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BACKGROUND: The poor prognosis of esophageal adenocarcinoma (EAC) has focused efforts on early detection by serial endoscopic surveillance of Barrett’s esophagus (BE). Previously, we reported that receipt of endoscopy before EAC diagnosis was associated with improved survival. AIM: We aimed to refine our previous analysis, assessing surveillance as measured by performance of serial endoscopy before EAC diagnosis and evaluating its association with stage and survival. METHODS: A retrospective cohort study was performed using the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients aged ≥ 70 years with EAC diagnosed 1998–2009 were identified. Diagnosis with BE and receipt of ≥ 2 upper endoscopic procedures within 5 years before cancer diagnosis were identified. We compared a reference group not receiving serial endoscopy to 3 patterns based on ≥ 2 endoscopy dates relative to a timepoint 2 years before cancer diagnosis: “remote,” “recent,” and “sustained.” RESULTS: Among 5,532 patients, 28% (n=1,575) had localized stage. Thirteen percent (n=703) received ≥ 2 endoscopic procedures before cancer diagnosis: 224, 298, and 181 in the “recent,” “remote,” and “sustained” groups. Serial endoscopy and prior BE were associated with localized stage (“sustained” group OR 2.95, 95% confidence interval [CI] 2.07, 4.19; prior BE OR 2.68, 95% CI 2.03, 3.56). Serial endoscopy was associated with improved survival even with adjustment for lead time bias (“sustained” group HR 0.45, 95% CI 0.37, 0.55) and length time bias. CONCLUSIONS: Sustained endoscopy was associated with earlier stage and improved survival. These results support the role of sustained surveillance in early detection of EAC.

BACKGROUND People with HIV (PWH) are at an increased risk of both heart and kidney disease, but the relationship between kidney disease and cardiac structure and function in this population has not been well studied. In particular, whether the relationship between kidney disease and cardiac structure and function is stronger for PWH compared with uninfected controls is unknown. METHODS One hundred PWH on antiretroviral therapy were compared with 100 age-matched and sex-matched controls without HIV in Uganda. Multivariable regression models were used to examine associations between creatinine-based and cystatin C-based estimated glomerular filtration rate (eGFR), albumin-creatinine ratio, and echocardiographic measures of cardiac structure and function. RESULTS PWH had lower eGFRcr (β -7.486, 95% confidence interval: -13.868 to -1.104, P = 0.022) and a higher rate of albumin-creatinine ratio ≥30 (odds ratio 2.146, 95% confidence interval: 1.027 to 4.484, P = 0.042) after adjustment for traditional risk factors. eGFR was inversely associated with both left ventricular mass index and diastolic dysfunction in adjusted models but not with systolic function. Albuminuria was associated with more diastolic dysfunction among PWH but not controls (P for interaction = 0.046). The association of HIV with a higher left ventricular mass index (P = 0.005) was not substantially affected by adjusting for eGFRcr. CONCLUSION Among Ugandans, eGFR is associated with elevated LV mass and diastolic dysfunction. The association between albuminuria and diastolic dysfunction is particularly strong for PWH.

PURPOSE: Articular cartilage is known to be mechanically anisotropic. In this paper, the acoustic anisotropy of bovine articular cartilage and the effects of freeze-thaw cycling on acoustic anisotropy were investigated. METHODS: We developed apparatus and methods that use a magnetic L-shaped sample holder, which allowed minimal handling of a tissue, reduced the number of measurements compared to previous studies, and produced highly reproducible results. RESULTS: SOS was greater in the direction perpendicular to the articular surface compared to the direction parallel to the articular surface (N=17, P = 0.00001). Average SOS was 1,758 ± 107 m/s perpendicular to the surface, and 1,617 ± 55 m/s parallel to it. The average percentage difference in SOS between the perpendicular and parallel directions was 8.2% (95% CI: 5.4% to 11%). Freeze-thaw cycling did not have a significant effect on SOS (P>0.4). CONCLUSION: Acoustic measurement of tissue properties is particularly attractive for work in our laboratory since it has the potential for nondestructive characterization of the properties of developing engineered cartilage. Our approach allowed us to observe acoustic anisotropy of articular cartilage rapidly and reproducibly. This property was not significantly affected by freeze-thawing of the tissue samples, making cryopreservation practical for these assays.

Background Although there is a great deal of literature regarding effective recruitment and challenges of recruiting specific patient populations, there is less known about best practices for recruitment of nurses as study subjects. Objectives The purpose of this article is to report our experience with recruitment and retention for a randomized trial of an online educational program to prepare oncology nurses to discuss oncology clinical trials with patients. Methods The study population included currently employed oncology nurses with direct patient interaction. There were three phases of this study: (1) qualitative interviews, (2) a pilot test, and (3) the randomized trial. Phase 3 was rolled out in five waves of recruitment. The distinct phases of the study-and the gradual roll out of recruitment during Phase 3-allowed us to test and refine our recruitment and retention methods for the randomized trial. Upon analysis of our response rate and attrition after the first wave of recruitment in Phase 3, we made several changes to improve recruitment and retention, including adding incentives, shortening the survey, and increasing the number of reminders to complete the program. Results The response rate was higher when we used both e-mail and U.S. postal mail solicitations. After the first wave of recruitment in the final phase, changes in our strategies did not increase our overall response rate significantly; however, the rate of attrition following baseline declined. Discussion Recruitment planning is an important component of successful clinical research. The use of the Internet for both recruitment of subjects and testing of interventions remains a cost-effective and potentially high yield methodology. Our research demonstrated several successful approaches to yield increased participation and retention of subjects, including seeking formal relationships with professional organizations as sponsors or supporters, providing meaningful incentives to participants, keeping surveys or questionnaires as short as possible, and planning multiple follow-up contacts from the outset.

To develop and assess the reliability of a measure of primary care using items from the Medical Expenditure Panel Survey (MEPS), a US representative survey of community-dwelling persons.On the basis of the domains from the literature on primary care characteristics, we identified relevant items within the 2013-2014 MEPS family of surveys. In a sample of primary survey respondents with at least 1 office-based physician visit in the last 12 months, we conducted exploratory factor analysis, retaining items with a factor loading of 0.30 and factors ≥3 items. Using a hold-out sample, internal consistency, reproducibility, and confirmatory factor analyses were performed.On the basis of 16 care domains, we found 32 candidate items in the MEPS. Factor analyses of data from 4549 persons meeting inclusion criteria (27.6% of the total sample), yielded 3 unique factors involving 24 items. We named these subscales Relationship, Comprehensiveness, and Health Promotion, displaying internal consistency reliability of 0.86, 0.78, and 0.69, respectively. Confirmatory factor analysis corroborated the stability of the exploratory findings in the hold out sample. Sensitivity analyses showed robustness to differences in underlying correlation structure, alternative approach to missing data, and extension to indirect survey respondents.The MEPS Primary Care measure with 3 subscales is reliable and may be useful in conducting primary care health services and outcomes research in the rich MEPS dataset. Further validation is needed, and is described in a companion paper.

Background: Clinical trials are a critical source of evidence for oncology care, yet very few patients participate. Among healthcare providers, nurses spend the most time with cancer patients and are the most highly trusted professionals. We developed and evaluated an educational program for oncology nurses targeting knowledge, attitudes, self-efficacy and perceived norms to facilitate discussion about clinical trials and support patient decision making. Methods: A nationwide sample of oncology nurses were randomly assigned to receive general clinical trials education delivered as text (attention control) vs. tailored video vignettes (intervention) in a web-based continuing education program. Participants completed a baseline assessment and follow up assessments immediately after the educational program and three months later. The primary outcome was intention to discuss clinical trials with patients. Secondary outcomes were knowledge and attitudes about clinical trials, self-efficacy, and perceived norms. Results: 1393 nurses enrolled and completed the educational program and post-intervention assessment (720 control, 673 video). Both text education and tailored video education increased intention to discuss clinical trials with patients, with a greater effect in the video group (p

BACKGROUND Behavioral intervention studies in older breast cancer survivors, particularly older African American (AA) and socioeconomic status-disadvantaged breast cancer survivors, are lacking. To inform future studies, the authors examined recruitment strategies in older breast cancer survivors who participated in an exercise intervention study. METHODS IMPROVE is a randomized trial designed to evaluate a group-based exercise intervention versus a support group (ClinicalTrials.gov identifier, NCT02763228). Participants were aged ≥65 years who had survived stage I through III breast cancer and were within 5 years of treatment completion. Participants were recruited through multiple approaches, including peripheral, linguistic, and constituent-involving strategies that incorporated the identification of potentially eligible patients from 3 local hospitals and from State of Ohio registries and through direct clinician and community organization referrals. RESULTS Between October 2016 and November 2019, 7487 patients were screened, 4790 were potentially eligible, and 213 were randomized into the study. The eligible:randomization rates were 4.4% overall and 84%, 8%, and 2% for recruitment using direct referrals, hospital registries, and state registries, respectively. The median age of the randomized cohort was 70 years (range, 65-88 years) and included 44% AA and 44% socioeconomic status-disadvantaged breast cancer survivors. Compared with all registry-eligible patients, directly referred-eligible patients were more likely to be AA versus Non-Hispanic White (41% vs 19%; P = .006), to be contacted successfully (100% vs 33%; P < .0001), and to accept study participation (88% vs 16%; P < .0001). CONCLUSIONS Direct referrals appeared to be the most efficient strategy for recruiting AA survivors. Behavioral intervention studies seeking to target older AA and socioeconomic status-disadvantaged breast cancer survivors should include strategies that foster direct referrals to study participation.

