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Using proxy statement data describing the terms of compensation contracts, we examine how overlapping membership between compensation and audit committees influences the use of earnings metrics in compensation. Although research predicts that such overlap could either increase or decrease the reliance on earnings, we find that firms with overlapping directors rely less on earnings-based performance measures in incentive contracts without altering the overall level of performance-contingent cash bonuses. In addition, we provide evidence that firms substitute earnings measures with measures less subject to earnings management. Our findings are robust to potential alternative explanations, extend to an implicit relation between earnings and compensation for a larger sample, and are not driven by the tendency toward an overlapping committee structure more broadly. This paper was accepted by Suraj Srinivasan, accounting.

Self-care and patient engagement are important elements of heart failure (HF) care, endorsed in the guidelines. Digital health tools may improve quality of life (QOL) in HF patients by promoting care, knowledge, and engagement. This manuscript describes the rationale and challenges of the design and implementation of a pragmatic randomized controlled trial to evaluate the efficacy of three digital health technologies in improving QOL for patients with HF.We hypothesize that digital health interventions will improve QOL of HF patients through the early detection of warning signs of disease exacerbation, the opportunity of self-tracking symptoms, and the education provided, which enhances patient empowerment.Using a fully electronic enrollment and consent platform, the trial will randomize 200 patients across HF clinics in the Yale New Haven Health system to receive either usual care or one of three digital technologies designed to promote self-management and provide critical data to clinicians. The primary outcome is the change in QOL as assessed by the Kansas City Cardiomyopathy Questionnaire at 3 months.First enrollment occurred in September 2021. Recruitment was anticipated to last 6-8 months and participants were followed for 6 months after randomization. Our recruitment efforts have highlighted the large digital divide in our population of interest.Assessing clinical outcomes, patient usability, and ease of clinical integration of digital technologies will be beneficial in determining the feasibility of the integration of such technologies into the healthcare system.

The purpose of this article was to provide a quantitative review of technology-assisted reading fluency interventions for students with disabilities and select moderator variables that may modify the effects of the interventions.All reviewed 13 studies employed a single-case research design, targeting technology-assisted reading fluency interventions for students with learning disabilities (LDs) or learning difficulties. Studies were descriptively analysed and evaluated for methodological quality. Additionally, to examine the level and trend of reading fluency outcomes, Tau-Overall, studies showed a moderate to strong effect on reading fluency and there was a significant difference in moderator variables such as student status, type of technology, and features of technology. While the current study found positive outcomes from technology-based fluency interventions for struggling readers suggesting the effectiveness of using technology for the improvement of reading fluency, educators should consider using a rubric when utilising tablets because of the limited instructional components. Possible explanations about intervention effects, moderator effects, and study qualities along with limitations and future research were discussed. Implications for rehabilitationThis article examined a quantitative review of technology-assisted reading fluency interventions for students with disabilities and those considered at-risk. From this examination, we suggest the following implications:More research is needed to explore the effectiveness of technology-assisted reading fluency interventions. Some studies exist exploring the effect of overall reading interventions, but more specific analyses are needed related specifically to fluency and technology-assisted fluency interventions.Due to continuous advancements in technology, more research is also needed related to the integration of tablets and applications (or apps) on reading fluency.The use of technology to teach fluency has a general positive outcome for at-risk students. However, these types of interventions are more effective if they also provide vocabulary support.

Malnutrition is a common complication in children with cancer. Cancer treatment and malnutrition can disrupt gut microbiome diversity and composition. The gut microbiome is of broad interest to better understand the mechanisms of malnutrition in cancer therapy. This study aimed to compare the gut microbiome between children with solid tumors postchemotherapy and healthy controls, and investigated the association of the putative microbiome differences with diet. Study participants were 27 children (7–18 years) with solid tumors within the first year after the completion of chemotherapy and 22 healthy controls. The study groups did not have a statistically significant difference in age, race, sex, and body mass index. At study intake, the participants completed the Block Kids Food Screener for dietary intakes in the past week. Fecal specimens were collected and analyzed for the gut microbiome. The cancer and control groups differed in gut microbial β-diversity and abundance analyses. The macronutrient intakes such as carbohydrates, fiber, beta-carotene, and vitamin B6 were positively associated with α-diversity. Children with adequate vitamin B6 had a higher Chao1 diversity index than children with inadequate or excessive intake (p = 0.0004). Children with excessive selenium intake had a trend for higher Pielou's_e index than children with inadequate intake (p = 0.091). Maintaining a healthy gut microbiome is critical among children with cancer. This study provides new insights on the linkages between dietary intakes and the gut microbiome in children with solid tumors postchemotherapy. These findings, if replicated in future independent studies, may help anticipate malnutrition and plan for personalized nutrition approaches during chemotherapy in pediatric cancers.

