Quisinostat is a brain-penetrant radiosensitizer in glioblastoma.

Histone deacetylase (HDAC) inhibitors have garnered considerable interest for the treatment of adult and pediatric malignant brain tumors. However, owing to their broad-spectrum nature and inability to effectively penetrate the blood-brain barrier, HDAC inhibitors have failed to provide substantial clinical benefit to patients with glioblastoma (GBM) to date. Moreover, global inhibition of HDACs results in widespread toxicity, highlighting the need for selective isoform targeting. Although no isoform-specific HDAC inhibitors are currently available, the second-generation hydroxamic acid-based HDAC inhibitor quisinostat possesses subnanomolar specificity for class I HDAC isoforms, particularly HDAC1 and HDAC2. It has been shown that HDAC1 is the essential HDAC in GBM. This study analyzed the neuropharmacokinetic, pharmacodynamic, and radiation-sensitizing properties of quisinostat in preclinical models of GBM. It was found that quisinostat is a well-tolerated and brain-penetrant molecule that extended survival when administered in combination with radiation in vivo. The pharmacokinetic-pharmacodynamic-efficacy relationship was established by correlating free drug concentrations and evidence of target modulation in the brain with survival benefit. Together, these data provide a strong rationale for clinical development of quisinostat as a radiosensitizer for the treatment of GBM.

Rapid whole-brain myelin imaging with selective inversion recovery and compressed SENSE.

PURPOSE: Quantitative magnetization transfer (QMT) using selective inversion recovery (SIR) can quantify the macromolecular-to-free proton pool size ratio (PSR), which has been shown to relate closely with myelin content. Currently clinical applications of SIR have been hampered by long scan times. In this work, the acceleration of SIR-QMT using CS-SENSE (compressed sensing SENSE) was systematically studied. THEORY AND METHODS: Phantoms of varied concentrations of bovine serum albumin and human scans were first conducted to evaluate the SNR, precision of SIR-QMT parameters, and scan time. Based on these results, an optimized CS-SENSE factor of 8 was determined and the test-retest repeatability was further investigated. RESULTS: A whole-brain SIR imaging of 6 min can be achieved. Bland-Altman analyses indicated excellent agreement between the test and retest sessions with a difference in mean PSR of 0.06% (and a difference in mean R1f of -0.001 s-1 ). In addition, the assessment of the intraclass correlation coefficient (ICC) revealed high reliability in nearly all the white matter and gray matter regions. In white matter regions, the ICC was 0.93 (95% confidence interval [CI]: 0.88-0.96, p < 0.001) for PSR, and 0.90 (95% CI: 0.83-0.94, p < 0.001) for R1f . In gray matter, ICC was 0.84 (95% CI: 0.66-0.93, p < 0.001) in PSR, and 0.98 (95% CI: 0.95-0.99, p < 0.001) for R1f . The method also showed excellent capability to detect focal lesions in multiple sclerosis. CONCLUSION: Rapid, reliable, and sensitive whole-brain SIR imaging can be achieved using CS-SENSE, which is expected to significantly promote widespread clinical translation.

Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review.

BACKGROUND: Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials. METHODS: We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. The followings were key words for the literature search as index terms or free-text words: "phase II trials", "glioblastoma", and "two-stage design". We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status. RESULTS: Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Most trials (90%) used Simon's two-stage designs. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy. CONCLUSIONS: Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials.

A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma.

PURPOSE: Ceritinib is an orally bioavailable, small-molecule inhibitor of anaplastic lympoma kinase (ALK), insulin-like growth factor 1 receptor (IGFR1), and focal adhesion kinase (FAK), which are highly expressed in glioblastoma and many brain metastases. Preclinical and clinical studies indicate that ceritinib has antitumor activity in central nervous system (CNS) malignancies. This phase 0 trial measured the tumor pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in patients with brain metastasis or recurrent glioblastoma. PATIENTS AND METHODS: Preoperative patients with brain tumors demonstrating high expression of pSTAT5b/pFAK/pIGFR1 were administered ceritinib for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at predefined timepoints following the final dose. Total and unbound drug concentrations were determined using LC-MS/MS. In treated tumor and matched archival tissues, tumor PD was quantified through IHC analysis of pALK, pSTAT5b, pFAK, pIGFR1, and pIRS1. RESULTS: Ten patients (3 brain metastasis, 7 glioblastoma) were enrolled and no dose-limiting toxicities were observed. Ceritinib was highly bound to human plasma protein [median fraction unbound (Fu), 1.4%] and to brain tumor tissue (median Fu, 0.051% and 0.045% in gadolinium-enhancing and -nonenhancing regions respectively). Median unbound concentrations in enhancing and nonenhancing tumor were 0.048 and 0.006 µmol/L, respectively. Median unbound tumor-to-plasma ratios were 2.86 and 0.33 in enhancing and nonenhancing tumor, respectively. No changes in PD biomarkers were observed in the treated tumor samples as compared to matched archival tumor tissue. CONCLUSIONS: Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastases and patients with recurrent glioblastoma were insufficient for target modulation.

