OBJECTIVES: Contingency management (CM), long known to be efficacious in the treatment of substance-dependent men and women, has also been found to be efficacious for substance-dependent pregnant ...women. However, the specific CM reinforcement parameters in the special population of opioid-dependent pregnant women have been less fully and systematically studied. The Drug Abuse Incentive Systems (DAISY) study, a randomized controlled trial (RCT) of opioid-dependent pregnant patients, found that escalating reinforcement was not superior to a fixed reinforcement CM schedule after a 13-week intervention. To further examine CM's reinforcement parameters in this population, this study aims to test the hypothesis that there is an early treatment response showing an escalating reinforcement schedule to be significantly more efficacious than a fixed schedule after 5 weeks of intervention in opioid-dependent pregnant patients. METHODS: Nine measures of opioid and cocaine abstinence among fixed and escalating CM schedule participants in the DAISY RCT (N=90) were compared over the initial 5 weeks of the intervention. RESULTS: No statistically significant difference in the opioid and cocaine abstinence measures was found between escalating and fixed conditions after 5 weeks (14 opportunities for each participant to leave a urine sample). The mean (SD) number of drug negative urine samples was 8.1 (4.5) and 7.4 (4.3), for escalating and fixed groups, respectively (p=0.46). CONCLUSIONS: These results further the scientific knowledge regarding CM treatment in opioid-dependent pregnant women by supporting the finding that the escalating and fixed CM schedules produce similar amounts of drug negatives urine samples early in treatment.
Abstract
Background: Diet is a modifiable risk factor for multiple cancers. It is also known to modulate gut microbial composition and metabolic activity, and plays an important role in maintaining ...gut homeostasis. However, our understanding of dietary quality and mucosa-associated microbiota in the large intestine in humans is limited. We examined the association between diet quality and gut microbiota in adults underwent routine colonoscopy in a cross-sectional study. Methods: We enrolled 21 men (50-75 years old, 71% White) who were found to have grossly normal colons at colonoscopy completed between July 2013 and April 2016. We obtained 98 colonic mucosa biopsies, with microbial DNA extracted from snap frozen biopsy. The 16S rRNA V4 region was amplified and sequenced on the Illumina MiSeq platform. The UPARSE and SILVA were used for operational taxonomic unit (OTU) classification. A self-administered BLOCK Food Frequency Questionnaire was used to assess dietary intake in the past year. Dietary quality was defined using the Healthy Eating Index (HEI)-2005, and further categorized as low or high using the median of total HEI or 12 individual component scores. We compared alpha-diversity (OTU and Shannon index), beta-diversity (Weighted UniFrac principal coordinates analysis), and relative abundance of bacterial phylum and genus by total HEI and all 12 individual HEI components using Mann-Whitney test. Reported P values were adjusted for multiple testing using false discovery rate. Results: The most abundant bacterial phyla observed were Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, and Fusobacteria. High-quality diet (total HEI score ≥ 63) was not associated with higher richness and evenness of gut microbiome (P = 0.12), but was significantly associated with bacterial composition (P = 0.046). Compared to men who had low-quality diet (total HEI score < 63), those with high-quality diet had a higher abundance of Proteobacteria (12.2% vs. 8.1%, P = 0.006), and lower abundance of Fusobacteria (0.13% vs. 3.37%, P = 0.004). At the genus level, those with high-quality diet had significantly lower abundance of Fusobacterium than those with low-quality diet (0.11% vs. 3.77%, P = 0.004). At the HEI component level, individuals with a higher consumption of solid fruits and milk had higher richness and evenness of gut microbiome (P < 0.05) as well as higher abundance of phylum Verrucomicrobia (P < 0.05) and genus Akkermansia (P < 0.001). Consuming more solid and saturated fat, alcohol, and added sugar were associated with a higher abundance of phylum Fusobacteria (P < 0.0001) and genus Fusobacterium (P = 0.0001). Conclusions: The colonic microbiome of men consuming a low-quality diet exhibited increased levels of Fusobacteria, which has been associated with colorectal cancer risk. If replicated in prospective research, our findings suggest low quality diet may contribute to colorectal cancer by modulating gut microbiome.
