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A primary goal of this study was to examine the impact of an Integrated Brain, Body, and Social (IBBS) intervention (multi-faceted treatment consisting of computerized cognitive training, physical exercise, and behavior management) on ERPs of attentional control (P3 & N2) in children with ADHD. The secondary goal was to test the differences between children with and without ADHD on ERP and Go/No-Go behavioral measures. A total of twenty-nine participants (M age = 7.14 years; 52% male; 41.4% white) recruited from the IBBS efficacy study comparing IBBS to Treatment-As-Usual (TAU) completed a Go/No-Go task before and after treatment as brain activity was recorded using EEG. Thirty-four matched healthy controls (HC) completed the same EEG procedures at a single time point. Following treatment, the Go P3 latency was significantly earlier for the IBBS group relative to the TAU group. No treatment effects were found on any behavioral measures. Prior to treatment, there was a significant difference between the ADHD group and HC group for the N2 difference wave. Children with ADHD also showed slower reaction times on behavioral measures. Although this pilot study did not reveal robust treatment effects, it suggests that IBBS may prevent the worsening of attentional systems in the brain and larger studies are needed for replication purposes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Prenatal cocaine exposure (PCE) has ramifications for feedback processing. Measuring neural oscillatory dynamics (during electroencephalography) provides insight into the time signatures and neural processes of feedback processing in adolescents with PCE. We measured spectral power in alpha and theta frequency bands while 49 adolescents with PCE and 34 non-drug exposed (NDE) performed a task with win/no-win feedback. Compared to NDE individuals, those with PCE showed reduced alpha power and increased theta power in response to no-win feedback. These findings suggest altered reactivity in PCE adolescents.

Telemedicine can facilitate population health management by extending the reach of providers to efficiently care for high-risk, high-utilization populations. However, for telemedicine to be maximally useful, data collected using telemedicine technologies must be reliable and readily available to healthcare providers. To address current gaps in integration of patient-generated health data into the electronic health record (EHR), we examined 2 patient-facing platforms, Epic MyChart and Apple HealthKit, both of which facilitated the uploading of blood glucose data into the EHR as part of a diabetes telemedicine intervention. All patients were offered use of the MyChart platform; we subsequently invited a purposive sample of patients who used the MyChart platform effectively (n = 5) to also use the Apple HealthKit platform. Patients reported both platforms helped with diabetes self-management, and providers appreciated the convenience of the processes for obtaining patient data. Providers stated that the EHR data presentation format for Apple HealthKit was challenging to interpret; however, they also valued the greater perceived accuracy the Apple HealthKit data. Our findings indicate that patient-facing platforms can feasibly facilitate transmission of patient-generated health data into the EHR and support telemedicine-based care., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: Telehealth interventions for alcohol misuse may be especially impactful in hypertensive populations because of the increased blood pressure associated with alcohol overconsumption. This review examines emerging telehealth interventions for alcohol misuse and categorizes them according to phases of the treatment process., Recent Findings: Evidence for telehealth cognitive behavioral therapy (CBT) is preliminary but suggests it is efficacious and increased access to treatment. Evidence for contingency management (CM) is growing, and mobile adaptation of CM for alcohol misuse suggests it is efficacious in initial abstinence induction. Evidence for mobile health (mHealth) texts and applications is large and variable but generally suggests it is efficacious for reducing alcohol misuse and relapse prevention. Variability in telehealth interventions for alcohol misuse may hinder conclusion implementation. Matching specific telehealth interventions with phases of alcohol misuse treatment and focusing on high-impact populations (i.e., those with hypertension) may maximize benefits on population health.

Background: Self-management is integral for control of type 2 diabetes mellitus (T2DM). Patient self-management is improved when they receive real-time information on their health status and behaviors and ongoing facilitation from health professionals. However, timely information for these behaviors is notably absent in the health care system. Providing real-time data could help improve patient understanding of the dynamics of their illness and assist clinicians in developing targeted approaches to improve health outcomes and in delivering personalized care when and where it is most needed. Mobile technologies (eg, wearables, apps, and connected scales) have the potential to make these patient-provider interactions a reality. What strategies might best help patients overcome self-management challenges using self-generated diabetes-related data? How might clinicians effectively guide patient self-management with the advantage of real-time data?, Objective: This study aims to describe the protocol for an ongoing study (June 2016-May 2019) that examines trajectories of symptoms, health behaviors, and associated challenges among individuals with T2DM utilizing multiple mobile technologies, including a wireless body scale, wireless glucometer, and a wrist-worn accelerometer over a 6-month period., Methods: We are conducting an explanatory sequential mixed methods study of 60 patients with T2DM recruited from a primary care clinic. Patients were asked to track relevant clinical data for 6 months using a wireless body scale, wireless glucometer, a wrist-worn accelerometer, and a medication adherence text message (short message service, SMS) survey. Data generated from the devices were then analyzed and visualized. A subset of patients is currently being interviewed to discuss their challenges and successes in diabetes self-management, and they are being shown visualizations of their own data. Following the data collection period, we will conduct interviews with study clinicians to explore ways in which they might collaborate with patients., Results: This study has received regulatory approval. Patient enrollment ongoing with a sample size of 60 patients is complete, and up to 20 clinicians will be enrolled. At the patient level, data collection is complete, but data analysis is pending. At the clinician level, data collection is currently ongoing., Conclusions: This study seeks to expand the use of mobile technologies to generate real-time data to enhance self-management strategies. It also seeks to obtain both patient and provider perspectives on using real-time data to develop algorithms for software that will facilitate real-time self-management strategies. We expect that the findings of this study will offer important insight into how to support patients and providers using real-time data to manage a complex chronic illness., International Registered Report Identifier (irrid): DERR1-10.2196/13517., (©Ryan J Shaw, Angel Barnes, Dori Steinberg, Jacqueline Vaughn, Anna Diane, Erica Levine, Allison Vorderstrasse, Matthew J Crowley, Eleanor Wood, Daniel Hatch, Allison Lewinski, Meilin Jiang, Janee Stevenson, Qing Yang. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 03.06.2019.)