(1) Background: Abnormal liver function tests are commonly encountered in clinical practice, often leading to additional workup to determine the underlying etiology of these abnormal laboratory studies. As part of this evaluation, if less invasive imaging studies are performed and are without evidence of biliary obstruction, liver biopsy may be performed, and the finding of large duct obstruction on liver biopsy is commonly encountered. The utility of endoscopic retrograde cholangiopancreatography (ERCP) for evaluation and management of possible biliary obstruction in patients with large duct obstruction on liver biopsy has not been studied to date. (2) Methods: To assess the utility of ERCP in patients with large bile duct obstruction on liver biopsy, we retrospectively evaluated patients with large duct obstruction on liver biopsy from 2010–2019 at our tertiary care and transplant center. Demographic and clinical characteristics were evaluated for all patients, with sub-group analysis for patients who underwent ERCP and those who had intervenable findings at the time of ERCP. Descriptive statistics with proportions, means, and standard deviations were performed for demographics and clinical variables using absolute standardized difference. (3) Results: During the study period, 189 liver biopsies with evidence of large duct obstruction were performed. After exclusion criteria were applied, 166 unique patients were eligible for the study. Ninety-one patients with evidence of large duct obstruction on liver biopsy underwent ERCP and 75 did not. Of the 91 patients who underwent ERCP, 76 patients (84%) had an intervenable finding at ERCP. Patients who underwent ERCP were overall more likely to have had a liver transplant (65% ASD 0.63), have previously undergone cholecystectomy (80%, ASD 0.56), and be immunocompromised (80%, ASD 0.56). (4) Conclusions: ERCP is high yield when large duct obstruction is apparent on liver biopsy, with the majority of patients (84%) who undergo ERCP in this clinical context having a biliary finding necessitating therapeutic endoscopic intervention.

The transition towards a low-carbon power system presents immense challenges and opportunities to the workforce. Studies of the energy transition’s regional and distributional employment impacts are mainly qualitative or disconnected from prevailing energy modeling scenarios. Here, we couple a power sector optimization model, an employment impact model, and demographic databases to further understand the state-level job characteristics and societal implications in the US. Major fossil fuel producers risk job losses even without new emission reduction policies, requiring the reskilling of up to 30% of the current workforce. The results highlight the need for investments in human capital and a supply chain restructuring. Blue-collar workers are crucial to delivering the transition. Expanding renewable energy could improve job opportunities for women in states dependent on fossil fuels, but not enough to disrupt the national status quo. This work sets a new quantitative perspective to inform proactive local Just Transition policymaking.

We contribute to understanding the previously unrecognized consequences of individualized employment arrangements on the relationship between pay and performance. Increases in the application of pay-for-performance (PFP) idiosyncratic deals (PFP i-deals) raise questions about how individualized PFP arrangements affect the performance of peers who do not receive such customized deals. As pay systems become more individualized, understanding the economic ramifications of how PFP i-deals affect peer performance is essential for understanding the total unit effects of implementing PFP i-deals. To examine these peer effects, we explored peer responses to PFP i-deals and identified boundary conditions on broad theoretical assumptions underlying the conclusion that PFP increases unit performance. We tested our predictions by applying multilevel random-coefficient discontinuous growth models to a sample of 451 peers nested in 117 business units of a for-profit health-care organization. Immediately after PFP i-deal implementation in the unit, the performance level of peers was negatively affected. Additionally, peer performance trends after PFP i-deal implementation were lower than they were before the PFP i-deal implementation. Our study also identified contextual factors that influence peer responses to PFP i-deal implementation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Heart failure (HF) is one of the most common causes of hospitalization in the United States and carries a significant risk of morbidity and mortality. Use of evidence-based interventions may improve outcomes, but their use is encumbered in part by limitations in accurate prognostication. The REVeAL-HF (Risk EValuation And its Impact on ClinicAL Decision Making and Outcomes in Heart Failure) trial is the first to definitively evaluate the impact of knowledge about prognosis on clinical decision making and patient outcomes. The REVeAL-HF trial is a pragmatic, completely electronic, randomized controlled trial that has completed enrollment of 3,124 adults hospitalized for HF, defined as having an N-terminal pro–B-type natriuretic peptide level of >500 pg/ml and receiving intravenous diuretic agents within 24 h of admission. Patients randomized to the intervention had their risk of 1-year mortality generated with information in the electronic health record and presented to their providers, who had the option to give feedback on their impression of this risk assessment. The authors are examining the impact of this information on clinical decision-making (use of HF pharmacotherapies, referral to electrophysiology, palliative care referral, and referral for advanced therapies like heart transplantation or mechanical circulatory support) and patient outcomes (length of stay, post-discharge 30-day rehospitalizations, and 1-year mortality). The REVeAL-HF trial will definitively examine whether knowledge about prognosis in HF has an impact on clinical decision making and patient outcomes. It will also examine the relationship between calculated, perceived, and real risk of mortality in this patient population. (Risk EValuation And Its Impact on ClinicAL Decision Making and Outcomes in Heart Failure [REVeAL-HF]; NCT03845660 ).

