A positive affect intervention alters leukocyte DNA methylation in sexual minority men with HIV who use methamphetamine.

OBJECTIVE: This epigenomics sub-study embedded within a randomized controlled trial examined whether an evidenced-based behavioral intervention model that decreased stimulant use altered leukocyte DNA methylation (DNAm). METHODS: Sexual minority men with HIV who use methamphetamine were randomized to a five-session positive affect intervention (n = 32) or an attention-control condition (n = 21), both delivered during three months of contingency management for stimulant abstinence. All participants exhibited sustained HIV virologic control - an HIV viral load less than 40 copies/mL at baseline and six months post-randomization. The Illumina EPIC BeadChip measured leukocyte methylation of cytosine-phosphate-guanosine (CpG) sites mapping onto five a priori candidate genes of interest (i.e., ADRB2, BDNF, FKBP5, NR3C1, OXTR). Functional DNAm pathways and soluble markers of immune dysfunction were secondary outcomes. RESULTS: Compared to the attention-control condition, the positive affect intervention significantly decreased methylation of CpG sites on genes that regulate ß2 adrenergic and oxytocin receptors. There was an inconsistent pattern for the direction of the intervention effects on methylation of CpG sites on genes for glucocorticoid receptors and brain-derived neurotrophic factor. Pathway analyses adjusting for the false discovery rate (padj < 0.05) revealed significant intervention-related alterations in DNAm of Reactome pathways corresponding to neural function as well as dopamine, glutamate, and serotonin release. Positive affect intervention effects on DNAm were accompanied by significant reductions in the self-reported frequency of stimulant use. CONCLUSIONS: There is an epigenetic signature of an evidence-based behavioral intervention model that reduced stimulant use, which will guide the identification of biomarkers for treatment responses.

Mindfulness-Based Stress Reduction for Symptom Management in Older Individuals with HIV-Associated Neurocognitive Disorder.

The growing number of people aging with HIV represents a group vulnerable to the symptom burdens of HIV-associated neurocognitive disorder (HAND). Among younger groups, Mindfulness-Based Stress Reduction (MBSR) has been shown to help people living with HIV manage HIV-related and other life stress, and although there is some theoretical and empirical evidence that it may be effective among those with cognitive deficits, the approach has not been studied in older populations with HAND. Participants (n = 180) 55 years or older with HIV and cognitive impairment were randomly assigned to either an 8-week MBSR arm or a waitlist control. We assessed the impact of MBSR compared to a waitlist control on psychological outcomes [stress, anxiety, depression, and quality of life (QOL)] and cognitive metrics (e.g., speed of information processing, working memory, attention, impulsivity) measured at baseline, immediately post intervention (8 weeks) and one month later (16 weeks). Intent to treat analyses showed significant improvement in the MBSR group compared to control on symptoms of depression from baseline to 8 weeks, however, the difference was not sustained at 16 weeks. The MBSR group also showed improvement in perceived QOL from baseline to 16 weeks compared to the waitlist control group. Cognitive performance did not differ between the two treatment arms. MBSR shows promise as a tool to help alleviate the symptom burden of depression and low QOL in older individuals living with HAND and future work should address methods to better sustain the beneficial impact on depression and QOL.

A web-based positive-affect intervention to reduce stress and improve well-being in women living with HIV - feasibility and acceptability of a single-arm, pilot study.

Women living with HIV (WLWH) experience high rates of depression but are underrepresented in mental health research. Positive emotions are associated with beneficial health outcomes in WLWH and should be a targeted component of psychological interventions in this population. Positive psychological interventions aim to increase positive emotions through the use of simple exercises, such as keeping a gratitude journal. We conducted a single-arm feasibility/acceptability study of a five-week, self-guided, web-based positive affect skills intervention in a sample of WLWH (N = 23) who also participate in a longitudinal observational study, the Women's Interagency HIV Study. The intervention was feasible as measured by home practice and post-intervention assessment completion, and acceptable as measured by exit interview feedback regarding recommendation of the program to friends or others living with HIV. On average, participants completed home practice for about 8 out of 9 skills. The mean response for recommendation of the program to a friend was 9.26/10 (SD = 1.63) and the mean response for recommendation of the program to others living with HIV was 9.68/10 (SD = 0.82). Participant feedback will be used to adapt and enhance the delivery of this intervention. Further studies are needed to assess efficacy and impact on psychological outcomes.

