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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.

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.

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.

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.

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.

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 .

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.

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.

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.

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.

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.

Objectives/Hypothesis: To evaluate the efficacy of photodynamic therapy (PDT) with the phthalocyanine photosensitizer Pc 4 for treating an animal model of recurrent respiratory papillomatosis (RRP). Methods: Rabbit skin was grafted onto the dorsum of severe combined immunodeficient mice, two xenografts per animal. After the graft healed, it was inoculated with cottontail rabbit papillomavirus (CRPV). When papillomas developed, Pc 4 (0.6 or 1.0 mg/kg) was administered systemically, and 48 hours later, one papilloma of the two on each animal was exposed to 675-nm photoactivating light at either 100 or 150 J/cm 2 . In addition to the contralateral tumors, which received Pc 4 but no light, other controls included animals receiving light only or neither agent. Response was assessed by measuring papilloma size with a caliper. Some papillomas and residual skin were harvested for histological assessment. Results: For the lower-dose PDT regimens, papilloma growth rates were not significantly different from the controls. In contrast, 13 of 15 papillomas receiving the higher Pc 4 dose (1.0 mg/kg) and the higher light fluence (150 J/cm 2 ) regressed completely and did not regrow within the observation period of up to 79 days. The response of these papillomas was significantly different from the controls (P < .001). Histological analysis confirmed the absence of residual tumor following complete response and replacement with near-normal epithelium. Conclusions: Pc 4-PDT is highly effective in treating virally induced (CRPV) papillomas in a murine model of RRP, and thus warrants further study as a treatment for HPV-induced papillomas.

High rates of asthma treatment nonadherence have been reported, particularly in economically disadvantaged African American youth. The relationship between adherence to combined medication treatment and asthma outcomes has potential clinical significance but is not well understood. Using electronic monitoring, we describe the pattern of adherence to daily corticosteroid (fluticasone) and leukotriene receptor antagonist (montelukast) medication over the course of 1 year in a population of African American youth with moderate to severe asthma. On average, adherence to montelukast was higher than adherence to fluticasone (p0.01); however, for both medications, adherence rates significantly declined over the course of the study. After 1 year, participants took only 31% of prescribed doses of montelukast and 23% of prescribed doses of fluticasone. The decline in adherence to both fluticasone (p0.05) and montelukast (p0.001) was related to increased healthcare utilization. Furthermore, asthma symptom ratings were related montelukast (p0.001), but not fluticasone adherence. These results suggest that adherence promotion intervention strategies are warranted to improve health-related outcomes in families who are at-risk for treatment nonadherence.

Bryostatin 1, isolated from a marine bryozoan, enhances the efficacy of cytotoxic agents through modulation of the protein kinase C pathway and is active in combination with vincristine for diffuse large B-cell lymphoma. Further, the apoptotic frequency of peripheral blood T lymphocytes as determined by flow cytometry may predict which patients will respond to this combination. We tested the efficacy and safety of bryostatin 1 50 microg/m(2) given over 24 hr and vincristine 1.4 mg/m(2) on days 1 and 15 every 28 days in aggressive B-cell non-Hodgkin lymphoma (NHL) relapsing after autologous stem cell transplantation. End points included tumor response, toxicity, and survival. Responses were correlated with an increase in apoptotic frequency of CD5+ cells by flow cytometry using annexin V staining. Fourteen patients were enrolled with 13 being evaluable for a response. The overall response rate was 31% with two patients achieving a complete response. The most common toxicities were Grade 3 lymphopenia (seven patients), Grade 3 to 4 neutropenia (two patients), and Grade 3 hypophosphatemia (two patients). Median progression-free and overall survivals for all patients were 5.7 and 21.4 months, respectively. One patient demonstrated an increase in T-cell apoptotic frequency, also achieving a complete response. Bryostatin 1 and vincristine have efficacy in select patients with aggressive NHL. Future investigations of agents targeting the protein kinase C pathway may benefit from early response assessment using flow cytometry to evaluate T-cell apoptosis.

