Change in body image flexibility and correspondence with outcomes in a digital early intervention for eating disorders based on acceptance and commitment therapy.

Body image flexibility (BIF) has been suggested as a transdiagnostic process of change in eating disorder (ED) interventions, but data remain sparse. The current study examined the relationship between BIF and treatment effects in a randomized controlled trial comparing a digital ACT-based intervention to a waitlist control for early ED intervention. Women and girls with elevated Weight Concern Scale (WCS) scores were randomized to either the ACT intervention or a waitlist control. Linear regression models were used to examine the impact of treatment on WCS scores controlling for age and body-mass index and BIF was examined as a mediator of change. Change in BIF was also examined as a predictor of Eating Disorder Examination-Questionnaire (EDE-Q) global scores at 1-month in the ACT condition. ACT participants had greater reductions in WCS scores, an effect partially mediated by BIF and concentrated almost entirely in the ACT condition. Increased BIF from baseline to end-of-treatment also predicted lower EDE-Q scores at 1-month post-intervention. The current study suggests additional research exploring BIF as a process of change in EDs is warranted and could expand understanding of how treatment works or treatment options. Additional studies with more frequent, complete and concordant assessments between groups are needed.

Seasonality of Pediatric Mental Health Emergency Department Visits, School, and COVID-19.

OBJECTIVES: The aim of this study was to explore how the academic calendar, and by extension school-year stressors, contributes to the seasonality of pediatric mental health emergency department (ED) visits. METHODS: The authors reviewed all pediatric mental health ED visits at a large urban medical center from 2014 to 2019. Patients who were younger than 18 years at time of presentation, were Durham residents, and had a primary payer of Medicaid were included in the sample population, and the dates of ED visits of the sample population were compared against dates of academic semesters and summer/winter breaks of a relevant school calendar. Of patients with multiple ED visits, only the first ED presentation was included, and descriptive statistics and a rate ratio were used to describe the study group and identify the rate of ED visits during semesters compared with breaks. RESULTS: Among the sample population from 2014 to 2019, there were 1004 first pediatric mental health ED visits. Of these ED visits, the average number of visits per week during summer/winter breaks was 2.2, and the average number of visits per week during academic semester dates was 3.4. The rate of ED visits was significantly greater during academic semesters compared with breaks (Rate Ratio, 1.6; 95% confidence interval, 1.4-2.0; P < 0.001). CONCLUSIONS: Children may be at greater risk of behavioral health crises or having increased mental needs when school is in session. As many children's mental health has worsened during the COVID-19 (coronavirus disease 2019) pandemic, these findings highlight the need for increased mental health services in the school setting as children return to in-person learning. In addition, it may benefit health systems to plan behavioral health staffing around academic calendars.

Exercise Prescription Practices to Improve Mental Health.

OBJECTIVE: There is growing evidence that higher levels of physical activity are associated with better mental health. Furthermore, interventional studies have shown that exercise may improve symptoms in a number of psychiatric conditions. Despite this evidence, relatively little information is available about how these findings have been translated into clinical practice. The goal of this study was to characterize the exercise prescribing practices of health care providers from different subspecialties and evaluate factors that may influence their prescribing practices. METHODS: We conducted a cross-sectional survey among faculty and staff from a large academic tertiary care medical center in the southeastern United States. Participants were invited to complete the survey via email or departmental newsletters. Descriptive statistics were used to characterize the sample and ordered logistic regression was used to analyze practices about exercise as a therapy for psychiatric illness. RESULTS: A total of 185 respondents completed the survey. More than half of the providers (58%) reported that they regularly recommend exercise as part of the treatment for patients with psychiatric conditions; however, few providers offered specific exercise instructions (24%) or followed national guidelines (30%). Depression (84.9%) and anxiety (69.2%) were the most common indications for exercise prescription, while insufficient knowledge or training was the most common barrier to prescribing exercise. We also found significant differences in prescription practices depending on the providers' formal clinical degree and their reported personal exercise habits. CONCLUSIONS: Exercise is recognized by most clinicians as a therapeutic option for psychiatric conditions. Despite this recognition, only a small proportion provide recommendations consistent with national guidelines or empirical research.

Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men). METHODS: CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015). RESULTS: Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences. CONCLUSION: Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.

An open trial of app-assisted acceptance and commitment therapy (iACT) for eating disorders in type 1 diabetes.

BACKGROUND: Eating disorders (EDs) among individuals with type 1 diabetes (T1D) increase the risk of early and severe diabetes-related medical complications and premature death. Conventional eating disorder (ED) treatments have been largely ineffective for T1D patients, indicating the need to tailor treatments to this patient population and the unique conditions under which ED symptoms emerge (in the context of a chronic illness with unrelenting demands to control blood glucose, diet and exercise). The current study was a pilot open trial of iACT, a novel intervention for EDs in T1D grounded in Acceptance and Commitment Therapy (ACT). iACT was based on the premise that ED symptoms emerge as individuals attempt to cope with T1D and related emotional distress. iACT taught acceptance and mindfulness as an alternative to maladaptive avoidance and control, and leveraged personal values to increase willingness to engage in T1D management, even when it was upsetting (e.g., after overeating). A tailored mobile application ("app") was used in between sessions to facilitate the application of ACT skills in the moment that individuals are making decisions about their diabetes management. METHODS: Adults with T1D who met criteria for an ED completed 12 sessions of iACT (with three optional tapering sessions). In addition to examining whether treatment was acceptable and feasible (the primary aim of the study), the study also examined whether iACT was associated with increased psychological flexibility (i.e., the ability to have distressing thoughts/feelings about diabetes while pursuing personally meaningful values), and improvements in ED symptoms, diabetes management and diabetes distress. RESULTS: Treatment was acceptable to T1D patients with EDs and feasible to implement. Participants reported increased psychological flexibility with diabetes-related thoughts/feelings, and less obstruction and greater progress in pursuing personal values. There were large effects for change in ED symptoms, diabetes self-management and diabetes distress from baseline to end-of-treatment (Cohen's d = .90-1.79). Hemoglobin A1c also improved, but the p-value did not reach statistical significance, p = .08. CONCLUSIONS: Findings provide preliminary evidence for iACT to improve outcomes for T1D patients with EDs and support further evaluation of this approach in a controlled trial. TRIAL REGISTRATION: NCT02980627 . Registered 8 July 2016.

"Pain is Subjective": A Mixed-Methods Study of Provider Attitudes and Practices Regarding Pain Management in Sickle Cell Disease Across Three Countries.

CONTEXT: Sickle cell disease (SCD), an autosomal recessive blood disorder, affects millions of people worldwide. Approximately 80% of all cases are located in Africa. OBJECTIVES: This cross-national, interdisciplinary, collaborative study investigated provider attitudes about, and practices for, managing (assessing and treating) SCD pain. METHODS: We conducted 111 quantitative surveys and 52 semistructured interviews with health-care providers caring for adults and/or children with SCD in Cameroon, Jamaica, and the U.S. RESULTS: Applying Haywood's scale for assessing SCD provider attitudes, the Jamaica site scored lower on "Negative Attitudes" than the Cameroonian and U.S. sites (P = 0.03 and <0.001, respectively). Providers at the U.S. site scored lower on "Positive Attitudes" than other sites (P < 0.001). "Red Flag" scores at the Cameroon sites were lower than at other sites (P < 0.001). Qualitative results across all three sites describe the current practices for SCD pain management, as well as the challenges surrounding management for health providers, including pain subjectivity, patient-provider and parent-provider relationships, resource availability, perceptions of drug-seeking behavior, and adherence. Providers also spontaneously offered solutions to reported challenges. CONCLUSION: Overall, findings reveal that SCD provider attitudes toward their patients differed across sites, yet at all three sites, treating SCD pain is multidimensional.

Sickle cell disease is a global prototype for integrative research and healthcare.