Background: Children with cancer (CWC) receiving chemotherapy (chemo) report significant suffering from a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. Continuous or severe PNS reduce a child’s quality of life. Chemo can disturb the gut microbiome (GM), which is associated with PNS based on the gut-brain axis. This study aimed to examine associations of GM with PNS and the PNS cluster in CWC undergoing chemo. Methods: An observational prospective study was conducted in 21 CWC enrolled from Children’s Healthcare of Atlanta. Children with at least 1 cycle of chemo were consented pre-cycle 2 chemo (T1) and followed at the end of chemo (T2). At T1, parents reported children’s demographics; at T1 and T2, PNS (pain, fatigue, anxiety, depression, cognitive dysfunction) were reported by children by the Pediatric PROMIS scales and fecal specimens were collected for GM. T-score of the PROMIS scales was computed; an average of T-scores of the five PNS was computed for the PNS cluster. T-score >50 indicates a significant symptom or symptom cluster. 16S rRNA V4 gene from fecal specimens was sequenced for GM. QIIME 2 was used to examine associations of α- and β-diversity with PNS. Linear discriminant analysis effect size identified microbial taxa associated with each PNS and the PNS cluster. Results: We analyzed 21 CWC with a mean age of 13 years, 67% male, and 67% white. Children at T2 had higher fatigue (54% vs. 43%), cognitive dysfunction (69% vs. 43%), depressive symptoms (23% vs. 19%), and multiple PNS (62% vs. 48%), but lower pain interference (31% vs. 38%) and anxiety (23% vs. 38%) than those at T1. No association was found for α-diversity at T1; higher α-diversity was associated with lower cognitive dysfunction (Faith’s phylogenetic diversity, p=0.04) and anxiety (Pielou’s_e, p=0.08) at T2; β-diversity (Jaccard distance) showed the GM dissimilarities by levels of pain interference (moderate vs. severe, p=0.02) and levels of anxiety (mild vs. moderate, p=0.07). After controlling for study timepoint, children with low pain interference had an enriched Bacteroides; those with low fatigue had enriched Bacteroides and Turicibacter; those with normal cognitive function had enriched Parasutterella, UBA1819, NK4A214, Sellimonas, and Ruminococcaceae. Children without the PNS cluster had enriched Bacteroides, while those with the PNS cluster had enriched Enterobacteriaceae. Children without multiple PNS had enriched UCG_003. Conclusions: Children with low PNS showed a higher α-diversity and a higher abundance of taxa involved in nutrition and vitamin metabolism (eg, Bacteroides), reducing inflammation (eg, Turicibacter), and producing short chain fatty acids (eg, Ruminococcaceae). These findings provide potential solutions to treat PNS. Further work is needed to corroborate these associations in CWC. Citation Format: Jinbing Bai, Melissa Martin, Kathryn S. Sutton, Christie Powell, Thomas Olson, Hye In Noh, Maria C. Swartz, Deborah Watkins Bruner. Gut microbiome associated with the psychoneurological symptom cluster among children with solid tumors receiving chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6731.

IntroductionAlthough studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients.Methods and analysisKAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid–base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8–51.5) min.Ethics and disseminationThe study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion.Trial registration numberNCT04040296.

Adult liver-related hospitalizations have recently increased in the USA, but data are limited for the pediatric population. Utilizing the Office of Statewide Health Planning and Development hospital claims database (covering > 98% of all California hospitalizations), we aimed to characterize the demographic, clinical, and socioeconomic factors of liver disease-associated admissions among children between 2005 and 2015. We used ICD-9 codes to identify admissions associated with liver disease in patients up to 21 years of age. Patient characteristics were described as percentages and evaluated using the χ2 test. We used linear regression to examine changes over time. We analyzed 37,372 eligible admissions. Overall, close to one-third (28%) and one-half (48.0%) of admissions occurred in the age group 0–5 years and 16–21 years, respectively, with the remaining 23.1% occurring in the age group between 5 and 15 years. Over half (54.9%) were in males. By race, blacks made up half of the admission (49.7%), while by ethnicity, Hispanic also accounted for half of the admission (49.7%). Medicaid and Medicare payors were also disproportionately represented (54.6%). The most common liver disease was Alagille syndrome (29.2%) in 2005. Between 2005 and 2015, both the number of pediatric liver-associated admissions and the proportion of pediatric liver admissions over total admissions increased from 3130 to 3429 and 1.2% to 1.6%, respectively (both p = 0.001). By 2015, while Alagille syndrome admissions decreased to 26.4% (p = 0.004), NAFLD admission increased to 19.7% (p