Citation Format: Yanhong Liu, Nadim J. Ajami, Diane Hutchinson, David Graham, Sarah Plew, Ashley Johnson, Preksha Shah, Liang Chen, Kathryn Royse, Donna L. White, Jennifer Kramer, Matthew C. Wong, Rhonda Cole, Clark Hair, Jason Hou, Nisreen Husain, Maria Jarbrink-Sehgal, Fasiha Kanwal, Gyanprakash Ketwaroo, Rajesh Shah, Maria Velez, Melissa L. Bondy, Hashem B. El-Serag, Joseph F. Petrosino, Li Jiao. Healthy eating index 2005 and the mucosa associated gut microbiome in healthy individuals abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3265.
Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we ...demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1. Increased levels of ROS, a by-product of activated mtOXPHOS, led to the accumulation of HIF-1α. Pharmacological inhibition of HIF-1α attenuated CSC enrichment and tumor initiation in vivo. These data suggest that (1) MYC and MCL1 confer resistance to chemotherapy by expanding CSCs via mtOXPHOS and (2) targeting mitochondrial respiration and HIF-1α may reverse chemotherapy resistance in TNBC.
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•MYC and MCL1 increase cancer stem cells in chemotherapy-resistant TNBC•MYC and MCL1 cooperatively promote mtOXPHOS, which in turn induces HIF-1α•MCL1 induces CSCs independent of its BH3-dependent, anti-apoptotic function•Inhibition of HIF1-α abolishes CSC enrichment in chemotherapy-resistant TNBC
MYC and MCL1 are co-amplified in drug-resistant breast cancer. Lee et al. reveal that MYC and MCL1 cooperate to maintain cancer stem cells (CSCs) resistant to chemotherapy by increasing mitochondrial OXPHOS, ROS production, and HIF-1α expression. Inhibition of HIF-1α blocks CSC expansion and restores chemotherapy sensitivity.
Purpose
This study examined the influence of parental marital status, parent‐child sexual communication, parent‐child closeness on the HIV‐related knowledge, safer‐sex intentions, and behaviors of ...late adolescent urban African American males.
Design
The study employed a cross‐sectional design with retrospective recall of salient parental influences and behaviors.
Methods
Data were collected via paper‐and‐pencil questionnaire from 134 late adolescent African American males, 18 to 22 years of age, recruited from urban communities in and around Boston, Massachusetts. Data were analyzed using bivariate correlations, paired t tests, and regression modeling.
Findings
Young men reported greater amounts of sexual communication with mothers than fathers (p < .001). Parent‐child closeness was positively correlated with amount of parent‐child sexual communication with both mothers and fathers (p < .001 for both). Parent‐child closeness was, in turn, associated with greater condom use self‐efficacy (p < .01), less permissive sexual attitudes (p < .001), fewer sexual partners (p < .01), and less unprotected sex (p < .01). Greater amounts of parent‐child sexual communication were associated with fewer sexual risk behaviors, more consistent condom use, and greater intentions to use condoms in the future. There was evidence that parental influences on sexual risk behaviors and condom use intentions were mediated through young men's condom use self‐efficacy, attitudes, and beliefs.
Conclusions
These findings highlight the importance of the parent‐child relationship and the role of parent‐child communication between parents and sons. Further studies are needed to better understand the nature of father‐son communication and develop strategies to help parents communicate effectively with sons.
Clinical Relevance
Evidence has shown that African American adolescent males are more likely to engage in high‐risk sexual behaviors. Understanding the sexual risk communication between African American adolescent males and their parents is important to developing strategies in reducing sexual risk behavior.
