Donor-derived regulatory dendritic cell infusion results in host cell cross-dressing and T cell subset changes in prospective living donor liver transplant recipients.

Regulatory dendritic cells (DCreg) promote transplant tolerance following their adoptive transfer in experimental animals. We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte-derived DCreg infused into prospective, living donor liver transplant patients, 7 days before transplantation. The DCreg expressed a tolerogenic gene transcriptional profile, high cell surface programed death ligand-1 (PD-L1):CD86 ratios, high IL-10/no IL-12 productivity and poor ability to stimulate allogeneic T cell proliferation. Target DCreg doses (range 2.5-10 × 106 cells/kg) were achieved in all but 1 of 15 recipients, with no infusion reactions. Following DCreg infusion, transiently elevated levels of donor HLA and immunoregulatory PD-L1, CD39, and CD73 were detected in circulating small extracellular vesicles. At the same time, flow and advanced image stream analysis revealed intact DCreg and "cross-dressing" of host DCs in blood and lymph nodes. PD-L1 co-localization with donor HLA was observed at higher levels than with recipient HLA. Between DCreg infusion and transplantation, T-bethi Eomeshi memory CD8+ T cells decreased, whereas regulatory (CD25hi CD127- Foxp3+ ): T-bethi Eomeshi CD8+ T cell ratios increased. Thus, donor-derived DCreg infusion may induce systemic changes in host antigen-presenting cells and T cells potentially conducive to modulated anti-donor immune reactivity at the time of transplant.

Ecological Momentary Assessment in Behavioral Research: Addressing Technological and Human Participant Challenges.

BACKGROUND: Ecological momentary assessment (EMA) assesses individuals' current experiences, behaviors, and moods as they occur in real time and in their natural environment. EMA studies, particularly those of longer duration, are complex and require an infrastructure to support the data flow and monitoring of EMA completion. OBJECTIVE: Our objective is to provide a practical guide to developing and implementing an EMA study, with a focus on the methods and logistics of conducting such a study. METHODS: The EMPOWER study was a 12-month study that used EMA to examine the triggers of lapses and relapse following intentional weight loss. We report on several studies that informed the implementation of the EMPOWER study: (1) a series of pilot studies, (2) the EMPOWER study's infrastructure, (3) training of study participants in use of smartphones and the EMA protocol and, (4) strategies used to enhance adherence to completing EMA surveys. RESULTS: The study enrolled 151 adults and had 87.4% (132/151) retention rate at 12 months. Our learning experiences in the development of the infrastructure to support EMA assessments for the 12-month study spanned several topic areas. Included were the optimal frequency of EMA prompts to maximize data collection without overburdening participants; the timing and scheduling of EMA prompts; technological lessons to support a longitudinal study, such as proper communication between the Android smartphone, the Web server, and the database server; and use of a phone that provided access to the system's functionality for EMA data collection to avoid loss of data and minimize the impact of loss of network connectivity. These were especially important in a 1-year study with participants who might travel. It also protected the data collection from any server-side failure. Regular monitoring of participants' response to EMA prompts was critical, so we built in incentives to enhance completion of EMA surveys. During the first 6 months of the 12-month study interval, adherence to completing EMA surveys was high, with 88.3% (66,978/75,888) completion of random assessments and around 90% (23,411/25,929 and 23,343/26,010) completion of time-contingent assessments, despite the duration of EMA data collection and challenges with implementation. CONCLUSIONS: This work informed us of the necessary preliminary steps to plan and prepare a longitudinal study using smartphone technology and the critical elements to ensure participant engagement in the potentially burdensome protocol, which spanned 12 months. While this was a technology-supported and -programmed study, it required close oversight to ensure all elements were functioning correctly, particularly once human participants became involved.

The Presence of Genetic Mutations at Key Loci Predicts Progression to Esophageal Adenocarcinoma in Barrett's Esophagus.

OBJECTIVES: Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS: In this case-control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created. RESULTS: There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95. CONCLUSIONS: ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.

The use of mHealth to deliver tailored messages reduces reported energy and fat intake.