Background Inflammation has been associated with whole heart coronary artery calcification (CAC) among people with HIV (PWH) on antiretroviral therapy (ART); however, prior studies have not evaluated the distribution of calcium or separated mass versus volume scores, which are differentially associated with clinical events in the general population. Statins may also have a greater effect on CAC mass compared with volume. Methods 147 PWH were randomized 1:1 to rosuvastatin 10 mg or placebo and followed for 96 weeks. We re-analysed coronary calcium scans from 0, 48 and 96 weeks to determine mass and volume scores and measures of CAC diffusivity. Mixed effects models and generalized estimating equations were used to examine longitudinal associations of CAC with treatment and biomarkers. Results Median age at study entry was 46 years; 78% were male and 68% African American. Median CD4+ was 613 and half were on protease inhibitors. Randomization to statin therapy was not associated with a change in mass score, volume score, number of involved vessels or diffusivity index (all P>0.1). Soluble CD14 was associated with the presence of CAC ( P=0.05) and borderline associated with number of involved vessels ( P=0.07) across all three time points. Conclusions In PWH on ART, moderate intensity rosuvastatin does not appear to have a significant effect on volume, mass or regional distribution of CAC over 96 weeks. We extend previous cross-sectional observations to show that soluble CD14 is associated with whole heart CAC over time and independently of age and systolic blood pressure.

PURPOSE Access to a usual source of care is associated with improved health outcomes, but research on how the physician-patient relationship affects a patient’s health, particularly long-term, is limited. The aim of this study was to investigate the longitudinal effect of changes in the physician-patient relationship on functional health. METHODS We conducted a prospective cohort study using the Medical Expenditure Panel Survey (MEPS, 2015-2016). The outcome was 1-year change in functional health (12-Item Short-Form Survey). The predictors were quality of physician-patient relationship, and changes in this relationship, operationalized with the MEPS Primary Care (MEPS-PC) Relationship subscale, a composite measure with preliminary evidence of reliability and validity. Confounders included age, sex, race/ethnicity, educational attainment, insurance status, US region, and multimorbidity. We conducted analyses with survey-weighted, covariate-adjusted, predicted marginal means, used to calculate Cohen effect estimates. We tested differences in trajectories with multiple pairwise comparisons with Tukey contrasts. RESULTS Improved physician-patient relationships were associated with improved functional health, whereas worsened physician-patient relationships were associated with worsened functional health, with 1-year effect estimates ranging from 0.05 (95% CI, 0-0.10) to 0.08 (95% CI, 0.02-0.13) compared with −0.16 (95% CI, −0.35 to −0.03) to −0.33 (95% CI, −0.47 to −0.02), respectively. CONCLUSION The quality of the physician-patient relationship is positively associated with functional health. These findings could inform health care strategies and health policy aimed at improving patient-centered health outcomes.

This study examined associations of a caregiver-based diagnosis of attention deficit hyperactivity disorder (ADHD) in kindergarten with early learning progress in 139 extremely preterm/extremely low birth weight (EPT/ELBW, gestational age

Background African Americans (AA) and socioeconomic status (SES) disadvantaged older breast cancer survivors (BCS) are more likely to experience poor functional and health outcomes. However, few studies have evaluated the putative beneficial effects of exercise on these outcomes in older racial minority and SES-disadvantaged BCS. Methods This is a mixed-methods study that includes a randomized-controlled trial, “IMPROVE”, to evaluate a group-based exercise intervention compared to a support group program in older BCS, followed by post-intervention semi-structured interviews to evaluate the intervention. The trial aims to recruit 220 BCS with 55 in each of four strata defined by race (AA versus Non-Hispanic Whites) and SES (disadvantaged vs. non-disadvantaged). Participants are ≥65 years old and within five years of treatment completion for stage I-III breast cancer. Participants are randomized to a 52-week, three sessions/week, one-hour/session, moderate intensity aerobic and resistance group exercise intervention, (n = 110) or a 52-week, one hour/week, support group intervention [attention-control arm], (n = 110). The first 20 weeks of both programs are supervised and the last 32 week s , unsupervised. The primary outcome is the change in Short Physical Performance Battery (SPPB) Scores at 20 weeks from baseline, between the two arms. Secondary outcomes include change in SPPB scores at 52 weeks, change in body composition and biomarkers, at 20 and 52 weeks from baseline, between arms. Discussion Results of the trial may contribute to a better understanding of factors associated with recruitment, and acceptability, and will inform future exercise programs to optimally improve health outcomes for older BCS.

Objective To examine racial differences in physical performance among older women with newly diagnosed non-metastatic breast cancer and identify clinical, behavioral and biological factors that might contribute to such disparities. Methods This is a cross-sectional study of women aged ≥65 years with newly diagnosed stage I–III breast cancer recruited from ambulatory oncology clinics at an academic center, between September 2010 and August 2015. Participants completed a Comprehensive Geriatric Assessment and laboratory testing for biomarkers of inflammation [interleukin-6 (IL6)] prior to receiving systemic treatment for cancer. The primary outcome was poor physical performance, defined as scoring ≤7 on the Short Physical Performance Battery, Yes or No. Logistic regression analyses were undertaken. Results Among 135 women with mean age of 74.8 years (SD = 6.9), 31% were African-American (AA), and 33% had poor physical performance. Controlling for age, education, comorbidities and geriatric syndromes, participants with poor physical performance were more likely to be AA [versus (vs.) Non-Hispanic Whites (NHW)], odds ratio (OR) = 3.10, 95% confidence interval (CI) = 1.18–8.15. Controlling further for physical activity (PA) attenuated the racial disparity in physical performance (OR = 2.50, CI = 0.91–6.84). Lastly, controlling for IL6 further diminished the racial disparity in physical performance (OR = 1.93, CI = 0.67–5.56). In adjusted models, PA and IL6 explained 29% and 38%, respectively, of the racial disparity in poor physical performance. Conclusion Among older women with newly diagnosed non-metastatic breast cancer, poor physical performance was prevalent and AA were disproportionately affected. Less engagement in physical activity and subclinical inflammation partly contributed to this disparity.

Many longitudinal studies observe time to occurrence of a clinical event such as death, while also collecting serial measurements of one or more biomarkers that are predictive of the event, or are surrogate outcomes of interest. Joint modeling can be used to examine the relationship between the biomarker and the event, and also as a way of adjusting analyses of the biomarker for non-ignorable dropout. In settings such as registry studies, an additional complexity is caused when follow-up of subjects is delayed, referred to as left-truncation of follow-up in the survival analysis setting. If not adjusted for, this can cause bias in estimation of parameters of the survival distribution for the clinical event and in parameters of the longitudinal outcome such as the profile or rate of change over time because subjects may die or have the clinical event before follow-up starts. This paper illustrates how a broad class of shared parameter models can be used to jointly model a time to event outcome along with a longitudinal marker using available nonlinear mixed modeling software, when follow-up times are left truncated. Methods are applied to jointly model survival and decline in lung function in cystic fibrosis patients.

