Purpose Taste and smell abnormalities (TSA) are common in patients receiving chemotherapy and may lead to altered nutritional intake, treatment withdrawal, and impaired quality of life. Lipid peroxidation in the oral cavity is one cause of TSA. Lactoferrin (LFN), an iron-binding salivary protein, reduces production of lipid oxidation byproducts and has been shown to reduce perception of unpleasant flavors. To assess the feasibility of LFN as a treatment for TSA, we conducted pilot investigations among patients with cancer who self-reported TSA following onset of chemotherapy. The primary objective was to assess change in subjective taste and smell perception from baseline to completion of 30 days of LFN supplementation. Methods Patients were treated with 750 mg LFN daily for 30 days and followed for an additional 30 days without LFN. TSA was measured via the taste and smell questionnaire (TSQ) including taste (score 0–10), smell (score 0–6), and composite scores (0–16) (0 = no TSA) at baseline, day 30, and day 60. Results A total of 26 patients enrolled; 19 remained on study at day 30 and 17 at day 60. Baseline mean TSQ scores were 6.5 (taste), 3.1 (smell), and 9.6 (composite). By day 30, mean composite TSQ score improved by 1.7 ( p = 0.018); taste and smell improved by 0.6 ( p = 0.062) and 1.1 ( p = 0.042), respectively. From baseline to day 60, mean composite TSQ score improved by 3.8 ( p < 0.0001); taste and smell improved by 1.9 ( p = 0.001) and 1.8 ( p = 0.003). Conclusions Further evaluation of LFN is warranted to determine its value for improving self-reported TSA among patients receiving chemotherapy.

OBJECTIVE:Although brain radiation therapy (RT) impacts cognitive function, little is known about the subset of survivors with minimal cognitive deficits. This study compares the characteristics of patients receiving brain irradiation as part of cancer treatment with minimal cognitive deficits to those with poorer cognitive functioning.METHODS:Adults at least 6 months postbrain RT (N = 198) completed cognitive measures of attention, memory, and executive functions. Cognitive functioning was categorized into better- and poorer-performing groups, with better-performing survivors scoring no worse than 1.5 standard deviations below the published normative mean on all cognitive measures. Logistic regression was used to identify variables associated with better-performing group membership.RESULTS:Approximately 25% of the sample met the criteria for the better-performing group. In unadjusted analyses, RT type (whole brain irradiation and partial brain irradiation), sedating medications, and fatigue were independently associated with cognition. Sociodemographic and other clinical characteristics were not significant. In adjusted analyses, only fatigue remained significantly associated with group membership (OR = 1.05, 95% CI = 1.01-1.09, P = .009).CONCLUSIONS:There is a subgroup of survivors with minimal long-term cognitive deficits despite undergoing a full course of brain RT as part of cancer treatment. Lower fatigue had the strongest association with better cognitive performance. Interventions targeting cancer-related fatigue may help buffer the neurotoxic effects of brain RT.

OBJECTIVE HELP PD was a clinical trial of 301 adults with prediabetes. Participants were randomized to enhanced usual care (EUC) or to a lifestyle weight loss (LWL) intervention led by community health workers that consisted of a 6-month intensive phase (phase 1) and 18 months of maintenance (phase 2). At 24 months, participants were asked to enroll in phase 3 to assess whether continued group maintenance (GM) sessions would maintain improvements realized in phases 1 and 2 compared with self-directed maintenance (SM) or EUC. RESEARCH DESIGN AND METHODS In phase 3, LWL participants were randomly assigned to GM or SM. EUC participants remained in the EUC arm and, along with participants in SM, received monthly newsletters. All participants received semiannual dietitian sessions. Anthropometrics and biomarkers were assessed every 6 months. Mixed-effects models were used to assess changes in outcomes over time. RESULTS Eighty-two of the 151 intervention participants (54%) agreed to participate in phase 3; 41 were randomized to GM and 41 to SM. Of the 150 EUC participants, 107 (71%) continued. Ninety percent of clinic visits were completed. Over 48 months of additional follow-up, outcomes remained relatively stable in the EUC participants; the GM group was able to maintain body weight, BMI, and waist circumference; and these measures all increased significantly (P < 0.001) in the SM group. CONCLUSIONS Participants in the GM arm maintained weight loss achieved in phases 1 and 2, while those in the SM arm regained weight. Because group session attendance by the participants in the GM arm was low, it is unclear what intervention components led to successful weight maintenance.