Differences in health outcomes and treatment responses within and between global populations have been well documented. There is growing recognition of the need to move beyond simple inventories and descriptions of these differences and our linear explanations for them, and gain a better understanding of the multifaceted systems and networks underlying them in order to develop more precise and effective remedies. Typical targets for such integrative research have been common multifactorial diseases. We propose sickle cell disease, one of the most common monogenic diseases, as an ideal candidate for elucidating the complexity of the influences of endogenous and exogenous factors on disease pathophysiology, phenotypic diversity, and variations in responses to treatments at both the individual and population levels. We provide data-informed representations of diverse contributors to sickle cell disease complications that could guide innovative efforts to advance scientific knowledge, clinical practice, and policy formulation related to the disease; help improve outcomes for people worldwide with sickle cell disease; and inform approaches to studying and addressing other diseases.

The role of comorbid anxiety in exercise and depression trials: Secondary analysis of the SMILE-II randomized clinical trial.

OBJECTIVES: To explore the anxiolytic effects of a 4-month randomized, placebo-controlled trial of exercise and antidepressant medication in patients with major depressive disorder (MDD), and to examine the potential modifying effects of anxiety in treating depressive symptoms. MATERIALS AND METHODS: In this secondary analysis of the SMILE-II trial, 148 sedentary adults with MDD were randomized to: (a) supervised exercise, (b) home-based exercise, (c) sertraline, or (d) placebo control. Symptoms of state anxiety measured by the Spielberger Anxiety Inventory were examined before and after 4 months of treatment. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory-II (BDI-II). Analyses were carried out using general linear models. RESULTS: Compared to placebo controls, the exercise and sertraline groups had lower state anxiety scores (standardized difference = 0.3 [95% CI = -0.6, -0.04]; p = 0.02) after treatment. Higher pretreatment state anxiety was associated with poorer depression outcomes in the active treatments compared to placebo controls for both the HAMD (p = .004) and BDI-II (p = .02). CONCLUSION: Aerobic exercise as well as sertraline reduced symptoms of state anxiety in patients with MDD. Higher levels of pretreatment anxiety attenuated the effects of the interventions on depressive symptoms, however, especially among exercisers. Patients with MDD with higher comorbid state anxiety appear to be less likely to benefit from exercise interventions in reducing depression and thus may require supplemental treatment with special attention to anxiety.

Evaluating the precision of EBF1 SNP x stress interaction association: sex, race, and age differences in a big harmonized data set of 28,026 participants.

In prior work, we identified a novel gene-by-stress association of EBF1's common variation (SNP rs4704963) with obesity (i.e., hip, waist) in Whites, which was further strengthened through multiple replications using our synthetic stress measure. We now extend this prior work in a precision medicine framework to find the risk group using harmonized data from 28,026 participants by evaluating the following: (a) EBF1 SNPxSTRESS interaction in Blacks; (b) 3-way interaction of EBF1 SNPxSTRESS with sex, race, and age; and (c) a race and sex-specific path linking EBF1 and stress to obesity to fasting glucose to the development of cardiometabolic disease risk. Our findings provided additional confirmation that genetic variation in EBF1 may contribute to stress-induced human obesity, including in Blacks (P = 0.022) that mainly resulted from race-specific stress due to "racism/discrimination" (P = 0.036) and "not meeting basic needs" (P = 0.053). The EBF1 gene-by-stress interaction differed significantly (P = 1.01e-03) depending on the sex of participants in Whites. Race and age also showed tentative associations (Ps = 0.103, 0.093, respectively) with this interaction. There was a significant and substantially larger path linking EBF1 and stress to obesity to fasting glucose to type 2 diabetes for the EBF1 minor allele group (coefficient = 0.28, P = 0.009, 95% CI = 0.07-0.49) compared with the same path for the EBF1 major allele homozygotes in White females and also a similar pattern of the path in Black females. Underscoring the race-specific key life-stress indicators (e.g., racism/discrimination) and also the utility of our synthetic stress, we identified the potential risk group of EBF1 and stress-induced human obesity and cardiometabolic disease.

Metabolic and Neurocognitive Changes Following Lifestyle Modification: Examination of Biomarkers from the ENLIGHTEN Randomized Clinical Trial.

