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ABSTRACT Importance Critically ill children with pre‐existing mental health conditions may have an increased risk of poor health outcomes. Objective We aimed to evaluate if pre‐existing mental health conditions in critically ill pediatric patients would be associated with worse clinical outcomes, compared to children with no documented mental health conditions. Methods This retrospective observational cohort study utilized the TriNetX electronic health record database of critically ill subjects aged 12–18 years. Data were analyzed for demographics, pre‐existing conditions, diagnostic, medication, procedural codes, and mortality. Results From a dataset of 102 027 critically ill children, we analyzed 1999 subjects (284 [14.2%] with a pre‐existing mental health condition and 1715 [85.8%] with no pre‐existing mental health condition). Multivariable analysis demonstrated that death within one year was associated with the presence of pre‐existing mental health conditions (odds ratio 8.97 [3.48–23.15], P < 0.001), even after controlling for the presence of a complex chronic condition. Interpretation The present study demonstrates that the presence of pre‐existing mental health conditions was associated with higher odds of death within 1 year after receiving critical care. However, the confidence interval was wide and hence, the findings are inconclusive. Future studies with a larger sample size may be necessary to evaluate the true long‐term impact of children with pre‐existing mental health conditions who require critical care services.

Abstract Background Chronic levels of inflammation are associated with higher risk of many chronic diseases. Physical activity (PA) lowers the risk of cancer, cardiovascular disease (CVD), diabetes and others. One mechanism for PA-induced protection may be through the immune system. We investigated the association between leisure-time PA and peripheral immune cell populations in a large nationally representative sample of the US general population. Methods A total of 17,093 participants [mean (SE) age of 41.6 (0.3) years] of the National Health and Nutrition Examination Survey 1999–2018 were included. Self-reported leisure-time PA was converted to metabolic equivalent of task hours per week (MET-hrs/wk). White blood cell (WBC) count, WBC ratios, and platelet count were derived. Multivariable linear regression analyses were used to estimate associations between leisure-time PA level and peripheral immune cell populations. Multivariable logistic regression analyses were used to estimate associations between leisure-time PA and metrics of WBC count and neutrophil-to-lymphocyte ratio (NLR) which may predict mortality. Results A higher leisure-time PA level was associated with a lower WBC count (> 14.0 vs. 14.0 vs. 8.1 × 109 cells/L; odds ratio [OR] = 0.76, 95% CI = 0.66–0.88) and high NLR (> 2.68; OR = 0.84, 95% CI = 0.72–0.99), which may predict CVD and all-cause mortality. The highest leisure-time PA level also linked to a lower probability of a high WBC count (≥ 8.3 × 109 cells/L; OR = 0.76, 95% CI = 0.66–0.88), which may predict cancer mortality. Conclusions We observed an inverse association between leisure-time PA level, WBC count, and NLR, particularly for neutrophil levels. These results suggest that participants at higher levels of leisure-time PA may have lower levels of inflammation, which may be important for future chronic disease outcomes.

Abstract Background Intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation may result in Takotsubo syndrome (TS), but the frequency, predisposing factors (age, sex, mental health disorders), and outcomes are currently unknown. This study sought to assess the frequency, predisposing factors, and outcomes of subjects who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation and were diagnosed with TS. Methods This was a retrospective observational cohort study utilizing TriNetX® electronic health record (EHR) data. We included subjects aged older than 18 years who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation. The study population was divided into two groups (no TS diagnostic code presence and TS diagnostic code presence). We analyzed the distributions of age, sex, race, diagnostic codes, common terminology procedures (CPT), and vasoactive medication codes and examined mortality rate within 30 days. Results We included 69,116 subjects. Of these, 27 (0.04%) had a TS diagnostic code, the cohort was comprised mostly of females [17 (63.0%)], and 1 (3.7%) death within 30 days was reported. There were no significant differences in age and frequency of mental health disorders between those patients in TS and non‐TS cohorts. Adjusting for age, sex, race, ethnicity, patient regionality, and mental health disorder diagnostic code, those patients who developed TS had a significantly higher odds of dying in 30 days after catheter ablation compared to those without TS (OR = 15.97, 95% CI: 2.10–121.55, p = .007). Conclusions Approximately 0.04% of subjects who underwent intracardiac catheter ablation of atrial fibrillation by pulmonary vein isolation had a subsequent diagnostic code of TS. Further study is needed to determine whether there are predisposing factors associated with the development of TS in subjects who undergo catheter ablation of atrial fibrillation by pulmonary vein isolation.

Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.

Abstract Background Guidelines allow for the omission of radiotherapy in older women with early‐stage, hormone‐receptor‐positive breast cancer, given that the patients receive adequate endocrine therapy (ET). However, the initiation of ET and survival outcomes after forgoing radiation therapy among these patients have not been well‐studied. Methods We identified patients aged 70 to 90 years old newly diagnosed in 2010–2015 with early‐stage, hormone receptor positive, and human epidermal growth factor receptor 2 (HER2) negative (HR+/Her2−) breast cancer who received lumpectomy and omitted radiation therapy using the SEER‐Medicare database. We examined the initiation of ET and the utilization patterns of ET using a multivariable logistic regression. We further examined the overall survival outcomes using Kaplan–Meier estimation and Cox proportional hazard model with inverse probability weighting. Results Of the 2618 patients, 808 (30.9%) received no ET. The multivariable logistic regression showed that more recent years had better ET initiation (2013–2015 vs. 2010–2012: OR = 1.39, 95% CI:[1.16, 1.66]), while older patients (81–90 vs. 70–80: OR = 0.45, 95% CI:[0.38, 0.54]) were less likely to receive ET. Both the Kaplan–Meier estimation (log‐rank p‐value

Background/objectives: There is limited research on the associated immediate and long-term outcomes of postpartum hemorrhage. Mothers with a pre-existing psychiatric disease prior to delivery may be especially vulnerable to postpartum hemorrhage outcomes but little is known on this topic. Barriers to studying this population exist and add to knowledge gaps. The goal of this study is to determine the clinical characteristics and frequency of complications within 1 year of a postpartum hemorrhage diagnosis and the psychiatric sequelae within 7 days of a postpartum hemorrhage diagnosis in mothers with a pre-existing mental health diagnosis prior to delivery versus those without. Methods/design: This is a multicenter retrospective observational cohort study using TriNetX, a de-identified electronic health record database. The following electronic health record data were collected and evaluated in postpartum females who were billed for either a vaginal or cesarean delivery: age, race, ethnicity, diagnostic codes, medication codes, and number of deaths. Results: We included 10,649 subjects (6994 (65.7%) no mental health diagnosis and 3655 (34.3%) pre-existing mental health diagnosis). Haloperidol administration (118 (3.2%) versus 129 (1.8%), p

Purpose: The prevalence of erectile dysfunction (ED) and the utilization of inflatable penile prosthesis (IPP) among prostate cancer patients are understudied. The aim of the study was to examine the relationships between ED, prostate cancer treatment type and IPP implantation in a national cohort. Materials and Methods: We identified a retrospective cohort of Surveillance, Epidemiology, and End Results (SEER)-Medicare patients diagnosed with locoregional prostate cancer between 2006 and 2011 and treated with surgery or radiation. Chi-square tests were used to detect significant differences in ED rates as well as use of IPP among the subset with ED. Multivariable logistic regression was used to examine factors associated with the use of IPP. Results: Among 31,233 patients in our cohort, 10,334 (33.1%) received prostatectomy and 20,899 (66.9%) received radiation. ED within 5 years was significantly more common in the prostatectomy group relative to those the radiation group (65.3% vs. 33.8%, p

Abstract Background Guidelines in 2013 and 2014 recommended Epidermal Growth Factor Receptor (EGFR) testing for metastatic lung adenocarcinoma patients as the efficacy of targeted therapies depends on the mutations. However, adherence to these guidelines and the corresponding costs have not been well-studied. Methods We identified 2362 patients at least 65 years old newly diagnosed with metastatic lung adenocarcinoma from January 2013 to December 2015 using the SEER-Medicare database. We examined the utilization patterns of EGFR testing and targeted therapies including erlotinib and afatinib. We further examined the costs of both EGFR testing and targeted therapy in terms of Medicare costs and patient out-of-pocket (OOP) costs. Results The EGFR testing rate increased from 38% in 2013 to 51% and 49% in 2014 and 2015 respectively. The testing rate was 54% among the 394 patients who received erlotinib, and 52% among the 42 patients who received afatinib. The median Medicare and OOP costs for testing were $1483 and $293. In contrast, the costs for targeted therapy were substantially higher with median 30-day costs at $6114 and $240 for erlotinib and $6239 and $471 for afatinib. Conclusion This population-based study suggests that testing guidelines improved the use of EGFR testing, although there was still a large proportion of patients receiving targeted therapy without testing. The costs of targeted therapy were substantially higher than the testing costs, highlighting the need to improve adherence to testing guidelines in order to improve clinical outcomes while reducing the economic burden for both Medicare and patients.