Randomized controlled trial of a positive emotion regulation intervention to reduce stress in family caregivers of individuals with Alzheimer's disease: protocol and design for the LEAF 2.0 study.

BACKGROUND: Caring for a loved one with Alzheimer's disease can be stressful, resulting in poorer emotional and physical health among family caregivers. Although supportive resources for caregivers are available, distance, caregiver health, and the daily demands of caregiving are barriers to access. Based on research demonstrating the importance of positive emotions in coping with stress, our previous trial showed that dementia caregivers who participated in facilitated, web-based delivery of a positive emotion regulation intervention called LEAF (Life Enhancing Activities for Family caregivers) experienced increased positive emotion and decreased depression and anxiety. Building on this evidence, the LEAF 2.0 study aims to test whether web-based, self-guided delivery can confer similar benefits for caregivers of individuals with Alzheimer's disease. METHODS: This paper presents the design and methods for LEAF 2.0, a 3-arm web-based randomized controlled trial (N = 500) in which family caregivers of patients with Alzheimer's disease (AD) are randomized to (1) the LEAF intervention facilitated remotely via the web (N = 200), (2) the LEAF intervention self-guided online (N = 200), or (3) an emotion reporting control (N = 100), which then crosses over to the intervention after approximately 6 months, half to the facilitated arm and half to the self-guided arm. We aim to (1) compare the effect of the facilitated and self-guided LEAF positive emotion interventions to an emotion reporting control condition on AD caregiver well-being (positive emotion, depression, anxiety, and perceived stress) and secondary outcomes (caregiving burden, caregiving self-efficacy, positive aspects of caregiving, quality of care, and AD patient quality of life); (2) assess whether effects are mediated by improvements in positive emotion or other aspects of caregiver well-being; and (3) test whether caregiver age or gender or the care recipient's dementia severity moderates the effects of the intervention. DISCUSSION: If demonstrated to be effective, LEAF can be widely disseminated and ultimately have a significant impact on the stress experienced by AD caregivers and the well-being of people living with Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03610698.

An eHealth, Positive Emotion Skills Intervention for Enhancing Psychological Well-Being in Young Adult Cancer Survivors: Results from a Multi-Site, Pilot Feasibility Trial.

BACKGROUND: Young adult (YA) cancer survivors experience clinically significant distress and have limited access to psychosocial support. Given growing evidence for unique adaptive benefits of positive emotion in the context of health-related and other life stress, we developed an eHealth positive emotion skills intervention for post-treatment survivors called EMPOWER (Enhancing Management of Psychological Outcomes With Emotion Regulation) and evaluated feasibility and proof of concept for reducing distress and enhancing well-being. METHOD: In this single-arm pilot feasibility trial, post-treatment YA cancer survivors (ages 18-39) participated in the EMPOWER intervention which included 8 skills (e.g., gratitude, mindfulness, acts of kindness). Participants completed surveys at baseline (pre-intervention), 8 weeks (post-intervention), and 12 weeks (1-month follow-up). Primary outcomes included feasibility (assessed by participation percentage) and acceptability (would recommend EMPOWER skills to a friend). Secondary outcomes included psychological well-being (mental health, positive affect, life satisfaction, meaning/purpose, general self-efficacy) and distress (depression, anxiety, anger). RESULTS: We assessed 220 YAs for eligibility; 77% declined. Of those screened, 44 (88%) were eligible and consented, 33 began the intervention, and 26 (79%) completed the intervention. Overall retention was 61% at 12 weeks. Average acceptability ratings were high (8.8/10). Participants (M = 30.8 years, SD = 6.6) were 77% women, 18% racial/ethnic minorities, and 34% breast cancer survivors. At 12 weeks, EMPOWER was associated with improved mental health, positive affect, life satisfaction, meaning/purpose, and general self-efficacy (ps < .05, ds = .45 to .63) and decreased anger (p < .05, d = - 0.41). CONCLUSION: EMPOWER demonstrated evidence of feasibility and acceptability as well as proof of concept for enhancing well-being and reducing distress. Self-guided, eHealth interventions show promise for addressing YA cancer survivors' needs and warrant additional research to optimize survivorship care. TRIAL REGISTRATION: ClinicalTrials .gov NCT02832154,  https://clinicaltrials.gov/ct2/show/NCT02832154.