Assessing the quality of tissue engineered (TE) cartilage has historically been performed by endpoint measurements including marker gene expression. Until the adoption of promoter-driven reporter constructs capable of quantitative and real time non-destructive expression analysis, temporal gene expression assessments along a timeline could not be performed on TE constructs. We further exploit this technique to utilize microRNA (miRNA or miR) through the use of firefly luciferase reporter (Luc) containing a 3' UTR perfect complementary target sequence to the mature miR-145-5p. We report the development and testing of a firefly luciferase (Luc) reporter responsive to miR-145-5p for longitudinal tracking of miR-145-5p expression throughout MSC chondrogenic differentiation. Plasmid reporter vectors containing a miR-145-5p responsive reporter (Luc reporter with a perfect complementary target sequence to the mature miR-145-5p sequence in the 3'UTR), a Luc reporter driven by a truncated Sox9 (one of the targets of miR-145-5p) promoter, or the Luc backbone (control) vector without a specific miRNA target were transfected into MSCs by electroporation. Transfected MSCs were mixed with untransfected MSC to generate chondrogenic pellets. Pellets were imaged by bioluminescent imaging (BLI) and harvested along a preset time line. The imaging signals from miR-145-5p responsive reporter and Sox9 promoter-driven reporter showed correlated time-courses (measured by BLI and normalized to Luc-control reporter; Spearman r=0.93, p=0.0002) during MSC chondrogenic differentiation. Expression analysis by qRT-PCR suggests an inverse relationship between miR-145-5p and Sox9 gene expression during MSC chondrogenic differentiation. Non-destructive cell-pellet imaging is capable of supplementing histological analyses to characterize TE cartilage. The miR-145-5p responsive reporter is relatively simple to construct and generates a consistent imaging signal responsive to miR-145-5p during MSC chondrogenesis in parallel to certain molecular and cellular events.

To determine the ability of three performance-based measures [Short Physical Performance Battery (SPPB), gait speed, and Grip Strength] and a self-report measure [Vulnerable Elders Survey (VES-13)] to predict functional decline among older women with breast cancer.Longitudinal data from a study of women ≥65years, with newly diagnosed stages I-III breast cancer, recruited from ambulatory oncology clinics between July 2010 and April 2014, was used. The primary outcome was functional decline, Yes or No, defined as a decrease in ≥1-point from baseline to 12months, on Activities of Daily Living Scales. Multivariable logistic regression and receiver operator curve analyses were conducted.Among 123 participants 18 (15%) developed functional decline. The predictive abilities for measures were: SPPB [Adjusted odds ratio (AOR)=1.65 per unit decrease in scores, 95% confidence interval (CI)=1.33-2.05; area under the receiver operator curve (AUC)=0.93; sensitivity=94%, specificity=80%]; gait speed (AOR=1.76 per unit increase in usual walking time, CI=1.29-2.41; AUC=0.93; sensitivity=87%, specificity=79%); VES-13 (AOR=1.64 per unit increase in scores, CI=1.31-2.05; AUC=0.87; sensitivity=83%, specificity=84%); and grip strength: (AOR=1.18 per unit decrease in grip strength, CI=1.06-1.30; AUC=0.80; sensitivity=67%, specificity=77%).SPPB, gait speed, grip strength and VES-13 all demonstrated excellent predictive abilities for functional decline. Larger studies are warranted to confirm the utility of these measures for identifying older adults with cancer at increased risk for functional decline, who may then be targeted for studies to explore the effects of interventions to improve function.

BACKGROUND As an organized screening program, the national Breast and Cervical Cancer Early Detection Program (BCCEDP) was launched in the early 1990s to improve breast cancer outcomes among underserved women. To analyze the impact of the BCCEDP on breast cancer outcomes in Ohio, this study compared cancer stages and mortality across BCCEDP participants, Medicaid beneficiaries, and “all others.” METHODS This study linked data across the Ohio Cancer Incidence Surveillance System, Medicaid, the BCCEDP database, death certificates, and the US Census and identified 26,426 women aged 40 to 64 years who had been diagnosed with incident invasive breast cancer during the years 2002-2008 (deaths through 2010). The study groups were as follows: BCCEDP participants (1-time or repeat users), Medicaid beneficiaries (women enrolled in Medicaid before their cancer diagnosis [Medicaid/prediagnosis] or around the time of their cancer diagnosis [Medicaid/peridiagnosis]), and all others (women identified as neither BCCEDP participants nor Medicaid beneficiaries). The outcomes included advanced-stage cancer at diagnosis and mortality. A multivariable logistic and survival analysis was conducted to examine the independent association between the BCCEDP and Medicaid status and the outcomes. RESULTS The percentage of women presenting with advanced-stage disease was highest among women in the Medicaid/peridiagnosis group (63.4%) and lowest among BCCEDP repeat users (38.6%). With adjustments for potential confounders and even in comparison with Medicaid/prediagnosis beneficiaries, those in the Medicaid/peridiagnosis group were twice as likely to be diagnosed with advanced-stage disease (adjusted odds ratio, 2.20; 95% confidence interval, 1.83-2.66). CONCLUSIONS Medicaid/peridiagnosis women are at particularly high risk to be diagnosed with advanced-stage disease. Efforts to reduce breast cancer disparities must target this group of women before they present to Medicaid. Cancer 2017. © 2017 American Cancer Society.

Background The advancement of primary care research requires reliable and validated measures that capture primary care processes embedded within nationally representative datasets. Objective The objective of this study was to assess the validity of a newly developed measure of primary care processes [Medical Expenditure Panel Survey (MEPS)-PC] with preliminary evidence of moderate to excellent reliability. Study design A retrospective cohort study of community-dwelling adults with history of office-based provider visit/s using the MEPS (2013-2014). Methods The 3 MEPS-PC subscales (Relationship, Comprehensiveness, and Health Promotion) were tested for construct validity against known measures of primary care: Usual Source of Care, Known Provider, and Family-Usual Source of Care. Concurrent and predictive logistic regression analyses were calculated and compared with a priori hypotheses for direction and strength of association. Results For concurrent validity, all odds ratio estimates conformed with hypotheses, with 91% displaying statistical significance. For predictive validity, all estimates were in the direction of hypotheses, with 92% displaying statistically significant results. Although Relationship and Health Promotion subscales conformed uniformly with hypotheses, the Comprehensiveness subscale yielded significant results in 60% of bivariate odds ratio estimates (P Conclusion The MEPS-PC composite measures display modest to strong preliminary evidence of concurrent and predictive validity relative to known indicators of primary care. Implications for policy and practice The MEPS-PC composite measures display preliminary evidence of concurrent and predictive construct validity, and it may be useful to researchers investigating primary care processes and complexities in the health care environment.

This study aims for targeted biopsy validation of magnetic resonance fingerprinting (MRF) and diffusion mapping for characterizing peripheral zone (PZ) prostate cancer and noncancers.One hundred four PZ lesions in 85 patients who underwent magnetic resonance imaging were retrospectively analyzed with apparent diffusion coefficient (ADC) mapping, MRF, and targeted biopsy (cognitive or in-gantry). A radiologist blinded to pathology drew regions of interest on targeted lesions and visually normal peripheral zone on MRF and ADC maps. Mean T1, T2, and ADC were analyzed using linear mixed models. Generalized estimating equations logistic regression analyses were used to evaluate T1 and T2 relaxometry combined with ADC in differentiating pathologic groups.Targeted biopsy revealed 63 cancers (low-grade cancer/Gleason score 6 = 10, clinically significant cancer/Gleason score ≥7 = 53), 15 prostatitis, and 26 negative biopsies. Prostate cancer T1, T2, and ADC (mean ± SD, 1660 ± 270 milliseconds, 56 ± 20 milliseconds, 0.70 × 10 ± 0.24 × 10 mm/s) were significantly lower than prostatitis (mean ± SD, 1730 ± 350 milliseconds, 77 ± 36 milliseconds, 1.00 × 10 ± 0.30 × 10 mm/s) and negative biopsies (mean ± SD, 1810 ± 250 milliseconds, 71 ± 37 milliseconds, 1.00 × 10 ± 0.33 × 10 mm/s). For cancer versus prostatitis, ADC was sensitive and T2 specific with comparable area under curve (AUC; (AUCT2 = 0.71, AUCADC = 0.79, difference between AUCs not significant P = 0.37). T1 + ADC (AUCT1 + ADC = 0.83) provided the best separation between cancer and negative biopsies. Low-grade cancer T2 and ADC (mean ± SD, 75 ± 29 milliseconds, 0.96 × 10 ± 0.34 × 10 mm/s) were significantly higher than clinically significant cancers (mean ± SD, 52 ± 16 milliseconds, 0.65 ± 0.18 × 10 mm/s), and T2 + ADC (AUCT2 + ADC = 0.91) provided the best separation.T1 and T2 relaxometry combined with ADC mapping may be useful for quantitative characterization of prostate cancer grades and differentiating cancer from noncancers for PZ lesions seen on T2-weighted images.

