7%). Among the male patients, high visceral adiposity also showed the highest prevalence (74.9%), while the most common overlapping phenotype was sarcopenia occurring concurrently with low subcutaneous adiposity (15.1%). Considering their jointly negative impact, the female patients experiencing three BC abnormalities had the lowest survival rate (33.3%, log-rank test: p = 0.0022). Still, this difference was only marginally significant in the male patients with three or more BC abnormalities (log-rank test: p = 0.068). Furthermore, overlapped BC abnormalities were associated with 722 and 331% higher risks, respectively, of 1-year all-cause mortality (p = 0.001) in the female patients relative to those with no BC abnormalities and those with an isolated BC abnormality. Lastly, our established nomogram integrated albumin, Model for End-Stage Liver Disease-Sodium (MELD-Na) score, and distinct overlapping BC abnormalities, demonstrating moderate accuracy, sufficient calibration, and clinical benefits for prognostication.ConclusionIn conclusion, sex-specific variations in BC profiles were observed among the patients with decompensated cirrhosis.

Pneumococcal vaccination effectively reduces the incidence of pneumococcal pneumonia and the associated mortality rates in older adults. Understanding trends in coverage and the influencing factors is essential for optimizing future vaccination programs. Two cross-sectional surveys were conducted in October 2022 and September 2024 among residents aged 60 and above in Pudong New Area, Shanghai. Data on demographic characteristics, pneumococcal vaccination status, and reasons for either receiving or not receiving the vaccine were also collected. A generalized linear mixed model (GLMM) investigated temporal trends in vaccination rates, adjusting for sociodemographic factors. Interactions with the survey year were evaluated to identify associated with time-varying effects on vaccination. The pneumococcal vaccination rate was 34.8% (95% confidence interval [CI]: 32.9-36.6) in 2024, a significant increase of 10.6% points from 24.1% (95% CI: 22.4-25.8) in 2022. (P < .01). Living alone and residence in a care facility were consistently associated with lower vaccination uptake. The proportion of people worried about adverse vaccine reactions increased compared to that in 2022. Although the pneumococcal vaccination coverage in Pudong New Area, Shanghai, has improved in recent years, it remains substantially lower than the rates observed in other developed countries and regions. Targeted monitoring and intervention programs need to be prioritized for vulnerable groups such as those living alone and in older adult care facilities.

Macrophages play an important role in the development of vascular diseases, with their homeostasis closely linked to metabolic reprogramming. This study aims to explore the role of circular RNA-mediated epigenetic remodeling in maintaining macrophage homeostasis during diabetes-induced microvascular dysfunction. We identified a circular RNA, circRNA-sperm antigen with calponin homology and coiled-coil domains 1 (cSPECC1), which is significantly up-regulated in diabetic retinas and in macrophages under diabetic stress. cSPECC1 knockdown in macrophages attenuates M1 macrophage polarization and disrupts macrophage-endothelial crosstalk in vitro. cSPECC1 knockdown in macrophages mitigates diabetes-induced retinal inflammation and ameliorates retinal vascular dysfunction. Mechanistically, cSPECC1 regulates GPX2 expression by recruiting eIF4A3, enhancing GPX2 mRNA stability and altering arachidonic acid metabolism. The metabolic intermediate 12-HETE has emerged as a key mediator, regulating both macrophage homeostasis and the crosstalk between macrophages and endothelial cells. Exogenous 12-HETE supplementation interrupts the anti-angiogenic effects of cSPECC1 knockdown. Collectively, circSPECC1 emerges as a novel regulator of macrophage-mediated vascular integrity and inflammation. Targeting the metabolic reprogramming of macrophages presents a promising therapeutic strategy for mitigating diabetes-induced vascular dysfunction.