Human papillomavirus vaccine guideline adherence among Arizona's Medicaid beneficiaries.

Cancers caused by human papillomavirus (HPV) can be prevented with the timely uptake and completion of the HPV vaccine series. Series completion is associated with increased vaccine effectiveness and longevity of protection. Medicaid beneficiaries are among populations with higher HPV vaccine uptake; however, little research describes factors that influence their HPV vaccine series completion. This study reports on a secondary data analysis of Arizona Medicaid data (Arizona Health Care Cost Containment System) from years 2008-2016. We summarized patient data using descriptive statistics and explored relationships between demographic variables and HPV vaccine administration information using bivariate logistic regression. Results of this analysis showed that females were more likely to complete the series as compared to males, and the age group that had the greatest odd of vaccine completion were 13-17-year-olds, the catch-up vaccine population. White Medicaid beneficiaries were most likely to adhere to HPV vaccine guidelines, followed by Hispanic beneficiaries. Patients receiving care in urban settings were more likely to complete the HPV vaccine series than people receiving care in rural areas of the state. Although statistically insignificant, people living with HIV were less likely to complete the 3-dose series. Future work should focus on ensuring that HPV vaccine age-eligible Medicaid, including people living with HIV, adhere to HPV vaccine guidelines. Expanding programs such as Vaccines for Children and scope of practice for dental professionals to offer the vaccine may provide additional options for Medicaid beneficiaries to vaccinate.

Former Foster System Youth: Perspectives on Transitional Supports and Programs.

Youth aging out of the foster care system have well-documented challenges when transitioning to adulthood. Multiple transition services provide support in the transition process; however, limited research is available regarding youth's perceptions of programming. In this pilot study, sixteen youth between ages 18 and 20 participated in semi-structured interviews, support mapping, and resiliency measurements to gather the experiences of the transition from foster care. Comparisons between those who chose initial transition supports and those who did not receive or delayed receiving transition supports were initially explored. Common themes emerged in participants' needs and perceived resiliency regardless of transition support services. All youth reported relationship, trust, and concern for well-being as highly important characteristics in transition team members. A need for earlier transition programming, decision-making opportunities, and life skills courses were important themes in transition programming needs. Implications for policy, research, and practice are presented based upon findings.

Patterns and Disparities in Human Papillomavirus (HPV) Vaccine Uptake for Young Female Adolescents among U.S. States: NIS-Teen (2008-2016).

BACKGROUND: Several studies have reported differential vaccine uptake outcomes that are associated with sociodemographic and socioeconomic characteristics, as well as provider type. However, none has examined a trend over a multiple-year span. In this study, we utilize a longitudinal data-based approach to examine state-level human papillomavirus (HPV) vaccine trends and their influences over time. METHODS: We analyzed National Immunization Survey - Teen data (2008-2016) to estimate HPV vaccine initiation rate in young female adolescent ages 13-17 years old among U.S. States. We identified growth patterns using the latent class growth method and explored state-level characteristics, including socioeconomic and sociodemographic attributes, and health legislation and policy-related programs among patterns. RESULTS: We identified three growth patterns, which showed gradually increasing vaccination trends but different baseline HPV uptake rates (high, moderate, low). States within Pattern 1 (highest HPV vaccination rates) included the lowest percentage of families with incomes below federal poverty level, the highest percentage of bachelor's degree or higher, and the lowest number of uninsured, while states within Pattern 3 (lowest HPV vaccination rates) included families with socioeconomic attributes along the opposite end of the spectrum. CONCLUSIONS: Latent class growth models are an effective tool to be able to capture health disparities in heterogeneity among states in relation to HPV vaccine uptake trajectories. IMPACT: These findings might lead to designing and implementing effective interventions and changes in policies and health care coverage to promote HPV vaccination uptake for states represented under the lowest trajectory pattern.