To describe the prevalence of behavioral problems and symptomatology suggestive of Autism and Asperger's disorders at age 8 years among extremely low birth weight (ELBW,1 kg) children, born 1992 through 1995.Parent reports of the behavior of 219 ELBW (mean birth weight, 810 g; gestational age 26 weeks) were compared with 176 normal birth weight children of similar maternal sociodemographic status, sex, and age. Behavior was assessed via the Child Symptom Inventory that includes both Symptom Severity Scores and scores meeting DSM-IV criteria for disorders.ELBW compared with normal birth weight children had significantly higher mean Symptom Severity Scores for the inattentive, hyperactive, and combined types of attention-deficit hyperactivity disorder (all p.001) as well as higher scores for Generalized Anxiety (p.01) and Autistic (p.001) and Asperger's (p.01) disorders. When DSM-IV criteria were considered, ELBW children also had significantly higher rates of attention-deficit hyperactivity disorder of the inattentive (10% vs 3%, p.01) and combined (5% vs 0.6%, p.05) types.Attention-deficit hyperactivity disorder, mainly the inattentive type is prevalent among ELBW children. Our findings of an increase in symptoms pertaining to Autistic and Asperger's disorders at school age agree with recent reports of others during early childhood. Early identification and intervention for these problems might improve child functioning and ameliorate parent and child distress.

Objective: The objective of this study was to demonstrate the reliability of cardiac-gated computerized tomography (CGCT) in diagnosing aortic atheroma in patients with ischemic stroke. Materials and Methods: Two radiologists each read 32 CGCT studies and estimated aortic atheroma and interreliability/intrareliability measures. Results: The intraobserver intraclass correlation coefficients (ICCs) were 0.95 and 0.87 for the diagnosis of aortic atheroma with CGCT. The interrater ICC was 0.93. Conclusion: This prospective study demonstrated that CGCT is a reliable imaging modality with good interreader and intrareader reproducibilities.

Objective We sought to determine the prevalence of unsuspected, pre-existing valvular regurgitation in a large, heterogeneous population of patients referred for an echocardiogram. Methods The echocardiograms of 6851 consecutive individuals without suspected valve disease were reviewed. Regurgitant severity was graded using a clinical composite of published methods and multiple logistic analyses were used to model various clinical variables. Results The overall prevalence of moderate or greater mitral regurgitation (MR) was 11.7% in male patients and 12.5% in female patients. For mild or greater aortic insufficiency (AI), the prevalence was 18.9% in male patients and 19.7% in female patients. Both MR and AI increased exponentially as a function of age. Female sex predicted MR, but AI was sex neutral. Regurgitant severity increased with decreasing ejection fraction and body mass index, a history of hypertension, the presence of left ventricular hypertrophy, and valvular abnormalities. Conclusions The prevalence of unsuspected MR and AI is substantial, increases exponentially with age, and is predicted by commonly used clinical variables.

OBJECTIVE. The goal was to evaluate whether changes in neonatal intensive care have improved outcomes for children with bronchopulmonary dysplasia (oxygen dependence at corrected age of 36 weeks).METHODS. We compared outcomes of extremely low birth weight (RESULTS. For both groups, significant practice changes between period I and period II included increased prenatal and decreased postnatal steroid therapy and increased surfactant therapy, indomethacin therapy, and patent ductus arteriosus ligation. Significant morbidity changes included decreased rates of severe cranial ultrasound abnormalities and increased rates of ventilator dependence. Rates of bronchopulmonary dysplasia did not change (52% vs 53%). Follow-up evaluation revealed significantly lower rates of neurosensory abnormalities during period II (extremely low birth weight: 29% vs 16%; extremely low gestational age: 31% vs 16%). There were no changes in rates of Mental Developmental Index scores of CONCLUSIONS. Neurosensory outcomes of infants with bronchopulmonary dysplasia improved during 2000 to 2003 but overall neurodevelopmental outcomes did not change.

High-dose ibuprofen in a 4-year controlled trial slowed FEV(1) decline in young subjects with cystic fibrosis, but the effectiveness of ibuprofen has not been assessed in a large group of patients treated clinically with this therapy.To assess the effect of ibuprofen therapy on FEV(1) decline in children and adolescents with cystic fibrosis, using observational data from the Cystic Fibrosis Foundation Patient Registry.The rate of decline in FEV(1) percent predicted over 2-7 years among patients age 6-17 years with FEV(1)60% predicted, and who were treated with ibuprofen (1,365), was compared with patients of similar age and disease severity who were not treated with this therapy (8,960). Multilevel repeated-measures mixed-regression models were used to estimate rates of decline, adjusting for characteristics and therapies that influenced FEV(1) decline. Adverse effects were compared among those treated versus not treated with ibuprofen.FEV(1) declined less rapidly among patients treated with ibuprofen (difference, 0.60% predicted per year; 95% confidence interval, 0.31 to 0.89; P0.0001); a 29% reduction in slope based on an average decline of 2.08% predicted per year for patients not treated. Those treated with ibuprofen were more likely to have an episode of gastrointestinal bleeding requiring hospitalization, but the occurrence was rare in both groups (annual incidence, 0.37 vs. 0.14%; relative risk, 2.72; P0.001).Slower rates of FEV(1) decline are seen in children and adolescents with cystic fibrosis who are treated with ibuprofen. The apparent benefits of ibuprofen therapy outweigh the small risk of gastrointestinal bleeding.