BACKGROUND Out-of-pocket expenditures are thought to be an important barrier to the receipt of cancer preventive services, especially for those of a lower socioeconomic status (SES). The Affordable Care Act (ACA) eliminated out-of-pocket expenditures for recommended services, including mammography and colonoscopy. The objective of this study was to determine changes in the uptake of mammography and colonoscopy among fee-for-service Medicare beneficiaries before and after ACA implementation. METHODS Using Medicare claims data, this study identified women who were 70 years old or older and had not undergone mammography in the previous 2 years and men and women who were 70 years old or older, were at increased risk for colorectal cancer, and had not undergone colonoscopy in the past 5 years. The receipt of procedures in the 2-year period before the ACA's implementation (2009-2010) and after its implementation (2011 to September 2012) was also identified. Multivariate generalized estimating equation models were used to determine the independent association and county-level quartile of median income and education with the receipt of testing. RESULTS For mammography, a lower SES quartile was associated with less uptake, but the post-ACA disparities were smaller than those in the pre-ACA period. In addition, mammography rates increased from the pre-ACA period to the post-ACA period in all SES quartiles. For colonoscopy, in both the pre- and post-ACA periods, there was an association between uptake and educational level and, to some extent, income. However, there were no appreciable changes in colonoscopy and SES after implementation of the ACA. CONCLUSIONS The removal of out-of-pocket expenditures may overcome a barrier to the receipt of recommended preventive services, but for colonoscopy, other procedural factors may remain as deterrents. Cancer 2017;123:1585–1589. © 2017 American Cancer Society.

BACKGROUND The purpose of this study was to determine the ability of the Vulnerable Elders Survey (VES-13) to predict the composite outcome of functional decline and death within 12 months of breast cancer treatment among women 65 years old or older with newly diagnosed stage I to III breast cancer. METHODS Two hundred and six participants were recruited from ambulatory oncology clinics at an academic center between April 2008 and April 2013. Participants competed the VES-13 at baseline just before neoadjuvant/adjuvant treatment. The primary outcome, functional decline/death, was defined as either a decrease of at least 1 point on the Activities of Daily Living scale and/or the Instrumental Activities of Daily Living scale or death between baseline and 12 months (yes or no). RESULTS One hundred and eighty four participants (89%) completed 12 months of follow-up. Twenty-two percent functionally declined (n = 34) or died (n = 7). Univariately, with increasing VES-13 scores, the estimated risk of functional decline/death rose from 23% for participants with a VES-13 score of 3 to 76% for participants with a VES-13 score of 10. In multivariate logistic regression analysis, VES-13 scores (adjusted odds ratio, 1.37; 95% confidence interval, 1.18-1.57) and having a high school education or less (adjusted odds ratio, 2.47; 95% confidence interval, 1.08-5.65) were independent predictors of functional decline/death (area under the receiver operator curve, 0.79). CONCLUSIONS Among older women with newly diagnosed nonmetastatic breast cancer, approximately 1 in 5 functionally declined and/or died within 12 months of breast cancer treatment initiation. Women with high school education or less were disproportionately affected. The VES-13 is a useful instrument for the early identification of those at risk for functional decline and/or death. Cancer 2016;122:2579–86. © 2016 American Cancer Society.

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer. In this study, we explored the feasibility of targeted delivery of an antimitotic drug, monomethyl auristatin E (MMAE), to tumor tissue using a small-molecule based PSMA lig-and. With the aid of Cy5.5, we found that a cleavable linker is vital for the antitumor activity of the ligand&ndash, drug conjugate and have developed a new PSMA-targeting prodrug, PSMA-1-VcMMAE. In in vitro studies, PSMA-1-VcMMAE was 48-fold more potent in killing PSMA-positive PC3pip cells than killing PSMA-negative PC3flu cells. In in vivo studies, PSMA-1-VcMMAE significantly inhibited tumor growth leading to prolonged animal survival in different animal models, including metastatic prostate cancer models. Compared to anti-PSMA antibody-MMAE conjugate (PSMA-ADC) and MMAE, PSMA-1-VcMMAE had over a 10-fold improved maximum tolerated dose, resulting in improved therapeutic index. The small molecule&ndash, drug conjugates reported here can be easily synthesized and are more cost efficient than anti-body&ndash, drug conjugates. The therapeutic profile of the PSMA-1-VcMMAE encourages further clin-ical development for the treatment of advanced prostate cancer.

e24052 Background: We conducted an exercise study to IMPROVE health outcomes in older breast cancer survivors (BCS) from diverse racial and socioeconomic backgrounds. Here, we report cohort recruitment strategies and baseline characteristics. Methods: ‘IMPROVE’ is a randomized trial, designed to evaluate a group-based exercise intervention compared to support group. Participants were ≥ 65 years, had stage I-III breast cancer and within five years of treatment completion. Enrollment target was 220 participants, 25% in each of four strata defined by race (AA versus Non-Hispanic Whites [NHW]) and SES (low vs. high). Participants were recruited through hospital-based tumor registries, the state tumor registry or direct referrals. Results: Between October 2016 and November 2019, 7487 patients were screened, 4790 were potentially eligible, 230 were consented and 213 randomized into the study. The Eligible-to-Randomization rates were 4.4% overall, and 84%, 8%, and 2% for recruitment utilizing direct referrals, hospital and state registries, respectively. Median age of the randomized cohort was 70 years (range: 65-88 years) and included 25% AA/Low SES, 20% AA/High SES, 19% NHW/Low SES and 36% NHW/High SES Older BCS. Compared with registry-eligible patients, directly referred patients were more likely to be AA vs. NHW (41% vs. 19%, p = 0.003) and to accept study participation (88% vs. 16%, p < 0.0001). Conclusions: Direct referrals resulted in the highest recruitment yield and was the most effective strategy for recruiting AA patients. Behavioral intervention studies seeking to target older BCS from racial minority and SES disadvantaged backgrounds should focus on strategies that foster direct referrals to study participation. Clinical trial information: NCT02763228 .

OBJECTIVE The study was designed to investigate the effect of extreme prematurity on growth in academic achievement across the early school years and the validity of kindergarten neuropsychological skills as predictors of achievement. METHOD A 2001-2003 birth cohort of 145 extremely preterm/extremely low birth weight (EPT/ELBW) children from a single medical center, along with 111 normal birth weight (NBW) classmate controls, were recruited during their first year in kindergarten and followed annually across the next 2 years in school. Mixed model analysis was conducted to compare the groups on growth in achievement across years and examine kindergarten neuropsychological skills as predictors of growth. RESULTS The EPT/ELBW group scored significantly below NBW controls on all achievement tests across years and had higher rates of special education placement and grade repetition. Despite limited catch-up of the EPT/ELBW group to the NBW controls in spelling, group differences were generally stable. Differences in spelling and mathematics achievement remained significant when controlling for global intelligence or excluding children who had intellectual or neurosensory impairments or repeated a grade. Higher scores on kindergarten tests of multiple neuropsychological ability domains predicted higher achievement levels and steeper growth in achievement. CONCLUSIONS The findings document persistent academic weaknesses in EPT/ELBW children across the early school years. Results point to the need for preschool interventions to enhance academic readiness and suggest that neuropsychological skills assessed in kindergarten are useful in identifying individual differences in early learning progress. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Tissue engineering requires large numbers of cells with enhanced differentiation properties. Thus, the effect of expansion conditions must be explored. Human and rat marrow-derived mesenchymal stem cells (hMSCs and rMSCs, respectively) were comparatively culture expanded through seven passages in the presence of either fibroblast growth factor-2 (FGF-2) or platelet-derived growth factor BB (PDGF-BB). Proliferation of both hMSCs and rMSCs was enhanced by FGF-2 and PDGF-BB. Population doubling times for hMSCs were 2.4 days for control and 1.75 and 2.0 days for FGF-2 and PDGF-BB, respectively, and 3.25, 3.06, and 2.95 days for rMSCs. Supplementation with FGF-2 during cell expansion resulted in significantly greater in vivo bone formation for hMSCs. Use of PDGF-BB resulted in greater bone formation than that observed for control conditions, but the differences were only significant for P1. For rMSCs, significant increases in bone formation were noted in either FGF-2 or PDGF-BB expanded cells implanted at P4 or P7, but not for P1. Under in vitro osteogenic stimulation, calcium content was elevated and bone matrix deposition was enhanced for P1 and P7 rMSCs expanded with FGF-2. Although culture conditions, including FBS, were held constant, these observations suggest that medium must be optimized separately for each species of MSCs. IMPACT STATEMENT: The presented research emphasizes the importance of coordinated approaches in Tissue Engineering and cell culture involving growth factor supplementation of growth medium that involves complex effects on cells; these effects are species-specific and are understudied. Therefore, the importance of medium optimization for MSCs from different species. The effect of PDGF-BB on bone-marrow derived MSC differentiation and proliferation itself is understudied and under-reported.