Lability of prenatal stress during the COVID-19 pandemic links to negative affect in infancy.

The association between prenatal stress and children's socioemotional development is well established. The COVID-19 pandemic has been a particularly stressful period, which may impact the gestational environment. However, most studies to-date have examined prenatal stress at a single time point, potentially masking the natural variation in stress that occurs over time, especially during a time as uncertain as the pandemic. This study leveraged dense ecological momentary assessments from a prenatal randomized control trial to examine patterns of prenatal stress over a 14-week period (up to four assessments/day) in a U.S. sample of 72 mothers and infants. We first examined whether varied features of stress exposure (lability, mean, and baseline stress) differed depending on whether mothers reported on their stress before or during the pandemic. We next examined which features of stress were associated with 3-month-old infants' negative affect. We did not find differences in stress patterns before and during the pandemic. However, greater stress lability, accounting for baseline and mean stress, was associated with higher infant negative affect. These findings suggest that pathways from prenatal stress exposure to infant socioemotional development are complex, and close attention to stress patterns over time will be important for explicating these pathways.

Understanding the Association Between Mental Health Knowledge and Mental Health Service Utilization Among Black Adults.

Mental health knowledge limitations may contribute to the treatment gap among Black adults. We conducted an online cross-sectional study of Black adults in the United States (n = 262, aged 18-65 years) from diverse ethnic backgrounds (African-Americans, African immigrants, Afro-Caribbean immigrants). Gamma regression using generalized linear models was used to estimate the associations between mental health knowledge and willingness to seek help from mental health professionals. After adjusting for age, education and ethnicity, participants with higher specific knowledge about mental health (such as recognition of schizophrenia as a mental illness) were 26% more likely to report willingness to seek help from a mental health professional for personal and emotional problems (RR = 1.26, CI 1.12-1.41, p < 0.001). Knowledge building interventions (such as psychoeducation) that seek to increase specific knowledge (rather than general knowledge) may correlate more strongly with utilization of mental health services among Black adults.

Discrimination, Abuse, Harassment, and Burnout in Surgical Residency Training.

