Background
Health insurance plays a critical role in the accessibility to and quality of health care for patients with melanoma in the United States. Current knowledge regarding the association ...between insurance status and stage of melanoma is limited because few studies to date have simultaneously controlled for factors known to influence the risk of diagnosis of late‐stage melanoma. The current study was conducted to examine the association between health insurance status and stage of melanoma at the time of diagnosis in nonelderly adults, accounting for known risk factors for late‐stage diagnosis.
Methods
In this cross‐sectional study, the authors analyzed the National Cancer Data Base for cases of invasive melanoma diagnosed between 2004 and 2015 among individuals aged 26 to 64 years. Using the American Joint Committee on Cancer melanoma staging system, early‐stage melanoma was defined as stage I or stage II whereas late‐stage melanoma was defined as stage III or stage IV. Late‐stage diagnosis was the primary outcome compared across 4 insurance types (private, Medicaid, none, and unknown). Adjusted covariates were age, sex, race/ethnicity, educational level, income, year of diagnosis, number of comorbidities, and facility location. Logistic regression was used for univariable and multivariable analyses.
Results
Among 177,247 cases, individuals with Medicaid or no health insurance were found to have 3.12 (95% CI, 2.97‐3.28) and 2.21 (95% CI, 2.10‐2.33) times greater odds, respectively, of being diagnosed with late‐stage melanoma compared with individuals with private insurance after adjusting for risk factors in late‐stage diagnosis.
Conclusions
Future investigation into insurance disparities in the diagnosis of late‐stage melanoma may help to prioritize melanoma screening in populations with nonprivate insurance.
The odds of diagnosis with late‐stage melanoma (defined herein as American Joint Committee on Cancer stage III or stage IV disease) are 3.12 times and 2.21 times, respectively, higher for individuals with Medicaid and no insurance coverage compared with those with private insurance after adjusting for age, sex, race/ethnicity, income, educational level, year of diagnosis, number of comorbidities, and facility location. Nonprivate health insurance is strongly associated with a diagnosis of late‐stage melanoma versus early‐stage melanoma in the nonelderly adult population.
Preconception pregnancy risk profiles-characterizing the likelihood that a pregnancy attempt results in a full-term birth, preterm birth, clinical pregnancy loss, or failure to conceive-can provide ...critical information during the early stages of a pregnancy attempt, when obstetricians are best positioned to intervene to improve the chances of successful conception and full-term live birth. Yet the task of constructing and validating risk assessment tools for this earlier intervention window is complicated by several statistical features: the final outcome of the pregnancy attempt is multinomial in nature, and it summarizes the results of two intermediate stages, conception and gestation, whose outcomes are subject to competing risks, measured on different time scales, and governed by different biological processes. In light of this complexity, existing pregnancy risk assessment tools largely focus on predicting a single adverse pregnancy outcome, and make these predictions at some later, post-conception time point.
We reframe the individual pregnancy attempt as a multistate model comprised of two nested multinomial prediction tasks: one corresponding to conception and the other to the subsequent outcome of that pregnancy. We discuss the estimation of this model in the presence of multiple stages of outcome missingness and then introduce an inverse-probability-weighted Hypervolume Under the Manifold statistic to validate the resulting multivariate risk scores. Finally, we use data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial to illustrate how this multistate competing risks framework might be utilized in practice to construct and validate a preconception pregnancy risk assessment tool.
In the EAGeR study population, the resulting risk profiles are able to meaningfully discriminate between the four pregnancy attempt outcomes of interest and represent a significant improvement over classification by random chance.
As illustrated in our analysis of the EAGeR data, our proposed prediction framework expands the pregnancy risk assessment task in two key ways-by considering a broader array of pregnancy outcomes and by providing the predictions at an earlier, preconception intervention window-providing obstetricians and their patients with more information and opportunities to successfully guide pregnancy attempts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cluster‐randomized trials (CRTs) of infectious disease preventions often yield correlated, interval‐censored data: dependencies may exist between observations from the same cluster, and event ...occurrence may be assessed only at intermittent study visits. This data structure must be accounted for when conducting interim monitoring and futility assessment for CRTs. In this article, we propose a flexible framework for conditional power estimation when outcomes are correlated and interval‐censored. Under the assumption that the survival times follow a shared frailty model, we first characterize the correspondence between the marginal and cluster‐conditional survival functions, and then use this relationship to semiparametrically estimate the cluster‐specific survival distributions from the available interim data. We incorporate assumptions about changes to the event process over the remainder of the trial—as well as estimates of the dependency among observations in the same cluster—to extend these survival curves through the end of the study. Based on these projected survival functions, we generate correlated interval‐censored observations, and then calculate the conditional power as the proportion of times (across multiple full‐data generation steps) that the null hypothesis of no treatment effect is rejected. We evaluate the performance of the proposed method through extensive simulation studies, and illustrate its use on a large cluster‐randomized HIV prevention trial.