OBJECTIVE:To describe real-world patient characteristics, prior treatment patterns, and associated healthcare resource utilization (HRU) and costs among patients with locally advanced/metastatic urothelial carcinoma (la/mUC) treated with enfortumab vedotin (EV). METHODS:This retrospective study used the United States (US) Centers for Medicare and Medicaid Services 100% Medicare claims data from 2015 to 2020. Included patients had a diagnosis of la/mUC and received treatment with EV. The index date was the EV initiation date. Endpoints included HRU and costs 12 months before the index date (baseline period) and treatment patterns before EV initiation. Results were summarized descriptively using means and standard deviations for continuous variables, and frequency counts and percentages for categorical variables. RESULTS:Among the 529 included patients, the mean age at the time of EV initiation was 76.5 years. Most patients were White (88.1%) and male (77.1%). Common comorbidities were hypertension (85.1%), renal disease (65.2%), and peripheral vascular disease (42.5%). Platinum-based chemotherapy was the most frequent therapy two lines before EV initiation (43.9%). The most frequent therapy in the line before EV initiation was PD-1/L1 inhibitors (61.4%). The median duration of EV therapy was 4.1 months. The mean all-cause healthcare cost during the baseline period was $106 258 per patient, and 86% had at least one outpatient visit. CONCLUSIONS:This real-world study demonstrated that most US patients with la/mUC received platinum-based chemotherapy or a PD-1/L1 inhibitor prior to EV therapy from 2015 to 2020. HRU and costs 12 months before EV initiation suggest a substantial burden in this population. Long-term studies with more recent data are warranted.

Background Given the changing treatment landscape for locally advanced or metastatic urothelial carcinoma (la/mUC), this study aimed to describe real-world treatments, overall survival (OS), health care resource utilization (HCRU), and costs among US patients with la/mUC receiving first-line therapy. Methods This retrospective study was conducted using 100% Medicare claims data (2015-2020). Patients with la/mUC were selected; initiation of first-line therapy was the index date. Treatments and OS were assessed during follow-up (index date to the earliest of end of data availability, health plan coverage, or death). All-cause HCRU and costs (2021 USD) were assessed during the first-line treatment period (index date to the earliest of first-line discontinuation, switch to second-line therapy, end of follow-up, or death). Outpatient pharmacy costs were not included. All-cause OS from start of first-line therapy was estimated using the Kaplan-Meier approach. The HCRU, cost, and OS analyses were stratified by 3 index treatment groups-platinum-based chemotherapy, non-platinum-based chemotherapy, and programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor monotherapy-and adjusted for baseline characteristics. Results Of 9,939 patients included, 77.1% were men and mean age was 76 years. In total, 5,050 (50.8%) received platinum-based chemotherapy, 1,361 (13.7%) received non-platinum-based chemotherapy, and 3,242 (32.6%) received PD-1/L1 inhibitor monotherapy for first-line la/mUC. Median OS was 12.9, 12.9 (P = 0.960), and 9.0 months (P < 0.001) with platinum-based chemotherapy (reference), non-platinum-based chemotherapy, and PD-1/L1 inhibitor monotherapy, respectively. Most (> 99%) patients had >= 1 outpatient visit during the treatment period; mean number of visits per patient was 13.1 with platinum-based chemotherapy, 10.5 with non-platinum-based chemotherapy, and 18.3 with PD-1/L1 inhibitor monotherapy. In general, HCRU was significantly lower for patients receiving PD-1/L1 inhibitor monotherapy versus platinum-based chemotherapy. However, costs were significantly higher with PD-1/L1 inhibitor monotherapy versus platinum-based chemotherapy. Mean total monthly cost per patient was $10,285 for platinum-based chemotherapy, $8,982 for non-platinum-based chemotherapy, and $18,147 for PD-1/L1 inhibitor monotherapy. Conclusions From 2015 to 2020, patients with la/mUC had substantial HCRU and costs and short survival, regardless of first-line treatment. More effective therapies were needed to prolong survival and reduce the economic burden of la/mUC. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Objective:Routine immunization programs may reduce antibiotic use, but few studies have comprehensively examined their impact on antibiotic utilization. We aimed to explore temporal trends in vaccination and antibiotic use among young children in the United States. Design:Ecological study using the Merative® MarketScan Commercial Claims and Encounters database. Methods:We analyzed claims data on pediatric vaccine uptake (pneumococcal conjugate, Haemophilus influenzae type b, diphtheria-tetanus-pertussis, and influenza) and antibiotic prescriptions and antibiotic-treated respiratory tract infections among US children <5 years during 2000-2019. Vaccination status was assessed annually, and children were categorized based on receipt of all four vaccines, 1-3 vaccines, or no vaccines. Antibiotic prescriptions were classified by spectrum and drug class. Respiratory infections included otitis media, pharyngitis, pneumonia, sinusitis, and viral infections. Results:Among 6.7 million children, vaccine uptake increased from 32.5% receiving all four vaccines in 2004 to 66.8% in 2019. During this period, overall antibiotic prescriptions decreased from 1.89 to 1.01 per person-year, with the greatest reductions in macrolides (73.3%) and broad-spectrum antibiotics (57.0%). Antibiotic-treated respiratory tract infections declined from 2.43 to 1.61 episodes per person-year, with the largest decreases in sinusitis (64.7%) and pharyngitis (39.8%). Conclusions:The findings suggest a temporal association between routine childhood immunization uptake and reduced antibiotic utilization. Although immunization programs are primarily aimed at protecting children from vaccine-preventable diseases, their potential role in complementing antimicrobial stewardship efforts and other factors influencing antibiotic reduction warrants further investigation through more rigorous study designs.

Patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) require extensive care. Using the Merative® MarketScan® Commercial Claims and Encounters Database (2016 Q1-2020 Q2), we quantified the costs of care and assessed real-world complication rates among commercially-insured US patients diagnosed with a hematologic malignancy and aged 12-64 years undergoing inpatient allo-HCT. Healthcare resource use and costs were assessed from 100 days pre-HCT to 100 days post-HCT. Primary hospitalization was defined as the time from HCT until first discharge date. Incidence of complications was assessed using medical billing codes from HCT date to 100 days post-HCT. Among the 1082 patients analyzed, allo-HCT grafts included peripheral blood (79%), bone marrow (11%), and umbilical cord blood (3%). In the 100 days post-HCT, 52% experienced acute graft-versus-host disease; 21% had cytomegalovirus infection. The median primary hospitalization length of stay (LOS) was 28 days; 31% required readmission in first 100 days post-HCT. Across the transplant period (14 days pretransplant to 100 days posttransplant), 44% of patients were admitted to the intensive care unit with a median LOS of 29 days. Among those in noncapitated health plans (n = 937), median all-cause healthcare per-patient cost during the transplant period was $331,827, which was driven by primary hospitalization and readmission. Additionally, the predicted median incremental costs per additional day in an inpatient setting increased with longer LOS (e.g., $3381 to $4071 from 10th to 20th day.) Thus, decreasing length of primary hospitalization and avoiding readmissions should significantly reduce allo-HCT cost of care.

OBJECTIVE:To synthesize the evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of Chinese patent medicine (CPM) on atherosclerosis (AS) or with a high risk of atherosclerosis. METHODS:All RCTs in three databases (PubMed, EMBASE, and Cochrane Library) were included from the inception of the database to September 20, 2019. The methodological evaluation of the included trials was carried out using the Cochrane Collaboration Risk of Bias Tool. Meta-analysis was conducted using RevMan 5.3 software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the quality of evidence. RESULTS:Eighteen RCTs were included, involving a total of 3885 patients with AS or with a high risk of AS. Most trials had favorable methodology. Meta-analysis suggested significant differences in clinical endpoint (n = 1938, RR 0.53; 95% CI 0.40 to 0.69, P < 0.00001; I 2 = 0%); the change in carotid artery IMT (n = 1723, MD -0.09, 95% CI －0.14 to -0.04, P < 0.001; I 2 = 40%); change in FMD (n = 239, MD 0.87, 95% CI 0.52 to 1.21, P < 0.00001; I 2 = 0%); change in high sensitive C-reactive protein (hs-CRP) (n = 1527, MD －1.89, 95% CI －3.36 to －0.42, P = 0.01; I 2 = 94%) and incidence of total adverse events (RR 0.76, 95% CI 0.62 to 0.93, P = 0.009; I 2 = 40%) in favor of the experimental group. However, meta-analysis showed no significant differences in the change in low-density lipoprotein-C (LDL-C) (n = 2419, MD －0.19, 95% CI －0.50 to 0.12, P = 0.22, I 2 = 94%) between the experimental and control groups. CONCLUSION:CPM could have certain clinical efficacy in the treatment of AS. However, more double-blinded placebo-controlled RCTs are required in further evaluations to provide stronger evidence.