Purpose To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer. Patients and Methods Between 2012 and 2014, 207 female patients undergoing surgery for potential or known breast cancer were randomly assigned to receive either patient-selected live music (LM) preoperatively with therapist-selected recorded music intraoperatively (n = 69), patient-selected recorded music (RM) preoperatively with therapist-selected recorded music intraoperatively (n = 70), or usual care (UC) preoperatively with noise-blocking earmuffs intraoperatively (n = 68). Results The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation. Compared with the UC group, both the LM and the RM groups had greater reductions (P < .001) in anxiety scores preoperatively (mean changes [and standard deviation: −30.9 [36.3], −26.8 [29.3], and 0.0 [22.7]), respectively. The LM and RM groups did not differ from the UC group with respect to recovery time; however, the LM group had a shorter recovery time compared with the RM group (a difference of 12.4 minutes; 95% CI, 2.2 to 22.5; P = .018). Satisfaction scores for the LM and RM groups did not differ from those of the UC group. Conclusion Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe, effective, time-efficient, and enjoyable.

Purpose Unpleasant acoustic noise is a drawback of almost every MRI scan. Instead of reducing acoustic noise to improve patient comfort, we propose a technique for mitigating the noise problem by producing musical sounds directly from the switching magnetic fields while simultaneously quantifying multiple important tissue properties. Theory and Methods MP3 music files were converted to arbitrary encoding gradients, which were then used with varying flip angles and repetition times in a two- and three-dimensional magnetic resonance fingerprinting (MRF) examination. This new acquisition method, named MRF-Music, was used to quantify T1, T2, and proton density maps simultaneously while providing pleasing sounds to the patients. Results MRF-Music scans improved patient comfort significantly during MRI examinations. The T1 and T2 values measured from phantom are in good agreement with those from the standard spin echo measurements. T1 and T2 values from the brain scan are also close to previously reported values. Conclusions MRF-Music sequence provides significant improvement in patient comfort compared with the MRF scan and other fast imaging techniques such as echo planar imaging and turbo spin echo scans. It is also a fast and accurate quantitative method that quantifies multiple relaxation parameters simultaneously. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Objectives The goal of this study was to develop free-breathing high-spatiotemporal resolution dynamic contrast-enhanced liver magnetic resonance imaging using non-Cartesian parallel imaging acceleration, and quantitative liver perfusion mapping. Materials and methods This study was approved by the local institutional review board and written informed consent was obtained from all participants. Ten healthy subjects and 5 patients were scanned on a Siemens 3-T Skyra scanner. A stack-of-spirals trajectory was undersampled in-plane with a reduction factor of 6 and reconstructed using 3-dimensional (3D) through-time non-Cartesian generalized autocalibrating partially parallel acquisition. High-resolution 3D images were acquired with a true temporal resolution of 1.6 to 1.9 seconds while the subjects were breathing freely. A dual-input single-compartment model was used to retrieve liver perfusion parameters from dynamic contrast-enhanced magnetic resonance imaging data, which were coregistered using an algorithm designed to reduce the effects of dynamic contrast changes on registration. Image quality evaluation was performed on spiral images and conventional images from 5 healthy subjects. Results Images with a spatial resolution of 1.9 × 1.9 × 3 mm3 were obtained with whole-liver coverage. With an imaging speed of better than 2 s/vol, free-breathing scans were achieved and dynamic changes in enhancement were captured. The overall image quality of free-breathing spiral images was slightly lower than that of conventional long breath-hold Cartesian images, but it provided clinically acceptable or better image quality. The free-breathing 3D images were registered with almost no residual motion in liver tissue. After the registration, quantitative whole-liver 3D perfusion maps were obtained and the perfusion parameters are all in good agreement with the literature. Conclusions This high-spatiotemporal resolution free-breathing 3D liver imaging technique allows voxelwise quantification of liver perfusion.

Background We sought to explore the perspective of older breast cancer survivors (BCS) from diverse racial and socioeconomic backgrounds toward physical activity (PA) to inform the design of a PA program that fosters acceptability. Methods Participants included sixty women, ≥ 65 years, within two years of treatment completion for stage I-III breast cancer. We purposely sampled ≥ ten patients in each race [African-American (AA) and Non-Hispanic White (NHW)] and socioeconomic status (SES) [SES disadvantaged and SES non-disadvantaged] group. Participants completed in-person interviews (n = 60) and follow-up focus groups (n = 45). Thematic analyses were employed. Results The median age was 71.0 years (range: 65–87 years). Five themes emerged: 1) importance of PA; 2) current PA participants engaged in; 3) influence of race and culture on PA attitudes and beliefs; 4) barriers to PA and facilitators to PA; and 5) PA preferences. Barriers included health issues (43%), particularly cancer treatment side effects such as fatigue. Facilitators included religious faith (38%) and family (50%). Preferences included group exercise (97%) and strength training (80%) due to concerns participants had with diminished upper body strength after cancer treatment. Although AA (59%) and SES non-disadvantaged (78%) participants reported that race and culture influenced their attitudes toward PA, it did not translate to racial and SES differences in preferences. Conclusion Among older BCS, physical activity preferences were shaped by cancer experience, rather than by race and SES. Physical activity programs for older BCS should focus on addressing cancer treatment-related concerns and should include strength training to ensure PA programs are more acceptable to older BCS.

Treated human immunodeficiency virus (HIV) infection is characterized by ectopic fat deposition, a persistent inflammatory state, and increased cardiometabolic risk. In this secondary analysis of a placebo controlled trial of rosuvastatin among 147 HIV+ subjects (median age 46; 78% men) on stable antiretroviral therapy, we aimed to evaluate longitudinal associations between computed tomography (CT) measures of pericardial fat (PCF) volume and density, insulin resistance, and inflammation. We measured PCF volume and density (mean attenuation in Hounsfield units) by noncontrast gated CT at baseline and week 96. Homeostatic model of insulin resistance was calculated from fasting insulin and glucose at entry, 24, 48, and 96 weeks. At baseline, insulin resistance correlated positively with PCF volume and negatively with density. Similarly divergent correlations of volume and density were observed with waist:hip ratio, nadir CD4+ count, and duration of antiretroviral therapy. In a linear mixed model, PCF density was associated with insulin resistance independent of PCF volume, body mass index, metabolic syndrome, and biomarkers of immune activation and systemic inflammation; however, baseline PCF measures were not associated with longitudinal changes in insulin resistance. Soluble CD163, a marker of monocyte activation, positively correlated with PCF volume and was associated with insulin resistance in linear models. Statin treatment assignment did not affect PCF volume or density change (both p > 0.8). In conclusion, the quantity and quality (i.e., radiodensity) of PCF are differentially related to insulin resistance and inflammation in patients with treated HIV infection.

