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.

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.

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.

A prospective and retrospective analysis of smoking behavior changes in ever smokers with high risk for lung cancer from New Mexico and Pennsylvania.

Cigarette smoking is the leading preventable cause of death worldwide. The aim of this study is to conduct a prospective and retrospective analysis of smoking behavior changes in the Lovelace Smokers Cohort (LSC) and the Pittsburgh Lung Screening Study cohort (PLuSS). Area under the curve (AUC) for risk models predicting relapse based on demographic, smoking, and relevant clinical variables was 0.93 and 0.79 in LSC and PLuSS, respectively. The models for making a quit attempt had limited prediction ability in both cohorts (AUC≤0.62). We identified an ethnic disparity in adverse smoking behavior change that Hispanic smokers were less likely to make a quit attempt and were more likely to relapse after a quit attempt compared to non-Hispanic Whites. SNPs at 15q25 and 11p14 loci were associated with risk for smoking relapse in the LSC. Rs6495308 at 15q25 has a large difference in minor allele frequency between non-Hispanic Whites and Hispanics (0.46 versus 0.23, P<0.0001) and was associated with risk for ever relapse at same magnitude between the two ethnic groups (OR=1.36, 95% CI=1.10 to 1.67 versus 1.59, 95% CI=1.00 to 2.53, P=0.81). In summary, the risk prediction model established in LSC and PLuSS provided an excellent to outstanding distinguishing for abstainers who will or will not relapse. The ethnic disparity in adverse smoking behavior between Hispanics and non-Hispanic Whites may be at least partially explained by the sequence variants at 15q25 locus that contains multiple nicotine acetylcholine receptors.

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.

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.

Incentives to create and sustain healthy behaviors: technology solutions and research needs.

Health-related technology, its relevance, and its availability are rapidly evolving. Technology offers great potential to minimize and/or mitigate barriers associated with achieving optimal health, performance, and readiness. In support of the U.S. Army Surgeon General's vision for a "System for Health" and its Performance Triad initiative, the U.S. Army Telemedicine and Advanced Technology Research Center hosted a workshop in April 2013 titled "Incentives to Create and Sustain Change for Health." Members of government and academia participated to identify and define the opportunities, gain clarity in leading practices and research gaps, and articulate the characteristics of future technology solutions to create and sustain real change in the health of individuals, the Army, and the nation. The key factors discussed included (1) public health messaging, (2) changing health habits and the environmental influence on health, (3) goal setting and tracking, (4) the role of incentives in behavior change intervention, and (5) the role of peer and social networks in change. This report summarizes the recommendations on how technology solutions could be employed to leverage evidence-based best practices and identifies gaps in research where further investigation is needed.

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.

Key enablers to facilitate healthy behavior change: workshop summary.

The increases in preventable chronic diseases and the rising costs of health care are unsustainable. The US Army Surgeon General's vision to transition from a health care system to a system of health requires the identification of key health enablers to facilitate the adoption of healthy behaviors. In support of this vision, the US Army Telemedicine and Advanced Technology Research Center hosted a workshop in April 2013 titled "Incentives to Create and Sustain Change for Health." Members of government and academia participated to identify key health enablers that could ultimately be leveraged by technology. The key health enablers discussed included (1) public health messaging, (2) changing health habits and the environmental influence on health, (3) goal setting and tracking, (4) the role of incentives in behavior-change intervention, and (5) the role of peer and social networks on change. This report summarizes leading evidence and the group consensus on evidence-based practices with respect to the key enablers in creating healthy behavior change.

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.

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.

Longitudinal effects of weight loss and regain on cytokine concentration of obese adults.

OBJECTIVE: To describe patterns of weight loss and regain and their effect on the pro-inflammatory cytokines IL-6 and TNF-α, and anti-inflammatory cytokines adiponectin and IL-10 during a 24-month weight loss trial. MATERIALS/METHODS: Participants were obese adults (N=66) who lost and regained ≥ 10lb during a 24-month clinical trial of behavioral weight loss treatment. Measurements of cytokines and weight were conducted at baseline, 6, 12, 18, and 24 months. Linear mixed modeling was used to determine percent change in weight and cytokines from baseline. RESULTS: The sample was predominantly female (80.3%) and White (86.4%), with a mean age of 48.4 ± 7.3 years and mean BMI of 34.5 ± 4.4 kg/m(2). At baseline, men had higher waist circumference, body weight, and energy intake, and lower percent body fat and adiponectin. The largest decrease in weight was observed at 6 months with a mean 11% decrease (p<.0001).A significant gender-by-weight change interaction on percent change in adiponectin was observed [b(se)=0.9 (0.2), p=.0003], with men having a larger increase in adiponectin with weight loss compared to women. There was a significant effect of weight gain over time with increases in IL-6 [b(se)=0.9 (0.3), p=.001]. CONCLUSIONS: Overall, weight loss was significantly associated with improvements in adiponectin and IL-6. Those improvements remained at 24 months, following weight regain. The association between weight change and adiponectin was different between genders. Implementing strategies that support sustained weight loss can help prevent a state of chronic systemic inflammation and its associated adverse effects.