Background: Pneumococcal disease (PD) is a major cause of morbidity and mortality among children, particularly in the youngest age groups. This study aimed to assess the incidence of PD over time by age group in young children with commercial or Medicaid coverage in the US. Methods: Episodes of invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) were identified in the MarketScan (R) Commercial and Medicaid claims databases using diagnosis codes among children aged <= 48 months with confirmed date of birth (DoB), at any time during the study period (1998-2019). DoB was assigned using diagnosis codes for birth or delivery using the child's or mother's medical claims to ensure accurate age determination. Annual incidence rates (IRs) were calculated as number of disease episodes/100,000 person-years (PY) for IPD and ACP and episodes/1,000 PY for AOM, for children aged 0-6, 7-12, 12-24, and 25-48 months. Results: Annual IPD IRs declined from 53 to 7 episodes/100,000 PY between 1998 and 2019 in commerciallyinsured and 58 to 9 episodes/100,000 PY between 2001 and 2019 in Medicaid-insured children. Annual ACP IRs declined from 5,600 to 3,952 episodes/100,000 PY, and from 6,706 to 4,521 episodes/100,000 PY, respectively, over these periods. In both populations, children aged 0-6 months had the highest incidence of IPD and inpatient ACP. Annual AOM IRs declined from 1,177 to 738 episodes/1,000 PY (commercially-insured) and 633 to 624 episodes/1,000 PY (Medicaid-insured), over these periods. IRs were higher in rural vs. urban areas for all disease manifestations. Conclusions: Incidence rates of IPD, ACP, and AOM decreased in children with commercial insurance and Medicaid coverage from 1998 to 2019. However, burden of disease remained substantial, with higher annual IRs for IPD and ACP for Medicaid-insured vs. commercially-insured children. IPD and inpatient ACP were most common in the youngest children 0-6 months old, followed by the 7-12-month age group.

Streptococcus pneumoniae remains a leading cause of morbidity, mortality, and healthcare resource utilization (HRU) among children. This study quantified HRU and cost of acute otitis media (AOM), pneumonia, and invasive pneumococcal disease (IPD). The IBM MarketScan® Commercial Claims and Encounters and Multi-State Medicaid databases from 2014 to 2018 were analyzed. Children with AOM, all-cause pneumonia, or IPD episodes were identified using diagnosis codes in inpatient and outpatient claims. HRU and costs were described for each condition in the commercial and Medicaid-insured populations. National estimates of the number of episodes and total cost (US 2019 for each condition were extrapolated using data from the US Census Bureau. Approximately 6.2 and 5.6 million AOM episodes were identified in commercial and Medicaid-insured children, respectively, during the study period. Mean cost per AOM episode was329 (SD 1505) for commercial and184 (SD 1524) for Medicaid-insured children. A total of 619,876 and 531,095 all-cause pneumonia cases were identified among commercial and Medicaid-insured children, respectively. Mean cost per all-cause pneumonia episode was2304 (SD 32,309) in the commercial and1682 (SD 19,282) in the Medicaid-insured population. A total of 858 and 1130 IPD episodes were identified among commercial and Medicaid-insured children, respectively. Mean cost per IPD episode was53,213 (SD 159,904) for commercial and23,482 (SD 86,209) for the Medicaid-insured population. Nationally, there were over 15.8 million cases of AOM annually, with total estimated cost of4.3 billion, over 1.5 million cases of pneumonia annually, with total cost of 3.6 billion, and about 2200 IPD episodes annually, for a cost of98 million. The economic burden of AOM, pneumonia, and IPD among US children remains substantial. IPD and its manifestations were associated with higher HRU and costs per episode, compared to AOM and all-cause pneumonia. However, owing to their higher frequencies, AOM and all-cause pneumonia were the main contributors to the economic burden of pneumococcal disease nationally. Additional interventions, such as the development of pneumococcal conjugate vaccinees with sustained protection of existing vaccine type serotypes as well as broader inclusion of additional serotypes, are necessary to further reduce the burden of disease caused by these manifestations.