Background Timely prediction of AKI in children can allow for targeted interventions, but the wealth of data in the electronic health record poses unique modeling challenges. Methods We retrospectively reviewed the electronic medical records of all children younger than 18 years old who had at least two creatinine values measured during a hospital admission from January 2014 through January 2018. We divided the study population into derivation, and internal and external validation cohorts, and used five feature selection techniques to select 10 of 720 potentially predictive variables from the electronic health records. Model performance was assessed by the area under the receiver operating characteristic curve in the validation cohorts. The primary outcome was development of AKI (per the Kidney Disease Improving Global Outcomes creatinine definition) within a moving 48-hour window. Secondary outcomes included severe AKI (stage 2 or 3), inpatient mortality, and length of stay. Results Among 8473 encounters studied, AKI occurred in 516 (10.2%), 207 (9%), and 27 (2.5%) encounters in the derivation, and internal and external validation cohorts, respectively. The highest-performing model used a machine learning-based genetic algorithm, with an overall receiver operating characteristic curve in the internal validation cohort of 0.76 [95% confidence interval (CI), 0.72 to 0.79] for AKI, 0.79 (95% CI, 0.74 to 0.83) for severe AKI, and 0.81 (95% CI, 0.77 to 0.86) for neonatal AKI. To translate this prediction model into a clinical risk-stratification tool, we identified high- and low-risk threshold points. Conclusions Using various machine learning algorithms, we identified and validated a time-updated prediction model of ten readily available electronic health record variables to accurately predict imminent AKI in hospitalized children.

We investigate the extent to which market participants use compensation payouts released in the DEF 14A proxy statement (DEF14A) to assess future firm performance by examining sell‐side analysts' earnings forecasts. Consistent with prior work, we confirm that CEO compensation unexplained by current observable economic factors is positively associated with future firm performance. We find that both the likelihood that analysts revise their forecasts following release of the DEF14A and the magnitude and direction of analysts' forecast revisions are positively associated with unexplained CEO compensation. These associations are stronger after the SEC required additional compensation‐related disclosures in late 2006 but lower if the firm has weak corporate governance or more precise other information. Analysts' reactions are not complete, however. Analysts' forecast errors measured months after the DEF14A release are associated with past unexplained compensation, especially in the pre‐2006 period and for analysts who do not revise at the DEF14A release. Taken together, our results suggest that compensation payouts released in the DEF14A contain useful forward‐looking information that is recognized by at least some sophisticated market participants and that the increased disclosure regulations assisted market participants in incorporating this information. La publication d'information relative a la remuneration dans la circulaire de sollicitation de procurations oriente‐t‐elle les previsions de resultats? Les auteures se penchent sur la mesure dans laquelle les participants au marche utilisent les renseignements relatifs a la remuneration versee que contient la circulaire de sollicitation de procurations DEF 14A (la circulaire) pour evaluer la performance future de l'entreprise, en examinant les previsions de resultats que formulent les analystes aupres des placeurs. Leur analyse, comme de precedents travaux, confirme que la remuneration du chef de la direction que n'expliquent pas les facteurs economiques couramment observables affiche un lien positif avec la performance future de l'entreprise. Les auteures constatent que la probabilite que les analystes revisent leurs previsions a la suite de la publication de la circulaire de meme que l'ampleur et l'orientation de cette revision sont en relation positive avec la remuneration inexpliquee du chef de la direction. Ce double lien est plus fort apres la decision de la SEC, a la fin de 2006, d'exiger de l'information supplementaire relativement a la remuneration, mais plus faible si la gouvernance de l'entreprise est deficiente ou si l'entreprise communique d'autres renseignements plus precis. Les reactions des analystes ne sont toutefois pas completes. Les erreurs previsionnelles des analystes evaluees des mois apres la publication de la circulaire sont associees a une remuneration passee inexpliquee, en particulier au cours de la periode anterieure a 2006 et dans le cas des analystes qui ne revisent pas leurs previsions a la suite de la publication de la circulaire. Dans l'ensemble, les resultats obtenus par les auteures laissent croire que les renseignements relatifs a la remuneration versee que contient la circulaire livrent de l'information prospective dont l'utilite est reconnue par au moins certains participants au marche eclaires, et que les exigences accrues de la reglementation en matiere d'information ont contribue a ce que les participants au marche assimilent cette information.