The Trier Social Stress Test for children (TSST-C) adapted from TSST is one of the most commonly used laboratory paradigms for investigating the effects of stress on cognitive, affective and physiological responses in children and adolescents. Considering that laboratory procedures generate a significant amount of stress to children and adolescents, even in the absence of a stress paradigm, it is important to validate TSST-C against an inactive control condition in which the stress components were absent. Using a randomized design, we tested an inactive control condition, which replaced the TSST-C with a benign video clip (nature scenes viewed while standing), thus removing the stress associated components of the TSST-C. Eighty-eight youth between the ages of 10 and 17 years were randomly assigned to complete the TSST-C or the Inactive Control (IC). Subjective anxiety rating, salivary cortisol, systolic and diastolic blood pressure, and heart rate were collected at eight time points. Subjects in the Inactive Control condition showed no significant changes in blood pressure and heart rate, and decreased anxiety rating and salivary cortisol level throughout the study. Subjects in the stress condition (TSST-C) showed increased anxiety ratings, salivary cortisol, systolic and diastolic blood pressure, and heart rate immediately following TSST-C stress induction. Our findings validated that the TSST-C induced a systemic stress response, and that the Inactive Control can be a promising standardized control condition for the TSST-C and a tool for future psychobiological research. Our results also showed that anxiety reactivity decreased with age while HR reactivity increased with age. Cortisol reactivity did not fall in a linear relationship with age but rather via a quadratic curve, suggesting the mid-age adolescents had the highest cortisol responses to stress compared to their younger and older peers, potentially due to a dual factor of pubertal development and self-control and emotion regulation capacity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Individuals with autism spectrum disorder (ASD) exhibit impaired adult facial processing, as shown by the N170 event-related potential. However, few studies explore such processing in mothers of children with ASD, and none has assessed the early processing of infant faces in these women. Moreover, whether processing of infant facial expressions in mothers of children with ASD is related to their response to their child's needs (maternal sensitivity [MS]) remains unknown. This study explored the N170 related to infant faces in a group of mothers of children with ASD (MA) and a reference group of mothers of children without ASD. For both emotional (crying, smiling) and neutral expressions, the MA group exhibited larger amplitudes of N170 in the right hemisphere, while the reference group showed similar interhemispheric amplitudes. This lateralization effect within the MA group was not present for nonfaces and was stronger in the mothers with higher MS. We propose that mothers of ASD children use specialized perceptual resources to process infant faces, and this specialization is mediated by MS. Our findings suggest that having an ASD child modulates mothers' early neurophysiological responsiveness to infant cues. Whether this modulation represents a biological marker or a response given by experience remains to be explored. Autism Research 2019, 12: 744-758. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: When mothers of children with autism spectrum disorder (ASD) see baby faces expressing emotions, they show a right-sided electrical response in the brain. This lateralization was stronger in mothers who were more sensitive to their children's needs. We conclude that having a child with ASD and being more attuned to their behavior generates a specialized pattern of brain activity when processing infant faces. Whether this pattern is biological or given by experience remains to be explored., (© 2019 International Society for Autism Research, Wiley Periodicals, Inc.)

Prenatal drug exposure may have important repercussions across the lifespan for cognition and behavior. While alcohol is a recognized teratogen, the influences of other substances may also be substantial. The neural underpinnings of the influences of prenatal drug exposure have been examined using longitudinal approaches and multiple imaging techniques. Here we review the existing literature on the neural correlates of prenatal drug exposure. We focused the review on studies that have employed functional neuroimaging and electroencephalography and on substances other than alcohol. We also framed the review through the lens of four developmental life stages (infancy, childhood, adolescence and emerging adulthood). We included papers that have examined any drug use, including tobacco, opiates, cocaine, marijuana, methamphetamines, or polysubstance use. Data suggest that prenatal drug exposure has long-lasting, deleterious influences on cognition and reward processing in infancy and childhood that persist into adolescence and emerging adulthood and may underlie some behavioral tendencies, such as increased externalizing and risk-taking behaviors, seen in these groups., (Copyright © 2019. Published by Elsevier B.V.)

Aim: To examine whether sodium-glucose co-transporter-2 (SGLT2) inhibitors are associated with a higher risk of lower-extremity amputation than dipeptidyl-peptidase-4 (DPP-4) inhibitors and sulphonylureas., Methods: We conducted a retrospective cohort study, using the MarketScan Commercial Claims and Encounters Database (2013-2015), to compare the incidence of lower-extremity amputation (LEA) between initiators of SGLT2 inhibitors and initiators of two second-line drugs, DPP-4 inhibitors and sulphonylureas (SUs). We estimated crude incidence rates (IRs) and adjusted hazard ratios (aHR), with 95% confidence intervals (CIs), before and after propensity-score weighting. We additionally conducted sensitivity analyses using a comparator group of all non-metformin, non-SGLT2 inhibitor glucose-lowering drugs, as previous studies used this approach., Results: In a cohort of 328 150 individuals aged 18 to 64 years, the IR of LEA ranged from 1.5 to 2.4 per 1000 person-years. In as-treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP-4 inhibitor initiators (aHR 1.69, 95% CI 1.20-2.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67-1.55) or non-metformin, non-SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54-1.93). Results were consistent in intention-to-treat analysis and across a number of sensitivity analyses., Conclusions: Among commercially insured patients in the United States, our results suggest that initiation of SGLT2 inhibitors may increase the risk of LEA compared to initiation of DPP-4 inhibitors. Contrasting results when comparing SGLT2 inhibitor initiators to DPP-4 inhibitor and SU initiators highlight the importance of choosing appropriate comparator drugs when addressing comparative effectiveness and safety questions that can inform clinical decision-making., (© 2019 John Wiley & Sons Ltd.)

Background: Patients with diabetes and poorly controlled hypertension are at increased risk for adverse renal and cardiovascular outcomes. Identifying these patients early and addressing modifiable risk factors is central to delaying renal complications such as diabetic kidney disease. Mobile health (mHealth), a relatively inexpensive and easily scalable technology, can facilitate patient-centered care and promote engagement in self-management, particularly for patients of lower socioeconomic status. Thus, mHealth may be a cost-effective way to deliver self-management education and support., Objective: This feasibility study aimed to build a population management program by identifying patients with diabetes and poorly controlled hypertension who were at risk for adverse renal outcomes and evaluate a multifactorial intervention to address medication self-management. We recruited patients from a federally qualified health center (FQHC) in an underserved, diverse county in the southeastern United States., Methods: Patients were identified via electronic health record. Inclusion criteria were age between 18 and 75 years, diagnosis of type 2 diabetes, poorly controlled hypertension over the last 12 months (mean clinic systolic blood pressure [SBP] ≥140 mm Hg and/or diastolic blood pressure [DBP] ≥90 mm Hg), access to a mobile phone, and ability to receive text messages and emails. The intervention consisted of monthly telephone calls for 6 months by a case manager and weekly, one-way informational text messages. Engagement was defined as the number of phone calls completed during the intervention; individuals who completed 4 or more calls were considered engaged. The primary outcome was change in SBP at the conclusion of the intervention., Results: Of the 141 patients enrolled, 84.0% (118/141) of patients completed 1 or more phone calls and had follow-up SBP measurements for analysis. These patients were on average 56.9 years of age, predominately female (73/118, 61.9%), and nonwhite by self-report (103/118, 87.3%). The proportion of participants with poor baseline SBP control (50/118, 42.4%) did not change significantly at study completion (53/118, 44.9%) (P=.64). Participants who completed 4 or more phone calls (98/118, 83.1%) did not experience a statistically significant decrease in SBP when compared to those who completed fewer calls., Conclusion: We did not reduce uncontrolled hypertension even among the more highly engaged. However, 83% of a predominately minority and low-income population completed at least 67% of the multimodal mHealth intervention. Findings suggest that combining an automated electronic health record system to identify at-risk patients with a tailored mHealth protocol can provide education to this population. While this intervention was insufficient to effect behavioral change resulting in better hypertension control, it does suggest that this FQHC population will engage in low-cost population health applications with a potentially promising impact., Trial Registration: ClinicalTrials.gov NCT02418091; https://clinicaltrials.gov/ct2/show/NCT02418091 (Archived by WebCite at http://www.webcitation.org/76RBvacVU)., (©Allison A Lewinski, Uptal D Patel, Clarissa J Diamantidis, Megan Oakes, Khaula Baloch, Matthew J Crowley, Jonathan Wilson, Jane Pendergast, Holly Biola, L Ebony Boulware, Hayden B Bosworth. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.04.2019.)