Rationale: Survivorship from critical illness has improved; however, factors mediating the functional recovery of persons experiencing a critical illness remain incompletely understood. Objectives: To identify groups of acute respiratory failure (ARF) survivors with similar patterns of physical function recovery after discharge and to determine the characteristics associated with group membership in each physical function trajectory group. Methods: We performed a secondary analysis of a randomized controlled trial, using group-based trajectory modeling to identify distinct subgroups of patients with similar physical function recovery patterns after ARF. Chi-square tests and one-way analysis of variance were used to determine which variables were associated with trajectory membership. A multinomial logistic regression analysis was performed to identify variables jointly associated with trajectory group membership. Results: A total of 260 patients enrolled in a trial evaluating standardized rehabilitation therapy in patients with ARF and discharged alive (NCT00976833) were included in this analysis. Physical function was quantified using the Short Physical Performance Battery at hospital discharge and 2, 4, and 6 months after enrollment. Latent class analysis of the Short Physical Performance Battery scores identified four trajectory groups. These groups differ in both the degree and rate of physical function recovery. A multinomial logistic regression analysis was performed using covariates that have been previously identified in the literature as influencing recovery after critical illness. By multinomial logistic regression, age (P<0.001), female sex (P = 0.001), intensive care unit (ICU) length of stay (LOS) (P = 0.003), and continuous intravenous sedation days (P = 0.004) were the variables that jointly influenced trajectory group membership. Participants in the trajectory demonstrating most rapid and complete functional recovery consisted of younger females with fewer continuous sedation days and a shorter LOS. The participant trajectory that failed to functionally recover consisted of older patients with greater sedation time and the longest LOS. Conclusions: We identified distinct trajectories of physical function recovery after critical illness. Age, sex, continuous sedation time, and ICU length of stay impact the trajectory of functional recovery after critical illness. Further examination of these groups may assist in clinical trial design to tailor interventions to specific subgroups.

Objectives An increasing number of providers have begun to use a minimally invasive step-up approach as opposed to traditional surgical necrosectomy in the management of acute necrotizing pancreatitis. Studies have shown mixed results, thus we hypothesized that the step-up approach is safer and associated with decreased mortality and length of stay (LOS). Methods This is a retrospective cohort study of patients admitted from January 2010 to March 2015 who underwent interventions for walled-off pancreatic necrosis (WOPN). Primary outcomes included LOS after intervention and mortality, in-hospital and 90-day, with secondary outcomes of procedural complications. Results Sixty-nine patients developed WOPN requiring intervention during the study period. In-hospital mortality was 5.6% (n = 2) in the step-up cohort compared with 18.2% (n = 6) in the surgical cohort (relative risk, 3.27; 95% confidence interval, 0.71–15.09). Ninety-day mortality was 9.1% (n = 3) in the step-up cohort and 21.9% (n = 7) in the surgical cohort (relative risk, 2.41; 95% confidence interval, 0.68–8.50). Postintervention LOS was 8 days in the step-up cohort and 17 days in the surgical cohort (P = 0.62). Conclusions A step-up approach, as compared with primary surgical necrosectomy in the management of WOPN, results in clinically significant decreases in mortality and LOS.