Introduction The National Breast and Cervical Cancer Early Detection Program (BCCP) in Ohio provides screening and treatment services for uninsured low-income women aged 40 to 64. Because participation in the BCCP might engender greater self-efficacy for cancer screening, we hypothesized that breast cancer and survival outcomes would be better in BCCP participants who become age-eligible to transition to Medicare than in their low-income non-BCCP counterparts. Methods Linking data from the 2000 through 2009 Ohio Cancer Incidence Surveillance System with the BCCP database, Medicare files, Ohio death certificates (through 2010), and the US Census, we identified Medicare beneficiaries who were aged 66 to 74 and diagnosed with incident invasive breast cancer. We compared the following outcomes between BCCP women (n = 93) and low-income non-BCCP women (n = 420): receipt of screening mammography in previous year, advanced-stage disease at diagnosis, timely and standard care, all-cause survival, and cancer survival. We conducted multivariable logistic regression and survival analysis to examine the association between BCCP status and each of the outcomes, adjusting for patient covariates. Results Women who participated in the BCCP were nearly twice as likely as low-income non-BCCP women to have undergone screening mammography in the previous year (adjusted odds ratio, 1.77; 95% confidence interval, 1.01–3.09). No significant differences were detected in any other outcomes. Conclusion With the exception of screening mammography, the differences in outcomes were not significant, possibly because of the small size of the study population. Future analysis should be directed toward identifying the factors that explain these findings.

Purpose To evaluate the tolerability of escalating doses of stereotactic body radiotherapy (SBRT) for primary treatment of localized renal cell carcinoma (RCC) in poor surgical candidates. Patients and methods Eligible patients included those with clinically staged radiographic and or pathologically confirmed RCC who had not undergone previous abdominal or pelvic radiotherapy. All patients had comorbid medical conditions which precluded surgery. Median (range) patient age was 77.6years (range 59–89) years and all patients had Karnofsky Performance Status of ⩾60. Median tumor volume was 57.9cm 3 (range 13.8–174.7cm 3 ). Dose-limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal/genitourinary toxicity by Common Terminology Criteria of Adverse Events (version 4). Tumor response was assessed by imaging results using Response Evaluation Criteria In Solid Tumors (RECIST) measurement and percutaneous biopsy. Results A total of 19 patients (13 men and 6 women) were treated on protocol from June 2006 through August 2011. Groups of 3–6 patients received 24, 32, 40, and 48Gy in 4 fractions. Median (range) follow-up was 13. 7months (5.9–34.7months). For possibly treatment-related acute toxicities, one patient developed grade 2 fatigue and one developed grade 4 duodenal ulcer. For possibly treatment-related late toxicities, 2 patients experienced grade 3 renal toxicity (worsening chronic kidney disease), one reported grade 2 urinary incontinence and one developed grade 4 duodenal ulcer. Among the 15 patients with evaluable response, 3 and 12 had partial response and stable disease, respectively, utilizing RECIST criteria. Among the 11 patients who had post-SBRT biopsy, only one (9%) was negative on first biopsy and an additional one (9%) turned negative without further therapy on second biopsy. Conclusions Dose escalation to 48Gy in 4 fractions has been achieved successfully without dose-limiting toxicities. A planned extension of this phase I trial is currently underway treating patients to 60Gy in 3 fractions to further evaluate this experimental therapy.