Abstract Background Just Another Gibbs Sampling (JAGS) is a convenient tool to draw posterior samples using Markov Chain Monte Carlo for Bayesian modeling. However, the built-in function dinterval() for censored data misspecifies the default computation of deviance function, which limits likelihood-based Bayesian model comparison. Results To establish an automatic approach to specifying the correct deviance function in JAGS, we propose a simple and generic alternative modeling strategy for the analysis of censored outcomes. The two illustrative examples demonstrate that the alternative strategy not only properly draws posterior samples in JAGS, but also automatically delivers the correct deviance for model assessment. In the survival data application, our proposed method provides the correct value of mean deviance based on the exact likelihood function. In the drug safety data application, the deviance information criterion and penalized expected deviance for seven Bayesian models of censored data are simultaneously computed by our proposed approach and compared to examine the model performance. Conclusions We propose an effective strategy to model censored data in the Bayesian modeling framework in JAGS with the correct deviance specification, which can simplify the calculation of popular Kullback–Leibler based measures for model selection. The proposed approach applies to a broad spectrum of censored data types, such as survival data, and facilitates different censored Bayesian model structures.

Cannabigerol (CBG), derived from the cannabis plant, acts as an acute analgesic in a model of cisplatin-induced peripheral neuropathy (CIPN) in mice. There are no curative, long-lasting treatments for CIPN available to humans. We investigated the ability of chronic CBG to alleviate mechanical hypersensitivity due to CIPN in mice by measuring responses to 7 and 14 days of daily CBG. We found that CBG treatment (i.p.) for 7 and 14 consecutive days significantly reduced mechanical hypersensitivity in male and female mice with CIPN and reduced pain sensitivity up to 60–70% of baseline levels (p < 0.001 for all), 24 h after the last injection. Additionally, we found that daily treatment with CBG did not evoke tolerance and did not incur significant weight change or adverse events. The efficacy of CBG was independent of the estrous cycle phase. Therefore, chronic CBG administration can provide at least 24 h of antinociceptive effect in mice. These findings support the study of CBG as a long-lasting neuropathic pain therapy, which acts without tolerance in both males and females.

Abstract Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1–3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.

REAP-2 is an interactive dose-response curve estimation tool for Robust and Efficient Assessment of drug Potency. It provides user-friendly dose-response curve estimation for in vitro studies and conducts statistical testing for model comparisons with a redesigned user interface. We also make a major update of the underlying estimation method with penalized beta regression, which demonstrates great reliability and accuracy in dose estimation and uncertainty quantification. In this note, we describe the method and implementation of REAP-2 with a highlight on potency estimation and drug comparison.

The median-effect equation has been widely used to describe the dose-response relationship and identify compounds that activate or inhibit specific disease targets in contemporary drug discovery. However, the experimental data often contain extreme responses, which may significantly impair the estimation accuracy and impede valid quantitative assessment in the standard estimation procedure. To improve the quantitative estimation of the dose-response relationship, we introduce a novel approach based on robust beta regression. Substantive simulation studies under various scenarios demonstrate solid evidence that the proposed approach consistently provides robust estimation for the median-effect equation, particularly when there are extreme outcome observations. Moreover, simulation studies illustrate that the proposed approach also provides a narrower confidence interval, suggesting a higher power in statistical testing. Finally, to efficiently and conveniently perform common lab data analyses, we develop a freely accessible web-based analytic tool to facilitate the quantitative implementation of the proposed approach for the scientific community.

We propose a new model selection method, named the posterior averaging information criterion, for Bayesian model assessment to minimize the risk of predicting independent future observations. The theoretical foundation is built on the Kullback–Leibler divergence to quantify the similarity between the proposed candidate model and the underlying true model. From a Bayesian perspective, our method evaluates the candidate models over the entire posterior distribution in terms of predicting a future independent observation. Without assuming that the true distribution is contained in the candidate models, the new criterion is developed by correcting the asymptotic bias of the posterior mean of the in-sample log-likelihood against out-of-sample log-likelihood, and can be generally applied even for Bayesian models with degenerate non-informative priors. Simulations in both normal and binomial settings demonstrate superior small sample performance.