Radiation-induced cognitive decline (RICD) is a late effect of brain radiation therapy (RT) occurring in a substantial number of brain tumor survivors. The aim of this study was to 1) report the incidence of Mild Cognitive Impairment (MCI) after RT with prospectively collected cognitive data and 2) evaluate patient characteristics and dosimetric parameters associated with development of MCI after RT. Patients ≥ 18 years old with primary and metastatic brain tumors scheduled to receive ≥ 30 Gy and with a life expectancy > 12 months were eligible. Patients participated in a cognitive battery measuring memory, attention, executive function, visuospatial ability, and dexterity prior to RT and 1, 3, 6, 12, and 24 months after RT (CCCWFU #98511). For this analysis, patients were designated as MCI or non-MCI at each time point using standardized criteria that included a subjective cognitive complaint on the FACT-Brain scale and a cognitive deficit ≥ 1.5 SD below norm on ≥ 1 cognitive test without any functional impairment in performing activities of daily living. Patients were categorized as never MCI, baseline MCI, transient MCI (became MCI but then recovered to non-MCI status), and persistent MCI (became and remained MCI). Baseline patient characteristics and cognitive data were compared between groups using t, Kruskal-Wallis, and exact tests. For dosimetric analysis, anatomic segmentation of regions of interest was performed by registering each baseline T1 MRI and RT dose file to a template brain atlas and manually edited for accuracy. Logistic regression was performed in a voxelwise fashion for the binary outcome of MCI category vs. dose. From 2012-2014, 33 patients were enrolled. Sixty percent were female and 40% male with a mean age of 49. Fifty-five percent had 12-16 years of education. Thirty-two patients had baseline and post-RT cognitive data and were eligible for analysis. At baseline pre-RT, 5 (16%) met criteria for MCI. 10 (32%) patients were categorized as never MCI, 4 (12.5%) as transient MCI, and 13 (40%) as persistent MCI. No demographic variables were statistically different between groups. Baseline measures of attention and executive function (Trail Making A & B scores) were statistically higher in the never MCI patients v. persistent MCI patients (p=0.0235 and 0.0054). Voxelwise logistic regression for MCI category v. dose showed a significant relationship (p<0.05) in the precentral gyrus, insular cortex, precuneus cortex, corpus callosum, posterior cingulate gyrus, subventricular zones, and hippocampi. In this cohort, patients who developed MCI after RT had statistically lower scores at baseline on measures of attention and executive function compared to those who maintained normal cognition. Multiple anatomic regions within the brain showed a dose-dependent relationship with the development of post-RT MCI.

Background: The HEART Pathway (history, ECG, age, risk factors, and initial troponin) is an accelerated diagnostic protocol designed to identify low-risk emergency department patients with chest pain for early discharge without stress testing or angiography. The objective of this study was to determine whether implementation of the HEART Pathway is safe (30-day death and myocardial infarction rate <1% in low-risk patients) and effective (reduces 30-day hospitalizations) in emergency department patients with possible acute coronary syndrome. Methods: A prospective pre-post study was conducted at 3 US sites among 8474 adult emergency department patients with possible acute coronary syndrome. Patients included were ≥21 years old, investigated for possible acute coronary syndrome, and had no evidence of ST-segment–elevation myocardial infarction on ECG. Accrual occurred for 12 months before and after HEART Pathway implementation from November 2013 to January 2016. The HEART Pathway accelerated diagnostic protocol was integrated into the electronic health record at each site as an interactive clinical decision support tool. After accelerated diagnostic protocol integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or non-low risk (appropriate for further in-hospital evaluation). The primary safety and effectiveness outcomes, death, and myocardial infarction (MI) and hospitalization rates at 30 days were determined from health records, insurance claims, and death index data. Results: Preimplementation and postimplementation cohorts included 3713 and 4761 patients, respectively. The HEART Pathway identified 30.7% as low risk; 0.4% of these patients experienced death or MI within 30 days. Hospitalization at 30 days was reduced by 6% in the postimplementation versus preimplementation cohort (55.6% versus 61.6%; adjusted odds ratio, 0.79; 95% CI, 0.71–0.87). During the index visit, more MIs were detected in the postimplementation cohort (6.6% versus 5.7%; adjusted odds ratio, 1.36; 95% CI, 1.12–1.65). Rates of death or MI during follow-up were similar (1.1% versus 1.3%; adjusted odds ratio, 0.88; 95% CI, 0.58–1.33). Conclusions: HEART Pathway implementation was associated with decreased hospitalizations, increased identification of index visit MIs, and a very low death and MI rate among low-risk patients. These findings support use of the HEART Pathway to identify low-risk patients who can be safely discharged without stress testing or angiography. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02056964.