Background Lipidized dermatofibromas represent a rare variant of dermatofibroma that has been regarded as an incidental finding with no particular clinical significance. Objective The goal of this study was to investigate the relationship between lipidized dermatofibromas and patient age, anatomic location, and serum total cholesterol. Methods A retrospective case control format was used with an experimental group containing patients with biopsy-proven lipidized dermatofibromas and a control group containing patients with nonlipidized dermatofibromas. Results Ages in the experimental group ranged from 35 to 75 years with a mean value of 53 years whereas ages in the control group ranged from 27 to 72 years with a mean value of 48 years. A comparison between the mean of the ages between the two groups using the t test method showed no statistically significant difference ( P = .09). Lesion location on the body was grouped into 4 sites: leg, thigh, trunk, and upper extremity. Of the 23 patients in the experimental group, 10 had lesions on the legs, 5 had lesions on the thighs, 2 had lesions on the trunk, and 5 had lesions on the upper extremities. Of the 41 patients in the control group, 15 had lesions on the legs, 7 had lesions on the thighs, 9 had lesions on the trunk, and 10 had lesions on the upper extremities. A comparison between the two groups showed no statistically significant difference ( P = .60). In all, 16 of the 23 patients in the experimental group and 24 of the 41 patients in the control group were considered to have high cholesterol. A comparison showed no statistically significant difference between the cholesterol levels of the two groups ( P = .38). Limitations Limitations that we encountered during the study included the relative infrequency of lipidized dermatofibromas, limiting the number of patients in the study. In addition, medication histories and lipid levels on patients were not always available. In addition, we formed a control group from people who had their cholesterol checked often, which may cause them to have a higher average cholesterol than that of the general population. Conclusions Our data show that lipidized dermatofibromas do not differ clinically from nonlipidized dermatofibromas in age distribution of patients, tumor location, or underlying serum lipid levels.

Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator gene, which codes for a chloride channel, but the role of this chloride channel in inflammation induced by lung infection with Pseudomonas aeruginosa remains to be defined.We tested the hypothesis that loss of this chloride channel alone is sufficient to cause excessive inflammation in response to inflammatory stimuli.We investigated the response of cystic fibrosis and wild-type mice to mucoid P. aeruginosa administered by insufflation.The host responses measured included survival, weight change, lung morphometry, bacterial clearance, and inflammatory mediators, and cell counts were assessed in bronchoalveolar lavage fluid.Depending on the dose administered and frequency of dosing, cystic fibrosis mice experienced significantly higher mortality rates, greater weight loss, higher lung pathology scores, and higher inflammatory mediator and neutrophil levels compared with wild-type mice, even after the bacteria had been cleared. Surprisingly, bacteria were cleared just as rapidly in cystic fibrosis mice as in wild-type mice, and sepsis was not observed. Chronic lung infections could not be established with mucoid P. aeruginosa in either cystic fibrosis or wild-type mice.Absence of this chloride channel alone appears sufficient for exaggerated inflammation and excess mortality compared with wild-type controls in the face of mucoid P. aeruginosa lung infection. To establish chronic infection, additional factors such as bacterial trapping or poor clearance may be required.

Atopic dermatitis (AD) patients with predominantly head and neck involvement react to patch tests of the yeast Malassezia sympodialis (Ms). Protein patch testing methods and interpretation are controversial, but subgroups of AD patients may have unique triggers for disease activity. The aim of the study was to identify clinical characteristics of patients who are patch test-positive to Dermatophagoides farinae/pteronyssinus (Df) and Ms and characterize cutaneous cytokine profiles of the atopy patch tests (APTs). 25 AD patients and 27 control dermatitis patients were patch tested with Ms and Df. Qualitative analysis of Th-1 and Th-2 cytokines by RT-PCR mRNA was obtained from positive APTs. Atopic dermatitis patients with a textile pattern or head and neck involvement demonstrated more positive APTs to Ms than control patients. Early positive APTs (

Polymorphisms in genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene may modify the severity of pulmonary disease in patients with cystic fibrosis.We performed two studies with different patient samples. We first tested 808 patients who were homozygous for the DeltaF508 mutation and were classified as having either severe or mild lung disease, as defined by the lowest or highest quartile of forced expiratory volume in one second (FEV1), respectively, for age. We genotyped 16 polymorphisms in 10 genes reported by others as modifiers of disease severity in cystic fibrosis and tested for an association in patients with severe disease (263 patients) or mild disease (545). In the replication (second) study, we tested 498 patients, with various CFTR genotypes and a range of FEV1 values, for an association of the TGFbeta1 codon 10 CC genotype with low FEV1.In the initial study, significant allelic and genotypic associations with phenotype were seen only for TGFbeta1 (the gene encoding transforming growth factor beta1), particularly the -509 and codon 10 polymorphisms (with P values obtained with the use of Fisher's exact test and logistic regression ranging from 0.006 to 0.0002). The odds ratio was about 2.2 for the highest-risk TGFbeta1 genotype (codon 10 CC) in association with the phenotype for severe lung disease. The replication study confirmed the association of the TGFbeta1 codon 10 CC genotype with more severe lung disease in comparisons with the use of dichotomized FEV1 for severity status (P=0.0002) and FEV1 values directly (P=0.02).Genetic variation in the 5' end of TGFbeta1 or a nearby upstream region modifies disease severity in cystic fibrosis.