Abstract Opioid use among metastatic breast cancer (MBC) patients has not been well-studied. This study examined the trends and patterns of opioid use among working-age, privately insured patients diagnosed with MBC. Using MarketScan data, we identified female patients diagnosed with MBC in 2006–2015. We determined the proportion of patients who filled a prescription for an opioid and calculated days’ supply and daily morphine milligram equivalents (MMEs) from 1 year prior to diagnosis till 1 year after. We assessed the trend in opioid use over the 10-year study period and examined opioid usage patterns after the diagnosis of MBC. Among 24,752 patients included, 11,579 (46.8%) had an opioid prescription within 1 year before diagnosis of MBC, and 20,416 (81.4%) had an opioid prescription within 1 year after diagnosis. The proportion of patients with opioid prescriptions after diagnosis was relatively stable from 2006 to 2015. However, both the median daily MME and median days’ supply decreased over time with most of the decline from the subgroup of patients with prior prescription opioid use. Most patients received an opioid prescription in the first month after diagnosis (57.3%), dropping to approximately 20% from 3 to 12 months after diagnosis. Also, the median days’ supply increased substantially during the year after diagnosis for patients who received opioids (from 7 to 19). Most women with MBC require opioid analgesia within the first month after diagnosis. Judicious, long-term management of pain after diagnosis of MBC will continue to be necessary for many patients.

Abstract Background Excess adiposity and dysregulated metabolism are associated with increased cancer risk. Triglycerides, cholesterol, glucose, insulin, HOMA‐IR, and VO2max are robust clinical‐metabolic biomarkers of overall health. Aims Aerobic exercise may improve clinical‐metabolic biomarkers and decrease cancer risk. This secondary analysis of the WISER Sister randomized controlled trial investigated dose‐dependent effects of aerobic exercise on clinical biomarker levels in women at high genetic risk for breast cancer. Methods and Results One hundred thirty‐nine participants were randomized to: control (80% of their exercise dose. A significant dose‐dependent increase in VO2max was observed for the low‐dose and high‐dose groups compared to control. No intervention effects were observed for plasma biomarkers. Overweight women (BMI > 25) showed a significant decrease in insulin levels and a trend for decreased triglycerides following exercise intervention. Significant increases in VO2max were independent of BMI stratification. Conclusion Women at high genetic risk for breast cancer should maintain healthy weights and aerobic capacities through aerobic exercise to achieve measurable benefits on overall health. For overweight women, exercise appears to improve subclinical metabolic dysregulation. However, normal weight women were unaffected by aerobic exercise as their biomarker levels may be below the threshold for improvement. VO2max increases solely quantified the benefits of exercise in already healthy women at high‐risk for breast cancer.

The COVID-19 pandemic led to changes in hospital visitor policies and little is known about the impact on patients and their families. This study evaluated families’ understanding of and reactions to COVID-19-related visitor restriction policy at an academic children's hospital. We conducted a cross-sectional study with families of patients admitted to the pediatric ICU and general pediatric wards from September 2020 to November 2020. Parents (n = 73) completed a survey assessing communication, understanding of and satisfaction with visitor policies, strategies of coping with illness, and Hospital Anxiety and Depression Scale (HADS) scores. Descriptive analyses were performed to summarize data. Associations between outcomes and participant characteristics were examined. A majority (88%) of respondents reported hospital visitor restrictions were explained, usually in-person (94%), and understood the policy “very well” (68%), but none correctly identified all reasons for visitation restrictions. Eighty-five percent reported other family/friends would have visited, however minority families were more likely to report they would have had fewer visitors if restrictions were not in place ( P = 0.0385). A majority (69%) were satisfied with how the hospital handled visitor polices, and parents of older children were more satisfied ( P