BACKGROUND: Despite guideline recommendations to optimize low-density lipoprotein cholesterol (LDL-C) reduction with intensification of lipid-lowering therapy (LLT) in patients with atherosclerotic cardiovascular disease (ASCVD), few of these patients achieve LDL-C < 70 mg/dL in practice. PURPOSE: We developed a real-time, targeted electronic health record (EHR) alert with embedded ordering capability to promote intensification of evidence based LLT in outpatients with very high risk ASCVD. METHODS: We designed a pragmatic, multicenter, single-blind, cluster randomized trial to test the effectiveness of an EHR-based LLT intensification alert. The study will enroll about 100 providers who will be randomized to either receive the alert or undergo usual care for outpatients with high risk ASCVD with LDL-C > 70 mg/dL. Total enrollment will include 2,500 patients. The primary outcome will be the proportion of patients with LLT intensification at 90 days. Secondary outcomes include achieved LDL-C at 6 months and the proportion of patients with LDL-C < 70 mg/dL or < 55 mg/dL at 6 months. RESULTS: Enrollment of 1,250 patients (50% of goal) was reached within 47 days (50% women, mean age 72, median LDL-C 91). At baseline, 71%, 9%, and 3% were on statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors, respectively. CONCLUSIONS: PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia has rapidly reached 50% enrollment of patients with very high risk ASCVD, demonstrating low baseline LLT utilization. This pragmatic, EHR-based trial will determine the effectiveness of a real-time, targeted EHR alert with embedded ordering capability to promote LLT intensification. Findings from this low-cost, widely scalable intervention to improve LDL-C may have important public health implications.

The North American Imaging in Multiple Sclerosis (NAIMS) multisite project identified interscanner reproducibility issues with T1-based whole brain volume (WBV). Lateral ventricular volume (LVV) acquired on T2-fluid-attenuated inverse recovery (FLAIR) scans has been proposed as a robust proxy measure. Therefore, we sought to determine the relative magnitude of scanner-induced T2-FLAIR-based LVV and T1-based WBV measurement errors in relation to clinically meaningful changes.This was a post hoc analysis of the NAIMS pilot dataset in which a relapsing-remitting MS patient with no intrastudy clinical or radiological activity was imaged twice on seven different Siemens scanners across the United States. LVV was determined using the automated NeuroSTREAM technique on T2-FLAIR and WBV was determined with SIENAX on high-resolution T1-MPRAGE. Average LVV and WBV were measured, and absolute intrascanner and interscanner coefficients of variation (CoVs) were calculated. The variabilities were compared to previously established annual pathological and clinically meaningful cutoffs of 0.40% for WBV and of 3.51% for LVV.Mean LVV across all seven scan/rescan pairs was 45.87 ± 1.15 ml. Average LVV intrascanner CoV was 1.42% and interscanner CoV was 1.78%, both smaller than the reported annualized clinically meaningful cutoff of 3.51%. In contrast, intra- and interscanner CoVs for WBV (0.99% and 1.15%) were both higher than the established cutoff of 0.40%. Individually, 1/7 intrasite and 2/7 intersite pair-wise LVV comparisons were above the 3.51% cutoff, whereas 4/7 intrasite and 7/7 intersite WBV comparisons were above the 0.40% cutoff.Fully automated LVV segmentation has higher absolute variability than WBV, but much lower relative variability compared to clinically relevant changes, and may therefore be a meaningful proxy outcome measure of neurodegeneration.

Heart failure is a complex syndrome that contributes significantly to mortality and morbidity in the Unites States. Self-management is an ACC/AHA-recommended management tool for chronic conditions, however, those with congestive heart failure have historically poor compliance, low health literacy, and comorbidities that lead to reduced adherence to therapies and lifestyle modifications. Digital health technologies have the potential to enhance care and improve self-management. This manuscript describes the rationale and challenges of the design and implementation of a pragmatic randomized controlled trial to evaluate the efficacy of three digital health technologies in the management of congestive heart failure. Leveraging the use of a fully electronic enrollment and consent platform, the trial will randomize 200 patients across heart failure clinics in the Yale New Haven Health system to receive either usual care or one of three distinct digital technologies designed to promote self-management and provide critical data to clinicians. Our primary outcome will measure the change in quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 3 months. Initial recruitment efforts have highlighted the large digital divide in our population of interest. Assessing not only clinical outcomes, but patient usability and ease of clinical integration of digital technologies will prove beneficial in determining the feasibility and success of the integration of such technologies into the healthcare system. Future learnings will illustrate strategies to improve patient engagement with, and integration of, digital health technologies to enhance the patient-clinician relationship.Clinicaltrials.govNCT04394754