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.

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.

Cue-induced cigarette and food craving: a common effect?

Cue-induced cravings may hinder behavior change efforts such as smoking cessation. Correlation of cue-induced cravings across multiple stimuli would provide evidence for a cue-reactive phenotype that may have implications for behavior change therapies. The purpose of this study was to examine relationships between cue-induced cravings for cigarettes and cue-induced cravings for a highly preferred food (chocolate) in a sample of smokers not subjected to lengthy deprivation for either of these two appetitive outcomes. Adult smokers (N=164) were assessed for chocolate cravings before and after exposure to chocolate cues and cigarette cravings before and after exposure to smoking cues. Consistent with previous reports, cigarette cravings increased significantly post-cue exposure and chocolate cravings increased significantly post-cue exposure (p's<.0001). Consistent with study hypotheses, the magnitude of the increase in chocolate cravings after cue-exposure was significantly related to the increase in post-cue cigarette cravings (r=0.38; p<.0001), and was significantly related to scores on a retrospective, self-report, measure of cue-induced food cravings in daily life. These findings are consistent with the idea of a general "cue-reactive" phenotype that varies across individuals, a conceptualization of risk that may point the way toward improved interventions for a variety of hedonically mediated behaviors with negative health outcomes.

Using mHealth technology to enhance self-monitoring for weight loss: a randomized trial.

BACKGROUND: Self-monitoring for weight loss has traditionally been performed with paper diaries. Technologic advances could reduce the burden of self-monitoring and provide feedback to enhance adherence. PURPOSE: To determine if self-monitoring diet using a PDA only or the PDA with daily tailored feedback (PDA+feedback [FB]), was superior to using a paper diary on weight loss and maintenance. DESIGN: The Self-Monitoring and Recording Using Technology (SMART) Trial was a 24-month randomized clinical trial; participants were randomly assigned to one of three self-monitoring groups. SETTING/PARTICIPANTS: From 2006 to 2008, a total of 210 overweight/obese adults (84.8% female, 78.1% white) were recruited from the community. Data were analyzed in 2011. INTERVENTION: Participants received standard behavioral treatment for weight loss that included dietary and physical activity goals, encouraged the use of self-monitoring, and was delivered in group sessions. MAIN OUTCOME MEASURES: Percentage weight change at 24 months, adherence to self-monitoring over time. RESULTS: Study retention was 85.6%. The mean percentage weight loss at 24 months was not different among groups (paper diary: -1.94%, 95% CI = -3.88, 0.01; PDA: -1.38%, 95% CI= -3.38, 0.62; PDA+FB: -2.32%, 95% CI= -4.29, -0.35); only the PDA+FB group (p=0.02) demonstrated a significant loss. For adherence to self-monitoring, there was a time-by-treatment group interaction between the combined PDA groups and the paper diary group (p=0.03) but no difference between PDA and PDA+FB groups (p=0.49). Across all groups, weight loss was greater for those who were adherent ≥60% versus <30% of the time (p<0.001). CONCLUSIONS: PDA+FB use resulted in a small weight loss at 24 months; PDA use resulted in greater adherence to dietary self-monitoring over time. However, for sustained weight loss, adherence to self-monitoring is more important than the method used to self-monitor. A daily feedback message delivered remotely enhanced adherence and improved weight loss, which suggests that technology can play a role in improving weight loss. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov NCT00277771.

Gene-centric analysis of serum cotinine levels in African and European American populations.

To date, most genetic association studies of tobacco use have been conducted in European American subjects using the phenotype of smoking quantity (cigarettes per day). However, smoking quantity is a very imprecise measure of exposure to tobacco smoke constituents. Analyses of alternate phenotypes and populations may improve our understanding of tobacco addiction genetics. Cotinine is the major metabolite of nicotine, and measuring serum cotinine levels in smokers provides a more objective measure of nicotine dose than smoking quantity. Previous genetic association studies of serum cotinine have focused on individual genes. We conducted a genetic association study of the biomarker in African American (N=365) and European American (N=315) subjects from the Coronary Artery Risk Development in Young Adults study using a chip containing densely-spaced tag SNPs in ∼2100 genes. We found that rs11187065, located in the non-coding region (intron 1) of insulin-degrading enzyme (IDE), was the most strongly associated SNP (p=8.91 × 10(-6)) in the African American cohort, whereas rs11763963, located on chromosome 7 outside of a gene transcript, was the most strongly associated SNP in European Americans (p=1.53 × 10(-6)). We then evaluated how the top variant association in each population performed in the other group. We found that the association of rs11187065 in IDE was also associated with the phenotype in European Americans (p=0.044). Our top SNP association in European Americans, rs11763963 was non-polymorphic in our African American sample. It has been previously shown that psychostimulant self-administration is reduced in animals with lower insulin because of interference with dopamine transmission in the brain reward centers. Our finding provides a platform for further investigation of this, or additional mechanisms, involving the relationship between insulin and self-administered nicotine dose.

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.