BACKGROUND: Evidence supports the role of feedback in reinforcing motivation for behavior change. Feedback that provides reinforcement has the potential to increase dietary self-monitoring and enhance attainment of recommended dietary intake. OBJECTIVE: The aim of this study was to examine the impact of daily feedback (DFB) messages, delivered remotely, on changes in dietary intake. METHODS: This was a secondary analysis of the Self- Monitoring And Recording using Technology (SMART) Trial, a single-center, 24-month randomized clinical trial of behavioral treatment for weight loss. Participants included 210 obese adults (mean body mass index, 34.0 kg/m²) who were randomized to either a paper diary (PD), personal digital assistant (PDA), or PDA plus daily tailored feedback messages (PDA + FB). To determine the role of daily tailored feedback in dietary intake, we compared the self-monitoring with DFB group (DFB group; n = 70) with the self-monitoring without DFB group (no-DFB group, n = 140). All participants received a standard behavioral intervention for weight loss. Self-reported changes in dietary intake were compared between the DFB and no-DFB groups and were measured at baseline and at 6, 12, 18, and 24 months. Linear mixed modeling was used to examine percentage changes in dietary intake from baseline. RESULTS: Compared with the no-DFB group, the DFB group achieved a larger reduction in energy (-22.8% vs -14.0%; P = .02) and saturated fat (-11.3% vs -0.5%; P = .03) intake and a trend toward a greater decrease in total fat intake (-10.4% vs -4.7%; P = .09). There were significant improvements over time in carbohydrate intake and total fat intake for both groups (P values < .05). CONCLUSION: Daily tailored feedback messages designed to target energy and fat intake and delivered remotely in real time using mobile devices may play an important role in the reduction of energy and fat intake.

An exploratory investigation of links between changes in adipokines and quality of life in individuals undergoing weight loss interventions: possible implications for cancer research.

OBJECTIVE: Obesity has been linked to a wide spectrum of malignancies, with the strongest association demonstrated for endometrial cancer. Although the mechanisms are not yet entirely clear, a number of risk biomarkers have been proposed, including altered adipokines. Systemic levels of these adipose derived molecules have also been linked in prior research to self-reported quality of life (QOL). The study objective was to examine the hypothesis that adipokine changes during intentional weight loss may be associated with changes in QOL. METHODS: Fifty-two female participants were selected from two behavioral weight loss trials (SMART and PREFER) on the basis of achieving successful weight loss at 6month assessment, availability of blood samples and completion of standard SF-36 QOL questionnaires. Levels of adiponectin, leptin, and resistin were measured using xMAP immunoassays. Changes in QOL were examined using linear regression models in relation to pre- and post-intervention changes in biomarker levels and BMI. RESULTS: Significant changes between pre- and post-intervention were observed for leptin. Controlling for baseline BMI, leptin was the only biomarker that predicted change in QOL (Physical Component Scale, PCS). Linear regression models demonstrated that leptin continued to be a significant predictor of change in PCS when other possible predictor variables were included in the model. CONCLUSIONS: This study is among the first to demonstrate that changes in PCS may be regulated by levels of both metabolic variables and adipokines. An improved understanding of biological mechanisms associated with weight loss and the role of QOL may help guide preventive strategies for obesity-associated cancers.

The added value of using mutational profiling in addition to cytology in diagnosing aggressive pancreaticobiliary disease: review of clinical cases at a single center.