Although the neural correlates of social exclusion have been well-documented, most studies have examined single age groups. No studies have directly compared specific age-related differences in social exclusion across children, adolescents, and adults using event-related oscillatory electroencephalogram (EEG) dynamics. The authors examined event-related theta EEG power and phase coherence in fair play and social exclusion conditions during the Cyberball task in 166 participants: 42 children (ages 10-12), 56 adolescents (ages 14-17), and 68 adults (ages 18-28). Children and adolescents displayed the greatest theta power to rejection events, whereas adults displayed the greatest theta power to "not my turn" events. Moreover, the functional link between theta power to rejection and self-reported distress was strongest among the adolescents. These findings suggest that an enhanced neural response to social exclusion is present by preadolescence, but the association between neural and subjective responses is most prominent during adolescence. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Aims: To examine the outcomes of dipeptidyl peptidase-4 (DPP-4) inhibitor initiation with and without concurrent metformin treatment., Materials and Methods: We identified Medicare enrollees initiating a DPP-4 inhibitor, a sulphonylurea or a thiazolidinedione. Using propensity-score-weighted Poisson models, we evaluated 1-year cardiovascular (CV) outcome incidence among initiators of DPP-4 inhibitors versus comparators in subgroups with and without concurrent metformin use, and assessed the interaction between initiation drug and metformin. Outcomes included mortality, non-fatal myocardial infarction (MI), stroke, and a composite outcome., Results: For the DPP-4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP-4 inhibitors: -2.0/100 person-years among metformin users (95% confidence interval [CI] -2.7 to -1.3) and - 1.0/100 person-years (95% CI -1.8 to -0.2) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-1.5/100 person-years [95% CI -2.1 to -0.9] and -0.7/100 person-years [95% CI -1.4 to 0.0]) and non-fatal MI (-0.5/100 person-years [95% CI -0.8, -0.3] and 0.1/100 person-years [95% CI -0.2 to 0.4]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for non-fatal MI (P = 0.008). For the DPP-4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP-4 inhibitor initiation were -0.6/100 person-years (95% CI -1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-0.5/100 person-years [95% CI -1.3 to 0.1] and 0.8/100 person-years [95% CI -0.0 to 1.7]) and non-fatal MI (-0.1/100 person-years [95% CI -0.4 to 0.2] and 0.2/100 person-years [95% CI -0.1 to 0.6]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for the composite outcome (P = 0.024) and mortality (P = 0.023)., Conclusion: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin., (© 2018 John Wiley & Sons Ltd.)

Objective: Patients with persistent poorly-controlled diabetes mellitus (PPDM) despite engagement in clinic-based care are at particularly high risk for diabetes complications and costs. Understanding this population's demographics, comorbidities and care utilization could guide strategies to address PPDM. We characterized factors associated with PPDM in a large sample of Veterans with type 2 diabetes., Methods: We identified a cohort of Veterans with medically treated type 2 diabetes, who received Veterans Health Administration primary care during fiscal years 2012 and 2013. PPDM was defined by hemoglobin A1c levels uniformly >8.5% during fiscal year (FY) 2012, despite engagement with care during this period. We used FY 2012 demographic, comorbidity and medication data to describe PPDM in relation to better-controlled diabetes patients and created multivariable models to examine associations between clinical factors and PPDM. We also constructed multivariable models to explore the association between PPDM and FY 2013 care utilization., Results: In our cohort of diabetes patients (n = 435,820), 12% met criteria for PPDM. Patients with PPDM were younger than better-controlled patients, less often married, and more often Black/African-American and Hispanic or Latino/Latina. Of included comorbidities, only retinopathy (OR 1.68, 95% confidence interval (CI): 1.63,1.73) and nephropathy (OR 1.26, 95% CI: 1.19,1.34) demonstrated clinically significant associations with PPDM. Complex insulin regimens such as premixed (OR 10.80, 95% CI: 10.11,11.54) and prandial-containing regimens (OR 18.74, 95% CI: 17.73,19.81) were strongly associated with PPDM. Patients with PPDM had higher care utilization, particularly endocrinology care (RR 3.56, 95% CI: 3.47,3.66); although only 26.4% of patients saw endocrinology overall., Conclusion: PPDM is strongly associated with complex diabetes regimens, although heterogeneity in care utilization exists. While there is evidence of underutilization, inadequacy of available care may also contribute to PPDM. Our findings should inform tailored approaches to meet the needs of PPDM, who are among the highest-risk, highest-cost patients with diabetes., Competing Interests: The authors have declared that no competing interests exist.

Generalized spike-wave discharges (SWDs) are the hallmark of generalized epilepsy on the electroencephalogram (EEG). In clinically obvious cases, generalized SWDs produce myoclonic, atonic/tonic, or absence seizures with brief episodes of staring and behavioral unresponsiveness. However, some generalized SWDs have no obvious behavioral effects. A serious challenge arises when patients with no clinical seizures request driving privileges and licensure, yet their EEG shows generalized SWD. Specialized behavioral testing has demonstrated prolonged reaction times or missed responses during SWD, which may present a driving hazard even when patients or family members do not notice any deficits. On the other hand, some SWDs are truly asymptomatic in which case driving privileges should not be restricted. Clinicians often decide on driving privileges based on SWD duration or other EEG features. However, there are currently no empirically-validated guidelines for distinguishing generalized SWDs that are "safe" versus "unsafe" for driving. Here, we review the clinical presentation of generalized SWD and recent work investigating mechanisms of behavioral impairment during SWD with implications for driving safety. As a future approach, computational analysis of large sets of EEG data during simulated driving utilizing machine learning could lead to powerful methods to classify generalized SWD as safe vs. unsafe. This may ultimately provide more objective EEG criteria to guide decisions on driving safety in people with epilepsy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose of Review: Moderate hypertriglyceridemia is exceedingly common in diabetes, and there is growing evidence that it contributes to residual cardiovascular risk in statin-optimized patients. Major fibrate trials yielded inconclusive results regarding the cardiovascular benefit of lowering triglycerides, although there was a signal for improvement among patients with high triglycerides and low high-density lipoprotein (HDL)-the "diabetic dyslipidemia" phenotype. Until recently, no trials have examined a priori the impact of triglyceride lowering in patients with diabetic dyslipidemia, who are likely among the highest cardiovascular-risk patients., Recent Findings: In the recent REDUCE IT trial, omega-3 fatty acid icosapent ethyl demonstrated efficacy in lowering cardiovascular events in patients with high triglycerides, low HDL, and statin-optimized low-density lipoprotein (LDL). The ongoing PROMINENT trial is examining the impact of pemafibrate in a similar patient population. Emerging evidence suggests that lowering triglycerides may reduce residual cardiovascular risk, especially in high-risk patients with diabetic dyslipidemia.

