Lowewoodruff2013

Participants in clinical trials may experience benefits associated with new therapeutic strategies as well as tight adherence to best supportive care practices.

To investigate whether participation in a clinical trial is associated with improved survival among children with neuroblastoma and investigate potential recruitment bias of patients in clinical trials.

This cohort study included pediatric patients with intermediate- or high-risk neuroblastoma in North American studies who were included in the International Neuroblastoma Risk Group Data Commons and who received a diagnosis between January 1, 1991, and March 1, 2020.

Enrollment in a clinical trial.

Event-free survival and overall survival (OS) of patients with intermediate- or high-risk neuroblastoma enrolled in an up-front Children's Oncology Group (COG) clinical trial vs a biology study alone were analyzed using log-rank tests and Cox proportional hazards regression models. The racial/ethnic composition and the demographic characteristics ol.

Approximately 44% of patients in this large cohort of patients with neuroblastoma were enrolled in up-front clinical trials. Compared with children not enrolled in clinical trials, a higher prevalence of favorable prognostic markers was identified among patients with intermediate-risk neuroblastoma enrolled in clinical trials, and unfavorable features were more prevalent among patients with high-risk neuroblastoma enrolled in clinical trials. No evidence of recruitment bias according to race/ethnicity was observed. Participation in a clinical trial was not associated with OS in this cohort, likely reflecting the common practice of treating nontrial participants with therapeutic and supportive care regimens used in a previous therapeutic trial.

Quantitative volumetric measures of retinal disease in optical coherence tomography (OCT) scans are infeasible to perform owing to the time required for manual grading. Expert-level deep learning systems for automatic OCT segmentation have recently been developed. However, the potential clinical applicability of these systems is largely unknown.

To evaluate a deep learning model for whole-volume segmentation of 4 clinically important pathological features and assess clinical applicability.

This diagnostic study used OCT data from 173 patients with a total of 15 558 B-scans, treated at Moorfields Eye Hospital. The data set included 2 common OCT devices and 2 macular conditions wet age-related macular degeneration (107 scans) and diabetic macular edema (66 scans), covering the full range of severity, and from 3 points during treatment. Two expert graders performed pixel-level segmentations of intraretinal fluid, subretinal fluid, subretinal hyperreflective material, and pigment epithelial detachment, incl CI, 71%-84%) and 309 expert gradings (2 per scan) (89%; 95% CI, 86%-92%). The model was rated neutrally or positively in 86% to 92% of diabetic macular edema scans and 53% to 87% of age-related macular degeneration scans. Intraclass correlations ranged from 0.33 (95% CI, 0.08-0.96) to 0.96 (95% CI, 0.90-0.99). Dice similarity coefficients ranged from 0.43 (95% CI, 0.29-0.66) to 0.78 (95% CI, 0.57-0.85).

This deep learning-based segmentation tool provided clinically useful measures of retinal disease that would otherwise be infeasible to obtain. Qualitative evaluation was additionally important to reveal clinical applicability for both care management and research.

This deep learning-based segmentation tool provided clinically useful measures of retinal disease that would otherwise be infeasible to obtain. Qualitative evaluation was additionally important to reveal clinical applicability for both care management and research.With unprecedented increases, mortality trends in the US have received significant attention in recent years. To date, research on this topic has emphasized specific causes of death and proximal behavioral or physiological determinants. In this commentary, I consider novel contributions of Zheng & Echave (Am J Epidemiol. XXXX-XX) in examining trends in mental health, health behaviors, and physiologic dysregulation. I then discuss broader developments in related research and make a case for (1) not allowing recent health trends among Whites to overshadow the urgent work that needs to be done to mitigate persistent racial inequities, (2) further investigation of what accounts for increases in income inequality and its life span health consequences; and (3) broadening the scope of mechanisms considered to include under-discussed topics such as the role of increases in social media usage or environmental toxicant exposures. Underlying several potential explanations for observed trends in health and mortality is the fact that substantial change has occurred on multiple fronts in US society and that policy responses to these changes have been insufficient. An enhanced emphasis on innovative population health research will be essential to provide the evidence base needed for policy makers to rise to these urgent challenges.Obesity-induced secretory disorder of adipose tissue-derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)-infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow-specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.