BACKGROUND: Previous studies have demonstrated that aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet can improve neurocognition. However, the mechanisms by which lifestyle improves neurocognition have not been widely studied. We examined the associations between changes in metabolic, neurotrophic, and inflammatory biomarkers with executive functioning among participants from the Exercise and Nutritional Interventions for Neurocognitive Health Enhancement (ENLIGHTEN) trial. OBJECTIVE: To examine the association between changes in metabolic function and neurocognition among older adults with cognitive impairment, but without dementia (CIND) participating in a comprehensive lifestyle intervention. METHODS: ENLIGHTEN participants were randomized using a 2×2 factorial design to receive AE, DASH, both AE+DASH, or a health education control condition (HE) for six months. Metabolic biomarkers included insulin resistance (homeostatic model assessment [HOMA-IR]), leptin, and insulin-like growth factor (IGF-1); neurotrophic biomarkers included brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF); and inflammatory biomarkers included interleukin-6 (IL-6) and C-Reactive Protein (CRP). RESULTS: Participants included 132 sedentary older adults (mean age = 65 [SD = 7]) with CIND. Results demonstrated that both AE (d = 0.48, p = 0.015) and DASH improved metabolic function (d = 0.37, p = 0.039), without comparable improvements in neurotrophic or inflammatory biomarkers. Greater improvements in metabolic function, including reduced HOMA-IR (B = -2.3 [-4.3, -0.2], p = 0.033) and increased IGF-1 (B = 3.4 [1.2, 5.7], p = 0.004), associated with increases in Executive Function. CONCLUSION: Changes in neurocognition after lifestyle modification are associated with improved metabolic function.

Systolic Blood Pressure and Socioeconomic Status in a large multi-study population.

The present study used harmonized data from eight studies (N = 28,891) to examine the association between socioeconomic status (SES) and resting systolic blood pressure (SBP). The study replicates and extends our prior work on this topic by examining potential moderation of this association by race and gender. We also examined the extent to which body mass index (BMI), waist circumference (WC), and smoking might explain the association between SES and SBP. Data were available from six race/gender groups: 9200 Black women; 2337 Black men; 7248 White women; 6519 White men; 2950 Hispanic women; and 637 Hispanic men. Multivariable regression models showed that greater annual household income was associated with lower SBP in all groups except Hispanic men. The magnitude and form of this negative association differed across groups, with White women showing the strongest linear negative association. Among Black men and Hispanic women, the association was curvilinear: relatively flat among lower income levels, but then negative among higher income ranges. Education also was independently, negatively related to SBP, though evidence was weaker for race and gender differences in the strength of the association. Higher BMI and WC were associated with higher SBP, and current smoking with lower SBP. Inclusion of these risk factors resulted in only a modest change in the magnitude of the SBP and SES relation, accounting on average about 0.4 mmHg of the effect of income and 0.2 mmHg of the effect of education-effects unlikely to be clinically significant. Further understanding of mechanisms underlying the association between SBP and SES may improve risk stratification in clinical settings and potentially inform interventions aimed at reductions in social disparities in health.

Association Between Insulin Resistance, Plasma Leptin, and Neurocognition in Vascular Cognitive Impairment.

BACKGROUND: Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated. OBJECTIVE: To examine metabolic mechanisms underlying the association between obesity and neurocognition. METHODS: We conducted a secondary analysis of weight, neurocognition, and the potentially mediating role of metabolic and inflammatory biomarkers among 160 participants from the ENLIGHTEN trial of vascular cognitive impairment, no dementia (CIND). Neurocognition was assessed using a 45-minute assessment battery assessing Executive Function, Verbal and Visual Memory. We considered three metabolic biomarkers: insulin resistance (homeostatic model assessment [HOMA-IR]), plasma leptin, and insulin-like growth factor (IGF-1). Inflammation was assessed using C-reactive protein. Multiple regression analyses were used. RESULTS: Participants included 160 sedentary older adults with CIND. Participants tended to be overweight or obese (mean BMI = 32.5 [SD = 4.8]). Women exhibited higher BMI (p = 0.043), CRP (p < 0.001), and leptin (p < 0.001) compared with men. Higher BMI levels were associated with worse performance on measures of Executive Function (ß= -0.16, p = 0.024) and Verbal Memory (ß= -0.16, p = 0.030), but not Visual Memory (ß= 0.05, p = 0.500). Worse metabolic biomarker profiles also were associated with lower Executive Function (ß= -0.12, p = 0.050). Mediation analyses suggested leptin was a plausible candidate as a mediator between BMI and Executive Function. CONCLUSIONS: In overweight and obese adults with vascular CIND, the association between greater weight and poorer executive function may be mediated by higher leptin resistance.