PURPOSE To investigate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of inavolisib, a potent and selective small-molecule inhibitor of p110α that promotes the ...degradation of mutated p110α, in combination with palbociclib and endocrine therapy (ET), in a phase I/Ib study in patients with PIK3CA-mutated, hormone receptor–positive/human epidermal growth factor receptor 2–negative locally advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT03006172 ). METHODS Women ≥18 years of age received inavolisib, palbociclib, and letrozole (Inavo + Palbo + Letro arm) or fulvestrant (Inavo + Palbo + Fulv arm) until unacceptable toxicity or disease progression. The primary objective was to evaluate safety or tolerability. RESULTS Fifty-three patients were included, 33 in the Inavo + Palbo + Letro arm and 20 in the Inavo + Palbo + Fulv arm. Median duration of inavolisib treatment was 15.7 and 20.8 months (cutoff: March 27, 2023), respectively. Treatment-related adverse events (TRAEs) occurred in all patients; the most frequent were stomatitis, hyperglycemia, and diarrhea; grade ≥3 any TRAE rates were 87.9% and 85.0%; 6.1% and 10.0% discontinued any treatment due to TRAEs in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. No PK drug–drug interactions (DDIs) were observed among the study treatments when administered. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. Available paired pre- and on-treatment tumor tissue and circulating tumor DNA analyses confirmed the effects of study treatment on pharmacodynamic and pathophysiologic biomarkers of response. CONCLUSION Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.
To determine the incidence of serious chronic health conditions among survivors of pediatric Hodgkin lymphoma (HL), compare by era of therapy and by selected cancer therapies, and provide estimates ...of risks associated with contemporary therapy.
Assessing 2,996 5-year HL survivors in the Childhood Cancer Survivor Study diagnosed from 1970 to 1999, we examined the cumulative incidence of severe to fatal chronic conditions (grades 3-5) using self-report conditions, medically confirmed subsequent malignant neoplasms, and cause of death based on the National Death Index. We used multivariable regression models to estimate hazard ratios (HRs) per decade and by key treatment exposures.
HL survivors were of a mean age of 35.6 years (range, 12-58 years). The cumulative incidence of any grade 3-5 condition by 35 years of age was 31.4% (95% CI, 29.2 to 33.5). Females were twice as likely (HR, 2.1; 95% CI, 1.8 to 2.4) to have a grade 3-5 condition compared with males. From the 1970s to the 1990s, there was a 20% reduction (HR, 0.8; 95% CI, 0.7 to 0.9) in decade-specific risk of a grade 3-5 condition (
trend = .002). In survivors who had a recurrence and/or hematopoietic cell transplant, the risk of a grade 3-5 condition was substantially elevated, similar to that of survivors treated with high-dose, extended-field radiotherapy (HR, 1.2; 95% CI, 0.9 to 1.5). Compared with survivors treated with chest radiotherapy ≥ 35 Gy in combination with an anthracycline or alkylator, a contemporary regimen for low-intermediate risk HL was estimated to lead to a 40% reduction in risk of a grade 3-5 condition (HR, 0.6; 95% CI, 0.4 to 0.8).
This study demonstrates that risk-adapted therapy for pediatric HL has resulted in a significant reduction in serious long-term outcomes.