Abstract
Chlamydia genital infection by Chlamydia trachomatisis the most common bacterial sexually transmitted disease worldwide. The relationships between stress and chlamydia genital infection ...remain unknown. Beta2-adrenergic receptor(β2-AR), the major receptor of the stress hormone norepinephrine (NE), is known to impair the function of immune cells. Stress was induced by immersing mice in cold water for five minutes daily for 21 days before infection. This study determined profiles of immune cells of stressed β2-AR KO and stressed WT C57BL/6J after 48 h of Chlamydia muridarumgenital infection. Splenic T cells and differentiated bone marrow-derived macrophages and dendric cells (DCs) were purified by negative selection and stimulated by seeding T cells on anti-CD3/CD28 antibodies coated wells and by treating macrophages and DCs with LPS. After 48 h proliferation, cytokine levels in culture supernatants of the cells were determined using ELISA. Results show increased IFN-γ and IL-1β secretions but deceased IL-4 secretion by CD4+ T cells of β2-AR KO compared to WT (p<0.05). The secretion of IL-13, IL-5, and IL-10 but not IL-23 in CD4 T cells of stressed β2-AR KO mice was two-fold lower than that of stressed WT. TNF-α and IL-1β secretions in macrophages and DCs or IL-12 secretion in DCs was high in stressed β2-AR KO compared to WT (p<0.05). Overall, this study provides insights into the β2-AR signaling pathway’s role in suppressing the secretion of protective cytokines suggesting that inhibiting β2-AR signaling pathway may restore the function of immune cells during chlamydia genital infection. However, further study is warranted.
This work was funded by NIH grant # 1R15AI124156-01 awarded to Bluefield State University
The Botswana Combination Prevention Project was a cluster-randomized HIV prevention trial whose follow-up period coincided with Botswana's national adoption of a universal test and treat strategy for ...HIV management. Of interest is whether, and to what extent, this change in policy modified the preventative effects of the study intervention. To address such questions, we adopt a stratified proportional hazards model for clustered interval-censored data with time-dependent covariates and develop a composite expectation maximization algorithm that facilitates estimation of model parameters without placing parametric assumptions on either the baseline hazard functions or the within-cluster dependence structure. We show that the resulting estimators for the regression parameters are consistent and asymptotically normal. We also propose and provide theoretical justification for the use of the profile composite likelihood function to construct a robust sandwich estimator for the variance. We characterize the finite-sample performance and robustness of these estimators through extensive simulation studies. Finally, we conclude by applying this stratified proportional hazards model to a re-analysis of the Botswana Combination Prevention Project, with the national adoption of a universal test and treat strategy now modeled as a time-dependent covariate.
Numerous methods for classifying gene activity states based on gene expression data have been proposed for use in downstream applications, such as incorporating transcriptomics data into metabolic ...models in order to improve resulting flux predictions. These methods often attempt to classify gene activity for each gene in each experimental condition as belonging to one of two states: active (the gene product is part of an active cellular mechanism) or inactive (the cellular mechanism is not active). These existing methods of classifying gene activity states suffer from multiple limitations, including enforcing unrealistic constraints on the overall proportions of active and inactive genes, failing to leverage a priori knowledge of gene co-regulation, failing to account for differences between genes, and failing to provide statistically meaningful confidence estimates. We propose a flexible Bayesian approach to classifying gene activity states based on a Gaussian mixture model. The model integrates genome-wide transcriptomics data from multiple conditions and information about gene co-regulation to provide activity state confidence estimates for each gene in each condition. We compare the performance of our novel method to existing methods on both simulated data and real data from 907 E. coli gene expression arrays, as well as a comparison with experimentally measured flux values in 29 conditions, demonstrating that our method provides more consistent and accurate results than existing methods across a variety of metrics.
Kaitlyn Cook*, Tesfaye Belay, Ph.D*., *Department of Applied Science and Mathematics, Bluefield State College, Bluefield WV 24701 Production of CD4+ T Cell Subsets in a Beta2-Adrenergic Receptor ...Knockout Stress Mouse Model during Chlamydia muridarum Genital Infection
Chlamydia is the most widely spread sexually transmitted disease, with more than one hundred million new cases occurring every year worldwide. Studies show the effect of stress promoting infection, but little is known about Chlamydia and the impact of stress. Cold-induced stress was used to simulate stress in mice to understand the relationship between the stress hormone norepinephrine (NE) and the immune system. This study aims to determine the role of beta2-adrenergic receptor (β2-AR) under stressful conditions during infection. We hypothesize the β2-AR suppresses T helper cell 1 (Th1) and promotes the production of Th2 cytokines. Following stressing, infection, sacrificing, and dissection of mice, the spleen, lymph node, and genital tract cells were proliferated for 72 hours. ELISA data for IL-13 concentration shows stressed knockout (KO) mice had 273.6pg/mL compared to stressed wildtype (WT) mice with 120.6pg/mL. Various treatment of CD4+ T cells resulted in production of TNF- α, ranging from 595pg/mL to 398.7pg/mL. Viability of CD4+ T cells treated with β2-AR agonist Fenoterol, and antagonist ICI 118,551 were analyzed. The viability of CD4+ T cells treated with NE was 70.7% in KO, compared to 69.1% and 70.2% for the agonist and antagonist, respectively. NE, Fenoterol, and ICI 118,551 treatment resulted in 72.2%, 83.6% and 84.4% respectively for WT. No significant difference is found between the agonist and antagonist. Chlamydia muridarum isolation from the genital tract of treatment groups is underway. The ELISA data implies that β2-AR mice restored increased production of protective cytokines more than their WT counterparts.