BACKGROUND: Physicians, particularly trainees and those in surgical subspecialties, are at risk for burnout. Mistreatment (i.e., discrimination, verbal or physical abuse, and sexual harassment) may contribute to burnout and suicidal thoughts. METHODS: A cross-sectional national survey of general surgery residents administered with the 2018 American Board of Surgery In-Training Examination assessed mistreatment, burnout (evaluated with the use of the modified Maslach Burnout Inventory), and suicidal thoughts during the past year. We used multivariable logistic-regression models to assess the association of mistreatment with burnout and suicidal thoughts. The survey asked residents to report their gender. RESULTS: Among 7409 residents (99.3% of the eligible residents) from all 262 surgical residency programs, 31.9% reported discrimination based on their self-identified gender, 16.6% reported racial discrimination, 30.3% reported verbal or physical abuse (or both), and 10.3% reported sexual harassment. Rates of all mistreatment measures were higher among women; 65.1% of the women reported gender discrimination and 19.9% reported sexual harassment. Patients and patients' families were the most frequent sources of gender discrimination (as reported by 43.6% of residents) and racial discrimination (47.4%), whereas attending surgeons were the most frequent sources of sexual harassment (27.2%) and abuse (51.9%). Proportion of residents reporting mistreatment varied considerably among residency programs (e.g., ranging from 0 to 66.7% for verbal abuse). Weekly burnout symptoms were reported by 38.5% of residents, and 4.5% reported having had suicidal thoughts during the past year. Residents who reported exposure to discrimination, abuse, or harassment at least a few times per month were more likely than residents with no reported mistreatment exposures to have symptoms of burnout (odds ratio, 2.94; 95% confidence interval [CI], 2.58 to 3.36) and suicidal thoughts (odds ratio, 3.07; 95% CI, 2.25 to 4.19). Although models that were not adjusted for mistreatment showed that women were more likely than men to report burnout symptoms (42.4% vs. 35.9%; odds ratio, 1.33; 95% CI, 1.20 to 1.48), the difference was no longer evident after the models were adjusted for mistreatment (odds ratio, 0.90; 95% CI, 0.80 to 1.00). CONCLUSIONS: Mistreatment occurs frequently among general surgery residents, especially women, and is associated with burnout and suicidal thoughts.

Sexual Minority Stress and Cellular Aging in Methamphetamine-Using Sexual Minority Men With Treated HIV.

OBJECTIVE: Sexual minority men (e.g., gay, bisexual, and other men who have sex with men) experience stigma and sexual minority stress, which are theorized to drive negative health outcomes. Sexual minority men with treated HIV display persistent immune dysregulation, which could be amplified by sexual minority stress responses to potentiate cellular aging. METHODS: This cross-sectional study included 52 sexual minority men living with HIV who had undetectable viral load (<40 copies/mL) and biologically confirmed recent methamphetamine use. Participants completed measures assessing sexual minority stress and openness about sexual minority status (i.e., outness). DNA methylation-derived outcomes included the following: the extrinsic epigenetic age acceleration clock, telomere length, naive CD4+ T-helper cells, and naive CD8+ T-cytotoxic/suppressor cells. RESULTS: After adjusting for negative affect and recent stimulant use, higher sexual minority stress was associated with a faster extrinsic epigenetic age acceleration clock ( ß = 0.29, p = .030), shorter telomere length ( ß = -0.43, p = .002), and fewer naive CD4+ (ß = -0.57, p < .001) and naive CD8+ T cells ( ß = -0.57, p < .001). Greater outness was associated with higher naive CD4+ ( ß = 0.32, p = .030) and naive CD8+ T cells ( ß = 0.38, p = .008) as well as lower plasma interleukin 6 ( ß = -0.33, p = .027). CONCLUSIONS: Sexual minority stress processes are associated with markers of cellular aging and inflammation in methamphetamine-using sexual minority men living with HIV. Longitudinal research should elucidate biobehavioral mechanisms linking sexual minority stress processes with accelerated cellular aging in those with and without HIV.

Finding Sunshine on a Cloudy Day: A Positive Affect Intervention for Co-Occurring Methamphetamine Use and HIV.

Among sexual minority men (i.e., gay, bisexual, and other men who have sex with men) living with HIV, those who use methamphetamine experience profound health disparities. Affect Regulation Treatment to Enhance Methamphetamine Intervention Success (ARTEMIS) is an evidence-based, 5-session, individually delivered positive affect intervention adapted for sexual minority men living with HIV who use methamphetamine. ARTEMIS was designed to amplify the benefits of evidence-based substance use interventions such as contingency management (CM) with this high-priority population. Delivering ARTEMIS during CM has been shown to assist participants in reducing stimulant use, increasing positive affect, and achieving durable reductions in HIV viral load. We describe the theoretical underpinnings of the ARTEMIS intervention, provide details of the training and session protocols with a case example, and discuss implications for future applications in research and clinical settings.

Association of Surgical Resident Wellness With Medical Errors and Patient Outcomes.