BACKGROUND: This study aimed to better understand the supporting role that mutational profiling (MP) of DNA from microdissected cytology slides and supernatant specimens may play in the diagnosis of malignancy in fine-needle aspirates (FNA) and biliary brushing specimens from patients with pancreaticobiliary masses. METHODS: Cytology results were examined in a total of 30 patients with associated surgical (10) or clinical (20) outcomes. MP of DNA from microdissected cytology slides and from discarded supernatant fluid was analyzed in 26 patients with atypical, negative or indeterminate cytology. RESULTS: Cytology correctly diagnosed aggressive disease in 4 patients. Cytological diagnoses for the remaining 26 were as follows: 16 negative (9 false negative), 9 atypical, 1 indeterminate. MP correctly determined aggressive disease in 1 false negative cytology case and confirmed a negative cytology diagnosis in 7 of 7 cases of non-aggressive disease. Of the 9 atypical cytology cases, MP correctly diagnosed 7 as positive and 1 as negative for aggressive disease. One specimen that was indeterminate by cytology was correctly diagnosed as non-aggressive by MP. When first line malignant (positive) cytology results were combined with positive second line MP results, 12/21 cases of aggressive disease were identified, compared to 4/21 cases identified by positive cytology alone. CONCLUSIONS: When first line cytology results were uncertain (atypical), questionable (negative), or not possible (non-diagnostic/indeterminate), MP provided additional information regarding the presence of aggressive disease. When used in conjunction with first line cytology, MP increased detection of aggressive disease without compromising specificity in patients that were difficult to diagnose by cytology alone.

Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.

Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals--Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)--and in a separate cohort of related individuals--Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 × 10(-05)) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 × 10(-05)) and rs9839267 near cholecystokinin (P = 3.05 × 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.

CYP2A6 genotype and smoking behavior in current smokers screened for lung cancer.

Functional CYP2A6 genetic variation partially determines nicotine metabolism. In 2005, we examined functional CYP2A6 variants associated with reduced metabolism (CYP2A6*2, CYP2A6*9, CYP2A6*4), smoking history, and change in smoking in 878 adult smokers undergoing lung cancer screening in an urban setting. At one year, 216 quit smoking for more than 30 days while 662 continued smoking. Compared to subjects who smoked 30 cigarettes per day at baseline, the odds of a reduced metabolism genotype was 52% higher in subjects smoking 20-29 cigarettes per day and 86% higher in subjects smoking less than 20 cigarettes per day (p-trend = 0.016). Reduced metabolism genotypes appeared unrelated to quitting. Though related to smoking dose, CYP2A6 may not influence cessation.

Factors associated with health-related quality of life among overweight or obese adults.

AIMS AND OBJECTIVES: To identify factors associated with health-related quality of life among overweight or obese adults. BACKGROUND: The obesity epidemic presents a global challenge. Obesity is associated with lower health-related quality of life; however, no study has comprehensively examined correlates of health-related quality of life in this population. DESIGN: A cross-sectional design. METHODS: The physical component score, mental component score and eight domain scores of the Short Form-36 v2 were used to assess health-related quality of life. We identified 23 possible correlates of health-related quality of life, including age, body mass index, health and weight histories, perceived stress, cholesterol-lowering diet self-efficacy, problem-solving, binge eating, dietary intake and physical activity. Correlational analyses were used to examine the bivariate associations between correlates and health-related quality of life variables. All possible subsets regression was used to develop predictive models of health-related quality of life. RESULTS: The sample (n = 210) was predominantly White (84·8%), female (78·1%) and middle-aged (average age = 46·80 years). Age, body mass index, education, having children at home, and being hypertensive were identified as the best predictors of physical component score, explaining about 9% of the variance. Age, marital status, having hyperlipidaemia, perceived stress, problem-solving, self-efficacy, binge eating and barriers to healthy eating predicted mental component score, explaining approximately 48% of the variance. Physical functioning and role physical domains of health-related quality of life had similar sets of predictors, with 15% and 13% of the variance explained, respectively, while similar predictors were identified for bodily pain (6%), general health (26%), vitality (40%), social functioning (32%), role emotional (42%) and mental health (46%) domains. CONCLUSIONS: Psychosocial factors were associated with the mental-related quality of life. Further exploration of factors related to physical-related quality of life is warranted in this population. RELEVANCE TO CLINICAL PRACTICE: When working with overweight/obese adults who are trying to lose weight, nurses need to consider socio-demographic and psychosocial factors in the development of a treatment plan that will improve health-related quality of life in this population.

Donor-derived regulatory dendritic cell infusion modulates effector CD8+ T cell and NK cell responses after liver transplantation.