What is the problem and what is known about it so far? Many guidelines recommend that adults older than 50 years be screened for colon cancer. Screening tests can help find cancer earlier and decrease the chance of dying from this disease. Unfortunately, as many as 1 in 3 people do not get screened for colon cancer. There are many reasons for this. Doctors may be too busy to discuss all of the options and answer patients' questions. Some patients may be too embarrassed to be screened or may be against it. Different communication methods and ways of ordering these tests are needed to help increase the number of patients who get screened. Why did the researchers do this particular study? To see if an iPad health app that educated patients about different options for colon cancer screening and allowed them to choose the test they wanted would increase the rate of testing. Who was studied? 450 patients (aged 50 to 74 years) who were due for a colon cancer screening test and had an appointment to see their primary care doctor. The study was done in 6 community-based clinics that were associated with a health system in North Carolina. How was the study done? The researchers identified primary care patients who were due for colon cancer screening. Patients who were interested in participating were asked to come to their appointment 45 to 60 minutes early in order to join the study. They were randomly assigned to the colon cancer education group or control group. The colon cancer education group viewed an iPad app that provided information about different screening options, and they were able to order either a colonoscopy or a test that looked for blood in the stool. This information was given to the doctor before the visit. Patients also could have the app send them text message or e-mail reminders to help complete the screening test after the visit. The control group watched a video about diet and exercise. They were not given information about colon cancer screening before the visit, and they did not have the option to order their own screening test. Both groups answered questions about what type of colon cancer screening test they preferred, whether they planned to get screened, and whether they had discussed screening with the doctor during the visit. The researchers looked at medical charts and other information to see if patients had a colon cancer screening test within 6 months after the doctor visit. What did the researchers find? Nearly all patients in the colon cancer education group could say which screening test they would like to have. Test ordering and discussions about screening happened more often in the education group than the control group. Researchers found that the colon cancer education group was twice as likely to have the test done than the control group (30% vs. 15%). What were the limitations of the study? The study enrolled only patients who spoke English. What are the implications of the study? An iPad health app that allows patients to order tests can help increase rates of colon cancer screening. However, rates were still low (around 30%).

Purpose: Women with breast cancer were randomized to receive coenzyme Q10 (CoQ10) plus Vitamin E or placebo in a clinical trial. The objective of this evaluation is to examine the association between participant self-reported adherence to the study supplements and changes in plasma biomarker levels. Patients and methods: Correlation coefficients quantified the association between changes in alpha-tocopherol and CoQ10 levels and the association between self-reported adherence and changes in biomarkers. Participants were categorized by self-reported adherence; Kruskal- Wallis tests compared changes in alpha-tocopherol and CoQ10 levels between self-reported adherence groups. Results: Women (N=155) provided baseline and post-treatment biomarkers; 147 completed at least one diary. While changes in alpha-tocopherol and CoQ10 levels were moderately correlated, correlations ranged from 0.40 to 0.48, association between self-reported adherence and plasma alpha-tocopherol or CoQ10 levels was weak; correlations ranged from 0.10 to 0.29 at weeks 8, 16, and 24. Some participants with high self-reported adherence actually had decreases in their biomarker levels. Conclusion: These findings support that self-reported adherence is likely to be overestimated. Biological and other measures of adherence that can better identify true adherence to study pills provided in clinical trials are greatly needed as they may assist in improving the interpretation of findings of future clinical trials.