Objective To examine the longitudinal relationship between depressive symptoms at study entry (T1) on pain intensity (PI) and functional disability over a 1-year period among children with either sickle cell disease (SCD) or juvenile idiopathic arthritis (JIA). Methods 119 children, ages 8-17 years, completed measures of depression at T1 as well as pain and functional disability at T1, 6-month (T2), and 12-month (T3) follow-ups. Caregivers also rated their child's pain and disability at each time point. General linear mixed modeling was employed to examine longitudinal relationships between study variables. Results For children with JIA, T1 pain significantly moderated the effects of T1-depressive symptoms on T2 and T3 pain where T1-depressive symptoms predicted future child-reported pain only when T1 pain was relatively mild. Similarly, T1-depressive symptoms predicted future child-reported disability only when initial reports of disability were relatively low. Only family income significantly predicted T2 and T3 pain in children with SCD. Conclusions Study findings suggest that T1-depressive symptoms play a role in the longitudinal course of pain symptoms in children with JIA but not in children with SCD.

High levels of antibodies to multiple antigens may be more strongly associated with protection from infection than antibodies to a single antigen. Antibody-associated protection against Plasmodium falciparum infection was assessed in a cohort of 68 adults living in an area of holoendemic malaria in Kenya. Antibodies to the pre- erythrocytic antigens circumsporozoite protein (CSP), liver-stage antigen-1 (LSA-1), thrombospondin-related adhesive protein (TRAP), and blood-stage antigens apical membrane antigen-1 (AMA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein 1 (MSP-1) were tested. Peptides were used for CSP (NANP repeat) and LSA-1 (central repeat), and recombinant antigens were used for TRAP (aa D48-K394), AMA-1 (ectodomain, non- glycosylated), EBA-175 (non-glycosylated), and MSP-1 (MSP-119). Weekly microscopy testing for P. falciparum infec- tion was performed over a 12-week period after drug-mediated clearance of P. falciparum parasitemia. Individuals with high levels of IgG antibodies (> 2 arbitrary units) to CSP, LSA-1, and TRAP had a 57% decrease in the risk of infection (95% confidence interval 20-77%, P 0.016). This decreased risk remained significant after adjustment for age, prior parasitemia, bed net use, sickle cell trait, and village of residence. In contrast, protection against infection did not correlate with high levels of IgG antibodies to blood-stage antigens or IgM antibodies to pre-erythrocytic or blood-stage antigens. High levels of IgG antibodies to CSP, LSA-1, and TRAP may be useful immune correlates of protection against P. falciparum infection in malaria-endemic populations.

Although transesophageal echocardiography (TEE) is a well-established tool in delineating the cardiac and aortic sources of emboli in stroke patients, its reproducibility in detecting aortic atherosclerosis (AA) that may lead to stroke is not well documented. The aim of this study is to demonstrate the inter- and intra-observer agreement in diagnosing AA based on the TEE study. During the study period, 2 echocardiographers read 32 TEE studies performed on a group of stroke patients. The AA was estimated by measuring the largest atheroma thickness in millimeters (mm). The intra-observers and intraclass correlation coefficients (ICC) were 0.97 and 0.85, respectively, for the 2 TEE observers. The inter-rater ICC coefficient between TEE readers was 0.91. In conclusion, TEE detected AA and defined high proportions of the morphological characteristics of atheroma with good reproducibility among inter and intra-observers.