Immune cell-based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are innate immune cells that down-regulate alloimmune responses in preclinical models. Here, we performed clinical monitoring and comprehensive assessment of peripheral and allograft tissue immune cell populations in DCreg-infused live-donor liver transplant (LDLT) recipients up to 12 months (M) after transplant. Thirteen patients were given a single infusion of donor-derived DCreg 1 week before transplant (STUDY) and were compared with 40 propensity-matched standard-of-care (SOC) patients. Donor-derived DCreg infusion was well tolerated in all STUDY patients. There were no differences in postoperative complications or biopsy-confirmed acute rejection compared with SOC patients up to 12M. DCreg administration was associated with lower frequencies of effector T-bet+Eomes+CD8+ T cells and CD16bright natural killer (NK) cells and an increase in putative tolerogenic CD141+CD163+ DCs compared with SOC at 12M. Antidonor proliferative capacity of interferon-γ+ (IFN-γ+) CD4+ and CD8+ T cells was lower compared with antithird party responses in STUDY participants, but not in SOC patients, at 12M. In addition, lower circulating concentrations of interleukin-12p40 (IL-12p40), IFN-γ, and CXCL10 were detected in STUDY participants compared with SOC patients at 12M. Analysis of 12M allograft biopsies revealed lower frequencies of graft-infiltrating CD8+ T cells, as well as attenuation of cytolytic TH1 effector genes and pathways among intragraft CD8+ T cells and NK cells, in DCreg-infused patients. These reductions may be conducive to reduced dependence on immunosuppressive drug therapy or immunosuppression withdrawal.

Health-related quality of life among participants in the SMART weight loss trial.

Obesity has been associated with a decreased health-related quality of life (HRQoL); however, the association between weight change and HRQoL is unclear. This secondary analysis of the SMART (Self Monitoring And Recording using Technology) trial, a clinical trial of behavioral weight loss treatment, provides evidence that quality of life improves with weight loss.

Longitudinal relationship between physical activity and cardiometabolic factors in overweight and obese adults.

Few studies have reported longitudinal relationships between physical activity (PA) and cardiometabolic risk factors over time using repeated assessments in overweight or obese adults. We conducted a longitudinal study in 127 participants (81% with body mass index > 30 kg/m(2)) who completed a 12-month behavioral intervention for weight loss between 2003 and 2005 in Pittsburgh, PA, USA. Using absolute change scores from baseline to each time point (i.e., 6 and 12 months) for all studied variables (Delta = time point - baseline), we performed mixed effects modeling to examine relationships between PA and cardiometabolic risk factors, after adjusting for body weight, energy intake and other covariates (i.e., age, gender, and ethnicity). PA was assessed as energy expenditure (kcal/week) using the Paffenbarger activity questionnaire. Over the 12-month period, energy expenditure increased (Delta1,370 kcal/week at 6 months vs. Delta886 kcal/week at 12 months); body weight decreased (Delta8.9 kg at 6 months vs. Delta8.4 kg at 12 months). The average increase in energy expenditure over 12 months was significantly and independently related to reductions in total cholesterol (F = 6.25, p = 0.013), low-density lipoprotein cholesterol (LDL-C) (F = 5.08, p = 0.025) and fasting blood glucose (F = 5.10, p = 0.025), but not to other risk factors (i.e., fasting insulin, high-density lipoprotein cholesterol, triglycerides, and waist circumference). In conclusion, among overweight and obese adults undergoing a weight loss intervention, increased energy expenditure over 12 months may improve total cholesterol and LDL-C, important coronary risk factors, and fasting blood glucose, a metabolic risk factor.

The impact of genetic variation in DRD2 and SLC6A3 on smoking cessation in a cohort of participants 1 year after enrollment in a lung cancer screening study.