Background. Head and neck cancer (HNC) patients are at an increased risk for developing second primary tumors (SPTs). Diets rich in fruits and vegetables (FVs) may lower HNC risk. FV concentrates may offer a potential alternative to increasing FV intake. Methods. We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether Juice PLUS+ (JP; a commercial product with multiple FV concentrates) has an effect on p27 and Ki-67, biomarkers associated with the risk of SPTs. During 2004-2008, we randomized 134 HNC patients to 12 weeks of JP (n = 72) or placebo (n = 62). Oral cavity mucosal biopsies and whole blood were obtained at baseline and after 12 weeks. All participants were given the opportunity to receive JP for 5 years following the end of the intervention period, and they were followed yearly for the development of SPTs. Results. After 12 weeks, patients on JP had significantly higher serum α-carotene (P = .009), β-carotene (P < .0001), and lutein (P = .003) but did not differ significantly in p27 (P = .23) or Ki-67 (P = .95). JP use following the initial 12-week trial was not significantly associated with SPT prevention. Conclusions. Despite increased serum micronutrient levels, our results do not suggest a clinical benefit of JP in HNC patients. Future studies should focus on longer intervention periods and/or modified supplement formulations with demonstrated chemopreventive properties.

AIMS:Large-scale clinical trials and translational studies have demonstrated that weight loss achieved through diet and physical activity reduced the development of diabetes in overweight individuals with prediabetes. These interventions also reduced the occurrence of metabolic syndrome and risk factors linked to other chronic conditions including obesity-driven cancers and cardiovascular disease. The Healthy Living Partnerships to Prevent Diabetes (HELP PD) was a clinical trial in which participants were randomized to receive a community-based lifestyle intervention translated from the Diabetes Prevention Program (DPP) or an enhanced usual care condition. The objective of this study is to compare the 12 and 24 month prevalence of metabolic syndrome in the two treatment arms of HELP PD. MATERIALS AND METHODS:The intervention involved a group-based, behavioral weight-loss program led by community health workers monitored by personnel from a local diabetes education program. The enhanced usual care condition included dietary counseling and written materials. RESULTS:HELP PD included 301 overweight or obese participants (BMI 25-39.9kg/m2) with elevated fasting glucose levels (95-125mg/dl). At 12 and 24 months of follow-up there were significant improvements in individual components of the metabolic syndrome: fasting blood glucose, waist circumference, HDL, triglycerides and blood pressure and the occurrence of the metabolic syndrome in the intervention group compared to the usual care group. CONCLUSIONS:This study demonstrates that a community diabetes prevention program in participants with prediabetes results in metabolic benefits and a reduction in the occurrence of the metabolic syndrome in the intervention group compared to the enhanced usual care group.

BACKGROUND:The health-related quality of life (HRQL) and fatigue of brain cancer survivors treated with donepezil or placebo for cognitive symptoms after radiation therapy were examined.METHODS:One hundred ninety-eight patients who completed >30 Gy fractionated whole or partial brain irradiation at least 6 months prior to enrollment were randomized to either placebo or donepezil (5 mg for 6 weeks followed by 10 mg for 18 weeks) in a phase 3 trial. A neurocognitive battery, the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue, was administered at baseline, 12 weeks, and 24 weeks.RESULTS:At 12 weeks, donepezil resulted in improvements in only emotional functioning (P = .04), with no significant effects at week 24. Associations by level of baseline cognitive symptoms (above or below the median score of the baseline FACT-Br "additional concerns/brain" subscale), indicated that participants with more baseline symptoms who received donepezil versus placebo, showed improvements in social (P = .02) and emotional well-being (P = .038), other concerns/brain (P = .003) and the FACT-Br total score (P = .004) at 12 weeks, but not 24 weeks. However, participants with fewer baseline symptoms randomized to donepezil versus placebo reported lower functional well-being at both 12 (P = .015) and 24 weeks (P = .009), and greater fatigue (P = .02) at 24 weeks.CONCLUSIONS:The positive impact of donepezil on HRQL was greater in survivors reporting more baseline cognitive symptoms. Donepezil had significantly worse effects on fatigue and functional well-being among participants with fewer baseline symptoms. Future interventions with donepezil should target participants with more baseline cognitive complaints to achieve greater therapeutic impact and lessen potential side effects of treatment.