We studied associations of persistent respiratory morbidity (PRM) at 6 and 12 months after acute respiratory failure (ARF) in previously healthy children with single-nucleotide polymorphisms (SNPs) of surfactant protein (SP) genes. Of the 250 enrolled subjects, 155 and 127 were followed at 6 and 12 months after an ARF episode, respectively. Logistic regression analysis and SNP–SNP interaction models were used. We found that 1) in the multivariate analysis, an increased risk at 6 and 12 months was associated with rs1124_A and rs4715_A of SFTPC, respectively; 2) in a single SNP model, increased and decreased risks of PRM at both timepoints were associated with rs1124 of SFTPC and rs721917 of SFTPD, respectively; an increased risk at 6 months was associated with rs1130866 of SFTPB and rs4715 of SFTPC, and increased and decreased risks at 12 months were associated with rs17886395 of SFTPA2 and rs2243639 of SFTPD, respectively; 3) in a two-SNP model, PRM susceptibility at both timepoints was associated with a number of intergenic interactions between SNPs of the studied SP genes. An increased risk at 12 months was associated with one intragenic (rs1965708 and rs113645 of SFTPA2) interaction; 4) in a three-SNP model, decreased and increased risks at 6 and 12 months, respectively, were associated with an interaction among rs1130866 of SFTPB, rs721917 of SFTPD, and rs1059046 of SFTPA2. A decreased risk at 6 months was associated with an interaction among the same SNPs of SFTPB and SFTPD and the rs1136450 of SFTPA1. The findings revealed that SNPs of all SFTPs appear to play a role in long-term outcomes of ARF survivors and may serve as markers for disease susceptibility.

Abstract Background The influence of serious mental illness (SMI) on the treatment and survival of patients with high‐grade prostate cancer is not well understood. We compared the initial cancer treatment and cancer‐specific mortality of SEER‐Medicare patients with locoregional high‐grade (nonmetastatic) prostate cancer with and without preexisting SMI. Methods We identified SEER‐Medicare patients who were 67 years of age or older diagnosed between 2006 and 2013 with locoregional high‐grade (nonmetastatic) prostate cancer. Preexisting SMI was identified by claims indicative of bipolar disorder, schizophrenia, and other psychotic disorder, during the 2 years before cancer diagnosis. We used multivariable binary logistic regression to examine associations between SMI and receipt of surgery or radiation concurrent with hormone therapy (definitive initial treatment) within 1 year after cancer diagnosis. We used Kaplan‐Meier survival curves, as well as Cox proportional hazards and competing risk models to evaluate unadjusted and adjusted associations between SMI and 5‐year cancer‐specific survival. Results Among 49 985 patients with locoregional high‐grade (nonmetastatic) prostate cancer, 523 (1.1%) had SMI and 49 462 (98.9%) had no SMI. Overall, SMI was associated with reduced odds of receiving surgery (OR = 0.66, 95% CI: 0.49‐0.89) or radiation concurrent with hormone therapy (OR = 0.81, 95% CI: 0.67‐0.98) as initial treatments in the year after cancer diagnosis. Additionally, SMI was associated with higher hazard of 5‐year cancer‐specific death (HR = 1.41, 95% CI: 1.06‐1.89) after accounting for competing risks of non‐cancer death. Conclusion Among SEER‐Medicare patients with locoregional high‐grade (nonmetastatic) prostate cancer, those with preexisting SMI—relative to those without these conditions—were less likely to receive definitive initial treatment in the year after diagnosis and had poorer cancer‐specific survival 5 years after diagnosis.

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of common environmental organic particles. Surfactant proteins (SPs) play a role in innate immunity and surfactant function. We hypothesized that single nucleotide polymorphisms (SNPs) or haplotypes of the SP genes associate with HP.Methods: Seventy-five HP patients caused by avian antigen and 258 controls, asymptomatic antigen exposed and non-exposed were enrolled. SNP association was performed using logistic regression analysis and SNP-SNP interaction models.Results: Based on odds ratio, regression analyses showed association of (a) rs7316_G, 1A3 (protective) compared to antigen exposed; (b) male sex, smoking, rs721917_T and rs1130866_T (protective) compared to non-exposed controls with HP; (c) compared to antigen exposed, 25 interactions associated with HP in a three-SNP model; (d) compared to non-exposed, (i) rs1136451 associated with increased, whereas rs1136450 and rs1130866 associated with lower HP risk, (ii) 97 interactions associated with HP in a three-SNP model. The majority of SNP-SNP interactions associated with increased HP risk involved SNPs of the hydrophilic SPs, whereas, the majority of interactions associated with lower HP risk involved SNPs of both hydrophilic and hydrophobic SPs; (e) haplotypes of SP genes associated with HP risk.Conclusions: The complexity of SNPs interactions of the SFTP genes observed indicate that the lung inflammatory response to avian antigens is modulated by a complex gene interplay rather than by single SNPs.