OBJECTIVES: The aims of this study were to: (1) measure the prevalence of self-reported medical error among general surgery trainees, (2) assess the association between general surgery resident wellness (ie, burnout and poor psychiatric well-being) and self-reported medical error, and (3) examine the association between program-level wellness and objectively measured patient outcomes. SUMMARY OF BACKGROUND DATA: Poor wellness is prevalent among surgical trainees but the impact on medical error and objective patient outcomes (eg, morbidity or mortality) is unclear as existing studies are limited to physician and patient self-report of events and errors, small cohorts, or examine few outcomes. METHODS: A cross-sectional survey was administered immediately following the January 2017 American Board of Surgery In-training Examination to clinically active general surgery residents to assess resident wellness and self-reported error. Postoperative patient outcomes were ascertained using a validated national clinical data registry. Associations were examined using multivariable logistic regression models. RESULTS: Over a 6-month period, 22.5% of residents reported committing a near miss medical error, and 6.9% reported committing a harmful medical error. Residents were more likely to report a harmful medical error if they reported frequent burnout symptoms [odds ratio 2.71 (95% confidence interval 2.16-3.41)] or poor psychiatric well-being [odds ratio 2.36 (95% confidence interval 1.92-2.90)]. However, there were no significant associations between program-level resident wellness and any of the independently, objectively measured postoperative American College of Surgeons National Surgical Quality improvement Program outcomes examined. CONCLUSIONS: Although surgical residents with poor wellness were more likely to self-report a harmful medical error, there was not a higher rate of objectively reported outcomes for surgical patients treated at hospitals with higher rates of burnout or poor psychiatric well-being.

Tryptophan depletion predicts lower positive affect in sexual minority men living with HIV who use methamphetamine.

This longitudinal study with 76 sexual minority men living with HIV who use methamphetamine examined whether dysregulation of essential amino acid precursors for neurotransmitters at baseline predicted positive and negative affect at 15 months. After controlling for covariates including baseline positive affect, a higher baseline kynurenine/tryptophan (K/T) ratio independently predicted lower positive affect at 15 months (ß = - 18.31; 95% CI = - 35.35, - 1.27; p = 0.036). Future clinical research should examine whether bio-behavioral interventions targeting tryptophan degradation could optimize treatments for people living with co-occurring HIV and stimulant use disorders.

Positive Affect and Health: What Do We Know and Where Next Should We Go?

Positive affect (PA) is associated with better health across a wide range of physical health outcomes. This review reflects on why the study of PA is an essential component of our understanding of physical health and expands on pathways that connect these two variables. To encourage forward movement in this burgeoning research area, measurement and design issues in the study of PA and health are discussed, as are the connections between PA and a range of different health outcomes. Plausible biological, social, and behavioral pathways that allow for positive feelings to get under the skin and influence physical wellness are detailed and framed in the context of several theoretical models. Finally, new directions for the field and important methodological and interpretative considerations that are essential to moving this important research area forward are explored.

The relationship between emotion regulation and well-being in patients with mental disorders: A meta-analysis.

BACKGROUND: The importance of both specific emotion regulation strategies and overall deficits in emotion regulation in the context of psychopathology is widely recognized. Besides alleviating psychological symptoms, improving mental well-being is increasingly considered important in treatment of people with mental disorders. However, no comprehensive meta-analysis on the relationship between emotion regulation and well-being in people with mental disorders has been conducted yet. OBJECTIVE: The aim of the current study was to synthesize and meta-analyze evidence regarding the relationship between emotion regulation and well-being in clinical samples across studies. METHOD: A systematic literature search was conducted in PsycINFO, PubMed and Scopus and 94 cross-sectional effect sizes from 35 studies were meta-analyzed to explore this relationship. To be eligible for the meta-analysis, studies had to include a clinical sample, assess at least one specific emotion regulation strategy or overall deficits in emotion regulation and include well-being as outcome. RESULTS: The findings showed significant small to moderate negative relationships with well-being for the strategies avoidance (r = -0.31) and rumination (r = -0.19) and positive relationships with reappraisal (r = 0.19) and acceptance (r = 0.42). Grouping together putative adaptive and maladaptive strategies revealed similar sized relationships with well-being in the expected direction. Overall deficits in emotion regulation showed a negative moderate correlation with well-being (r = -0.47). No substantial difference in relationships was found when clustering studies into hedonic and eudaimonic well-being. CONCLUSION: Our findings suggest that emotion regulation is not merely related with psychopathology, but also with well-being in general as well as hedonic and eudaimonic well-being. Therefore, it might also be important to improve emotion regulation when aiming to improve well-being in people with mental disorders.