IMPORTANCEPhysical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure.OBJECTIVETo compare standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure.DESIGN, SETTING, AND PARTICIPANTSSingle-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina. Adult patients (mean age, 58 years; women, 55%) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were randomized to SRT (n=150) or usual care (n=150) from October 2009 through May 2014 with 6-month follow-up.INTERVENTIONSPatients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. For the SRT group, the median (interquartile range [IQR]) days of delivery of therapy were 8.0 (5.0-14.0) for passive range of motion, 5.0 (3.0-8.0) for physical therapy, and 3.0 (1.0-5.0) for progressive resistance exercise. The median days of delivery of physical therapy for the usual care group was 1.0 (IQR, 0.0-8.0).MAIN OUTCOMES AND MEASURESBoth groups underwent assessor-blinded testing at ICU and hospital discharge and at 2, 4, and 6 months. The primary outcome was hospital length of stay (LOS). Secondary outcomes were ventilator days, ICU days, Short Physical Performance Battery (SPPB) score, 36-item Short-Form Health Surveys (SF-36) for physical and mental health and physical function scale score, Functional Performance Inventory (FPI) score, Mini-Mental State Examination (MMSE) score, and handgrip and handheld dynamometer strength.RESULTSAmong 300 randomized patients, the median hospital LOS was 10 days (IQR, 6 to 17) for the SRT group and 10 days (IQR, 7 to 16) for the usual care group (median difference, 0 [95% CI, -1.5 to 3], P = .41). There was no difference in duration of ventilation or ICU care. There was no effect at 6 months for handgrip (difference, 2.0 kg [95% CI, -1.3 to 5.4], P = .23) and handheld dynamometer strength (difference, 0.4 lb [95% CI, -2.9 to 3.7], P = .82), SF-36 physical health score (difference, 3.4 [95% CI, -0.02 to 7.0], P = .05), SF-36 mental health score (difference, 2.4 [95% CI, -1.2 to 6.0], P = .19), or MMSE score (difference, 0.6 [95% CI, -0.2 to 1.4], P = .17). There were higher scores at 6 months in the SRT group for the SPPB score (difference, 1.1 [95% CI, 0.04 to 2.1, P = .04), SF-36 physical function scale score (difference, 12.2 [95% CI, 3.8 to 20.7], P = .001), and the FPI score (difference, 0.2 [95% CI, 0.04 to 0.4], P = .02).CONCLUSIONS AND RELEVANCEAmong patients hospitalized with acute respiratory failure, SRT compared with usual care did not decrease hospital LOS.TRIAL REGISTRATIONclinicaltrials.gov Identifier: NCT00976833.

Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors.Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks.Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life.Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal.Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

A number of research studies have attempted to translate the behavioral lifestyle intervention delivered in the Diabetes Prevention Program (DPP). To compare the active interventions of two trials, Diabetes Prevention Program DPP and Healthy Living Partnerships to Prevent Diabetes (HELP PD), after 1 and 2 years of intervention. DPP included 3234 adults with prediabetes randomized to intensive lifestyle intervention, metformin, troglitazone, or placebo. The lifestyle intervention, professionally delivered to individuals in a clinical setting, focused on diet and increased physical activity. HELP PD, a community-based translation of DPP, included 301 adults randomized to receive intensive lifestyle intervention or enhanced usual care. Mean weight-losses at 1 year (6.9 kg in DPP, 6.4 kg in HELP PD) and 2 years (5.5 kg in DPP, 4.4 kg in HELP PD) were similar across studies. Reductions in glucose were also similar across studies at both time points (5.2 mg/dL in DPP and 4.1 mg/dL in HELP PD at 1 year; 1.8 mg/dL and 1.6 mg/dL at 2 years). HELP PD participants achieved larger reductions in triglycerides at 1 and 2 years (38.4 mg/dL and 34.9 mg/dL, respectively) than DPP participants (24.8 mg/dL and 22.4 mg/dL). High-density lipoprotein decreased in HELP PD participants at year 1 (−0.6 mg/dL) and increased in DPP (1.2 mg/dL) but there were no significant differences in year 2. HELP PD, a community model for diabetes prevention, was similar to DPP in reducing body weight and lowering blood glucose, both important risk factors that should be controlled to reduce risk for developing type 2 diabetes.