Background. Robotic surgical systems are expensive to own and operate, and the purchase of such technology is an important decision for hospital administrators. Most prior literature focuses on the comparison of clinical outcomes between robotic surgery and other laparoscopic or open surgery. There is a knowledge gap about what drives hospitals’ decisions to purchase robotic systems. Objective. To identify factors associated with a hospital’s acquisition of advanced surgical systems. Method. We used 2002 to 2011 data from the State of California Office of Statewide Health Planning and Development to examine robotic surgical system purchase decisions of 476 hospitals. We used a probit estimation allowing heteroscedasticity in the error term including a set of two equations: one binary response equation and one heteroscedasticity equation. Results. During the study timeframe, there were 78 robotic surgical systems purchased by hospitals in the sample. Controlling for hospital characteristics such as number of available beds, teaching status, nonprofit status, and patient mix, the probit estimation showed that market-level directly relevant surgery volume in the previous year (excluding the hospital’s own volume) had the largest impact. More specifically, hospitals in high volume (>50,000 surgeries v. 0) markets were 12 percentage points more likely to purchase robotic systems. We also found that hospitals in less competitive markets (i.e., Herfindahl index above 2500) were 2 percentage points more likely to purchase robotic systems. Limitations. This study has limitations common to observational database studies. Certain characteristics such as cultural factors cannot be accurately quantified. Conclusions. Our findings imply that potential market demand is a strong driver for hospital purchase of robotic surgical systems. Market competition does not significantly increase the adoption of new expensive surgical technologies.

ObjectiveTo compare "virtual" unenhanced (VUE) computed tomography (CT) images, reconstructed from rapid kVp-switching dual-energy computed tomography (DECT), to "true" unenhanced CT images (TUE), in clinical abdominal imaging. The ability to replace TUE with VUE images would have many clinical and operational advantages.MethodsVUE and TUE images of 60 DECT datasets acquired for standard-of-care CT of pancreatic cancer were retrospectively reviewed and compared, both quantitatively and qualitatively. Comparisons included quantitative evaluation of CT numbers (Hounsfield Units, HU) measured in 8 different tissues, and 6 qualitative image characteristics relevant to abdominal imaging, rated by 3 experienced radiologists. The observed quantitative and qualitative VUE and TUE differences were compared against boundaries of clinically relevant equivalent thresholds to assess their equivalency, using modified paired t-tests and Bayesian hierarchical modeling.ResultsQuantitatively, in tissues containing high concentrations of calcium or iodine, CT numbers measured in VUE images were significantly different from those in TUE images. CT numbers in VUE images were significantly lower than TUE images when calcium was present (e.g. in the spine, 73.1 HU lower, p < 0.0001); and significantly higher when iodine was present (e.g. in renal cortex, 12.9 HU higher, p < 0.0001). Qualitatively, VUE image ratings showed significantly inferior depiction of liver parenchyma compared to TUE images, and significantly more cortico-medullary differentiation in the kidney.ConclusionsSignificant differences in VUE images compared to TUE images may limit their application and ability to replace TUE images in diagnostic abdominal CT imaging.

ABSTRACT IMPACT: A one-stage Bayesian multilevel model for meta-analysis integrating different survival data is introduced to complete the information synthesis without assuming proportional hazard. OBJECTIVES/GOALS: To develop a general modeling approach to perform efficient and robust meta-analyses using aggregated data (AD) for survival type endpoint and apply to a meta-analysis to examine the association between measurable residual disease (MRD) and disease-free survival (DFS) and overall survival (OS) in patients with acute myeloid leukemia (AML). METHODS/STUDY POPULATION: A Bayesian semi-parametric hierarchical model with a time-varying HR effect was presented. Three common types of survival information, including reconstructed survival data, the hazard ratio (HR) estimates with corresponding CIs and survival rates at specific time points, are synthesized such that all literature from the systematic review can contribute properly to the estimation and uncertainty quantification of the model parameters. The time-varying effects was modeled by assuming piecewise hazard risk and piecewise constant hazard ratio. The heterogeneity across studies was expressed by an additive random study effect and a random treatment-by-study interaction. The method was applied to a systematic review of 81 publications reporting on 11,151 AML patients. RESULTS/ANTICIPATED RESULTS: In simulation studies that the proportional hazard assumption is either valid or violated, the proposed method was efficient to achieve comparable performance to IPD meta-analysis, a gold standard approach, in estimating the survival rates, the restricted mean survival time at specific time points and median survival time with the point estimates close to the true values. When HR is not proportional over time, the proposed method was robust in estimating HR and significantly outperformed the classical random-effects meta-analysis. In the application to AML study, the average HR for achieving MRD negativity was 0.36 (95% CrI, 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.40) for DFS. The association of MRD negativity with OS and DFS was significant and consistent across all subgroups. DISCUSSION/SIGNIFICANCE OF FINDINGS: The proposed novel method provided a flexible framework for meta-analysis of survival data, to accommodate various types of survival data in one model without assuming proportional hazards assumption. The findings of AML meta-analysis suggest that achievement of MRD negativity is associated with superior DFS and OS in patients with AML.