Real-time predictors and consequences of binge eating among adults with type 1 diabetes.

BACKGROUND: Objective binge eating (OBE) is common among individuals with type 1 diabetes (T1D) and may have negative consequences for glycemic control. Recent studies have suggested that diabetes distress (i.e., emotional distress specific to diabetes and living with the burden of management) is a distinct emotional experience among individuals with diabetes. Preliminary studies have found diabetes distress is associated with eating disorder symptoms and poor glycemic control. The aim of the current study was to examine real-time emotional precursors and consequences of OBE in adults with T1D (i.e., general negative affect, specific emotional states and diabetes distress) using ecological momentary assessment methods. We also explore the impact of OBE on 2-h postprandial glycemic control relative to non-OBE eating episodes. METHODS: Adults with T1D (N = 83) completed 3-days of ecological momentary assessment assessing mood and eating behavior using a telephone-based survey system. Participants were prompted to rate momentary affect, including level diabetes distress, at random intervals and reported on eating episodes. Participants also wore continuous glucose monitors allowing for ongoing assessment of glycemic control. Multi-level modeling was used to examine between- and within-person effects of momentary increases in emotions prior to eating on the likelihood of OBE and the impact of OBE on postprandial blood glucose. Generalized linear mixed models examined whether change in post-meal affect differed between OBE and non-OBE episodes. RESULTS: Participants were predominately middle-aged (Mean = 42; SD = 12.43) Caucasian (87%) females (88%) reporting clinically significant eating disorder symptoms (76%). Nearly half of the sample (43%) reported OBE during the 3-day study period. The between-person effect for negative affect was significant (OR = 1.93, p < .05), indicating a 93% increased risk of OBE among individuals with higher negative affect compared to individuals with average negative affect. Between-person effects were also significant for guilt, frustration and diabetes distress (OR = 1.48-1.77, ps < .05). Analyses indicated that mean change in post-meal negative affect was significantly greater for OBE relative to non-OBE episodes (B = 0.44, p < .001). Blood glucose at 120 min postprandial was also higher for OBE than for non-OBE episodes (p = .03). CONCLUSIONS: Findings indicate that individuals who tend to experience negative affect and diabetes distress before eating are at increased risk of OBE at the upcoming meal. Results also suggest that engaging in binge eating may result in greater subsequent negative affect, including diabetes distress, and lead to elevated postprandial blood glucose levels. These findings add to a growing literature suggesting diabetes distress is related to eating disordered behaviors among individuals with T1D.

Lack of Association of a Functional Polymorphism in the Serotonin Receptor Gene With Body Mass Index and Depressive Symptoms in a Large Meta-Analysis of Population Based Studies.