Objective: The purpose of this study was to examine the routine screening of female students in college health centers for six priority health-related behaviors and experiences (tobacco use, alcohol ...use, eating disorders EDs, obesity, anxiety and depression, intimate partner violence/sexual violence IPV/SV), and to identify variations in practice. Participants: A nationally representative sample of 1,221 healthcare providers (HCPs), including nurse practitioners, physicians, and physician assistants, from 471 U.S. college health centers. Methods: HCPs completed surveys (on-line or paper) and reported on routine screening of female college students. Results: HCPs reported consistently high rates (75-85%) of screening for tobacco use, alcohol use, and anxiety/depression. Rates of screening for IPV/SV, obesity and EDs were much lower. Nurse practitioners reported the highest IPV/SV screening rates. Conclusions: College health centers present unique opportunities for screening, case-finding and intervening to reduce long-term sequelae. Providers are well-positioned to lead initiatives to improve screening practices.Objective: The purpose of this study was to examine the routine screening of female students in college health centers for six priority health-related behaviors and experiences (tobacco use, alcohol use, eating disorders EDs, obesity, anxiety and depression, intimate partner violence/sexual violence IPV/SV), and to identify variations in practice. Participants: A nationally representative sample of 1,221 healthcare providers (HCPs), including nurse practitioners, physicians, and physician assistants, from 471 U.S. college health centers. Methods: HCPs completed surveys (on-line or paper) and reported on routine screening of female college students. Results: HCPs reported consistently high rates (75-85%) of screening for tobacco use, alcohol use, and anxiety/depression. Rates of screening for IPV/SV, obesity and EDs were much lower. Nurse practitioners reported the highest IPV/SV screening rates. Conclusions: College health centers present unique opportunities for screening, case-finding and intervening to reduce long-term sequelae. Providers are well-positioned to lead initiatives to improve screening practices.
Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at ...individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date.
We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation measures and breast cancer risk, adjusted and unadjusted for cell-type composition. Study-specific ORs were combined using fixed-effect meta-analysis with inverse variance weights. Stratified analyses were conducted by age at diagnosis (< 50, ≥ 50), estrogen receptor (ER) status (+/-), and time since blood collection (< 5, 5-10, > 10 years). The false discovery rate (q value) was used to account for multiple testing.
The average age at blood draw ranged from 52.2 to 62.2 years across the four cohorts. Median follow-up time ranged from 6.6 to 8.4 years. The methylation measured at individual CpGs was not associated with breast cancer risk (q value > 0.59). In addition, higher average methylation level was not associated with risk of breast cancer (OR = 0.94, 95% CI = 0.85, 1.05; P = 0.26; P for study heterogeneity = 0.86). We found no evidence of modification of this association by age at diagnosis (P = 0.17), ER status (P = 0.88), time since blood collection (P = 0.98), or CpG location (P = 0.98).
Our data indicate that DNA methylation measured in the blood prior to breast cancer diagnosis in predominantly postmenopausal women is unlikely to be associated with substantial breast cancer risk on the HM450K array. Larger studies or with greater methylation coverage are needed to determine if associations exist between blood DNA methylation and breast cancer risk.
Student health services are associated with improved health outcomes and academic success, particularly among under-resourced college populations. This study compared student health services at ...Historically Black Colleges and Universities (HBCUs) and Predominantly Black Institutions (PBIs) and identified factors associated with the availability of comprehensive health services (CHS).
We conducted a secondary analysis of 2022 data from the Integrated Postsecondary Education Data System (IPEDS), the Minority Serving Institutions (MSIs) Directory, and the websites of HBCUs and PBIs (
=167). Bivariate and multivariate logistic regression analyses were undertaken to identify institutional variables associated with providing CHS. Institutional variables included college type (public vs. private), MSI category (HBCU vs. PBI), undergraduate enrollment, location, and proportion of Pell grant recipients.
Approximately 13% of HBCUs and 26% of PBIs offered no student health services; 65% of HBCUs and 39% of PBIs offered on-campus CHS with prescribing providers. Four-year HBCUs were five times more likely than 4-year PBIs to have CHS (
=0.014). Institutions with more Pell Grant recipients were less likely to offer CHS.
Access to health care is an important social determinant of health, academic persistence, and achievement for college students. HBCUs were significantly more likely than PBIs to offer CHS. HBCUs are more likely than PBIs to have resources from federal funding, donors, and endowments that may support the development of student health centers and services. Increased funding for PBI health centers could improve access and promote health equity among the most vulnerable student populations.
The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.
To assess outcomes in patients with ILD hospitalized for COVID-19 versus those ...without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.
An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.
Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio HR, 1.60; confidence interval, 1.17-2.18;
= 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).
Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
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