A novel technology-enhanced internalized stigma and shame intervention for HIV-positive persons with substance use disorders.

Internalized stigma, shame, and other negative self-conscious emotions are inadequately addressed barriers to HIV-related self-care, particularly among people actively using substances. Innovative approaches are needed to optimize antiretroviral treatment (ART) adherence as well as engagement in HIV care among people living with HIV and substance use disorders. Based on qualitative feedback from providers and patients, we iteratively developed and conducted a proof-of-concept study of a relatively brief transdiagnostic emotion regulation intervention designed to improve ART adherence care by addressing behavioral and psychological barriers, including internalized stigma and shame, among people living with HIV and active substance use disorders. The final intervention included 5 individual sessions focused on metacognitive awareness of emotions and thoughts, cognitive reframing of dysfunctional thoughts about the self using concepts such as self-compassion, and identifying and reaching the participants' personalized HIV-self-care goal(s). All participants received daily texts querying current emotion and weekly texts querying ART adherence and substance use. To extend the effects of the intervention, we developed a personalized bi-directional text component through which participants received their personalized compassionate self-statements, informed by the intervention content, in response to their answers to emotion queries for 8 weeks after the 5 sessions. The texts modeled using compassionate self-statements as a form of cognitive reframing, consistent with cognitive restructuring of distorted core beliefs. We consented 10 participants living with HIV and problematic substance use in the proof-of-concept pilot. Of the 8 participants who completed all intervention sessions, participants replied to 70% of all text messages sent. All 8 reported strong acceptability of the intervention content. This emotion-focused, technology-enhanced intervention demonstrated proof-of-concept, in that this patient population would participate in this intervention. A larger randomized controlled pilot is needed to determine feasibility and acceptability among people living with HIV and substance use disorders, a hard-to-reach and underserved population.

A Randomized Controlled Trial of a Text Messaging Intervention to Promote Virologic Suppression and Retention in Care in an Urban Safety-Net Human Immunodeficiency Virus Clinic: The Connect4Care Trial.

Background: Text messaging is a promising strategy to support human immunodeficiency virus (HIV) care engagement, but little is known about its efficacy in urban safety-net HIV clinics. Methods: We conducted a randomized controlled trial of a supportive and motivational text messaging intervention, Connect4Care (C4C), among viremic patients who had a history of poor retention or were new to the clinic. Participants were randomized (stratified by new or established HIV diagnosis status) to receive either of the following for 12 months: (1) thrice-weekly intervention messages, plus texted primary care appointment reminders and a monthly text message requesting confirmation of study participation or (2) texted reminders and monthly messages alone. Viral load was assessed at 6 and 12 months. The primary outcome was virologic suppression (<200 copies/mL) at 12 months, estimated via repeated-measures log-binomial regression, adjusted for new-diagnosis status. The secondary outcome was retention in clinic care. Results: Between August 2013 and November 2015, a total of 230 participants were randomized. Virologic suppression at 12 months was similar in intervention and control participants (48.8% vs 45.8%, respectively), yielding a rate ratio of 1.07 (95% confidence interval, .82-1.39). Suppression was higher in those with newly diagnosed infection (78.3% vs 45.3%). There were no intervention effects on the secondary outcome. Exploratory analyses suggested that patients with more responses to study text messages had better outcomes, regardless of arm. Conclusions: The C4C text messaging intervention did not significantly increase virologic suppression or retention in care. Response to text messages may be a useful way for providers to gauge risk for poor HIV outcomes. Clinical Trials Registration: NCT01917994.