As cancer treatment has become more individualized, oncologic clinical trials have become more complex. Increasingly numerous and stringent eligibility criteria frequently include tumor molecular or genomic characteristics that may not be readily identified in medical records, rendering it difficult to best match clinical trials with clinical sites and to identify potentially eligible patients once a clinical trial has been selected and activated. Partly because of these factors, enrollment rates for cancer clinical trials remain low, creating delays and increased costs for drug development. Information technology (IT) platforms have been applied to the implementation and conduct of clinical trials to improve efficiencies in several medical fields, and these platforms have recently been introduced to oncologic studies.

This review summarizes cancer and noncancer studies that used IT platforms for assistance with clinical trial site selection, patient recruitment, and patient screening. The review does notent to which these services will overcome ongoing and increasing challenges in cancer clinical research remains unclear.

This review found that an increasing number and variety of IT platforms were available to assist in the planning and conduct of clinical trials. Because oncologic clinical care and clinical trial protocols are particularly complex, nuanced, and individualized, published experience with this technology in other fields may not be fully applicable to cancer settings. The extent to which these services will overcome ongoing and increasing challenges in cancer clinical research remains unclear.Prior research provides important insights into employer discrimination against mothers but has focused exclusively on college-educated mothers in professional and managerial occupations. As a result, we lack evidence about whether less-educated mothers navigating the low-wage labor market experience similar disadvantages and whether the mechanisms underlying discrimination vary across contexts. These gaps are important because more- and less-educated mothers increasingly possess distinct resources and face unique demands both at home and at work, which may impact employer perceptions of conflicts between motherhood and job performance. This study reports results from an original field experiment in which 2,210 fictitious applications were submitted to low-wage service and professional/managerial job openings across six U.S. cities, experimentally manipulating signals of motherhood status. Findings provide causal evidence that employers in both contexts discriminate against mothers relative to equally qualified childless women. However, within labor market segments, distinct job demands listed in job advertisements are associated with stronger discrimination time pressure, collaboration, and travel in professional/managerial jobs and schedule instability in low-wage service jobs. These findings have important implications for our understanding of the mechanisms underlying mothers' disadvantages in an increasingly polarized labor market.

Many cancer subtypes, including KIT-mutant gastrointestinal stromal tumors (GISTs), are driven by activating mutations in tyrosine kinases and may initially respond to kinase inhibitors but frequently relapse owing to outgrowth of heterogeneous subclones with resistance mutations. KIT inhibitors commonly used to treat GIST (eg, imatinib and sunitinib) are inactive-state (type II) inhibitors.

To assess whether combining a type II KIT inhibitor with a conformation-complementary, active-state (type I) KIT inhibitor is associated with broad mutation coverage and global disease control.

A highly selective type I inhibitor of KIT, PLX9486, was tested in a 2-part phase 1b/2a trial. ALK inhibitor Part 1 (dose escalation) evaluated PLX9486 monotherapy in patients with solid tumors. Part 2e (extension) evaluated PLX9486-sunitinib combination in patients with GIST. Patients were enrolled from March 2015 through February 2019; data analysis was performed from May 2020 through July 2020.

Participants received 250, 350, 500, and.34-NA) months and clinical benefit rates (95% CI) of 14% (0%-58%), 50% (21%-79%), and 80% (52%-96%), respectively.

In this phase 1b/2a nonrandomized clinical trial, type I and type II KIT inhibitors PLX9486 and sunitinib were safely coadministered at the recommended dose of both single agents in patients with refractory GIST. Results suggest that cotargeting 2 complementary conformational states of the same kinase was associated with clinical benefit with an acceptable safety profile.

ClinicalTrials.gov Identifier NCT02401815.

ClinicalTrials.gov Identifier NCT02401815.

Emerging evidence suggests that increasing dietary nitrate intake may be an effective approach to improve cardiovascular health. However, the effects of a prolonged elevation of nitrate intake through an increase in vegetable consumption are understudied.

Our primary aim was to determine the impact of 12 wk of increased daily consumption of nitrate-rich vegetables or nitrate supplementation on blood pressure (BP) in (pre)hypertensive middle-aged and older adults.

In a 12-wk randomized, controlled study (Nijmegen, The Netherlands), 77 (pre)hypertensive participants (BP 144±13/87±7 mmHg, age 65±10 y) either received an intervention with personalized monitoring and feedback aiming to consume ∼250-300 g nitrate-rich vegetables/d (∼350-400 mg nitrate/d; n=25), beetroot juice supplementation (400 mg nitrate/d; n=26), or no intervention (control; n=26). Before and after intervention, 24-h ambulatory BP was measured. Data were analyzed using repeated measures ANOVA (time×treatment), followed by within-group (paired t-test) and between-group analyses (1-factor ANOVA) where appropriate.