Late-stage attentional processing of threatening stimuli, quantified through event-related potentials (ERPs), differentiates youth with and without anxiety disorders. It is unknown whether early-stage attentional processing of threatening stimuli differentiates these groups. Examining both early and late stage attentional processes in youth may advance knowledge and enhance efforts to identify biomarkers for translational prevention and treatment research. Twenty-one youth with primary DSM-IV-TR anxiety disorders (10 males, ages 8-15 years) and 21 typically developing Controls (15 males, ages 8-16 years) completed a dot probe task while electroencephalography (EEG) was recorded, and ERPs were examined. Youth with anxiety disorders showed significantly larger (more positive) P1 amplitudes for threatening stimuli than for neutral stimuli, and Controls showed the opposite pattern. Youth with anxiety showed larger (more negative) N170 amplitudes compared with Controls. Controls showed significantly larger (more positive) P2 and P3 amplitudes, regardless of stimuli valence, compared with youth with anxiety disorders. ERPs observed during the dot probe task indicate youth with anxiety disorders display distinct neural processing during early stage attentional orienting and processing of faces; this was not the case for Controls. Such results suggest these ERP components may have potential as biomarkers of anxiety disorders in youth.

Pregnancy is shaped by unfolding psychological and biological changes in preparation for parenthood. A growing literature has examined the postpartum maternal brain. However, few studies examine the maternal brain during pregnancy, and whether brain function in pregnancy may have implications for postpartum caregiving. Using event-related potentials, we examined the late positive potential (LPP) elicited by infant distress and neutral faces in 35 women during their third trimester of pregnancy. Then, at 3 months postpartum, mothers completed a measure of parental reflective functioning to capture how they regarded their capacity to consider their child's thoughts and feelings. We found that in the third trimester, infant distress faces elicited larger LPPs compared to infant neutral faces. Moreover, the LPP elicited by infant neutral faces predicted levels of postpartum reflective functioning. Specifically, a larger LPP elicited by neutral infant faces predicted greater maternal self-reported difficulty recognizing and understanding their own infant's thoughts and feelings. Our findings suggest that studying the pregnant brain may have predictive value for facets of postpartum caregiving and may inform clinical interventions with new mothers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Adolescence is a period of significant identity development and particular vulnerability to depression associated with negative self-evaluation. We investigated if increased depressive symptom severity was also associated with positive self-evaluation. We also considered pubertal developmental differences in positive and negative self-evaluation, and if these could reflect dissociated facets of the self. This cross-sectional sample consisted of healthy male and female adolescents (N = 109) aged 12-17 from the United States. Participants completed a self-referential encoding task, which required them to indicate if a single-word adjective was self-descriptive. We administered the Children's Depression Inventory, the Pubertal Development Scale, and the Child Narcissism Scale. Negative-word endorsement was significantly predicted by pubertal maturation level and depressive symptoms, but not by narcissism. Positive-word endorsement was significantly predicted by narcissism and negatively predicted by depressive symptoms, but not by pubertal maturation. In this typically developing sample, positive self-judgment does not vary across the pubertal range and is positively associated with narcissistic traits, and negatively associated with depressive symptom severity. Negative self-judgements are positively correlated with puberty and are associated with depressive symptom severity only. Our findings suggest that negative and positive aspects of the self are partially dissociable.

Background: Treatment nonadherence and clinical inertia perpetuate poor cardiovascular disease (CVD) risk factor control. Telemedicine interventions may counter both treatment nonadherence and clinical inertia., Introduction: We explored why a telemedicine intervention designed to reduce treatment nonadherence and clinical inertia did not improve CVD risk factor control, despite enhancing treatment adherence versus usual care., Methods: In this analysis of a randomized trial, we studied recipients of the 12-month telemedicine intervention. This intervention comprised two nurse-administered components: (1) monthly self-management education targeting improved treatment adherence; and (2) quarterly medication management facilitation designed to support treatment intensification by primary care (thereby reducing clinical inertia). For each medication management facilitation encounter, we ascertained whether patients met treatment goals, and if not, whether primary care recommended treatment intensification following the encounter. We assessed disease control associated with encounters, where intensification was/was not recommended., Results: We examined 455 encounters across 182 intervention recipients (100% African Americans with type 2 diabetes). Even after accounting for valid reasons for deferring intensification (e.g., treatment nonadherence), intensification was not recommended in 67.5% of encounters in which hemoglobin A1c was above goal, 72.5% in which systolic blood pressure was above goal, and 73.9% in which low-density lipoprotein cholesterol was above goal. In each disease state, treatment intensification was more likely with poorer control., Conclusions: Despite enhancing treatment adherence, this intervention was unsuccessful in countering clinical inertia, likely explaining its lack of effect on CVD risk factors. We identify several lessons learned that may benefit investigators and healthcare systems.

Psychopathy is a cluster of personality traits associated with high rates of aggression. While research on psychopathic traits largely focuses on neurobiological factors implicated in aggression, other research suggests that contextual factors, such as social exclusion, also contribute to promoting aggression. Yet, the relationships among psychopathic traits, neural processing of exclusion, and aggression remain unknown. A sample of 76 adolescents and young adults completed Cyberball, a task involving conditions of social inclusion, ambiguous exclusion, and unambiguous exclusion. During Cyberball, a slow wave (SW) event-related potential (an index of elaborative processing) and self-reported anger were measured. Additionally, acts of real-world aggression were assessed. Results indicated that as psychopathic traits increased, SW during ambiguous exclusion also increased, but SW during inclusion decreased. However, the combination of smaller SW during ambiguous exclusion and higher psychopathic traits predicted heightened anger following Cyberball and more frequent real-world aggression. This response to social exclusion among individuals with elevated psychopathic traits may represent an unreflective, reactive style that exacerbates anger and aggression in certain contexts. These data suggest that neurobiological dysfunction in elaborative processing is related to psychopathic traits, and social context comprises another important influence on the aggression of individuals with elevated psychopathic traits., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Medial frontal activity in the EEG is enhanced following negative feedback and varies in relation to dimensions of impulsivity. In 22 undergraduate students (M age  = 18.92 years, range 18-22 years), we employed a probabilistic negative reinforcement learning paradigm in which choices to avoid were followed by cues indicating successful or unsuccessful avoidance of an impending aversive noise. Our results showed that medial frontal theta power was enhanced following a cue that signaled avoidance was unsuccessful. In addition, self-reported lack of perseverance, a dimension of impulsivity characterized by an inability to maintain focus and determination during a challenging task, was negatively correlated with medial frontal theta elicited to an unsuccessful avoidance cue. We also observed robust differences in alpha attenuation and beta modulation following unsuccessful avoidance cue presentation. To our knowledge, this is the first study in humans to show a functional relation between medial frontal theta modulation and avoidance success. We discuss our findings in the context of frontal theta and self-regulation, negative reinforcement, and anxiety., (Copyright © 2018. Published by Elsevier B.V.)