The serotonin receptor 5-HTR2C is thought to be involved in the function of multiple brain structures. Consequently, the HTR2C gene has been studied extensively with respect to its association with a variety of phenotypes. One coding variant in the HTR2C gene, Cys23Ser (rs6318), has been associated with depressive symptoms. and adiposity; however, these findings have been inconsistent. The reasons for this mixed picture may be due to low statistical power or due to other factors such as failure to account for possible interacting environmental factors, such as psychosocial stress. Further, the literature around this polymorphism is marked by limited inclusion of persons of African ancestry. The present study sought to overcome these limitations and definitively determine the relationship of this polymorphism with depressive and obesity phenotypes in a large sample meta-analysis. Thus, we harmonized individual level data from 10 studies including the Women's Health Initiative, CARDIA, ARIC, Framingham Offspring, and the Jackson Heart Study, resulting in a sample of 27,161 individuals (10,457 Black women, 2,819 Black men, 7,419 White women, and 6,466 White men). We conducted a random effects meta-analysis using individual level data to examine whether the Cys23Ser variant-either directly, or conditionally depending on the level of psychosocial stress-was associated with depressive symptoms and body mass index (BMI). We found that psychosocial stress was associated with both depression and BMI, but that Cys23Ser was not directly associated with, nor did it modify the associations of psychosocial stress with depression or BMI. Thus, in the largest study of this polymorphism, we have determined that rs6318 is not associated with depression, or BMI.

Long-Chain Omega-3 Fatty Acid Supplements in Depressed Heart Failure Patients: Results of the OCEAN Trial.

OBJECTIVES: The goal of this study was to test the effects of long-chain omega-3 fatty acid supplementation on omega-3 levels, depressive symptoms, and other psychosocial factors, as well as other chronic heart failure (CHF)-related functional measures. BACKGROUND: Patients with CHF and depression had low blood omega-3 concentrations that were associated with an elevated risk of mortality. METHODS: This study was a randomized, double-blind, placebo-controlled pilot clinical trial using a 400/200 eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) fish oil at 2 g and an almost pure EPA at 2 g, compared with a matched placebo, daily for 12 weeks for patients with CHF and major depressive disorder. Statistical analyses included the intention-to-treat population and "completers" (defined as participants consuming ≥70% of the capsules and completing the final endpoint evaluation between 10 and 14 weeks). RESULTS: A total of 108 patients with CHF and major depressive disorder and a score ≥18 on the Hamilton Depression Scale who were randomized at 1:1:1 to the 3 interventions at 3 enrolling centers from June 12, 2014, to May 19, 2016; 80 (74.1%) qualified as completers. Intention-to-treat analyses revealed that the levels of all omega-3 variables were significantly elevated in the omega-3 groups, whereas the placebo group showed little change; there were no between-group differences with overall depression measurements. Per-protocol exploratory analyses showed that scores on the social functioning measurement of the 36-item Short Form Health Survey improved notably in the 400/200 EPA/DHA (p = 0.040) and EPA (p = 0.10) groups compared with the placebo group. Spearman correlation analysis indicated that increased omega-3 indices were associated with improved cognitive depressive symptoms. CONCLUSIONS: Omega-3 supplementation resulted in significant increases in omega-3 levels in red blood cell counts, corresponding to a particular compound of omega-3. Changes in cognitive depressive symptoms and social function were in favor of the omega-3 supplementation. Further studies with larger sample sizes are necessary to confirm the benefits of omega-3 supplementation on modifying psychosocial factors for patients with CHF. (Omega-3 Supplementation for Co-Morbid Depression and Heart Failure Treatment [OCEAN]; NCT02057406).

Developing a synthetic psychosocial stress measure and harmonizing CVD-risk data: a way forward to GxE meta- and mega-analyses.

OBJECTIVES: Among many challenges in cardiovascular disease (CVD) risk prediction are interactions of genes with stress, race, and/or sex and developing robust estimates of these interactions. Improved power with larger sample size contributed by the accumulation of epidemiological data could be helpful, but integration of these datasets is difficult due the absence of standardized phenotypic measures. In this paper, we describe the details of our undertaking to harmonize a dozen datasets and provide a detailed account of a number of decisions made in the process. RESULTS: We harmonized candidate genetic variants and CVD-risk variables related to demography, adiposity, hypertension, lipodystrophy, hypertriglyceridemia, hyperglycemia, depressive symptom, and chronic psychosocial stress from a dozen studies. Using our synthetic stress algorithm, we constructed a synthetic chronic psychosocial stress measure in nine out of twelve studies where a formal self-rated stress measure was not available. The mega-analytic partial correlation between the stress measure and depressive symptoms while controlling for the effect of study variable in the combined dataset was significant (Rho = 0.27, p < 0.0001). This evidence of the validity and the detailed account of our data harmonization approaches demonstrated that it is possible to overcome the inconsistencies in the collection and measurement of human health risk variables.