A randomized, controlled trial of mindfulness-based stress reduction in HIV infection.

OBJECTIVE: Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ T-cell counts) and psychological outcomes in persons with HIV-1 infection. METHODS: We randomly assigned participants with HIV-1 infection and CD4 T-cell counts >350 cells/µl who were not on antiretroviral therapy in a 1:1 ratio to either an MBSR group (n = 89) or an HIV disease self-management skills group (n = 88). The study was conducted at the University of California at San Francisco. We assessed immunologic (CD4, c-reactive protein, IL-6, and d-dimer) and psychological measures (Beck Depression Inventory for depression, modified Differential Emotions Scale for positive and negative affect, Perceived stress-scale, and mindfulness) at 3, 6 and 12 months after initiation of the intervention; we used multiple imputation to address missing values. RESULTS: We observed statistically significant improvements from baseline to 3-months within the MBSR group in depression, positive and negative affect, perceived stress, and mindfulness; between group differences in change were significantly greater in the MBSR group only for positive affect (per item difference on DES-positive 0.25, 95% CI 0.049, 0.44, p = .015). By 12 months the between group difference in positive affect was not statistically significant, although both groups had trends toward improvements compared to baseline in several psychological outcomes that were maintained at 12-months; these improvements were only statistically significant for depression and negative affect in the MBSR group and perceived stress for the control group. The groups did not differ significantly on rates of antiretroviral therapy initiation (MBSR = 39%, control = 29%, p = .22). After 12 months, the mean decrease in CD4+ T-cell count was 49.6 cells/µl in participants in the MBSR arm, compared to 54.2 cells/µl in the control group, a difference of 4.6 cells favoring the MBSR group (95% CI, -44.6, 53.7, p = .85). The between group differences in other immunologic-related outcomes (c-reactive protein, IL-6, HIV-1 viral load, and d-dimer) were not statistically significant at any time point. CONCLUSIONS: MBSR improved positive affect more than an active control arm in the 3 months following the start of the intervention. However, this difference was not maintained over the 12-month follow-up and there were no significant differences in immunologic outcomes between intervention groups. These results emphasize the need for further carefully designed research if we are to translate evidence linking psychological states to immunological outcomes into evidence-based clinical practices.

Feasibility of an Internet-based positive psychological intervention for hemodialysis patients with symptoms of depression.

BACKGROUND: Depression is a pervasive psychological issue facing hemodialysis (HD) patients. Novel technology-based treatment strategies that deploy psychology-based interventions have not been the focus for therapy and few published studies exist. The aim of the current trial is to determine the feasibility and acceptability of an Internet-based positive psychological intervention in HD patients with comorbid depressive symptoms. METHODS: HD patients (n = 14) with elevated symptoms of depression were enrolled in a single-arm pre-post trial with clinical assessments at baseline and immediately post intervention. Chairside during regularly scheduled HD treatment, patients utilized a web browser to complete online modules promoting skills for increasing positive emotion over a 5-week period using Apple IPads. Targeted skills included noting of daily positive events, gratitude, positive reappraisal, acts of kindness, and mindfulness/meditation. RESULTS: Twelve of 14 patients completed the program for an 85.7% retention rate. Participants felt satisfied with each session and offered consistently positive feedback. On average, participants visited the website 3.5 times per week. Significant improvements were evident for depressive symptoms (15.3 vs. 10.9; p = 0.04), as per the Center for Epidemiological Studies Depression Scale. CONCLUSIONS: An innovative Internet-based positive psychological intervention represents a feasible and useful therapeutic option for HD patients with depressive symptoms.

A randomized pilot trial of a positive affect skill intervention (lessons in linking affect and coping) for women with metastatic breast cancer.