Purpose To develop and evaluate an examination consisting of magnetic resonance (MR) fingerprinting-based T1, T2, and standard apparent diffusion coefficient (ADC) mapping for multiparametric characterization of prostate disease. Materials and Methods This institutional review board-approved, HIPAA-compliant retrospective study of prospectively collected data included 140 patients suspected of having prostate cancer. T1 and T2 mapping was performed with fast imaging with steady-state precession-based MR fingerprinting with ADC mapping. Regions of interest were drawn by two independent readers in peripheral zone lesions and normal-appearing peripheral zone (NPZ) tissue identified on clinical images. T1, T2, and ADC were recorded for each region. Histopathologic correlation was based on systematic transrectal biopsy or cognitively targeted biopsy results, if available. Generalized estimating equations logistic regression was used to assess T1, T2, and ADC in the differentiation of (a) cancer versus NPZ, (b) cancer versus prostatitis, (c) prostatitis versus NPZ, and (d) high- or intermediate-grade tumors versus low-grade tumors. Analysis was performed for all lesions and repeated in a targeted biopsy subset. Discriminating ability was evaluated by using the area under the receiver operating characteristic curve (AUC). Results In this study, 109 lesions were analyzed, including 39 with cognitively targeted sampling. T1, T2, and ADC from cancer (mean, 1628 msec ± 344, 73 msec ± 27, and 0.773 × 10

Background Obesity is a leading risk factor for endometrial cancer (EC), particularly Type I forms, which are increasing in the U.S. Although death rates from most cancers have been decreasing, overall mortality in EC is increasing in the U.S. EC survivors' poor fitness combined with their surgical treatments may make weight loss particularly challenging. High intensity exercise increases neurotrophins and neurological reward via altered striatal dopamine in animals, and, in humans, chronic high intensity exercise enhances meal-induced satiety and may reduce hedonic eating. “Assisted” exercise, a mode of exercise whereby a patient's voluntary exercise rate is augmented mechanically, may modulate brain dopamine levels in Parkinson's Disease patients but has not been previously evaluated as a treatment for obesity. Methods We describe the rationale and design of the REWARD trial, which has the overarching goal of randomizing 120 obese EC survivors to “assisted” or voluntary rate cycling to evaluate the efficacy of “assisted” exercise in enhancing and sustaining weight loss. Patients in both arms will receive 3 days/week of supervised exercise and 1 day/week of a group dietary behavioral intervention for 16 weeks and, then, will be followed for 6 months. Outcomes The primary outcome is weight loss. Secondary outcomes include measures for body composition, fitness, eating behavior, exercise motivation and, quality of life as well as cognition and food reward and motivation as assessed by functional magnetic resonance imaging (fMRI) tasks. Conclusions If successful, the REWARD program could be extended to help sustain weight loss in obese cancer and non-cancer patients.

The objective of this study was to demonstrate the feasibility of improving perceived acoustic comfort for a standard clinical magnetic resonance imaging protocol via gradient wave form optimization and validate parallel imaging as a means to achieve a further reduction of acoustic noise.The gradient wave forms of a standard T2 axial turbo spin-echo (TSE) sequence in head examinations were modified for acoustic performance while attempting to keep the total acquisition and inter-echo spacing the same. Parallel imaging was then used to double the inter-echo spacing and allow further wave form optimization. Along with comparative acoustic noise measurements, a statistical analysis of radiologist scoring was conducted on volumes from standard and modified sequences acquired from 10 patients after informed consent was obtained.Compared with TSE, significant improvement of acoustic comfort was measured for modified-sequences quiet TSE and quiet TSE with generalized autocalibrating partially parallel acquisitions (P = 0.0034 and P = 0.0003, respectively), and no statistically significant difference in diagnostic quality was observed without the use of parallel imaging.Standard clinical magnetic resonance imaging protocols can be made quieter through adequate gradient wave form optimization. In scans with high signal-to-noise ratio, parallel imaging can be used to further reduce acoustic noise.

Our ultimate goal is to non-destructively evaluate mechanical properties of tissue-engineered (TE) cartilage using ultrasound (US). We used agarose gels as surrogates for TE cartilage. Previously, we showed that mechanical properties measured using conventional methods were related to those measured using US, which suggested a way to non-destructively predict mechanical properties of samples with known volume fractions. In this study, we sought to determine whether the mechanical properties of samples, with unknown volume fractions could be predicted by US. Aggregate moduli were calculated for hydrogels as a function of SOS, based on concentration and density using a poroelastic model. The data were used to train a statistical model, which we then used to predict volume fractions and mechanical properties of unknown samples. Young's and storage moduli were measured mechanically. The statistical model generally predicted the Young's moduli in compression to within

BACKGROUND AND PURPOSE: MR imaging and PET/CT are integrated in the work-up of head and neck cancer patients. The hybrid imaging technology 18 F-FDG-PET/MR imaging combining morphological and functional information might be attractive in this patient population. The aim of the study was to compare whole-body 18 F-FDG-PET/MR imaging and 18 F-FDG-PET/CT in patients with head and neck cancer, both qualitatively in terms of lymph node and distant metastases detection and quantitatively in terms of standardized uptake values measured in 18 F-FDG-avid lesions. MATERIALS AND METHODS: Fourteen patients with head and neck cancer underwent both whole-body PET/CT and PET/MR imaging after a single injection of 18 F-FDG. Two groups of readers counted the number of lesions on PET/CT and PET/MR imaging scans. A consensus reading was performed in those cases in which the groups disagreed. Quantitative standardized uptake value measurements were performed by placing spheric ROIs over the lesions in 3 different planes. Weighted and unweighted κ statistics, correlation analysis, and the Wilcoxon signed rank test were used for statistical analysis. RESULTS: κ statistics for the number of head and neck lesion lesions counted (pooled across regions) revealed interreader agreement between groups 1 and 2 of 0.47 and 0.56, respectively. Intrareader agreement was 0.67 and 0.63. The consensus reading provided an intrareader agreement of 0.63. For the presence or absence of metastasis, interreader agreement was 0.85 and 0.70. The consensus reading provided an intrareader agreement of 0.72. The correlations between the maximum standardized uptake value in 18 F-FDG-PET/MR imaging and 18 F-FDG-PET/CT for primary tumors and lymph node and metastatic lesions were very high (Spearman r = 1.00, 0.93, and 0.92, respectively). CONCLUSIONS: In patients with head and neck cancer, 18 F-FDG-PET/MR imaging and 18 F-FDG-PET/CT provide comparable results in the detection of lymph node and distant metastases. Standardized uptake values derived from 18 F-FDG-PET/MR imaging can be used reliably in this patient population.

BACKGROUND This study sought to assess racial differences in functional disability among older women with nonmetastatic breast cancer. METHODS In this cross-sectional study, between April 2008 and December 2012, women aged ≥ 65 years with newly diagnosed stage I through III breast cancer were recruited from ambulatory oncology clinics at an academic center. Prior to receiving any adjuvant treatment, participants completed a comprehensive geriatric assessment. The primary outcome was functional disability, defined as dependency in any basic or instrumental activity of daily living, categorized as “yes” or “no.” Logistic regression analyses were undertaken. RESULTS The study enrolled 190 women whose mean age was 75.0 years at diagnosis (standard deviation=7.0, range=65-93 years). Thirty-two percent were African American (AA), and 39% had functional disability. Controlling for age, participants with functional disability were more likely to be AA (versus non-Hispanic white), odds ratio=4.19, 95% confidence interval=2.12-8.27. Fifty-nine percent of the racial difference in functional disability was explained by a higher prevalence of lower income and education among AAs. In addition, the higher prevalence of chronic medical conditions and obesity among AAs, after accounting for socioeconomic factors, further explained 40% of the black–white difference in functional disability. CONCLUSIONS Among older women with newly diagnosed nonmetastatic breast cancer, functional disability is highly prevalent, and AAs are disproportionately affected. Interventions to optimize the functional status of at-risk individuals, particularly AAs, during and after cancer treatment may improve treatment tolerance and overall survival outcomes. Cancer 2013;119:3839–3846. © 2013 American Cancer Society.

Treatment of pain in palliative care patients is challenging. Adjunctive methods of pain management are desirable. Music therapy offers a nonpharmacologic and safe alternative.To determine the efficacy of a single music therapy session to reduce pain in palliative care patients.Two hundred inpatients at University Hospitals Case Medical Center were enrolled in the study from 2009 to 2011. Patients were randomly assigned to one of two groups: standard care alone (medical and nursing care that included scheduled analgesics) or standard care with music therapy. A clinical nurse specialist administered pre- and post-tests to assess the level of pain using a numeric rating scale as the primary outcome, and the Face, Legs, Activity, Cry, Consolability Scale and the Functional Pain Scale as secondary outcomes. The intervention incorporated music therapist-guided autogenic relaxation and live music.A significantly greater decrease in numeric rating scale pain scores was seen in the music therapy group (difference in means [95% CI] -1.4 [-2.0, -0.8]; P0.0001). Mean changes in Face, Legs, Activity, Cry, Consolability scores did not differ between study groups (mean difference -0.3, [95% CI] -0.8, 0.1; P0.05). Mean change in Functional Pain Scale scores was significantly greater in the music therapy group (difference in means -0.5 [95% CI] -0.8, 0.3; P0.0001) [corrected]: A single music therapy intervention incorporating therapist-guided autogenic relaxation and live music was effective in lowering pain in palliative care patients.