Smoking cessation strategies continue to have disappointing results. By determining the interindividual genetic differences that influence smoking behaviors, we may be able to develop tailored strategies that increase the likelihood of successful cessation. This study attempts to determine genetic influences on the relationship between the dopamine pathway and smoking cessation by examining associations with a variable number tandem repeat variation in SLC6A3 and the DRD2 variants TaqIA (A2 vs. A1), TaqIB (B2 vs. B1), C957T (C vs. T), and -141C Ins/Del (C vs. Del). Baseline smokers in the Pittsburgh Lung Screening Study who provided information on smoking status 1 year later were evaluated. We frequency-matched those who were not abstinent at 1 year to those who were abstinent at 1 year by gender, decade of age, and time of enrollment (3-month intervals) in a 3:1 ratio (N = 881). Logistic regression was used to identify the effect of genotype on abstinence at 1 year. In a model containing the matching variables and other genotypes, DRD2 TaqIA was significantly associated with being abstinent at 1 year (P = 0.01). Compared to participants who were homozygous for the TaqIA major allele (A2A2), participants who carried at least one minor allele (A1) were less likely to quit (Odds Ratio: 0.47, 95% CI: 0.24-0.94). The other dopamine receptor genotypes and the SLC6A3 genotype were not associated with smoking status at 1 year. The association between DRD2 TaqIA and smoking cessation supports the hypothesis that genetic variation in the dopamine pathway influences smoking cessation.

A descriptive study of past experiences with weight-loss treatment.

BACKGROUND: Overweight and obesity affect more than 60% of the adult population in the United States. Most adults who are overweight have a history of previous weight-loss treatment. Exploring individuals' past experiences with weight-loss treatment may allow improvements to the current approach to treatment. OBJECTIVE: To examine individuals' prior experiences with weight-loss treatment, their treatment preferences, and what they found to be most and least satisfying. DESIGN: Cross-sectional descriptive study. SUBJECTS/SETTING: Individuals (N=155) who had registered for a weight-loss study wait list and met standard criteria for a weight-loss program (aged 18 to 55 years and body mass index between 25 and 42). METHODS: Questionnaire packets were mailed to participants. STATISTICAL ANALYSES PERFORMED: Descriptive analyses of the participants' past history with weight-loss treatment, treatment preference, self-efficacy, therapeutic efficacy, barriers to adherence to weight-loss treatment, barriers to healthy eating, and experiences associated with following a low-fat diet. RESULTS: One hundred ten participants (71%) returned completed questionnaire packets. The sample (82% white, 84% female, aged 42.6+/-8.5 years, and body mass index 33.5+/-5.3) was representative of those who seek weight-loss treatment in research settings. Participants were, on average, aged 21.1+/-8.9 years when they first tried a weight-loss program; 96.3% had tried to lose weight since that first time. The two most frequently tried programs were doing it on their own (93.5%) and commercial programs (70.8%). Barriers included having trouble controlling what I eat when hungry (71.3%), difficulty motivating myself to eat appropriately (66.2%), and using food as a reward (59.3%). Preferred weight-loss regimens were doing it on their own (30.6%) and a research program (22.4%). CONCLUSIONS: Participants were not seeking their preferred treatment. These data can be used to improve weight-loss programs by tailoring programs to meet the needs and preferences of participants.

Using instrumented paper diaries to document self-monitoring patterns in weight loss.

Self-monitoring of eating is associated with successful weight loss, but adherence is imperfect and deteriorates over time. Moreover, intentionally or not, many individuals have difficulty keeping faithful records. We used instrumented paper diaries (IPDs) to study self-monitoring in randomly chosen participants in the PREFER trial, a behavioral treatment for weight-loss study. The diaries they used to self-report eating were periodically replaced with IPDs at various times during an 18-month weight-loss program, consisting of three successive phases: intense treatment (n=35), less-intense treatment (n=13), and maintenance (n=16). We compared electronically documented self-monitoring data, showing when and how often IPDs were used, with self-reported data, then compared the electronically validated adherence and weight loss. Self-reported diary usage exceeded IPD-documented usage while the electronic data demonstrated a significant decline in self-monitoring over time. Diary recording often was not timely. Percentage weight lost correlated significantly with frequency of IPD use (p=.001) and the number of diary entries made within 15 min of opening the IPD (p=.002). This is the first study to document patterns of self-monitoring among participants in a weight-loss program, which demonstrated that individuals may falsify the times and frequency of self-monitoring. Furthermore, our results showed that adherence to self-monitoring and the timeliness of recording significantly correlate with improved weight loss.

