Adverse Childhood Experiences Among Females in Substance Use Treatment and Their Children: A Pilot Study

Women with substance use disorder (SUD) often have experienced adverse childhood experiences (ACEs). The intergenerational nature of ACEs also put their children at risk for experiencing ACEs. However, no research has explored the prevalence of ACEs in children whose mothers have SUD. This study assessed ACE scores in mothers with SUD and their children and compared them with non-SUD participants. Females with SUD were recruited from a treatment center (n = 50) and compared to females without SUD from the same area (n = 50). The ACE scores of the participants and their children were measured as well as sociodemographic variables. ANOVA and Fisher’s Exact tests were used to examine univariate differences. Multivariate regression models assessed the difference in ACE scores between the groups and their children and the relationship between maternal and child ACE scores while including sociodemographic confounders. The mean ACE score was significantly higher in SUD participants (4.9, SD = 2.9) when compared to non-SUD participants (1.9, SD = 2.0) after controlling for sociodemographic variables (p \u3c .01). Children of treatment participants also had significantly higher mean ACE scores (3.9, SD = 2.3) than children of comparison participants (1.3, SD = 2.0, p \u3c .01). Maternal ACE score was positively related to children’s ACE score after controlling for sociodemographic variables. Given the intergenerational nature of ACEs and their high burden in both mothers and children in substance use treatment, these preliminary findings suggest that mother–child trauma-informed interventions may be appropriate for this population

The impact of different calibration matrices on the determination of insulin-like growth factor 1 by high-resolution-LC-MS in acromegalic and growth hormone deficient patients

Objectives: Calibration is an important source of variability in liquid chromatography mass spectrometry (LC-MS) methods for insulin-like growth factor 1 (IGF-1). This study investigated the impact of different calibrator matrices on IGF-1 measurements by LC-MS. Moreover, the comparability of immunoassays and LC-MS was assessed. Design & Methods: Calibrators from 12.5 to 2009 ng/ml were prepared by spiking WHO international Standard (ID 02/254 NIBSC, UK) into the following matrices: native human plasma, fresh charcoal-treated human plasma (FCTHP), old charcoal-treated human plasma, deionized water, bovine serum albumin (BSA), and rat plasma (RP). A validated in-house LC-MS method was calibrated repeatedly with these calibrators. Then, serum samples from 197 growth hormone excess and deficiency patients were analysed with each calibration. Results: The seven calibration curves had different slopes leading to markedly different patient results. The largest differences in IGF-1 concentration from the median (interquartile range) was observed with the calibrator in water and the calibrator in RP (336.4 [279.6–417.0] vs. 112.5 [71.2–171.2], p < 0.001). The smallest difference was observed with calibrators in FCTHP and BSA (141.8 [102.0–198.5] vs. 127.9 [86.9–186.0], p < 0.049). Compared to LC-MS with calibrators in FCTHP, immunoassays showed relevant proportional bias (range: −43% to −68%), constant bias (range: 22.84 to 57.29 ng/ml) and pronounced scatter. Comparing the immunoassays with each other revealed proportional bias of up to 24%. Conclusions: The calibrator matrix is critical for the measurement of IGF-1 by LC-MS. Regardless of the calibrator matrix, LC-MS shows poor agreement with immunoassays. Also, the agreement between different immunoassays is variable

Cancer Incidence Among Patients of the U.S. Veterans Affairs Health Care System

Approximately 40,000 incident cancer cases are reported in VA Central Cancer Registry (VACCR) annually (~3% of United States cancer cases). Our objective was to provide the first comprehensive description of cancer incidence as reported in VACCR

Early dissemination of bevacizumab for advanced colorectal cancer: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>We describe early dissemination patterns for first-line bevacizumab given for metastatic colorectal cancer treatment.</p> <p>Methods</p> <p>We analyzed patient surveys and medical records for a population-based cohort with metastatic colorectal cancer treated in multiple regions and health systems in the United States (US). Eligible patients were diagnosed with metastatic colorectal cancer and initiated first-line chemotherapy after US Food & Drug Administration (FDA) bevacizumab approval in February 2004. First-line bevacizumab therapy was defined as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic colorectal cancer. We evaluated factors associated with first-line bevacizumab treatment using logistic regression.</p> <p>Results</p> <p>Among 355 patients, 31% received first-line bevacizumab in the two years after FDA approval, including 26% of men, 41% of women, and 16% of those ≥ 75 years. Use rose sharply within 6 months after FDA approval, then plateaued. 20% of patients received bevacizumab in combination with irinotecan; 53% received it with oxaliplatin. Men were less likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p = 0.026). Patients ≥ 75 years were less likely to receive bevacizumab than patients < 55 years (adjusted OR 0.13; 95% CI 0.04-0.46; p = 0.001).</p> <p>Conclusions</p> <p>One-third of eligible metastatic colorectal cancer patients received first-line bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab as part of the regimen used in the pivotal study leading to FDA approval.</p