Abstract Background Pneumococcal disease (PD) leads to considerable morbidity, mortality, and healthcare resource utilization in children. This study estimated incidence rates (IRs) for invasive PD (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) among children ≤ 48 months old, between 2010 and 2019 in the US. Methods This was a retrospective observational study using MarketScan® Commercial Claims and Encounters (CCAE) and Multi-State Medicaid databases (2010-2019). Date of birth was imputed using dates of live-birth claims for accurate age determination. IPD, ACP, and AOM claims in children ≤48 months old were identified using International Classification of Diseases (ICD) versions 9 and 10 diagnosis codes. Episodes were defined as one or more PD-related claims, with a gap of 90 days between two IPD or ACP claims, and 14 days between two AOM claims. IRs were defined as number of episodes per 100,000 person-years (PY) for IPD and ACP, and per 1,000 PY for AOM. Annual IRs were stratified by age (0-6, 7-12, 13-24, and 25-48 months), and reported separately for CCAE and Medicaid populations. Results Overall IPD IRs declined between 2010-2019 from 11 to 7 episodes per 100,000 PY in CCAE and from 20 to 9/100,000 PY in Medicaid; IPD IRs were highest in children 0-6 months old, followed by 7-12 months old, in both populations (Fig. 1). Overall ACP IRs changed little between 2010-2019 from 3,996 to 3,952/100,000 PY in CCAE and declined from 6,225 to 4,521 per 100,000 PY in Medicaid; ACP IRs were highest in CCAE among children aged 13-24 and 25-48 months, and in Medicaid among children aged 13-24 and 7-12 months. (Fig. 2). Overall AOM IRs changed little between 2010-2019 from 723 to 738/1,000 PY in 2018 in CCAE and decreased from 773 to 624/1,000 PY in Medicaid (Fig. 3). AOM IRs were highest for children 7-12 months in both populations.Figure 1.IPD incidence in commercially and Medicaid-insured children ages 0 - 48 months, episodes per 100,000 patient-years (2010 - 2019)Figure 2.ACP incidence in commercially and Medicaid-insured children ages 0 - 48 months, episodes per 100,000 patient-years (2010 - 2019)Figure 3.AOM incidence in commercially and Medicaid-insured children ages 0 - 48 months, episodes per 1,000 patient-years (2010 - 2019) Conclusion IPD, ACP, and AOM IRs disease burden remains substantial with a disproportionately high impact of the most severe disease manifestations (IPD and inpatient ACP) among infants in the first year of life, despite marked declines following the introduction of PCV13. Disease IRs were generally higher in Medicaid children, particularly at the start of the study period, but also declined more significantly over time compared to IRs in CCAE children. Disclosures Salini Mohanty, DrPH, MPH, Employee of Merck & Co., Inc.: Stocks/Bonds Nicolae Done, PhD, Merck & Co., Inc.: Grant/Research Support Qing liu, PhD, Merck & Co., Inc.: Advisor/Consultant Yan Song, PhD, Merck & Co., Inc.: Grant/Research Support Katherine Gaburo, n/a, Merck & Co., Inc.: I am an employee of Analysis Group, Inc., which received consulting fees for participation in this research Travis Wang, MS, MBBS, Merck & Co., Inc.: Grant/Research Support Meghan White, PharmD, Merck: Employee|Merck: Stocks/Bonds Jessica P. Weaver, PhD, Employee of Merck & Co., Inc.: Stocks/Bonds James Signorovitch, PhD, Merck & Co., Inc.: Grant/Research Support Thomas Weiss, DrPH, MPH, Employee of Merck & Co., Inc.: Stocks/Bonds