Objective: To assess the extent to which initial, intentional weight loss-associated improvements in glucose tolerance and insulin action are diminished with weight regain.Methods: 138 overweight and obese (BMI: 32.4 +/- 3.9 kg/m(2)), adults (59.0 +/- 9.7 years), with pre-diabetes were followed through a 6-month weight loss intervention and subsequent 18-month weight maintenance period, or usual care control condition. Longitudinal change in weight (baseline, 6, 24 months) was used to classify individuals into weight pattern categories (Loser/Maintainer (LM), n=50; Loser/Regainer (LR), n = 51; and Weight Stable (WS), n = 37). Fasting plasma glucose(FPG), insulin, and insulin resistance (HOMA-IR) were measured at baseline, 6, 12,18 and 24 months and model adjusted changes, by weight pattern category, were assessed.Results: LMs and LRs lost 8.3 +/- 4.7 kg (8.7 +/- 4.5%) and 9.6 +/- 4.7 kg (10.2 +/- 4.7%) during the first 6 months, respectively. LM continued to lose 1.1 +/- 3.4 kg over the next 18 months (9.9 +/- 6.5% reduction from baseline; p < 0.05), while LRs regained 6.5 +/- 3.7 kg (3.3 +/- 5.3% reduction from baseline; p < 0.05). Weight change was directly associated with change in all DM risk factors (all p < 0.01). Notably, despite an absolute reduction in body weight (from baseline to 24 months) achieved in the LR group, 24 month changes in FPG, insulin, and HOMA-IR did not differ between WS and LR groups. Conversely, LM saw sustained improvements in all measured DM risk factors.Conclusions: Significant weight loss followed by weight loss maintenance is associated with sustained improvements in FPG, insulin, and HOMA-IR; conversely, even partial weight regain is associated with regression of initial improvements in these risk factors towards baseline values. (C) 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors.

The authors investigated the feasibility of using computer-assisted instruction in patients of varying literacy levels by examining patients’ preferences for learning and their ability to use 2 computer-based educational programs. A total of 263 participants 50–74 years of age with varying health literacy levels interacted with 1 of 2 educational computer programs as part of a randomized trial of a colorectal cancer screening decision aid. A baseline and postprogram evaluation survey were completed. More than half (56%) of the participants had limited health literacy. Regardless of literacy level, doctors were the most commonly used source of medical information—used frequently by 85% of limited and adequate literacy patients. In multivariate logistic regression, only those with health insurance (OR = 2.35, p = .06) and computer use experience (OR = 0.39, p = .03) predicted the ability to complete the programs without assistance compared with those without health insurance or prior computer use, respectively. Although patients with limited health literacy had less computer experience, the majority completed the programs without any assistance and stated that they learned more than they would have from a brochure. Future research should investigate ways that computer-assisted instruction can be incorporated in medical care to enhance patient understanding.

BACKGROUND:Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation.METHODS:Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43.RESULTS:Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support detected by NG2 staining.CONCLUSIONS:Our data indicate that i) functional Cx43 is required for mural cell-induced endothelial quiescence, and ii) downregulation of Cx43 GJ by tumors frees endothelium to respond to angiogenic cues. These data define a novel and important role for maintained Cx43 function in regulation of vessel quiescence, and suggest its loss may contribute to pathological tumor angiogenesis.