Validity of a Food and Fluid Exercise Questionnaire for Macronutrient Intake during Exercise against Observations.

Information about the accuracy of self-reported food and fluid intake during competitions is scarce. The objective of this study was to validate a previously developed food and fluid exercise questionnaire (FFEQ) against direct observations made during competitions in athletes. Fifty-eight recreational endurance athletes participating in four different running events and one cross duathlon in the Netherlands between 2015 and 2017 were recruited. The FFEQ overestimated the median energy and carbohydrate intake by 27.6 kcal/h (20.6%) and 9.25 g/h (30.8%) (p < 0.001), respectively, compared to direct observation. Reporting bias (i.e., correlation between the difference between methods and average of both methods) increased with a higher energy (r: 0.41, p < 0.01) and carbohydrate intake (r: 0.44, p < 0.01). No statistically significant difference was found between FFEQ-reported fluid intake per hour and observations (median difference: -2.93 mL, -1.1%; p = 0.48) and no fluid reporting bias was identified (r: 0.23, p = 0.08). FFEQ-reported energy (r: 0.74), carbohydrate (r: 0.74), and fluid (r: 0.85) intake was strongly correlated with the observed intake (all p-values < 0.001). In conclusion, the FFEQ accurately estimates the fluid intake on a group level during competitions in recreational athletes. Even though FFEQ overestimates the energy and carbohydrate intake, it is still a useful tool for ranking individuals based on their intake.

Smartphone-Based Meditation for Myeloproliferative Neoplasm Patients: Feasibility Study to Inform Future Trials.

BACKGROUND: Myeloproliferative neoplasm (MPN) patients often report high symptom burden that persists despite the best available pharmacologic therapy. Meditation has gained popularity in recent decades as a way to manage cancer patient symptoms. OBJECTIVE: The aim of this study was to examine the feasibility of 2 different consumer-based meditation smartphone apps in MPN patients and to examine the limited efficacy of smartphone-based meditation on symptoms compared with an educational control group. METHODS: Patients (n=128) were recruited nationally through organizational partners and social media. Eligible and consented patients were enrolled into 1 of 4 groups, 2 of which received varying orders of 2 consumer-based apps (10% Happier and Calm) and 2 that received one of the apps alone for the second 4 weeks of the 8-week intervention after an educational control condition. Participants were asked to perform 10 min of meditation per day irrespective of the app and the order in which they received the apps. Feasibility outcomes were measured at weeks 5 and 9 with a Web-based survey. Feasibility outcomes were acceptability, demand, and limited efficacy for depression, anxiety, pain intensity, sleep disturbance, sexual function, quality of life, global health, and total symptom burden. RESULTS: A total of 128 patients were enrolled across all 4 groups, with 73.4% (94/128) patients completing the intervention. Of the participants who completed the 10% Happier app, 61% (46/76) enjoyed it, 66% (50/76) were satisfied with the content, and 77% (59/76) would recommend to others. Of those who completed the Calm app, 83% (56/68) enjoyed it, 84% (57/68) were satisfied with the content, and 97% (66/68) would recommend to others. Of those who completed the educational control, 91% (56/61) read it, 87% (53/61) enjoyed it, and 71% (43/61) learned something. Participants who completed the 10% Happier app averaged 31 (SD 33) min/week; patients completing the Calm app averaged 71 (SD 74) min/week. 10% Happier app participants saw small effects on anxiety (P<.001 d=-0.43), depression (P=.02; d=-0.38), sleep disturbance (P=.01; d=-0.40), total symptom burden (P=.13; d=-0.27), and fatigue (P=.06; d=-0.30), and moderate effects on physical health (P<.001; d=0.52). Calm app participants saw small effects on anxiety (P=.29; d=-0.22), depression (P=.09; d=-0.29), sleep disturbance (P=.002; d=-0.47), physical health (P=.005; d=0.44), total symptom burden (P=.13; d=-0.27), and fatigue (P=.13; d=-0.27). Educational control participants (n=61) did not have effects on any patient-reported outcome except for a moderate effect on physical health (P<.001; d=0.77). CONCLUSIONS: Delivering meditation via the Calm app is feasible and scored higher in terms of feasibility when compared with the 10% Happier app. The Calm app will be used to implement a randomized controlled trial, testing the effects of meditation on symptom burden in MPNs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03726944; https://clinicaltrials.gov/ct2/show/NCT03726944 (Archived by WebCite at http://www.webcitation.org/77MVdFJwM).