Background: Malnutrition is a common complication in children with cancer. Cancer treatment and malnutrition can disrupt gut microbiome diversity and composition. This study aims to compare the dietary intakes between children with solid tumors post-chemotherapy and healthy controls, and investigate associations between the dietary intakes and the gut microbiome. Procedure: Children (7-18 years) with solid tumors were recruited during year 1 after the completion of chemotherapy from Children’s Healthcare of Atlanta, Atlanta, Georgia. Healthy controls were recruited via flyers. Children completed the Block Kids Food Screener for dietary intakes in the past week. Fecal specimens were collected and processed for the gut microbiome. QIIME2 and Mann-Whitney U tests were conducted to answer the research questions. Results: Forty-nine children (25 cancers vs 24 controls) were analyzed. Two groups had no differences in age, race, sex, and body mass index. Children with solid tumors reported significantly higher mean daily intakes of macronutrients: calories, protein, fat, carbohydrate, and fiber, and antioxidant nutrients (vitamin E, vitamin C, and selenium) than controls. Children with adequate vitamin B6 had a higher Chao1 diversity index than children with inadequate or excessive intake (P = 0.0004). Children with excessive selenium intake had a trend of higher Pielou’s_e index than children with inadequate intake (P = 0.091). Conclusion: Children with cancer reported significantly higher intakes of macronutrients and antioxidant nutrients than healthy children, but no differences in major energy ratios. Macronutrients, particularly antioxidant nutrients, were associated with disruptions of the gut microbiome in children with solid tumors.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline.Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM’s Executive Committee May 28, 2019

The purpose of this study was to determine if reading achievement of students from high-poverty US schools differs as a function of participation in summer tutoring versus access to books. Data fro...

Heart failure is a major cause of morbidity and mortality worldwide. The use of risk scores has the potential to improve targeted use of interventions by clinicians that improve patient outcomes, but this hypothesis has not been tested in a randomized trial.To evaluate whether prognostic information in heart failure translates into improved decisions about initiation and intensity of treatment, more appropriate end-of-life care, and a subsequent reduction in rates of hospitalization or death.This was a pragmatic, multicenter, electronic health record-based, randomized clinical trial across the Yale New Haven Health System, comprising small community hospitals and large tertiary care centers. Patients hospitalized for heart failure who had N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of greater than 500 pg/mL and received intravenous diuretics within 24 hours of admission were automatically randomly assigned to the alert (intervention) or usual-care groups.The alert group had their risk of 1-year mortality calculated using an algorithm that was derived and validated using similar historic patients in the electronic health record. This estimate, including a categorical risk assessment, was presented to clinicians while they were interacting with a patient's electronic health record.The primary outcome was a composite of 30-day hospital readmissions and all-cause mortality at 1 year.Between November 27, 2019, through March 7, 2021, 3124 patients were randomly assigned to the alert (1590 [50.9%]) or usual-care (1534 [49.1%]) group. The alert group had a median (IQR) age of 76.5 (65-86) years, and 796 were female patients (50.1%). Patients from the following race and ethnicity groups were included: 13 Asian (0.8%), 324 Black (20.4%), 136 Hispanic (8.6%), 1448 non-Hispanic (91.1%), 1126 White (70.8%), 6 other ethnicity (0.4%), and 127 other race (8.0%). The usual-care group had a median (IQR) age of 77 (65-86) years, and 788 were female patients (51.4%). Patients from the following race and ethnicity groups were included: 11 Asian (1.4%), 298 Black (19.4%), 162 Hispanic (10.6%), 1359 non-Hispanic (88.6%), 1077 White (70.2%), 13 other ethnicity (0.9%), and 137 other race (8.9%). Median (IQR) NT-proBNP levels were 3826 (1692-8241) pg/mL in the alert group and 3867 (1663-8917) pg/mL in the usual-care group. A total of 284 patients (17.9%) and 270 patients (17.6%) were admitted to the intensive care unit in the alert and usual-care groups, respectively. A total of 367 patients (23.1%) and 359 patients (23.4%) had a left ventricular ejection fraction of 40% or less in the alert and usual-care groups, respectively. The model achieved an area under the curve of 0.74 in the trial population. The primary outcome occurred in 619 patients (38.9%) in the alert group and 603 patients (39.3%) in the usual-care group (P = .89). There were no significant differences between study groups in the prescription of heart failure medications at discharge, the placement of an implantable cardioverter-defibrillator, or referral to palliative care.Provision of 1-year mortality estimates during heart failure hospitalization did not affect hospitalization or mortality, nor did it affect clinical decision-making.ClinicalTrials.gov Identifier NCT03845660.