Purpose: Radiomics has shown great promise to use quantifiable imaging characteristics to predict the behavior and prognosis of neoplasms. This is the first study to evaluate whether radiomic texture analysis can predict outcomes in gastroesophageal junction adenocarcinoma (GEJAC) treated with neoadjuvant chemoradiotherapy (CRT). Materials and Methods: Pretreatment contrast-enhanced CT images of 146 patients with stage II-III GEJAC were reviewed (2009–2011), and randomly split into training and validation groups at a 1:1 ratio stratified with baseline clinical characteristics. Whole-tumor texture was assessed using quantitative image features based on intensity, shape, and gray-level co-occurrence matrix. The relevant pretreatment texture features, in addition to the significant baseline clinical features to predict survival, were identified using multivariate Cox proportional hazard regression model with stepwise variable selection in the training sample and verified in the validation sample, to facilitate the proposal of a multi-point index for standard patient pre-treatment risk classification. Results: Of the factors identified in the training cohort independently associated with OS, only shape compactness (p = 0.04) and pathologic grade differentiation (PDG) (p = 0.02) were confirmed in the validation sample. Using both parameters, we created a 3-point risk classification index: low-risk (well-moderate PDG and high compactness), medium-risk (poor PDG or low compactness), and high-risk (poor PDG and low compactness). The risk index showed a strong negative association with postoperative pathologic complete response (pCR) (p = 0.04). Median OS for the high-, medium-, and low-risk groups were 23, 51, and ≥72 months, respectively (p

Background: Acupuncture is a recognized integrative modality for managing hot flashes. However, data regarding predictors for response to acupuncture in cancer patients experiencing hot flashes are limited. We explored associations between patient characteristics, including traditional Chinese medicine (TCM) diagnosis, and treatment response among cancer patients who received acupuncture for management of hot flashes. Methods: We reviewed acupuncture records of cancer outpatients with the primary reason for referral listed as hot flashes who were treated from March 2016 to April 2018. Treatment response was assessed using the hot flashes score within a modified Edmonton Symptom Assessment Scale (0-10 scale) administered immediately before and after each acupuncture treatment. Correlations between TCM diagnosis, individual patient characteristics, and treatment response were analyzed. Results: The final analysis included 558 acupuncture records (151 patients). The majority of patients were female (90%), and 66% had breast cancer. The median treatment response was a 25% reduction in the hot flashes score. The most frequent TCM diagnosis was qi stagnation (80%) followed by blood stagnation (57%). Older age ( P = .018), patient self-reported anxiety level ( P = .056), and presence of damp accumulation in TCM diagnosis ( P = .047) were correlated with greater hot flashes score reduction. Conclusions: TCM diagnosis and other patient characteristics were predictors of treatment response to acupuncture for hot flashes in cancer patients. Future research is needed to further explore predictors that could help tailor acupuncture treatments for these patients.