Background: Diabesity defines the concurrent manifestation of type 2 diabetes (T2D) and obesity (BMI≥30 kg/m 2 ) in the development of cardiovascular diseases, although the genetic basis for this joint phenotype remain poorly understood. Objective: This study aimed to identify the overlapping genetic patterns for diabesity incidence in 3,231 self-reported African American (AA) and 8,252 European Americans (EA) participated in four cohorts of the Trans-Omics for Precision Medicine (TOPMed) consortium. Methods: Using marker set enrichment analysis (MSEA) of whole genome sequencing data, specific gene sets (pathways) and key driver (KD) genes (important hub genes overrepresented in a network of pathways) were identified for diabesity incidence. Using multi-tissue and multi-species gene expression signatures as molecular indicators of drug functions, their potential drug signatures were also examined. Results: Testing genome-wide significance (P-value < 10 -8 ) identified seven independent loci, six of which were replicated in the T2D Knowledge Portal (https://t2d.hugeamp.org/ )( NPFFR1, TRIO, G6PD, BCL11A, IGF1, and TCF7L2, P<0.05) for diabetes and/or such obesity-related traits as blood pressure, lipids, glucose and insulin levels. One novel variant for diabesity, rs144540309, is an intronic region of GPAT3 (G>A, AA MAF = 0.004, beta=3.66 and P=1.00e-8) whose enzyme plays important roles in dietary lipid absorption, enteric and hepatic lipid homeostasis, and entero-endocrine hormone production, along with 12 KEGG/Reactome/Biocarta pathways enriched for diabesity in AAs and 11 for EAs. In AAs, the top three pathways (ranked by P-value and false discovery rate [FDR]) were mitotic spindle checkpoint, resolution of sister chromatid cohesion, and rho GTPases activate formins, along with six KD genes ( NCKAP1L, CDCA8 , BUB1 , IRF5 , FYB , and C15orf23 ); in EAs, colorectal cancer, prostate cancer, and beta Catenin independent WNT signaling were the top 3 pathways (FDR≤0.25) including LEF1 . Top repositioned drugs derived from diabesity-related gene sets (FDR≤0.25) included Benzbromarone, Fenofibrate, Interleukin-1β, and antihypertensive. Conclusion: Our study supports the notion that both pathway and network-based analytical approaches may identify novel signals from gene sets for highly clustering clinical phenotypes such as diabetes and obesity and improve their target validation for intervention.

This study compared the real-world healthcare resource utilization (HRU), costs, adverse events (AEs), and AE treatments associated with the chimeric antigen receptor T-cell (CAR-T) therapies, tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel), for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Adults with DLBCL who received tisa-cel or axi-cel were identified in the Premier Healthcare Database (2017-2020). Non-CAR-T costs, HRU, and AE rates during the infusion and follow-up periods were compared between the tisa-cel and axi-cel cohorts. Of 119 patients, 33 received tisa-cel (86% as inpatient infusion) and 86 received axi-cel (100% inpatient). Tisa-cel was associated with significantly shorter mean inpatient length of stay than axi-cel during infusion (11.3 vs. 18.3 days) and follow-up ([monthly] 3.9 vs. 6.9 days). Non-CAR-T costs were significantly lower for tisa-cel compared with axi-cel during infusion ($27594.8 vs. $51378.3) and follow-up ([monthly] $28777.3 vs. $46575.7; both p< .05). Rates of AEs and AE treatments were similar.