Organized Social Activity, Physical Exercise, and the Risk of Insomnia Symptoms Among Community-Dwelling Older Adults.

Objectives: To compare the risk of insomnia symptoms among community-dwelling older adults who participated and did not participate in organized social activity and physical exercise. Design: Secondary data analysis of a prospective cohort study. Material and Methods: Community-dwelling older adults ≥65 years of age with no insomnia symptoms at baseline were included in the study. Participants were followed up yearly for 3 years. Insomnia symptoms, social activity, and physical exercise status of study participants were assessed at baseline and during follow-up. Results: Study participants who reported engaging in organized social activity and low-intensity physical exercise and organized social activity and high-intensity physical exercise were less likely to report insomnia symptoms during follow-up compared with those who did not engage in any activity. Conclusion: These results suggest beneficial effect of organized social activity and physical exercise in maintaining sleep quality in old age.

Patient-Centered Medical Home Status and Preparedness to Assess Resident Milestones: A CERA Study.

PURPOSE: The patient-centered medical home (PCMH) model has been proposed as the ideal model for delivering primary care and is focused on improving patient safety and quality, reducing costs, and enhancing patient satisfaction. The mandated Accreditation Council for Graduate Medical Education educational milestones for evaluation of resident competency represent the skills graduates will utilize after graduation. Many of these skills are reflected in the PCMH model. We sought to determine if residency programs whose main family medicine (FM) practice sites have achieved PCMH recognition are therefore more prepared to evaluate milestones. METHOD: A national Council of Academic Family Medicine Educational Research Alliance (CERA) survey of family medicine program directors (PDs) was conducted during June and July 2015 to determine if PCMH recognition influences PDs' ability to evaluate training methods and their level of preparedness to evaluate milestones. RESULTS: The response rate for the survey was 53.3% (252/473). Nearly two-thirds of the PDs (62.7%) reported that their main FM practice site had earned PCMH recognition. There was no statistical difference between non-PCMH-recognized vs PCMH-recognized programs in how PDs perceived that their program was prepared to assess residents' milestone levels overall (P=0.414). Residents of PCMH-recognized programs were more likely to receive training for team-based care (P=0.009), system improvement plans (P<0.001), root-cause analysis (P=0.002), and health behavior change (P=0.003). CONCLUSIONS: PCMH recognition itself did not improve preparedness of FM residency programs to assess milestones. Residents from programs whose main FM practice site is PCMH-recognized are more likely to be trained in the key concepts and tasks associated with the PCMH model, tools that they are expected to utilize extensively after graduation.

Multimorbidity patterns and associations with functional limitations among an aging population in prison.

OBJECTIVES: Co-occurring chronic diseases are associated with functional limitations, particularly for the aging population ≥50 years old. Aging offenders (individual who are imprisoned) tend to have greater prevalence of chronic, mental health, and substance use disorders compared to non-imprisoned populations. Our primary aim was to determine patterns of co-occurring conditions associated with functional limitations among aging offenders. MATERIALS AND METHODS: We included all male offenders from one correctional system who were ≥50 years old (n = 2270) and extracted diagnoses for chronic diseases, mental health, substance use disorders, and functional limitations from an electronic health record. We performed a principal factor analysis (PFA) to identify patterns and chi-square to determine if the multimorbid population (≥3 diagnoses) differed from peer groups in regard to functional limitations. RESULTS: Three patterns (chronic diseases, geriatric conditions, and mental health/substance use) emerged from PFA. Functional limitations were associated with the chronic disease pattern (p = .03) where the multimorbid group compared to non-multimorbid peers had 1.5 odds, 95% CI [1.0, 2.1], for having a physical impairment. The geriatric (p = .10) and mental health/substance use disorders (p = .07) patterns were not associated with having a functional limitation compared to the population without multiple diagnoses. Controlling for multimorbidity, functional limitations, and overlapping patterns, increasing age was the only significant factor (p = .02) associated with having a physical impairment. CONCLUSION: The chronic disease pattern was consistent with investigations that included non-imprisoned populations. However, the geriatric pattern was not significant, which was unexpected.