Radiomics studies require large patient cohorts, which often include patients imaged using different imaging protocols. We aimed to determine the impact of variability in imaging protocol parameters and interscanner variability using a phantom that produced feature values similar to those of patients. Positron emission tomography (PET) scans of a Hoffman brain phantom were acquired on GE Discovery 710, Siemens mCT, and Philips Vereos scanners. A standard-protocol scan was acquired on each machine, and then each parameter that could be changed was altered individually. The phantom was contoured with 10 regions of interest (ROIs). Values for 45 features with 2 different preprocessing techniques were extracted for each image. To determine the impact of each parameter on the reliability of each radiomics feature, the intraclass correlation coefficient (ICC) was calculated with the ROIs as the subjects and the parameter values as the raters. For interscanner comparisons, we compared the standard deviation of each radiomics feature value from the standard-protocol images to the standard deviation of the same radiomics feature from PET scans of 224 patients with non-small cell lung cancer. When the pixel size was resampled prior to feature extraction, all features had good reliability (ICC > 0.75) for the field of view and matrix size. The time per bed position had excellent reliability (ICC > 0.9) on all features. When the filter cutoff was restricted to values below 6 mm, all features had good reliability. Similarly, when subsets and iterations were restricted to reasonable values used in clinics, almost all features had good reliability. The average ratio of the standard deviation of features on the phantom scans to that of the NSCLC patient scans was 0.73 using fixed-bin-width preprocessing and 0.92 using 64-level preprocessing. Most radiomics feature values had at least good reliability when imaging protocol parameters were within clinically used ranges. However, interscanner variability was about equal to interpatient variability; therefore, caution must be used when combining patients scanned on equipment from different vendors in radiomics data sets.

Radiomics studies require many patients in order to power them, thus patients are often combined from different institutions and using different imaging protocols. Various studies have shown that imaging protocols affect radiomics feature values. We examined whether using data from cohorts with controlled imaging protocols improved patient outcome models. We retrospectively reviewed 726 CT and 686 PET images from head and neck cancer patients, who were divided into training or independent testing cohorts. For each patient, radiomics features with different preprocessing were calculated and two clinical variables-HPV status and tumor volume-were also included. A Cox proportional hazards model was built on the training data by using bootstrapped Lasso regression to predict overall survival. The effect of controlled imaging protocols on model performance was evaluated by subsetting the original training and independent testing cohorts to include only patients whose images were obtained using the same imaging protocol and vendor. Tumor volume, HPV status, and two radiomics covariates were selected for the CT model, resulting in an AUC of 0.72. However, volume alone produced a higher AUC, whereas adding radiomics features reduced the AUC. HPV status and one radiomics feature were selected as covariates for the PET model, resulting in an AUC of 0.59, but neither covariate was significantly associated with survival. Limiting the training and independent testing to patients with the same imaging protocol reduced the AUC for CT patients to 0.55, and no covariates were selected for PET patients. Radiomics features were not consistently associated with survival in CT or PET images of head and neck patients, even within patients with the same imaging protocol.

Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and the immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs traverse the monocyte cytoplasm, cause a reorganization of the actin cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype, including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch. Western blot analysis revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM-patient-infiltrating CD14+ cells predominantly correlates with increased phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released factors that are potent modulators of the GBM-associated immunosuppressive microenvironment.

Background: Persistent post-COVID conditions (PCCs) have become inevitable challenges for individuals who have survived COVID. The National Research Plan on Long COVID-19 underscores the priority of addressing post-COVID conditions (PCCs) within specific subgroups of the United States (US) population. This study aimed to investigate the prevalence and factors associated with PCCs among stroke survivors in the US., Method: In this retrospective cross-sectional study, we utilized the Behavioral Risk Factor Surveillance System (BRFSS) 2022 dataset. First, we identified respondents with a positive history of both COVID-19 and stroke. Subsequently, we categorized these respondents based on whether they experienced PCCs and conducted a comparative analysis of their characteristics. Additionally, our study included a comparison of our findings with those among individuals who have survived myocardial infarction (MI) and cancer., Results: A total of 3999 stroke, 5406 MI, and 10551 cancer survivors were included. The estimated prevalence of PCCs among stroke survivors was 30.6 %, compared to 22.4 %, 29.2 %, and 24.6 % among non-stroke (p < 0.001), MI, and cancer survivors, respectively. Fatigue, dyspnea, and taste/smell loss were the most common primary symptoms. In multivariate regression analysis, female sex (adjusted odds ratio (aOR):1.62, 95 %CI:[1.17-2.24]), stroke-belt residence (aOR:1.67, 95 %CI: [1.13-2.46]), pulmonary disease (aOR:2.12, 95 %CI:[1.53-2.92]), and depression (aOR:1.55, 95 %CI: [1.1-2.2]) were independent factors associated with higher odds of PCCs among stroke survivors. Additionally, age above 64 years was associated with lower odds of PCCs (aOR:0.6, 95 %CI: [0.41-0.86])., Conclusion: Our study highlights a considerable prevalence of PCCs among stroke survivors, particularly among younger women and individuals with other chronic conditions., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)