Changes in self-efficacy and dietary adherence: the impact on weight loss in the PREFER study.

Findings from studies examining self-efficacy and its relationship to weight loss have been inconsistent. We examined self-efficacy specific to changing eating behaviors in the PREFER trial, an 18-month behavioral weight-loss study, to determine if self-efficacy and dietary adherence were associated with weight change, and what impact self-efficacy had on weight change after controlling for adherence. Measurements included the weight efficacy lifestyle (WEL) questionnaire, body weight, self-reported fat gram intake, kilocalorie intake, and adherence to kilocalorie and fat gram goals at baseline, 6, 12, and 18 months. The sample (N = 170) was 88.2% female and 70.0% Caucasian; the mean age was 44.1 years (SD = 8.8). Mean weight loss at 18 months was 4.64% (SD = 6.24) of baseline body weight and the mean increase in self-efficacy was 11.70% (SD = 38.61). Self-efficacy improved significantly over time (p = 0.04) and was associated with weight loss (p = 0.02). Adherence to the fat gram goal was associated with weight loss (p = 0.0003), and self-efficacy remained associated with weight loss after controlling for fat gram adherence (p = 0.0001). Consistent with self-efficacy theory, improvement in self-efficacy over time supported greater weight loss. Adherence to the fat gram goal also influenced weight loss.

Effects of a vegetarian diet and treatment preference on biochemical and dietary variables in overweight and obese adults: a randomized clinical trial.

BACKGROUND: A vegetarian diet may lead to numerous health benefits, including weight loss. OBJECTIVE: We examined the joint effects of personal preference of dietary treatment and a calorie-restricted, low-fat lactoovovegetarian diet (LOV-D) compared with a standard calorie-restricted, low-fat omnivorous diet (STD-D) on changes in weight, total cholesterol, ratio of LDL to HDL cholesterol (LDL:HDL cholesterol), triacylglycerols, insulin resistance, and macronutrient intake during an 18-mo study. DESIGN: This was a randomized clinical trial of 176 overweight and obese adults who were recruited and randomly assigned first to 1 of 2 preference conditions (yes or no). If assigned to Preference-No, they were randomly assigned to 1 of the 2 diet conditions (STD-D or LOV-D). If assigned to Preference-Yes, they were assigned to the diet they indicated as preferred at screening. The 12-mo intervention was followed by a 6-mo maintenance phase. RESULTS: Participants were mainly women (86.9%) and white (70.5%); 75% completed the 18-mo study. A significant interaction between preference and dietary treatment was not observed for any of the outcome variables. However, participants in the Preference-No groups significantly decreased their triacylglycerols (P = 0.04). The only effect observed for diet was a borderline significant decrease in LDL:HDL cholesterol for the LOV-D group (P = 0.06). Within the LOV-D groups, those who were 100% adherent to the LOV-D had significant and marginally significant reductions in monounsaturated fat (P = 0.02) and total fat (P = 0.05) intakes at 18 mo. CONCLUSIONS: Our findings suggest that neither prescribing a vegetarian diet nor allowing persons to choose their preferred diet had a significant effect on outcome measures. However, all participants had a significant reduction in total energy and fat intakes and an increase in energy expenditure, which was reflected in reduced body weight. This clinical trial was registered at www.clinicaltrials.gov as NCT00330629.

African Americans in Standard Behavioral Treatment for Obesity, 2001-2015: What Have We Learned?