Cyclic-GMP-Elevating Agents Suppress Polyposis in ApcMin mice by Targeting the Preneoplastic Epithelium.

The cGMP signaling axis has been implicated in the suppression of intestinal cancers, but the inhibitory mechanism and the extent to which this pathway can be targeted remains poorly understood. This study has tested the effect of cGMP-elevating agents on tumorigenesis in the ApcMin/+ mouse model of intestinal cancer. Treatment of ApcMin/+ mice with the receptor guanylyl-cyclase C (GCC) agonist linaclotide, or the phosphodiesterase-5 (PDE5) inhibitor sildenafil, significantly reduced the number of polyps per mouse (67% and 50%, respectively). Neither of the drugs affected mean polyp size, or the rates of apoptosis and proliferation. This was possibly due to increased PDE10 expression, as endogenous GCC ligands were not deficient in established polyps. These results indicated that the ability of these drugs to reduce polyp multiplicity was primarily due to an effect on nonneoplastic tissues. In support of this idea, ApcMin/+ mice exhibited reduced levels of endogenous GCC agonists in the nonneoplastic intestinal mucosa compared with wild-type animals, and this was associated with crypt hyperplasia and a loss of goblet cells. Administration of either sildenafil or linaclotide suppressed proliferation, and increased both goblet cell numbers and luminal apoptosis in the intestinal mucosa. Taken together, the results demonstrate that targeting cGMP with either PDE5 inhibitors or GCC agonists alters epithelial homeostasis in a manner that reduces neoplasia, and suggests that this could be a viable chemoprevention strategy for patients at high risk of developing colorectal cancer. Cancer Prev Res; 11(2); 81-92. ©2018 AACR.

Determinants of adherence to physical activity guidelines among overweight and obese African American breast cancer survivors: implications for an intervention approach.

OBJECTIVE: Public health agencies encourage breast cancer survivors (BCSs) to follow their physical activity guidelines (PAGs). However, adherence to these guidelines is low. African American (AA) BCSs are more often overweight or obese and less likely than women of other races to report adherence to physical activity recommendations. This study examined socioeconomic, clinical, and psychosocial correlates with meeting PAGs. DESIGN: AA women diagnosed and treated for breast cancer and participating in a breast cancer support group (N = 193) completed a lifestyle assessment tool capturing demographic characteristics; breast cancer diagnosis and treatment history; health-related quality of life; weight history, including body mass index and post-diagnosis weight gain; and physical activity. Logistic regressions were used to determine if these covariates were associated with meeting [>8.3 metabolic equivalent task (MET) hr/wk]; partially meeting (4.15-8.3 MET hr/wk); or not meeting (<4.15 MET hr/wk) PAGs. RESULTS: Only 54% of AA BCSs reported meeting current PAGs. Participants reporting weight gain of ≤5 lbs post-diagnosis, and those who received surgical treatment for breast cancer were more likely to complete at least 8.3 MET hr/wk. Better physical functioning and lesser pain intensity were associated with meeting PAGs. CONCLUSION: Several factors influence physical activity behaviors and are likely to be important in developing effective interventions to assist AA survivors manage their weight. It is essential that providers and breast cancer support groups that assist survivors to remain physically active and to manage their weight should be aware of these factors. These findings may help generate hypotheses for future research to undergird efforts to increase physical activity among African American BCSs.

Patient web portals, disease management, and primary prevention.

BACKGROUND: Efforts aimed at health care reform and continued advances in information technologies have prompted interest among providers and researchers in patient web portals. Patient web portals are password-protected online websites that offer the patients 24-hour access to personal health information from anywhere with an Internet connection. METHODS: This article, which is based upon bibliographic searches in PubMed, reviews important developments in web portals for primary and secondary disease prevention, including patient web portals tethered to electronic medical records, disease-specific portals, health disparities, and health-related community web portals. RESULTS: Although findings have not been uniformly positive, several studies of the effectiveness of health care system patient portals in chronic disease management have shown promising results with regard to patient outcomes. Patient web portals have also shown promising results in increasing adherence with screening recommendations. Racial and ethnic minorities, younger persons, and patients who are less educated or have lower health literacy have been found to be less likely to use patient portals. CONCLUSION: Additional studies are needed of the utility and effectiveness of different elements of web portals for different patient populations. This should include additional diseases and health topics such as smoking cessation and weight management.