Patients with cystic fibrosis have a lesion in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which is associated with abnormal regulation of other ion channels, abnormal glycosylation of secreted and cell surface molecules, and vulnerability to bacterial infection and inflammation in the lung usually leading to the death of these patients. The exact mechanism(s) by which mutation in CFTR leads to lung infection and inflammation is not clear. Mice bearing different mutations in the murine homolog to CFTR ( Cftr) (R117H, S489X, Y122X, and ΔF508, all backcrossed to the C57BL/6J background) were compared with respect to growth and in their ability to respond to lung infection elicited with Pseudomonas aeruginosa-laden agarose beads. Body weights of mice bearing mutations in Cftr were significantly smaller than wild-type mice at most ages. The inflammatory responses to P. aeruginosa-laden agarose beads were comparable in mice of all four Cftr mutant genotypes with respect to absolute and relative cell counts in bronchoalveolar lavage fluid, and cytokine levels (TNF-α, IL-1β, IL-6, macrophage inflammatory protein-2, and keratinocyte chemoattractant) and eicosanoid levels (PGE2 and LTB4) in epithelial lining fluid: the few small differences observed occurred only between cystic fibrosis mice bearing the S489X mutation and those bearing the knockout mutation Y122X. Thus we cannot implicate either misprocessing of CFTR or failure of CFTR to reach the plasma membrane in the genesis of the excess inflammatory response of CF mice. Therefore, it appears that any functional defect in CFTR produces comparable inflammatory responses to lung infections with P. aeruginosa.

Despite lack of evidence for effectiveness, obstetricians in the United States prescribe antepartum bed rest for more than 700,000 women per year. However, in nonpregnant samples, bed rest treatment produces weight loss. This study assessed maternal weight change (gain) during antepartum hospitalization for bed rest treatment; compared appropriateness of infant birth weights for gestational age, race, and gender; and determined whether maternal weight change predicted infant birth weight. The convenience sample for this longitudinal study consisted of 141 women with high-risk pregnancies who were treated with hospital bed rest. Weekly rate of pregnancy weight change by body mass index was compared with Institute of Medicine recommendations for rate of pregnancy weight gain. Infant birth weight was compared with current US infant birth weights for matching gestational age, gender, and race. Weekly antepartum weight change was significantly lower than Institute of Medicine recommendations (P < 0.001). Infant birth weights were also significantly lower than the national mean when matched for each infant’s gestational age, race, and gender ( P < 0.001). Maternal weight change predicted infant birth weight ( P = 0.05). Bed rest treatment is ineffective for improving pregnancy weight gain. Lower infant birth weights across all gestational ages suggest that maternal weight loss during bed rest may be associated with an increased risk of fetal growth restriction. A randomized trial comparing women with high-risk pregnancies who are ambulatory with those on bed rest is needed to determine whether bed rest treatment, underlying maternal-fetal disease, or both influence inadequate maternal weight gain and poor intrauterine growth.

Objectives To operationalize a comprehensive description of attrition, including pre-inclusion, dropout, and attrition due to intermittent missing data, and to test a predictive model of attrition using a data set from a randomized controlled intervention in pediatric asthma. Methods Participants included children, ages 4-12, diagnosed with asthma and their caregivers. Demographic variables and outcome measures of asthma morbidity were examined in 327 families to determine their association with attrition. Results Families who did not complete randomization and the intervention tended to have younger caregivers than did completers. Caregiver age emerged as the most consistent predictor of pre-inclusion and dropout attrition. There were no significant predictors of attrition due to intermittent missing data. Conclusion Younger caregivers may be at particular risk for attrition in pediatric asthma intervention studies and warrant special attention by investigators.