Much remains unknown about the role of added sugar in relation to cardiovascular disease (CVD) and the relative contributions of sugar-sweetened beverages (SSB) or artificially sweetened beverages (ASB) to CVD risk. Among the 109,034 women who participated in Women’s Health Initiative, we assessed average intakes of added sugar, SSB and ASB, and conducted Cox regression to estimate the hazard ratios (HRs) and their 95% confidence intervals for CVD risk. The consistency of findings was compared to a network meta-analysis of all available cohorts. During an average of 17.4 years of follow-up, 11,597 cases of total CVD (nonfatal myocardial infarction, coronary heart disease (CHD) death, stroke, coronary revascularization, and/or incident heart failure) were confirmed. Added sugar as % energy intake daily (%EAS) at ≥15.0% was positively associated with total CVD (HR = 1.08 [1.01, 1.15]) and CHD (HR = 1.20 [1.09, 1.32]). There was also a higher risk of total CVD associated with ≥1 serving of SSB intake per day (HR = 1.29 [1.17, 1.42]), CHD (1.35 [1.16, 1.57]), and total stroke (1.30 [1.10, 1.53]). Similarly, ASB intake was associated with an increased risk of CVD (1.14 [1.03, 1.26]) and stroke (1.24 [1.04, 1.48]). According to the network meta-analysis, there was a large amount of heterogeneity across studies, showing no consistent pattern implicating added sugar, ASB, or SSB in CVD outcomes. A diet containing %EAS ≥15.0% and consuming ≥1 serving of SSB or ASB may be associated with a higher CVD incidence. The relative contribution of added sugar, SSB, and ASB to CVD risk warrants further investigation.

Abstract Background Acute otitis media (AOM) is a leading cause of office visits and antibiotic prescriptions in children. Pneumococcal conjugate vaccines were introduced in the USA in 2000 (7-valent, PCV7) and 2010 (13-valent, PCV13). Expanded valency PCVs are currently under development. To describe the impact of PCVs and quantify the residual burden of AOM, this study estimated annual incidence rates (IRs) of AOM and AOM-related complications and surgical procedures in children < 18 years in the USA before and after the introduction of PCV7 and PCV13. Methods AOM episodes were identified in the IBM MarketScan® Commercial and Medicaid databases using diagnosis codes (ICD-9-CM: 382.x; ICD-10-CM: H66.xx and H67.xx). Annual IRs were calculated as the number of episodes per 1000 person-years (PYs) for all children < 18 years and by age group (< 2, 2–4, and 5–17 years). National estimates of annual AOM IRs were extrapolated using Census Bureau data. Interrupted time series analyses were used to assess immediate and gradual changes in monthly AOM IRs, controlling for seasonality. Results In the commercially insured population, AOM IRs declined between the pre-PCV7 period (1998–1999) and the late PCV13 period (2014–2018) from 1170.1 to 768.8 episodes per 1000 PY for children < 2 years, from 547.4 to 410.3 episodes per 1000 PY in children 2–4 years, and from 115.6 to 91.8 episodes per 1000 PY in children 5–17 years. The interrupted time series analyses indicated significant immediate or gradual decreases in the early PCV7 period (2001–2005), and gradual increases in the late PCV7 period (2006–2009) in children < 2 years; however, crude IRs trended downward in all time periods. In older children, IRs decreased in the early PCV7 and early PCV13 period (2011–2013), but gradually increased in the late PCV7 period. IRs of AOM-related surgical procedures decreased, and IRs of AOM-related complications increased during the study timeframe. Conclusions AOM disease burden remains high in children of all ages despite overall reductions in AOM IRs during 1998–2018 following the introduction of PCV7 and PCV13. The impact of investigational PCVs on the disease burden of AOM will likely depend on AOM etiology and circulating pneumococcal serotypes.