Recent trends in racial and regional disparities in cervical cancer incidence and mortality in United States.

BACKGROUND: Although black women experienced greater cervical cancer incidence and mortality rate reduction in recent years, they continue to have higher incidence rates than whites. Great variations also exist among geographic regions of the US, with the South having both the highest incidence and mortality rates compared to other regions. The present study explores the question of whether living in the South is associated with greater racial disparity in cervical cancer incidence and mortality by examining race- and region-specific rates and the trend between 2000 and 2012. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 18 Program data was used. Cervical cancer incidence and mortality rates, annual percent changes, and disparity ratios were calculated using SEER*Stat software and Joinpoint regression for four groups: US14-Non-Hispanic White (NHW), US14-Non-Hispanic Black (NHB), South-NHW, and South-NHB, where South included 4 registries from Georgia and Louisiana and US14 were 14 US registries except the four South registries. RESULTS: The average age-adjusted cervical cancer incidence rate was the highest among South-NHBs (11.1) and mortality rate was the highest among US14-NHBs (5.4). In 2012, the degree of racial disparities between South-NHBs and South-NHWs was greater in terms of mortality rates (NHB:NHW = 1.80:1.35) than incidence rates (NHB:NHW = 1.45:1.15). While mortality disparity ratios decreased from 2000-2012 for US14-NHB (APC: -1.9(-2.3,-1.4), mortality disparity ratios for South-NHWs (although lower than NHBs) increased compared to US14-NHW. Incidence rates for NHBs continued to increase with increasing age, whereas rates for NHWs decreased after age 40. Mortality rates for NHBs dramatically increased at age 65 compared to a relatively stable trend for NHWs. The increasing racial disparity with increasing age in terms of cervical cancer incidence rates became more pronounced when corrected for hysterectomy prevalence. CONCLUSIONS: Black race and South region were associated with higher cervical cancer incidence and mortality. Cervical cancer rates uncorrected for hysterectomy may underestimate regional and racial disparities. Increasing incidence rates for older NHBs compared to NHWs warrant further research to determine whether screening should continue for NHBs over age 65.

Persons Who Failed to Obtain Colorectal Cancer Screening Despite Participation in an Evidence-Based Intervention.

In a previous report, we demonstrated the efficacy of an educational intervention focused on increasing colorectal cancer screening rates among African Americans. Despite participating in the intervention, however, nearly two-thirds of participants did not seek and receive screening. Participants were African-Americans over age 49 (N = 257) who had not been screened for colorectal cancer according to guidelines. At baseline, participants completed tests measuring fatalism, perceived stress, self-esteem, attitudes/benefits/barriers, social support, and social network diversity. Those who completed the educational intervention were followed up by telephone to learn if they had been screened. We compared the scores on the psychometric tests of the participants who had been screened against the scores of those who had not. Only the mean scores on the attitudes, benefits, and barriers scale distinguished participants who had been screened from those who had not (p = 0.0816 on bivariate testing and p = 0.0276 in the logistic regression model). Social interaction among participants or social cognitive learning may have played a role in determining which participants were screened, but we were not able to demonstrate this. The major factor distinguishing participants who were not screened was their attitude toward screening at baseline. There is a subset of African Americans who are persistently resistant to screening, and their perspective in this regard must be addressed if colorectal cancer disparities are to be reduced.

Systemic Levels of Estrogens and PGE2 Synthesis in Relation to Postmenopausal Breast Cancer Risk.