Objective. Intrauterine and neonatal growth failure of very low birth weight (VLBW; Design, Setting, Participants. A cohort of 103 male and 92 female VLBW infants who had a mean birth weight of 1189 g and mean gestational age of 29.8 weeks, were born from 1977 through 1979 and treated at Rainbow Babies and Children’s Hospital in Cleveland, Ohio, and were free of neurosensory impairment were followed prospectively from birth and compared with a population-based sample of 101 male and 107 female normal birth weight (NBW) controls selected at 8 years old. Maternal sociodemographic status and infant birth and neonatal data did not differ significantly between male and female VLBW subjects. However, male VLBW subjects had significantly higher rates of rehospitalization during infancy than female VLBW (39% vs 21%). At 20 years, their rates of chronic illness were similar (18% vs 24%).Main Outcome Measures. Weight and height z scores were computed at birth, 40 weeks, 8 and 20 months, and 8 and 20 years among the VLBW subjects, and at 8 and 20 years among the NBW controls. Body mass index (BMI) z scores were computed at 8 and 20 years. Among the VLBW subjects, gender-specific longitudinal growth measures were examined at birth, at the expected term date (40 weeks corrected age), and at 8 and 20 months, and 8 and 20 years of age. In addition, we compared the weight, height, and BMI of the VLBW and NBW controls at 8 and 20 years. Predictors of 20-year growth were examined via multivariate analyses.Results. Among the VLBW males, mean weight for age z scores at birth, 40 weeks, and 8 years were −0.7, −1.8, and −0.5; and height for age z scores were −1.2, −2.6, and −0.5, respectively. For VLBW females, mean weight for age z scores were −1.1, −2.0, and −0.2 and height for age z scores were −1.2, −2.4, and −0.2, respectively. At 8 years of age, VLBW males had a significantly lower mean weight, height, and BMI than NBW controls, whereas VLBW females differed significantly from their NBW controls in mean weight and BMI but not in height. Catch-up growth in weight, height, and BMI occurred between 8 and 20 years among VLBW females but not among VLBW males who remained significantly smaller than their controls at 20 years old. At 20 years mean weight of VLBW males was 69 kg versus 80 kg for controls (z score −0.4 vs +0.5); mean height was 174 cm versus 177 cm (z score −0.4 vs +0.03) and mean BMI was 23 versus 26, respectively. For VLBW females, mean weight was 65 kg versus 68 kg for controls (z score +0.3 vs +0.5), mean height was 162 versus 163 cm (z score −0.3 vs −0.1) and mean BMI was 25 versus 25, respectively. Rates of obesity (BMI >30) for VLBW males were 7% compared with 15% for controls and for VLBW females 15% compared with 18% for controls. Age of menarche was 12.4 years for VLBW females and 12.3 years for controls.Nineteen (18%) male and 20 (22%) female VLBW subjects were born small for gestational age (SGA; weight less than −2 standard deviation for gestational age). At 20 years, significantly more SGA than appropriate for gestational age VLBW males remained subnormal (less than −2 standard deviation) in weight (32% vs 6%) and height (21% vs 4%), whereas rates of subnormal growth did not differ significantly between SGA and appropriate for gestational age females (weight 5% vs 1%, height 0% vs 7%).Predictor variables included in the multivariate analyses of 20-year growth attainment were maternal education and height, race, birth weight z score (a measure of intrauterine growth failure), neonatal hospital stay (a measure of neonatal illness), and chronic illness at 20 years.Twenty-year weight was predicted by black race and chronic illness among females. Twenty-year height was predicted by maternal height and birth weight z score among both males and females and by duration of neonatal hospital stay among males only. In a separate model, when we examined the effect of being SGA at birth instead of the effect of birth weight z score, SGA birth was predictive of 20-year height among males but not among females.Conclusions. VLBW females catch up in growth by 20 years of age whereas VLBW males remain significantly shorter and lighter than controls. Since catch-up growth may be associated with metabolic and cardiovascular risk later in life, these findings may have implications for the future adult health of VLBW survivors.

Study objectives: To describe patterns of prescribing augmentation therapy, and types and rates of adverse events in the National Heart, Lung, and Blood Institute Registry for Individuals with Severe Deficiency of Alpha 1 -Antitrypsin. Design: Observational cohort study with follow-up visits every 6 to 12 months for up to 7 years. Measurements: The rate and dosing frequency with which Registry participants were prescribed to receive augmentation therapy by their managing physicians, and the type and frequency of adverse events, classified in two ways: severity of self-reported symptoms, and actions taken as a consequence of the symptom. Results: Over the course of Registry follow-up, 66% (n = 747) of the participants received augmentation therapy at some time. In keeping with recommendations made in the 1989 American Thoracic Society (ATS) statement, 75% of participants with airflow obstruction at first visit (defined as FEV 1 1 ≥ 80% predicted (14%) also received augmentation therapy. Among those with COPD for whom augmentation therapy was not prescribed, financial constraints were the reported cause in 30%. Observed patterns also varied from approved practice, in that dosing frequencies other than the US Food and Drug Administration-approved, once-weekly regimen were frequently prescribed. The overall rate of reported adverse events was 0.02 per patient-month, with 83% of participants reporting no events. This overall rate was composed of 16% considered mild events, 76% moderate events, and 9% severe events. Conclusions: We conclude that augmentation therapy was generally well tolerated and, consistent with ATS guidelines, physicians generally did not prescribe augmentation therapy for subjects with FEV 1 ≥ 80% predicted. However, the large percentage of subjects with FEV 1