Despite the critical importance of attention for children's self-regulation and mental health, there are few task-based measures of this construct appropriate for use across a wide childhood age ...range including very young children. Three versions of a combined go/no-go and continuous performance task (GNG/CPT) were created with varying length and timing parameters to maximize their appropriateness for age groups spanning early to middle childhood. As part of the baseline assessment of a clinical trial, 452 children aged 3-12 years (50% male, 50% female; 52% White, non-Hispanic, 27% Black, 16% Hispanic/Latinx; 6% other ethnicity/race) completed the task. Confirmatory factor analysis indicated that all task versions assessed two latent factors, labeled response inhibition and sustained attention. Versions for older children elicited lower overall accuracy while equating levels of inhibitory demand. All versions showed limited floor and ceiling effects, as well as developmental sensitivity. Boys showed higher commission error rates and children from lower income households showed lower performance across multiple task metrics. Task metrics, especially d prime and accuracy summary scores, correlated with parent-reported executive function and externalizing behavior. Task scores show promise as valid and sensitive indicators of inhibition and sustained attention across heterogeneous pediatric age groups.
Public Significance Statement
There are very few well-developed measures of children's management of their attention, although attention is fundamental to children's learning and well-being. This study describes and validates a task that can be used even with very young children to measure and monitor their attention skills. The task may be especially useful for clinicians and researchers hoping to understand and support attention in children of widely varying ages.
Assays for cancer diagnosis via the analysis of biomarkers on circulating extracellular vesicles (EVs) typically have lengthy sample workups, limited throughput or insufficient sensitivity, or do not ...use clinically validated biomarkers. Here we report the development and performance of a 96-well assay that integrates the enrichment of EVs by antibody-coated magnetic beads and the electrochemical detection, in less than one hour of total assay time, of EV-bound proteins after enzymatic amplification. By using the assay with a combination of antibodies for clinically relevant tumour biomarkers (EGFR, EpCAM, CD24 and GPA33) of colorectal cancer (CRC), we classified plasma samples from 102 patients with CRC and 40 non-CRC controls with accuracies of more than 96%, prospectively assessed a cohort of 90 patients, for whom the burden of tumour EVs was predictive of five-year disease-free survival, and longitudinally analysed plasma from 11 patients, for whom the EV burden declined after surgery and increased on relapse. Rapid assays for the detection of combinations of tumour biomarkers in plasma EVs may aid cancer detection and patient monitoring.
It is unknown whether children with primary snoring and children with mild obstructive sleep apnea (OSA) represent populations with substantially different clinical characteristics. Nonetheless, an ...obstructive apnea-hypopnea index (AHI) of 1 or greater is often used to define OSA and plan for adenotonsillectomy (AT).
To assess whether a combination of clinical characteristics differentiates children with primary snoring from children with mild OSA.
Baseline data from the Pediatric Adenotonsillectomy Trial for Snoring (PATS) study, a multicenter, single-blind, randomized clinical trial conducted at 6 academic sleep centers from June 2016 to January 2021, were analyzed. Children aged 3.0 to 12.9 years with polysomnography-diagnosed (AHI <3) mild obstructive sleep-disordered breathing who were considered candidates for AT were included. Data analysis was performed from July 2022 to October 2023.
Logistic regression models were fitted to identify which demographic, clinical, and caregiver reports distinguished children with primary snoring (AHI <1; 311 patients 67.8%) from children with mild OSA (AHI 1-3; 148 patients 32.2%).
A total of 459 children were included. The median (IQR) age was 6.0 (4.0-7.5) years, 230 (50.1%) were female, and 88 (19.2%) had obesity. A total of 121 (26.4%) were Black, 75 (16.4%) were Hispanic, 236 (51.5%) were White, and 26 (5.7%) were other race and ethnicity. Black race (odds ratio OR, 2.08; 95% CI, 1.32-3.30), obesity (OR, 1.80; 95% CI, 1.12-2.91), and high urinary cotinine levels (>5 µg/L) (OR, 1.88; 95% CI, 1.15-3.06) were associated with greater odds of mild OSA rather than primary snoring. Other demographic characteristics, clinical examination findings, and questionnaire reports did not distinguish between primary snoring and mild OSA. A weighted combination of the statistically significant clinical predictors had limited ability to differentiate children with mild OSA from children with primary snoring.
In this analysis of baseline data from the PATS randomized clinical trial, primary snoring and mild OSA were difficult to distinguish without polysomnography. Mild OSA vs snoring alone did not identify a clinical group of children who may stand to benefit from AT for obstructive sleep-disordered breathing.
ClinicalTrials.gov Identifier: NCT02562040.
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