Emerging evidence points to interactions between inflammatory markers and stress reactivity in predicting mental health risk, but underlying mechanisms are not well understood. Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic cytokine involved in inflammatory signaling and Hypothalamus Pituitary Adrenal (HPA) axis stress-response, and has recently been identified as a candidate biomarker for depression and anxiety risk. We examined polymorphic variations of the MIF gene in association with baseline MIF levels, HPA axis reactivity, and self-reported anxiety responses to a social stressor in 74 adolescents, ages 10-14 years. Genotyping was performed for two polymorphisms, the -794 CATT5-8 tetranucleotide repeat and the -173*G/C single nucleotide polymorphism (SNP). Youth carrying the MIF-173*C and CATT7 alleles displayed attenuated cortisol reactivity when compared with non-carriers. Children with the CATT7-173*C haplotype displayed lower cortisol reactivity to the stressor compared to those without this haplotype. Additionally, the CATT5-173*C and CATT6-173*C haplotypes were associated with lower self-reported anxiety ratings across the stressor. Results extend prior work pointing to the influence of MIF signaling on neuroendocrine response to stress and suggest a potential pathophysiological pathway underlying risk for stress-related physical and mental health disorders. To our knowledge, these are the first data showing associations between the MIF gene, HPA axis reactivity, and anxiety symptoms during adolescence., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Success of immune checkpoint inhibitors in advanced non-small-cell lung cancer (NSCLC) has invigorated their use in the neoadjuvant setting for early-stage disease. However, the cellular and molecular mechanisms of the early immune responses to therapy remain poorly understood. Through an integrated analysis of early-stage NSCLC patients and a Kras mutant mouse model, we show a prevalent programmed cell death 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) axis exemplified by increased intratumoral PD-1+ T cells and PD-L1 expression. Notably, tumor progression was associated with spatiotemporal modulation of the immune microenvironment with dominant immunosuppressive phenotypes at later phases of tumor growth. Importantly, PD-1 inhibition controlled tumor growth, improved overall survival, and reprogrammed tumor-associated lymphoid and myeloid cells. Depletion of T lymphocyte subsets demonstrated synergistic effects of those populations on PD-1 inhibition of tumor growth. Transcriptome analyses revealed T cell subset-specific alterations corresponding to degree of response to the treatment. These results provide insights into temporal evolution of the phenotypic effects of PD-1/PD-L1 activation and inhibition and motivate targeting of this axis early in lung cancer progression.

Sleep disturbances are often observed in child and adolescent mental health disorders. Although previous research has identified consistent subjective reports of sleep disturbances, specific objective sleep markers have not yet been identified. We evaluated the current research on subjective and objective sleep markers in relation to attention deficit hyperactivity disorders, autism spectrum disorders, anxiety and depressive disorders. Subjective sleep markers are more consistent than objective markers of actigraphy, polysomnography, and circadian measures. We discuss the causes of variability in objective sleep findings and suggest future directions for research.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the United States. Multiple risk factors contribute to DKD development, yet few interventions target more than a single DKD risk factor at a time. This manuscript describes the study protocol, recruitment, and baseline participant characteristics for the Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. The STOP-DKD study is a randomized controlled trial designed to evaluate the effectiveness of a multifactorial behavioral and medication management intervention to mitigate kidney function decline at 3 years compared to usual care. The intervention consists of up to 36 monthly educational modules delivered via telephone by a study pharmacist, home blood pressure monitoring, and medication management recommendations delivered electronically to primary care physicians. Patients seen at seven primary care clinics in North Carolina, with diabetes and [1] uncontrolled hypertension and [2] evidence of kidney dysfunction (albuminuria or reduced estimated glomerular filtration rate [eGFR]) were eligible to participate. Study recruitment completed in December 2014. Of the 281 participants randomized, mean age at baseline was 61.9; 52% were male, 56% were Black, and most were high school graduates (89%). Baseline co-morbidity was high- mean blood pressure was 134/76 mmHg, mean body mass index was 35.7 kg/m 2 , mean eGFR was 80.7 ml/min/1.73 m 2 , and mean glycated hemoglobin was 8.0%. Experiences of recruiting and implementing a comprehensive DKD program to individuals at high risk seen in the primary care setting are provided., Trial Registration: NCT01829256., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Monitoring social threat is essential for maintaining healthy social relationships, and recent studies suggest a neural alarm system that governs our response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power might act as a neural correlate of this system by being sensitive to unexpected social rejection. Here, we examined whether frontal-midline theta is modulated by individual differences in personality constructs sensitive to social disconnection. In addition, we examined the sensitivity of feedback-related brain potentials (i.e., the feedback-related negativity and P3) to social feedback. Sixty-five undergraduate female participants (mean age = 19.69 years) participated in the Social Judgment Paradigm, a fictitious peer-evaluation task in which participants provided expectancies about being liked/disliked by peer strangers. Thereafter, they received feedback signaling social acceptance/rejection. A community structure analysis was employed to delineate personality profiles in our data. Results provided evidence of two subgroups: one group scored high on attachment-related anxiety and fear of negative evaluation, whereas the other group scored high on attachment-related avoidance and low on fear of negative evaluation. In both groups, unexpected rejection feedback yielded a significant increase in theta power. The feedback-related negativity was sensitive to unexpected feedback, regardless of valence, and was largest for unexpected rejection feedback. The feedback-related P3 was significantly enhanced in response to expected social acceptance feedback. Together, these findings confirm the sensitivity of frontal midline theta oscillations to the processing of social threat, and suggest that this alleged neural alarm system behaves similarly in individuals that differ in personality constructs relevant to social evaluation.

Background: Comprehensive programs addressing tailored patient self-management and pharmacotherapy may reduce barriers to cardiovascular disease (CVD) risk reduction., Methods: This is a 2-arm (clinical pharmacist specialist-delivered, telehealth intervention and education control) randomized controlled trial including Veterans with poorly controlled hypertension and/or hypercholesterolemia. Primary outcome was Framingham CVD risk score at 6 and 12 months, with systolic blood pressure; diastolic blood pressure; total cholesterol; low-density lipoprotein; high-density lipoprotein; body mass index; and, for those with diabetes, HbA1c as secondary outcomes., Results: Among 428 Veterans, 50% were African American, 85% were men, and 33% had limited health literacy. Relative to the education control group, the clinical pharmacist specialist-delivered intervention did not show a reduction in CVD risk score at 6 months (-1.8, 95% CI -3.9 to 0.3; P = .10) or 12 months (-0.3, 95% CI -2.4 to 1.7; P = .74). No differences were seen in systolic blood pressure, diastolic blood pressure, or low-density lipoprotein at 6 or 12 months. We did observe a significant decline in total cholesterol at 6 months (-7.0, 95% CI -13.4 to -0.6; P = .03) in the intervention relative to education control group. Among patients in the intervention group, 34% received at least 5 of the 12 planned intervention calls and were considered "compliers." A sensitivity analysis of the "complier average causal effect" of intervention compared to control showed a mean difference in CVD risk score reduction of 5.7 (95% CI -12.0 to 0.7) at 6 months and -1.7 (95% CI -7.6 to 4.8) at 12 months., Conclusions: Despite increased access to pharmacist resources, we did not observe significant improvements in CVD risk for patients randomized to the intervention compared to education control over 12 months. However, the intervention may have positive impact among those who actively participate, particularly in the short term., (Copyright © 2018. Published by Elsevier Inc.)