African Americans (AAs) bear a disproportionate burden of the obesity epidemic, yet have historically been underrepresented in weight loss research. We conducted a narrative review of large ( N > 75) randomized prospective clinical trials of standard behavioral treatment for weight loss that reported results in the past 15 years (2001-2015) to (a) determine the rates of inclusion and reported results for AAs and (b) further identify strategies that may result in improved outcomes. Of the 23 trials reviewed, 69.6% of the studies met or exceeded population estimates for AAs in the United States. However, only 10 reported outcomes and/or considered race in the analytic approach. At 6 months, AA participants consistently lost less weight than White participants. The use of culturally tailored intervention materials and monthly personal telephone calls were reported as factors that may have enhanced treatment response. Future behavioral weight loss trials should also increase reporting of outcomes by race.

PREFER study: a randomized clinical trial testing treatment preference and two dietary options in behavioral weight management--rationale, design and baseline characteristics.

BACKGROUND: Obesity, a disorder associated with a myriad of comorbidities, is increasing at an alarming rate around the world. Given that pharmacotherapy has limited available options and that bariatric surgery is reserved for those who are morbidly obese or who have significant comorbidities, the most common approach to the treatment of obesity is standard behavioral treatment. This approach includes behavior modification related to eating and activity habits. The purpose of this paper is to describe the rationale, design, methods and baseline sample characteristics of a randomized controlled trial of a behavioral intervention in weight loss management, referred to as the PREFER study. METHODS: The PREFER study, using a four-group design, includes: (1) a randomization scheme that permits participants to indicate a preferred dietary treatment approach, and (2) two dietary options, one of which is a lacto-ovo-vegetarian diet that has demonstrated potential for long-term adherence. The intervention (32 treatment sessions) is delivered over 12 months and is followed by a 6-month maintenance phase; final assessment occurs at 18 months. RESULTS: We screened 932 individuals and randomized 197 to the study: Treatment Preference-Yes (n=84) and Treatment Preference-No (n=98). To maintain a balance across the four treatment groups, 15 subjects who preferred the standard diet had to be discarded from the Treatment Preference-Yes group. Retention at 18 months for the first of three cohorts was 82%. CONCLUSIONS: The PREFER study is a single center study and is the first randomized controlled trial examining a lacto-ovo-vegetarian diet as part of weight loss treatment. The ethnically diverse sample includes males and females with a body mass index of 27 to 43. The study has the potential to make a contribution to understanding the role of treatment preference and the potential of a lacto-ovo-vegetarian diet for long-term weight loss.

Endoscopic ablation is a cost-effective cancer preventative therapy in patients with Barrett's esophagus who have elevated genomic instability.

BACKGROUND: The surveillance of patients with nondysplastic Barrett's esophagus (NDBE) has a high cost and is of limited effectiveness in preventing esophageal adenocarcinoma (EAC). Ablation for NDBE remains expensive and controversial. Biomarkers of genomic instability have shown promise in identifying patients with NDBE at high risk for progression to EAC. Here, we evaluate the cost-effectiveness of using such biomarkers to stratify patients with NDBE by risk for EAC and, subsequently, the cost-effectiveness of ablative therapy. METHODS: A Markov decision tree was used to evaluate four strategies in a hypothetical cohort of 50-year old patients with NDBE over their lifetime: strategy I, natural history without surveillance; strategy II, surveillance per current guidelines; strategy III, ablation for all patients; strategy IV, risk stratification with use of a biomarker panel to assess genomic instability (i. e., mutational load [ML]). Patients with no ML underwent minimal surveillance, patients with low ML underwent standard surveillance, and patients with high ML underwent ablation. The incremental cost-effectiveness ratio (ICER) and incremental net health benefit (INHB) were assessed. RESULTS: Strategy IV provided the best values for quality-adjusted life years (QALYs), ICER, and INHB in comparison with strategies II and III. RESULTS were robust in sensitivity analysis. In a Monte Carlo analysis, the relative risk for the development of cancer in the patients managed with strategy IV was decreased. Critical determinants of strategy IV cost-effectiveness were the complete response rate, cost of ablation, and surveillance interval in patients with no ML. CONCLUSION: The use of ML to stratify patients with NDBE by risk was the most cost-effective strategy for preventive EAC treatment. Targeting ablation toward patients with high ML presents an opportunity for a paradigm shift in the management of NDBE.