Background: Prostaglandin E2 (PGE2) induces aromatase expression in adipose tissue, leading to increased estrogen production that may promote the development and progression of breast cancer. However, few studies have simultaneously investigated systemic levels of PGE2 and estrogen in relation to postmenopausal breast cancer risk.Methods: Here, we determined urinary estrogen metabolites (EM) using mass spectrometry in a case-cohort study (295 incident breast cancer cases and 294 subcohort members), and using linear regression estimated the effect of urinary levels of a major PGE2 metabolite (PGE-M) on EMs. HRs for the risk of developing breast cancer in relation to PGE-M and EMs were compared between Cox regression models with and without mutual adjustment.Results: PGE-M was a significant predictor of estrone (E1), but not estradiol (E2) levels in multivariable analysis. Elevated E2 levels were associated with an increased risk of developing breast cancer [HRQ5vs.Q1, 1.54; 95% confidence interval (CI), 1.01-2.35], and this association remained unchanged after adjustment for PGE-M (HRQ5vs.Q1, 1.52; 95% CI, 0.99-2.33). Similarly, elevated levels of PGE-M were associated with increased risk of developing breast cancer (HRQ4vs.Q1, 2.01; 95% CI, 1.01-4.29), and this association was only nominally changed after consideration of E1 or E2 levels.Conclusions: Urinary levels of PGE-M and estrogens were independently associated with future risk of developing breast cancer among these postmenopausal women.Impact: Increased breast cancer risk associated with PGE-M might not be fully explained by the estrogens-breast cancer association alone but also by additional effects related to inflammation. Cancer Epidemiol Biomarkers Prev; 26(3); 383-8. ©2016 AACR.

Gender and race disparities in weight gain among offenders prescribed antidepressant and antipsychotic medications.

BACKGROUND: Studies have found that antipsychotics and antidepressants are associated with weight gain and obesity, particularly among women and some minority groups. Incarcerated populations (also referred to as offenders, prisoners or inmates) have a high prevalence of mental health problems and 15 % of offenders have been prescribed medications. Despite rates of antidepressant and antipsychotic use, investigations of weight gain and obesity in regard to these agents seldom have included offenders. METHODS: This retrospective descriptive study (2005-2011) was conducted with a Department of Corrections in the east south central United States to investigate the relationship between antidepressant and antipsychotic agents, weight gain, obesity and race or gender differences. We sampled adult offenders who had an active record, at least two weight observations and height data. Offenders were classified into one of four mutually exclusive groups depending upon the type of medication they were prescribed: antidepressants, antipsychotics, other medications or no pharmacotherapy. RESULTS: The sample population for this study was 2728, which was 25.2 % of the total population. The population not on pharmacotherapy had the lowest baseline obesity rate (31.7 %) compared to offenders prescribed antipsychotics (43.6 %), antidepressants (43.6 %) or other medications (45.1 %). Offenders who were prescribed antidepressants or antipsychotics gained weight that was significantly different from zero, p < .001 and p = .019, respectively. Women in the antidepressant group gained 6.4 kg compared to 2.0 kg for men, which was significant (p = .007). Although women in the antipsychotic group gained 8.8 kg compared to 1.6 kg for men, the finding was not significant (p = .122). Surprisingly, there were no significant differences in weight gain between African Americans and Whites in regard to antidepressants (p = .336) or antipsychotic agents (p = .335). CONCLUSION: This study found that women and men offenders prescribed antidepressant or antipsychotic agents gained weight during their incarceration. Women prescribed antidepressants gained significantly more weight than men. However, there was no significant difference in weight gain between African Americans and Whites. Results suggest further investigation is needed to understand the effect of medication history, metabolic syndrome and to explain gender disparities.

A Call to Develop Evidence-based Interventions to Reduce Sexually Transmitted Infections in Juvenile Justice Populations.

Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV) risk, are a significant health issue for young women (ages 16-21), especially African Americans with a juvenile justice history. Studies have found that 44% of young African American women have had at least one STI compared to 24.1% for all young women. The rate of STIs among young women with juvenile justice histories, particularly African Americans, is likely much higher than their non-detained peers. Yet, there are few evidence-based interventions (EBIs) designed specifically for the detained population. In 2014, the Centers for Disease Control and Prevention's Compendium of Evidence-Based Interventions and Best Practices for HIV Prevention listed few programs that comprehensively included components related to mental health, intimate relationships and high risk sexual behaviors that would be salient for a detained population. Further, many EBIs have had limited or no long-term protective effect. We propose that interrelated factors (mental health, substance use, trauma and intimate relationships) can effectively decrease risk and increase protective behaviors for the detained population most at risk.