Background: Group Mindfulness Therapy (GMT) is a program tailored for adolescents that targets anxiety with mindfulness skills including present moment awareness, mindfulness in everyday life (breathing, eating, walking), body scan, loving-kindness, and self-acceptance. Youth with anxiety may benefit from mindfulness exercises precisely because they learn to redirect their mind, and presumably their attention, away from wandering in the direction of worry and negative self-appraisals and toward greater acceptance of internal states. This open trial assessed the feasibility and initial effectiveness of GMT in a school setting., Method: Twelve 6th and 7th grade adolescents with elevated anxiety [Screen for Child Anxiety Disorders (SCARED) ≥ 30] participated in GMT after school. Youth completed measures of anxiety and perceived stress and their parents completed measures of internalizing and externalizing behavior problems at pretreatment and posttreatment. We hypothesized that GMT would significantly reduce youth anxiety and stress., Results: Significant improvements were observed in anxiety, internalizing, stress, and attention, with effect sizes ranging from .88 to 1.34., Conclusions: We demonstrate that GMT is feasible and acceptable to adolescents presenting with anxiety as a primary concern. We provide further support for the use of a mindfulness-based intervention for anxiety reduction. The group format suggests a cost-effective way to deliver services in a school setting., (© 2017 Association for Child and Adolescent Mental Health.)

Parental reflective functioning (PRF) describes a parent's capacity for considering both their own and their child's thoughts, feelings, and behaviors, which can help parents to guide interactions with children. Given the cognitive demands of keeping infants in mind whilst caregiving, we examined the association between aspects of executive function (i.e., working memory and set-shifting) and PRF (employing the Parental Reflective Functioning Questionnaire) in recent mothers. In Study 1 (N=50), we found that better working memory was associated with higher levels of maternal interest and curiosity in their child's feelings. In Study 2 (N=68), we found that visual working memory and set-shifting capacity were also associated with higher levels of maternal interest and curiosity in their child's thoughts and feelings. Our results provide preliminary support for the association between executive processes and maternal reflective functioning. The implications of these findings and important future directions are discussed, including advancing our understanding of executive processes and PRF to support the broader family system., Competing Interests: Disclosure of potential conflicts of interest The authors declare they have no conflicts of interest.

Background: Many young investigators are interested in cardiovascular (CV) outcomes research; however, the current training experience of early investigators across the United States is uncertain., Methods: From April to November 2014, we surveyed mentees and mentors of early-stage CV outcomes investigators across the United States. We contacted successful grantees of government agencies, members of professional organizations, and trainees in CV outcomes training programs., Results: A total of 185 (of 662) mentees and 76 (of 541) mentors completed the survey. Mentees were equally split by sex; most had completed training >3 years before completing the survey and were clinicians. Mentors were more likely women, mostly ≥20 years posttraining, and at an associate/full professor rank. Mentors reported devoting more time currently to clinical work than when they were early in their career and mentoring 2-4 people simultaneously. More than 80% of mentees started training to become academicians and completed training with the same goal. More than 70% of mentees desired at least 50% research time in future jobs. More than 80% of mentors believed that future investigators would need more than 50% time dedicated to research. Most mentees (80%) were satisfied with their relationship with their mentor and reported having had opportunities to develop independently. Mentors more frequently than mentees reported that funding cutbacks had negatively affected mentees' ability to succeed (84% vs 58%). Across funding mechanisms, mentees were more optimistic than mentors about securing funding. Both mentees and mentors reported greatest preparedness for job/career satisfaction (79% for both) and publications (84% vs 92%) and least preparedness for future financial stability (48% vs 46%) and work-life balance (47% vs 42%)., Conclusions: Survey findings may stimulate future discourse and research on how best to attract, train, and retain young investigators in CV outcomes research. Insights may help improve existing training programs and inform the design of new ones., (Copyright © 2017. Published by Elsevier Inc.)

Tactile interactions are of developmental importance to social and emotional interactions across species. In beginning to understand the affective component of tactile stimulation, research has begun to elucidate the neural mechanisms that underscore slow, affective touch. Here, we extended this emerging body of work and examined whether affective touch (C tactile [CT]-optimal speed), as compared to nonaffective touch (non-CT-optimal speed) and no touch conditions, modulated EEG oscillations. We report an attenuation in alpha and beta activity to affective and nonaffective touch relative to the no touch condition. Further, we found an attenuation in theta activity specific to the affective, as compared to the nonaffective touch and no touch conditions. Similar to theta, we also observed an attenuation of beta oscillations during the affective touch condition, although only in parietal scalp sites. Decreased activity in theta and parietal-beta ranges may reflect attentional-emotional regulatory mechanisms; however, future work is needed to provide insight into the potential neural coupling between theta and beta and their specific role in encoding slow, tactile stimulation.

Background: Outcomes research training programs should prepare trainees to successfully compete for research funding. We examined how early-career investigators' prior and desired training aligns with recently funded cardiovascular (CV) outcomes research., Methods: We (1) reviewed literature to identify 13 core competency areas in CV outcomes research; (2) surveyed early-career investigators to understand their prior and desired training in each competency area; (3) examined recently funded grants commonly pursued by early-career outcomes researchers to ascertain available funding in competency areas; and (4) analyzed alignment between investigator training and funded research in each competency area. We evaluated 185 survey responses from early-career investigators (response rate 28%) and 521 funded grants from 2010 to 2014., Results: Respondents' prior training aligned with funded grants in the areas of clinical epidemiology, observational research, randomized controlled trials, and implementation/dissemination research. Funding in community-engaged research and health informatics was more common than prior training in these areas. Respondents' prior training in biostatistics and systematic review was more common than funded grants focusing on these specific areas. Respondents' desired training aligned similarly with funded grants, with some exceptions; for example, desired training in health economics/cost-effectiveness research was more common than funded grants in these areas. Restricting to CV grants (n=132) and National Heart, Lung, and Blood Institute-funded grants (n=170) produced similar results., Conclusions: Identifying mismatch between funded grants in outcomes research and early-career investigators' prior/desired training may help efforts to harmonize investigator interests, training, and funding. Our findings suggest a need for further consideration of how to best prepare early-career investigators for funding success., (Copyright © 2017. Published by Elsevier Inc.)