The purpose of this study was to compare and correlate standardized uptake values (SUV) derived from magnetic resonance attenuation correction (MRAC) with those derived from computed tomography attenuation correction (CTAC) in an oncology patient population.The HIPAA-compliant study was approved by the Internal Review Board and all subjects gave written informed consent prior to inclusion in the study. Forty patients (mean age 61 ± 15.1; 20 male) referred for clinically indicated 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans also underwent a PET/magnetic resonance imaging (MRI) examination. MRAC was performed using an automatic three-segment model. Regions of interest were drawn over eight normal structures in order to obtain SUVmax and SUVmean values. Spearman rank correlation coefficients (r) were calculated and two-tailed paired t tests were performed to compare the SUVmax and SUVmean values obtained from CTAC with those from MRAC.The mean time after FDG injection was 66 ± 7 min for PET/CT and 117 ± 15 min for PET/MRI examination. MRAC SUV values were significantly lower than the CTAC SUV values in mediastinal blood pool (p 0.001 for both SUVmax and SUVmean) and liver (p = 0.01 for SUVmean). The MRAC SUV values were significantly higher in bone marrow (p 0.001 for both SUVmax and SUVmean), psoas major muscle (p 0.001 for SUVmax), and left ventricular myocardium (p 0.001 for SUVmax and p = 0.01 for SUVmean). For the other normal structures, no significant difference was observed. When comparing SUV values generated from CTAC versus MRAC, high correlations between CTAC and MRAC were observed in myocardium (r = 0.96/0.97 for SUVmax/mean), liver (r = 0.68 for SUVmax), bone marrow (r = 0.80/0.83 for SUVmax/mean), lung tissue (r = 0.70 for SUVmax), and mediastinal blood pool (r = 0.0.68/.069 for SUVmax/mean). Moderate correlations were found in lung tissue (r = 0.67 for SUV mean), liver (r = 0.66 for SUVmean), fat (r = 0.48/0.53 for SUVmax/mean), psoas major muscle (r = 0.54/0.58 for SUVmax/mean), and iliacus muscle (r = 0.41 for SUVmax). Low correlation was found in iliacus muscle (r = 0.32 for SUVmean).Using the automatic three-segment model, our study showed high correlation for measurement of SUV values obtained from MRAC compared to those from CTAC, as the reference standard. Differences observed between MRAC and CTAC derived SUV values may be attributed to the time-delay between the PET/CT and PET/MRI scans or biologic clearance of radiotracer. Further studies are required to assess SUV measurements when performing different MR attenuation correction techniques.

BACKGROUND: Professional society guidelines recommend follow-up colonoscopy for patients with resected colonic adenomas. However, adherence to guideline recommendations in routine clinical practice has not been well characterized. METHODS: The authors used a population-based sample of Medicare beneficiaries to identify all patients aged ≥70 years who had a claim for colonoscopy with polypectomy or hot biopsy during the period from 2001 to 2004. Medicare claims through 2009 identified colonoscopy within the following 5 years as well as fecal occult blood testing, sigmoidoscopy, and barium enema. RESULTS: In total, 12,771 patients were included. At 5 years, 45.7% of patients underwent another colonoscopy, and 32.3% of procedures included a polypectomy. The rates of fecal occult blood testing, flexible sigmoidoscopy, and barium enema at 5 years were 54%, 3.8%, and 2.9%, respectively. There was a marked decrease in repeat colonoscopy at 1 year, 3 years, and 5 years with more recent years of index procedures. Other predictors of undergoing repeat colonoscopy were younger age, African American race, and a colonoscopy before the index examination. There was no association with physician specialty. The decreasing use of colonoscopy with time was maintained in a multivariable analysis. CONCLUSIONS: In a sample of elderly Medicare beneficiaries, there was under use of follow-up colonoscopy at 5 years after polypectomy, and

Background Mohs micrographic surgery examines all margins of the resected sample and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not readily amenable to Mohs micrographic surgery. This defines an unmet clinical need to assess the completeness of non-Mohs micrographic surgery resections during surgery to prevent re-excision/recurrence. Objective We sought to examine the utility of quenched activity-based probe imaging to discriminate cancerous versus normal-appearing skin tissue. Methods The quenched activity-based probe GB119 was applied to NMSC excised from 68 patients. We validated activation of the probe for hematoxylin-eosin–confirmed cancerous tissue versus normal-appearing skin tissue. Results Topical application of the probe differentiated basal cell carcinoma and squamous cell carcinoma from normal-appearing skin with overall estimated sensitivity and specificity of 0.989 (95% confidence interval 0.940-1.00) and 0.894 (95% confidence interval 0.769-0.965), respectively. Probe activation accurately defined peripheral margins of NMSC as compared with conventional hematoxylin-eosin–based pathology. Limitations This study only examined NMSC debulking excision specimens. The sensitivity and specificity for this approach using final NMSC excision margins will be clinically important. Conclusions These findings merit further studies to determine whether quenched activity-based probe technology may enable cost-effective increased cure rates for patients with NMSC by reducing re-excision and recurrence rates with a rapid and easily interpretable technological advance.

Out-of-pocket expenditures are thought to be an important barrier to the receipt of cancer preventive services, especially for those of a lower socioeconomic status (SES). The Affordable Care Act (ACA) eliminated out-of-pocket expenditures for recommended services, including mammography and colonoscopy. The objective of this study was to determine changes in the uptake of mammography and colonoscopy among fee-for-service Medicare beneficiaries before and after ACA implementation.Using Medicare claims data, this study identified women who were 70 years old or older and had not undergone mammography in the previous 2 years and men and women who were 70 years old or older, were at increased risk for colorectal cancer, and had not undergone colonoscopy in the past 5 years. The receipt of procedures in the 2-year period before the ACA's implementation (2009-2010) and after its implementation (2011 to September 2012) was also identified. Multivariate generalized estimating equation models were used to determine the independent association and county-level quartile of median income and education with the receipt of testing.For mammography, a lower SES quartile was associated with less uptake, but the post-ACA disparities were smaller than those in the pre-ACA period. In addition, mammography rates increased from the pre-ACA period to the post-ACA period in all SES quartiles. For colonoscopy, in both the pre- and post-ACA periods, there was an association between uptake and educational level and, to some extent, income. However, there were no appreciable changes in colonoscopy and SES after implementation of the ACA.The removal of out-of-pocket expenditures may overcome a barrier to the receipt of recommended preventive services, but for colonoscopy, other procedural factors may remain as deterrents. Cancer 2017;123:1585-1589. © 2017 American Cancer Society.

BACKGROUND AND PURPOSE: MR fingerprinting allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assessed the utility of MR fingerprinting in differentiating common types of adult intra-axial brain tumors. MATERIALS AND METHODS: MR fingerprinting acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 World Health Organization grade II lower grade gliomas, and 8 metastases. T1, T2 of the solid tumor, immediate peritumoral white matter, and contralateral white matter were summarized within each ROI. Statistical comparisons on mean, SD, skewness, and kurtosis were performed by using the univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple-comparison testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases, and area under the receiver operator curve was calculated. RESULTS: Mean T2 values could differentiate solid tumor regions of lower grade gliomas from metastases (mean, 172 ± 53 ms, and 105 ± 27 ms, respectively; P = .004, significant after Bonferroni correction). The mean T1 of peritumoral white matter surrounding lower grade gliomas differed from peritumoral white matter around glioblastomas (mean, 1066 ± 218 ms, and 1578 ± 331 ms, respectively; P = .004, significant after Bonferroni correction). Logistic regression analysis revealed that the mean T2 of solid tumor offered the best separation between glioblastomas and metastases with an area under the curve of 0.86 (95% CI, 0.69–1.00; P CONCLUSIONS: MR fingerprinting allows rapid simultaneous T1 and T2 measurement in brain tumors and surrounding tissues. MR fingerprinting–based relaxometry can identify quantitative differences between solid tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas.