Rationale and objective While COVID-19 infection has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI. Study Design Multicenter, observational, cohort study. Setting and participants Patients admitted to one of six hospitals within the Yale-New Haven Health System between 3/10/2020 and 8/31/2020 and tested for SARS-CoV-2 via nasopharyngeal PCR test. Exposure Positive test for SARS-CoV-2. Outcome AKI by Kidney Disease: Improving Global Outcomes criteria. Analytic approach Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (e.g., demographics, comorbidities) and time-varying factors updated continuously during hospitalization (e.g., vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models. Results Of the 22,122 patients hospitalized between, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared to patients who tested negative, patients with COVID-19 had more AKI [30.6% vs. 18.2%, absolute risk difference 12.5 (95% CI, 10.6, 14.3)%] and dialysis-requiring AKI (8.5% vs. 3.6%) and lower recovery from AKI (58% vs. 69.8%]. Compared to patients who tested negative, patients with COVID-19 had higher inflammatory markers (C-reactive protein, ferritin), and greater use of vasopressors and diuretics. Compared to patients who tested negative, patients with COVID-19 had higher rate of AKI in univariable analysis (HR, 1.84 [1.73, 1.95]). In fully adjusted model controlling for demographics, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted HR, 1.40 [1.29-1.53]). Limitations Possibility of residual confounding. Conclusions COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI., One-third of patients hospitalized with COVID-19 experience acute kidney injury (AKI), which is higher than in other hospitalized patients. Patients with COVID-19 carry many well-known risk factors for AKI including severe lung disease requiring mechanical ventilation, shock and significant inflammation. Whether higher rates of AKI in COVID-19 are above what could be expected in patients with similar risk factors is unknown. We compared AKI rates between those with and without COVID-19 after controlling for risk factors for AKI both before and during hospitalization. We found that COVID-19 was independently associated with high rates of AKI. This indicates that some of the AKI risk in patients with COVID-19 is unexplained by traditional AKI risk factors and is unique to this disease.

Heart failure (HF) is one of the most common causes of hospitalization in the United States and carries a significant risk of morbidity and mortality. Use of evidence-based interventions may improve outcomes, but their use is encumbered in part by limitations in accurate prognostication. The REVeAL-HF (Risk EValuation And its Impact on ClinicAL Decision Making and Outcomes in Heart Failure) trial is the first to definitively evaluate the impact of knowledge about prognosis on clinical decision making and patient outcomes. The REVeAL-HF trial is a pragmatic, completely electronic, randomized controlled trial that has completed enrollment of 3,124 adults hospitalized for HF, defined as having an N-terminal pro-B-type natriuretic peptide level of500 pg/ml and receiving intravenous diuretic agents within 24 h of admission. Patients randomized to the intervention had their risk of 1-year mortality generated with information in the electronic health record and presented to their providers, who had the option to give feedback on their impression of this risk assessment. The authors are examining the impact of this information on clinical decision-making (use of HF pharmacotherapies, referral to electrophysiology, palliative care referral, and referral for advanced therapies like heart transplantation or mechanical circulatory support) and patient outcomes (length of stay, post-discharge 30-day rehospitalizations, and 1-year mortality). The REVeAL-HF trial will definitively examine whether knowledge about prognosis in HF has an impact on clinical decision making and patient outcomes. It will also examine the relationship between calculated, perceived, and real risk of mortality in this patient population. (Risk EValuation And Its Impact on ClinicAL Decision Making and Outcomes in Heart Failure [REVeAL-HF]; NCT03845660).

Objective To determine whether electronic health record alerts for acute kidney injury would improve patient outcomes of mortality, dialysis, and progression of acute kidney injury. Design Double blinded, multicenter, parallel, randomized controlled trial. Setting Six hospitals (four teaching and two non-teaching) in the Yale New Haven Health System in Connecticut and Rhode Island, US, ranging from small community hospitals to large tertiary care centers. Participants 6030 adult inpatients with acute kidney injury, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. Interventions An electronic health record based “pop-up” alert for acute kidney injury with an associated acute kidney injury order set upon provider opening of the patient’s medical record. Main outcome measures A composite of progression of acute kidney injury, receipt of dialysis, or death within 14 days of randomization. Prespecified secondary outcomes included outcomes at each hospital and frequency of various care practices for acute kidney injury. Results 6030 patients were randomized over 22 months. The primary outcome occurred in 653 (21.3%) of 3059 patients with an alert and in 622 (20.9%) of 2971 patients receiving usual care (relative risk 1.02, 95% confidence interval 0.93 to 1.13, P=0.67). Analysis by each hospital showed worse outcomes in the two non-teaching hospitals (n=765, 13%), where alerts were associated with a higher risk of the primary outcome (relative risk 1.49, 95% confidence interval 1.12 to 1.98, P=0.006). More deaths occurred at these centers (15.6% in the alert group v 8.6% in the usual care group, P=0.003). Certain acute kidney injury care practices were increased in the alert group but did not appear to mediate these outcomes. Conclusions Alerts did not reduce the risk of our primary outcome among patients in hospital with acute kidney injury. The heterogeneity of effect across clinical centers should lead to a re-evaluation of existing alerting systems for acute kidney injury. Trial registration ClinicalTrials.gov NCT02753751 .