Cardiovascular Risk Factor Disparities in Adult Survivors of Childhood Cancer Compared With the General Population

BACKGROUND: It is unknown whether a history of childhood cancer modifies the established disparities in cardiovascular risk factors (CVRFs) observed in the general population. OBJECTIVES: We sought to determine if disparities in CVRFs by race/ethnicity are similar among childhood cancer survivors compared with the general population. METHODS: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort with a longitudinal follow-up of 24,084 5-year survivors diagnosed between 1970 and 1999. Multivariable piecewise exponential regression estimated incidence rate ratios (IRRs) for hypertension, hyperlipidemia, diabetes, obesity, and ≥2 CVRFs by race/ethnicity. The CCSS sibling cohort and the National Health and Nutrition Examination Survey cohort were used to compare the sociodemographic-adjusted IRRs for same-race/same-ethnicity disparities. RESULTS: Non-Hispanic Black (NHB) (n = 1,092) and Hispanic (n = 1,405) survivors compared with non-Hispanic White (NHW) (n = 13,960) survivors reported a higher cumulative incidence of diabetes (8.4%, 9.7%, and 5.1%, respectively); obesity (47.2%, 48.9%, and 30.2%, respectively); multiple CVRFs (17.7%, 16.6%, and 12.3%, respectively); and, for NHB survivors, hypertension (19.5%, 13.6%, and 14.3%, respectively) by 40 years of age ( CONCLUSIONS: The higher burden of CVRFs among NHB and Hispanic survivors compared with NHW survivors was similar to the general population. The promotion of cardiovascular health equity is critical in this high-risk population

P-Type ATPase TAT-2 Negatively Regulates Monomethyl Branched-Chain Fatty Acid Mediated Function in Post-Embryonic Growth and Development in C. elegans

Monomethyl branched-chain fatty acids (mmBCFAs) are essential for Caenorhabditis elegans growth and development. To identify factors acting downstream of mmBCFAs for their function in growth regulation, we conducted a genetic screen for suppressors of the L1 arrest that occurs in animals depleted of the 17-carbon mmBCFA C17ISO. Three of the suppressor mutations defined an unexpected player, the P-type ATPase TAT-2, which belongs to the flippase family of proteins that are implicated in mediating phospholipid bilayer asymmetry. We provide evidence that TAT-2, but not other TAT genes, has a specific role in antagonizing the regulatory activity of mmBCFAs in intestinal cells. Interestingly, we found that mutations in tat-2 also suppress the lethality caused by inhibition of the first step in sphingolipid biosynthesis. We further showed that the fatty acid side-chains of glycosylceramides contain 20%–30% mmBCFAs and that this fraction is greatly diminished in the absence of mmBCFA biosynthesis. These results suggest a model in which a C17ISO-containing sphingolipid may mediate the regulatory functions of mmBCFAs and is negatively regulated by TAT-2 in intestinal cells. This work indicates a novel connection between a P-type ATPase and the critical regulatory function of a specific fatty acid

Chemotherapy use and patient treatment preferences in advanced colorectal cancer: A prospective cohort study

Our objective was to determine how patient preferences guide the course of palliative chemotherapy for advanced colorectal cancer

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems

© 2008 Zafar et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background : Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. Methods : Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. Results : 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58–1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race. Conclusion : Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare

Human Integrin α3β1 Regulates TLR2 Recognition of Lipopeptides from Endosomal Compartments

Toll-like receptor (TLR)-2/TLR1 heterodimers recognize bacterial lipopeptides and initiate the production of inflammatory mediators. Adaptors and co-receptors that mediate this process, as well as the mechanisms by which these adaptors and co-receptors function, are still being discovered.Using shRNA, blocking antibodies, and fluorescent microscopy, we show that U937 macrophage responses to the TLR2/1 ligand, Pam(3)CSK(4), are dependent upon an integrin, α(3)β(1). The mechanism for integrin α(3)β(1) involvement in TLR2/1 signaling is through its role in endocytosis of lipopeptides. Using inhibitors of endosomal acidification/maturation and physical tethering of the ligand, we show that the endocytosis of Pam(3)CSK(4) is necessary for the complete TLR2/1-mediated pro-inflammatory cytokine response. We also show that TLR2/1 signaling from the endosome results in the induction of different inflammatory mediators than TLR2/1 signaling from the plasma membrane.Here we identify integrin α(3)β(1) as a novel regulator for the recognition of bacterial lipopeptides. We demonstrate that induction of a specific subset of cytokines is dependent upon integrin α(3)β(1)-mediated endocytosis of the ligand. In addition, we address an ongoing controversy regarding endosomal recognition of bacterial lipopeptides by demonstrating that TLR2/1 signals from within endosomal compartments as well as the plasma membrane, and that downstream responses may differ depending upon receptor localization. We propose that the regulation of endosomal TLR2/1 signaling by integrin α(3)β(1) serves as a mechanism for modulating inflammatory responses