We examined the P3 (250-500ms) and Late Positive Potential (LPP; 500-2000ms) event-related potentials (ERPs) to food vs. nonfood cues among adolescents reporting on emotional eating (EE) behavior. Eighty-six adolescents 10-17 years old were tested using an instructed food versus nonfood cue viewing task (imagine food taste) during high-density EEG recording. Self-report data showed that EE increased with age in girls, but not in boys. Both P3 and LPP amplitudes were greater for food vs. nonfood cues (food-cue bias). Exploratory analyses revealed that, during the LPP time period, greater EE was associated with a more positive food-cue bias in the fronto-central region. This heightened fronto-central food-cue bias LPP is in line with a more activated prefrontal attention system. The results suggest that adolescents with higher EE may engage more top-down cognitive resources to regulate their automatic emotional response to food cues, and/or they may exhibit greater reward network activation to food cues than do adolescents with lower EE, even in the absence of an emotional mood induction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Chronic lower extremity venous disease (LECVD) is twice as prevalent as coronary heart disease, and invasive therapies to treat LECVD accounted for an estimated $290 million in Medicare expenditures in 2015. Despite increasing use of these invasive therapies, their comparative effectiveness is unknown., Methods: We conducted a systematic review and meta-analysis of treatments for patients (symptomatic and asymptomatic) with lower extremity varicosities and/or lower extremity chronic venous insufficiency/incompetence/reflux. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 2000 to July 2016. We included comparative randomized controlled trials (RCTs) with >20 patients and observational studies with >500 patients. Short-, intermediate-, and long-term outcomes of placebo, mechanical compression therapy, and invasive therapies (surgical and endovascular) were included. Quality ratings and evidence grading was performed. Random-effects models were used to compute summary estimates of effects., Results: We identified a total of 57 studies representing 105,878 enrolled patients, including 53 RCTs comprised of 10,034 patients. Among the RCTs, 16 were good quality, 28 were fair quality, and 9 were poor quality. Allocation concealment, double blinding, and reporting bias were inadequately addressed in 25 of 53 (47%), 46 of 53 (87%), and 15 of 53 (28.3%), respectively. Heterogeneity in therapies, populations, and/or outcomes prohibited meta-analysis of comparisons between different endovascular therapies and between endovascular intervention and placebo/compression. Meta-analysis evaluating venous stripping plus ligation (high ligation/stripping) compared with radiofrequency ablation revealed no difference in short-term bleeding (odds ratio [OR]=0.30, 95% CI -0.16 to 5.38, P=.43) or reflux recurrence at 1-2 years (OR=0.76, 95% CI 0.37-1.55, P=.44). Meta-analysis evaluating high ligation/stripping versus endovascular laser ablation revealed no difference in long-term symptom score (OR 0.02, 95% CI -0.19 to 0.23, P=.84) or quality of life at 2 years (OR 0.06, 95% CI -0.12 to 0.25, P=.50)., Conclusions: The paucity of high-quality comparative effectiveness and safety data in LECVD is concerning given the overall rise in endovascular procedures. More high-quality studies are needed to determine comparative effectiveness and guide policy and practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Impaired cognitive control is a consequence of cocaine exposure. Difficulty with feedback processing may underlie this impairment. We examined neural correlates of feedback processing using event-related potentials (ERPs) in 49 prenatally cocaine-exposed (PCE) and 34 nondrug exposed (NDE) adolescents. Adolescents performed a reward-feedback task with win/no-win feedback in a chance-based task. We investigated amplitude and latency of the feedback-related negativity (FRN) and P300 ERP components and source-based estimates elicited during feedback processing. PCE adolescents had smaller P300 amplitudes for no-win feedback, and source analysis in the P300 time window revealed differences between groups localized to the dorsal anterior cingulate cortex.

Objective: To explore prevalent metformin use as a potential moderator of the cardiovascular effects of dipeptidyl peptidase 4 inhibitors (DPP-4i)., Research Design and Methods: We performed a meta-analysis of the three major cardiovascular outcomes trials examining DPP-4i. We used meta-regression to examine how the cardiovascular effects of DPP-4i differ between prevalent metformin users and baseline nonusers., Results: While prevalent metformin users experienced a trend toward improved cardiovascular outcomes with DPP-4i (summary hazard ratio [HR] 0.92 [95% CI 0.84, 1.01]), baseline metformin nonusers showed a trend toward harm (HR 1.10 [95% CI 0.97, 1.26]). The difference in overall DPP-4i effect between metformin user and nonuser subgroups was statistically significant ( P = 0.036)., Conclusions: Baseline metformin status may have a moderating effect on cardiovascular outcomes with DPP-4i use. This hypothesis-generating analysis suggests there is residual uncertainty as to how DPP-4i affect cardiovascular outcomes, depending on concurrently prescribed medications., (© 2017 by the American Diabetes Association.)

We measured skin conductance response (SCR) to escalating levels of a direct social threat from a novel, ecologically-relevant experimental paradigm, the Intruder Threat Task. We simultaneously evaluated the contribution of social symptom severity and behavioral movement. Children with AS group showed less psychophysiological reactivity to social threat than controls across all three phases of the experiment. In the AS group, greater social impairment was significantly associated with reduced SCR. However, movement activity predicted SCR while diagnosis did not. Research and treatment need to account for the complex interplay of emotional reactivity and social behavior in AS. Psychophysiology studies of AS should consider the impact of possible confounds such as movement.

Background: The enduring impact of childhood maltreatment on biological systems and ensuing psychopathology remains incompletely understood. Long-term effects of stress may be reflected in cumulative cortisol secretion over several months, which is now quantifiable via hair cortisol concentrations (HCC). We conducted a first comprehensive investigation utilizing the potential of hair cortisol analysis in a large sample of maltreated and nonmaltreated children and adolescents., Method: Participants included 537 children and adolescents (3-16 years; 272 females) with maltreatment (n = 245) or without maltreatment histories (n = 292). Maltreated subjects were recruited from child protection services (CPS; n = 95), youth psychiatric services (n = 56), and the community (n = 94). Maltreatment was coded using the Maltreatment Classification System drawing on caregiver interviews and complemented with CPS records. Caregivers and teachers reported on child mental health. HCC were assessed in the first 3 cm hair segment., Results: Analyses uniformly supported that maltreatment coincides with a gradual and dose-dependent reduction in HCC from 9 to 10 years onwards relative to nonmaltreated controls. This pattern emerged consistently from both group comparisons between maltreated and nonmaltreated subjects (27.6% HCC reduction in maltreated 9-16-year-olds) and dimensional analyses within maltreated subjects, with lower HCC related to greater maltreatment chronicity and number of subtypes. Moreover, both group comparisons and dimensional analyses within maltreated youth revealed that relative HCC reduction mediates the effect of maltreatment on externalizing symptoms., Conclusions: From middle childhood onwards, maltreatment coincides with a relative reduction in cortisol secretion, which, in turn, may predispose to externalizing symptoms., (© 2017 Association for Child and Adolescent Mental Health.)

We greatly appreciate Dr. Fisher's commentary that provides an excellent backdrop and well-considered perspective on our findings. We agree that our results mesh well with previous work documenting hypocortisolism among youth who experienced early adversity, especially neglect. Moreover, as also perceptively noted by Dr. Fisher, our cross-sectional data provide support for the notion that hypocortisolism is not simply a transient phenomenon, but, rather, a persistent pattern characterizing maltreated youth. Specifically, the consistency of the between group effect (from age 9.69 onwards) on a multimonth index of cumulative cortisol and the dose-dependent gradient of cortisol secretion within the maltreated group, which was related to the number of subtypes and the length of exposure to maltreatment, lend weight to this view., (© 2017 Association for Child and Adolescent Mental Health.)