In this chapter, the authors situate mental health issues in the context of U.S. institutes of higher education. They provide a brief history of the provision of mental health services on campus and contends that postsecondary schools should shift to a campus-wide, preventive, proactive approach to promote student flourishing. Four specific areas for interventions are discussed. These include academic or curricular adjustments, increased awareness and knowledge, supportive environments, and appropriate policies and procedures. These initiatives (which are not only the responsibility of “experts”) rely on the open communication and collaboration of all members of the campus community.

As firms evolve, the tasks required to generate firm value change, as does the ability of earnings to reflect changes in that value. To the extent earnings differentially captures managers’ effort toward desire tasks, contracting theory suggests its role in incentive pay should also change. However, anecdotal evidence suggests boards often fail to alter the weights on earnings in response to changes in the firm over time, relying instead on the status quo. In this study, we use a large longitudinal sample research design to investigate whether and how boards alter the weight on earnings in bonus contracts as its contracting usefulness changes over time. Our results suggest that although some contract evolution occurs, it often lacks timeliness. We find that boards often rely on contracting decisions made in prior periods, suggesting evidence of the status quo bias. Consistent with the status quo bias affecting board decisions, we document that process accountability mitigates a lack of concurrent contract evolution with shifts in firm evolution. Finally, we show that firms trade off earnings for other more idiosyncratic performance measures, suggesting alternate measures incrementally inform manager effort in early and late stages of firm development.

Background: Chemotherapy is commonly used for children with cancer. Intensive chemotherapy can disturb the gut microbiome, which may be associated with treatment-related toxicities. This study aimed to compare profiles of the gut microbiome in children with solid tumors pre- and post-chemotherapy with those of healthy children. Methods: A case-control study was conducted in 44 children (21 with solid tumors and 23 healthy). Children aged 7-18 years with solid tumors receiving chemotherapy were recruited from Children’s Healthcare of Atlanta (CHOA); healthy children were recruited by e-news in CHOA. The gut microbiome was measured using stool specimens that were collected pre cycle 2 chemotherapy and post the completion of all chemotherapy for cancers, and only once for healthy controls. Demographics and clinical variables (e.g., race and use of antibiotics) were reported by parents. Bacterial 16S rRNA gene V4 region was amplified and sequenced. Bacterial taxonomies were assigned using the Silva reference via QIIME 2. Permutational multivariate analysis of variance, analysis of composition of microbiomes, and linear discriminant analysis effect size were used to compare the gut microbiome between cancer and healthy children. Results: Children with solid tumors and healthy controls showed no differences in age, race, and BMI; more boys were enrolled in the solid tumor group than the healthy group (p=0.009). Both groups were dominated by phyla Firmicutes and Bacteroidetes. Compared to healthy children, children with solid tumors had significantly lower α-diversity metrics: Shannon p=0.042 and Chao1 p=0.015; children pre- (Shannon p=0.021; Chao1 p=0.024) and post-chemotherapy (Shannon p=0.011; Chao1 p=0.025) showed lower α-diversity metrics than healthy children; and difference was not significant between children pre- and post-chemotherapy. The β-diversity analysis (Bray-Curtis distance) showed that study group (p=0.008), gender (p=0.017), race (p=0.009), and cancer type (p=0.001) impacted the gut microbiome dissimilarities. Children with solid tumors had a lower abundance of phylum Verrucomicrobiotaand a higher abundance of genus Acidaminoccous than healthy controls; healthy children had a higher abundance of beneficial genera Prevotella and Akkermansia. Children with solid tumors had enriched in pathogenic oropportunistically pathogenic genera Clostridioides and Enterococcus. Children post all chemotherapy had enriched genera Blautia and CAG-352 associated with gut-brain axis. Conclusions: Children with solid tumors suggested different diversity profiles of the gut microbiome and a higher abundance of pathogenic taxa than healthy children. These different gut microbial profiles may be associated with treatment toxicities. Additional studies are needed to further corroborate these associations in children with cancer and reveal the underlying mechanisms. Citation Format: Jinbing Bai, Kumru Kocaman, Julia Slack, Melissa Martin, Christie Powell, Kathryn S. Sutton, Bradley George, Thomas Olson, Konstantinos T. Konstantinidis, Deborah W. Bruner. Comparison of the gut microbiome between children with solid tumor receiving chemotherapy and healthy children [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 720.