Objective Most prior studies on aggressive end-of-life care in older patients with cancer have accounted for social determinants of health (e.g., race, income, and education), but rarely for multimoribidity (MM). In this study, we examine the association between end-of-life care and each of the social determinants of health and MM, hypothesizing that higher MM is associated with less aggressive care. Methods From the linked 1991–2008 Health and Retirement Study, Medicare data, and the National Death Index, we identified fee-for-service patients age ≥66years who died from cancer ( n =835). MM was defined as the occurrence or co-occurrence of chronic conditions, functional limitations, and/or geriatric syndromes. Aggressive care was based on claims-derived measures of receipt of cancer-directed treatment in the last two weeks of life; admission to the hospital and/or emergency department (ED) within the last month; and in-hospital death. We also identified patients enrolled in hospice. In multivariable logistic regression models, we analyzed the associations of interest, adjusting for potential confounders. Results While 61.2% of the patients enrolled in hospice, 24.6% underwent cancer-directed treatment; 55.1% were admitted to the hospital and/or ED; and 21.7% died in the hospital. We observed a U-shaped distribution between income and in-hospital death. Chronic conditions and geriatric syndromes were associated with some outcomes, but not with others. Conclusions To improve quality end-of-life care and curtail costs incurred by dying patients, relevant interventions need to account for social determinants of health and MM in a nuanced fashion.

Long-term lentiviral transduction of human mesenchymal stem cells (hMSCs) greatly enhances the usefulness of these cells. However, such transduction currently requires the use of polybrene, which severely inhibits hMSC proliferation. In contrast, protamine sulfate at 100 μg/ml doubled transduction efficiencies without affecting proliferation or differentiation potential. Expression levels improved 2.2-fold with the addition of a woodchuck hepatitis post-transcriptional regulatory element. Further improvements in transduction efficiencies could be obtained by a modest increase in viral concentrations through increased viral titers or decreased transduction volumes without changing multiplicity of infection, by transducing over multiple days, or by culturing the cells in fibroblast growth factor-2. Centrifugation improved expression but had no effect on efficiency. Transgene expression was stable over 6 weeks in vitro and in vivo. Donor-to-donor and intradonor variability were observed in primary passage through passage 2 cultures, but not at passage 3. These results provide a better optimized approach for expanded use of hMSCs through genetic manipulation.

Aim: To assess academic achievement, rates of learning disabilities (LD) and special education in extremely low birth weight (ELBW

Human marrow-derived mesenchymal stem cells (hMSCs) have been investigated for more than 20 years. They have been shown to be therapeutic in a number of animal models and are currently in use in more than 200 clinical trials, thus documenting their importance in the field of translational medicine. Standard protocols for the passage and collection of hMSCs involve trypsinization of preconfluent cultures. This practice is based, at least in part, on concerns that the multipotency of these cells would be diminished if the cultures became confluent. To test this concern, hMSCs were isolated and maintained in standard culture conditions in primary culture and were then subcultured after 2 weeks. The resulting first passage cultures were divided into two groups: those that were subcultured at the normal frequency, usually at 7 days for each passage (referred to as standard conditions [SC]), and those that were maintained for up to 53 days without being further subcultured (extended first passage [EFP]). At the end of the second passage and each of five subsequent subcultures for cells in SC (i.e., through passage 7), complementary EFP cultures were also trypsinized. Cells from each group were counted, resuspended in serum-free medium, and assayed to determine the ability of the cells to differentiate along osteogenic, chondrogenic, and adipogenic lineages. Cells in SC experienced an average of 27 population doublings through seven passages, whereas hMSCs in EFP achieved approximately 16 population doublings after 34 days but demonstrated very little increase in cell number after that time. The ability of hMSCs in EFP to produce bone in ceramic cubes implanted subcutaneously in immunocompromised mice and to differentiate into cartilage in pellet or aggregate culture was at least equivalent to that of the cells in SC through seven passages, whereas the capacity of the EFP hMSCs to produce lipid droplets in adipogenic conditions was maintained but was diminished relative to that of SC cells.

Background: Despite the American Society of Echocardiography recommendation to use left atrial volume indexed for body surface area (LAVI) for quantification of left atrial size, a variety of methods are used in clinical practice. Our objectives were to evaluate the accuracy of M-mode and two-dimensional (2D) echocardiographic LA size estimates to LAVI and to determine their ability to predict left ventricular diastolic dysfunction. Methods: In 150 consecutive patients, LA diameter (LAD), LA diameter indexed for body surface area (LADI), LA area in the apical two- and four-chamber views (LAA 2c and LAA 4c), biplane area–length LA volume (LAV), and LAVI were obtained. The accuracy of these methods to quantify LA enlargement by LAVI, correlation with clinical parameters, and ability to act as a surrogate for diastolic dysfunction were determined using Pearson correlation coefficients along with univariate and multiple logistic analysis. Results: The true degree of LA size (with LAVI as standard) was identified by LAD in 45%, LADI in 42%, LAA 4c in 43%, and LAA 2c in 41%. All methods showed positive correlation with age, E/E′, mitral regurgitation, and right atrial size and negative correlation with ejection fraction. LAVI was the strongest method to predict any (c = 0.655, P = 0.012) or moderate–severe (P = 0.856 and P < 0.001) diastolic dysfunction. All methods have greater capacity to identify moderate or severe diastolic dysfunction than any degree of diastolic dysfunction alone. Conclusions: One-dimensional and 2D methods inaccurately quantify LA size and are inferior to LAVI to predict diastolic dysfunction. (Echocardiography 2012;29:379-384)

Background Following a colonoscopy that is negative for cancer, a subset of patients may be diagnosed with colorectal cancer, also termed interval cancer. The frequency and predictors have not been well studied in a population-based U.S. cohort.

BackgroundEsophagectomy for esophageal cancer carries high morbidity and mortality, particularly in older patients. Transthoracic esophagectomy allows formal lymphadenectomy, but leads to greater perioperative morbidity and pain than transhiatal esophagectomy. Epidural analgesia may attenuate the stress response and be less immunosuppressive than opioids, potentially affecting long-term outcomes. These potential benefits may be more pronounced for transthoracic esophagectomy due to its greater physiologic impact. We evaluated the impact of epidural analgesia on survival and recurrence after transthoracic versus transhiatal esophagectomy.MethodsA retrospective cohort study was performed using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients aged ≥66 years with locoregional esophageal cancer diagnosed 1994-2009 who underwent esophagectomy were identified, with follow-up through December 31, 2013. Epidural receipt and surgical approach were identified from Medicare claims. Survival analyses adjusting for hospital esophagectomy volume, surgical approach, and epidural use were performed. A subgroup analysis restricted to esophageal adenocarcinoma patients was performed.ResultsAmong 1,921 patients, 38% underwent transhiatal esophagectomy (n = 730) and 62% underwent transthoracic esophagectomy (n = 1,191). 61% (n = 1,169) received epidurals and 39% (n = 752) did not. Epidural analgesia was associated with transthoracic approach and higher volume hospitals. Patients with epidural analgesia had better 90-day survival. Five-year survival was higher with transhiatal esophagectomy (37.2%) than transthoracic esophagectomy (31.0%, p = 0.006). Among transthoracic esophagectomy patients, epidural analgesia was associated with improved 5-year survival (33.5% epidural versus 26.5% non-epidural, p = 0.012; hazard ratio 0.81, 95% confidence interval [0.70, 0.93]). Among the subgroup of esophageal adenocarcinoma patients undergoing transthoracic esophagectomy, epidural analgesia remained associated with improved 5-year survival (hazard ratio 0.81, 95% confidence interval [0.67, 0.96]); this survival benefit persisted in sensitivity analyses adjusting for propensity to receive an epidural.ConclusionAmong patients undergoing transthoracic esophagectomy, including a subgroup restricted to esophageal adenocarcinoma, epidural analgesia was associated with improved survival even after adjusting for other factors.

Objective Retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina in preterm infants, is associated with multiple factors, including oxygenation level. We explored whether the common intermittent hypoxemic events in preterm infants are associated with the development of ROP. Study design Oxygen desaturation events were quantified in 79 preterm infants (gestational age, 24 to 27-6/7 weeks) during the first 8 weeks of life. Infants were classified as requiring laser treatment for ROP versus having less severe or no ROP. A linear mixed model was used to study the association between the incidence of intermittent hypoxia and laser treatment of ROP, controlling for gestational age, sex, race, multiple births, and initial severity of illness. Results For all infants, hypoxemic events increased with postnatal age ( P .001). Controlling for all covariates, a higher incidence of oxygen desaturation events was found in the infants undergoing laser therapy for ROP ( P .001), males ( P .02), and infants of younger gestational age ( P .003). Conclusions The incidence of hypoxemic events was higher in infants with ROP requiring laser therapy. Therapeutic strategies to optimize oxygenation in preterm infants should include minimization of desaturation episodes, which may in turn decrease serious morbidity in this high-risk population.