Objectives: This study examined the directive and non-directive supervisors' instructional styles, supervisees' interactive communications within supervision sessions as well as the relative success of supervisees' learning to apply specific techniques within psychotherapy., Method: The developers of Time-Limited Dynamic Psychotherapy (TLDP) provided the supervised training for 16 therapists as part of the "Vanderbilt II" psychotherapy project. Supervision sessions were rated for supervisors' adherence to TLDP content. Both supervisors and supervisee were rated for classroom interactive behaviors of "initiation" speech (e.g., introducing ideas) and "responsive" speech (e.g., amplifying the other speaker's topic). The third therapy session was targeted for discussion within supervision. Therapy sessions immediately before and after supervision were rated on TLDP adherence., Results: One of the supervisors (Supervisor A) was found to use an instructional style of relatively more initiation-based speech, whereas the other (Supervisor B) used more response-based speech. Technical adherence for supervisees of Supervisor A was significantly higher than those assigned to Supervisor B. Supervisees' initiation-based speech during supervision predicted less use of TLDP techniques in the therapy session after supervision. Supervisors' interactive style was not associated with therapy adherence., Conclusions: Relatively more directive and structured supervision may influence the acquisition and use of manual-prescribed therapy techniques.

Background: Rates of glycemic control remain suboptimal nationwide. Medication intensification for diabetes can have undesirable side effects (weight gain, hypoglycemia), which offset the benefits of glycemic control. A Shared Medical Appointment (SMA) intervention for diabetes that emphasizes weight management could improve glycemic outcomes and reduce weight while simultaneously lowering diabetes medication needs, resulting in less hypoglycemia and better quality of life. We describe the rationale and design for a study evaluating a novel SMA intervention for diabetes that primarily emphasizes low-carbohydrate diet-focused weight management., Methods: Jump Starting Shared Medical Appointments for Diabetes with Weight Management (Jump Start) is a randomized, controlled trial that is allocating overweight Veterans (body mass index≥27kg/m 2 ) with type 2 diabetes into two arms: 1) a traditional SMA group focusing on medication management and self-management counseling; or 2) an SMA group that combines low-carbohydrate diet-focused weight management (WM/SMA) with medication management. Hemoglobin A1c reduction at 48weeks is the primary outcome. Secondary outcomes include hypoglycemic events, diabetes medication use, weight, medication adherence, diabetes-related quality of life, and cost-effectiveness. We hypothesize that WM/SMA will be non-inferior to standard SMA for glycemic control, and will reduce hypoglycemia, diabetes medication use, and weight relative to standard SMA, while also improving quality of life and costs., Conclusions: Jump Start targets two common problems that are closely related but infrequently managed together: diabetes and obesity. By focusing on diet and weight loss as the primary means to control diabetes, this intervention may improve several meaningful patient-centered outcomes related to diabetes., (Copyright © 2017. Published by Elsevier Inc.)

Background: Impairment in prediction and appreciation for choice outcomes could contribute to several core symptoms of ASD. We examined electroencephalography (EEG) oscillations in 27 youth and young adults diagnosed with autism spectrum disorder (ASD) and 22 IQ-matched neurotypical controls while they performed a chance-based reward prediction task., Method: We re-analyzed our previously published ERP data (Larson et al., 2011) and examined theta band oscillations (4-8 Hz) at frontal midline sites, within a timing window that overlaps with the feedback-related negativity (FRN). We focused on event-related changes after presentation of feedback for reward (WIN) and punitive (LOSE) outcomes, both for spectral power and inter-trial phase coherence., Results: In our reward prediction task, for both groups, medial frontal theta power and phase coherence were greater following LOSE compared to WIN feedback. However, compared to controls, inter-trial coherence of medial frontal theta was significantly lower overall (across both feedback types) for individuals with ASD. Our results indicate that while individuals with ASD are sensitive to the valence of reward feedback, comparable to their neurotypical peers, they have reduced synchronization of medial frontal theta activity during feedback processing., Conclusions: This finding are consistent with previous studies showing neural variability in ASD and suggest that the processes underlying decision-making and reinforcement learning may be atypical and less efficient in ASD., Competing Interests: Conflict of interest The authors declare no conflict of interest.

Women are vulnerable to anxiety during pregnancy and postpartum. However, little is known about antenatal anxiety and neural processing of infant-relevant information. In this experiment, the N170, P300, and LPP (late positive potential) event-related potentials were measured from 43 pregnant women as they viewed infant and adult faces, which were either neutral or distressed in expression. Mother's self-reported anxiety levels were also assessed. The N170 was comparable across face conditions and was not associated with anxiety. However, our central finding was that greater levels of antenatal anxiety were associated with a larger LPP, but only for neutral infant faces. Results suggest that antenatal anxiety may result in deeper processing of neutral, emotionally ambiguous, infant faces during pregnancy. These findings are discussed in light of other work indicating an interpretive bias toward threat in response to neutral stimuli in anxiety., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations., Purpose: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment., Data Sources: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015., Study Selection: English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest., Data Extraction: 2 reviewers abstracted data and independently rated study quality and strength of evidence., Data Synthesis: On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF., Limitations: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration., Conclusion: Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support the recent changes in metformin labeling., Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708).

Extant research documents impaired language among children with prenatal cocaine exposure (PCE) relative to nondrug exposed (NDE) children, suggesting that cocaine alters development of neurobiological systems that support language. The current study examines behavioral and neural (electrophysiological) indices of language function in older adolescents. Specifically, we compare performance of PCE (N = 59) and NDE (N = 51) adolescents on a battery of cognitive and linguistic assessments that tap word reading, reading comprehension, semantic and grammatical processing, and IQ. In addition, we examine event related potential (ERP) responses in in a subset of these children across three experimental tasks that examine word level phonological processing (rhyme priming), word level semantic processing (semantic priming), and sentence level semantic processing (semantic anomaly). Findings reveal deficits across a number of reading and language assessments, after controlling for socioeconomic status and exposure to other substances. Additionally, ERP data reveal atypical orthography to phonology mapping (reduced N1/P2 response) and atypical rhyme and semantic processing (N400 response). These findings suggest that PCE continues to impact language and reading skills into the late teenage years.

Deficiencies in resident diabetes care quality may relate to continuity clinic design. This retrospective analysis compared diabetes care processes and outcomes within a traditional resident continuity clinic structure (2005) and after the implementation of a practice partnership system (PPS; 2009). Under PPS, patients were more likely to receive annual foot examinations (odds ratio [OR] = 11.6; 95% confidence interval [CI] = 7.2, 18.5), microalbumin screening (OR = 2.4; 95% CI = 1.6, 3.4), and aspirin use counseling (OR = 3.8; 95% CI = 2.5, 6.0) and were less likely to receive eye examinations (OR = 0.54; 95% CI = 0.36, 0.82). Hemoglobin A1c and lipid testing were similar between periods, and there was no difference in achievement of diabetes and blood pressure goals. Patients were less likely to achieve cholesterol goals under PPS (OR = 0.62; 95% CI = 0.39, 0.98). Resident practice partnerships may improve processes of diabetes care but may not affect intermediate outcomes.