Time of Day When Type 1 Diabetes Patients With Eating Disorder Symptoms Most Commonly Restrict Insulin.

OBJECTIVE: Restricting insulin to lose weight is a significant problem in the clinical management of type 1 diabetes (T1D). Little is known about this behavior or how to effectively intervene. Identifying when insulin restriction occurs could allow clinicians to target typical high-risk times or formulate hypotheses regarding factors that influence this behavior. The current study investigated the frequency of insulin restriction by time of day. METHODS: Fifty-nine adults with T1D and eating disorder symptoms completed 72 hours of real-time reporting of eating and insulin dosing with continuous glucose monitoring. We used a generalized estimating equation model to test the global hypothesis that frequency of insulin restriction (defined as not taking enough insulin to cover food consumed) varied by time of day, and examined frequency of insulin restriction by hour. We also examined whether patterns of insulin restriction for 72 hours corresponded with patients' interview reports of insulin restriction for the past 28 days. RESULTS: Frequency of insulin restriction varied as a function of time (p = .016). Insulin restriction was the least likely in the morning hours (6:00-8:59 AM), averaging 6% of the meals/snacks consumed. Insulin restriction was more common in the late afternoon (3:00-5:59 PM), peaking at 29%. Insulin was restricted for 32% of the meals/snacks eaten overnight (excluding for hypoglycemia); however, overnight eating was rare. Insulin restriction was associated with higher 120-minute postprandial blood glucose (difference = 44.4 mg/dL, 95% confidence interval = 22.7-68.5, p < .001) and overall poorer metabolic control (r = 0.43-0.62, p's < .01). Patients reported restricting insulin for a greater percentage of meals and snacks for the past 28 days than during the 72 hour real-time assessment; however, the reports were correlated (Spearman's ρ = 0.46, p < .001) and accounted for similar variance in HbA1c (34% versus 35%, respectively). CONCLUSIONS: Findings suggest that insulin restriction may be less likely in the morning, and that late afternoon is a potentially important time for additional therapeutic support. Results also suggest that systematic clinical assessment and treatment of overnight eating might improve T1D management.

Usefulness of Myocardial Annular Velocity Change During Mental Stress to Predict Cardiovascular Outcome in Patients With Coronary Artery Disease (From the Responses of Mental Stress-Induced Myocardial Ischemia to Escitalopram Treatment Trial).

Mental stress-induced myocardial ischemia is common and a prognostic factor of adverse cardiovascular outcomes in patients with coronary artery disease (CAD). The present study aimed at examining associations between mental stress-induced myocardial annular velocity (MAV) and cardiovascular outcome in patients with CAD. MAV, specifically, diastolic early (e'), diastolic late (a'), and systolic (s') velocities were obtained at rest and during mental stress testing in 224 patients with clinically stable CAD. Using Cox regression models, age, sex, and baseline-adjusted mental stress-induced MAV measures were examined as predictors of a priori defined composite event term that comprised all-cause mortality and/or nonfatal cardiovascular events, resulting in an unplanned hospitalization (major adverse cardiovascular events [MACE]). Median follow-up was 4 years. The sample was predominantly male, Caucasian with New York Heart Association functional class I and a mean age of 63 ± 10.2 years. MS-induced changes in e' (hazard ratio [HR] = .73) and s' (HR = .73) were significant (p <0.05) predictors of MACE, and the change in a' (HR = .74) was marginal (p = 0.05). The pattern of the relation for each MAV measure was such that patients with a greater decrease in e' and/or s' velocity had a higher probability of experiencing an MACE, and the association of the change in a' and MACE was marginal (p = 0.05), but the same tendency. The associations between MS-induced values of e' and a' for MACE were independent of resting levels. Mental stress-induced MAV changes independently predict an adverse cardiovascular outcome in patients with stable CAD.