BACKGROUND: We conducted a randomized pilot trial to examine the feasibility, acceptability, and preliminary efficacy of a 5 week positive affect skills intervention (LILAC: lessons in linking affect and coping) for women with metastatic breast cancer. Additionally, we examined whether online delivery of the intervention would offer comparable benefits as in-person delivery. METHODS: Women with metastatic breast cancer (N = 39) were randomized to an in-person intervention, online intervention, or in-person attention-matched control. Psychological well-being (depression [Center for Epidemiologic Studies Depression Scale], positive and negative affect [Differential Emotions Scale], cancer-specific quality of life [Multidimensional Quality of Life Scale-Cancer Version]), and positive coping (mindfulness, positive-affect skill use, and self-compassion [Self-Compassion Scale: Short-Form]) were assessed at baseline, 1 week post-intervention, and 1 month post-intervention follow-up. RESULTS: The LILAC intervention showed good feasibility, acceptability, and retention. Although the study was not adequately powered to detect between-group differences in change on preliminary efficacy outcomes, within-group comparisons revealed that LILAC participants (in-person and online combined) showed reductions in depression and negative affect by the 1 month follow-up (d = -0.81). Notably, LILAC participants fell below the clinical threshold for depression (Center for Epidemiologic Studies Depression Scale = 16) by the 1 month follow-up (t[17] = -2.22, P = .04, d = -0.52), whereas control participants did not differ from threshold (t[9] = 0.45, P = .66, d = 0.14). CONCLUSIONS: The LILAC intervention, regardless of delivery method, shows feasibility, acceptability, and preliminary efficacy for promoting psychological well-being in women with metastatic breast cancer. This research provides support for a larger randomized trial to test more definitively the potential benefits of LILAC. A strength of the LILAC intervention includes its innovative focus on positive affect. The efficacy of the online delivery suggests the potential for widespread Internet dissemination.

An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Type 2 diabetes is a prevalent, chronic disease for which diet is an integral aspect of treatment. In our previous trial, we found that recommendations to follow a very low-carbohydrate ketogenic diet and to change lifestyle factors (physical activity, sleep, positive affect, mindfulness) helped overweight people with type 2 diabetes or prediabetes improve glycemic control and lose weight. This was an in-person intervention, which could be a barrier for people without the time, flexibility, transportation, social support, and/or financial resources to attend. OBJECTIVE: The aim was to determine whether an online intervention based on our previous recommendations (an ad libitum very low-carbohydrate ketogenic diet with lifestyle factors; "intervention") or an online diet program based on the American Diabetes Associations' "Create Your Plate" diet ("control") would improve glycemic control and other health outcomes among overweight individuals with type 2 diabetes. METHODS: In this pilot feasibility study, we randomized overweight adults (body mass index ≥25) with type 2 diabetes (glycated hemoglobin [HbA1c] 6.5%-9.0%) to a 32-week online intervention based on our previous recommendations (n=12) or an online diet program based around a plate method diet (n=13) to assess the impact of each intervention on glycemic control and other health outcomes. Primary and secondary outcomes were analyzed by mixed-effects linear regression to compare outcomes by group. RESULTS: At 32 weeks, participants in the intervention group reduced their HbA1c levels more (estimated marginal mean [EMM] -0.8%, 95% CI -1.1% to -0.6%) than participants in the control group (EMM -0.3%, 95% CI -0.6% to 0.0%; P=.002). More than half of the participants in the intervention group (6/11, 55%) lowered their HbA1c to less than 6.5% versus 0% (0/8) in the control group (P=.02). Participants in the intervention group lost more weight (EMM -12.7 kg, 95% CI -16.1 to -9.2 kg) than participants in the control group (EMM -3.0 kg, 95% CI -7.3 to 1.3 kg; P<.001). A greater percentage of participants lost at least 5% of their body weight in the intervention (10/11, 90%) versus the control group (2/8, 29%; P=.01). Participants in the intervention group lowered their triglyceride levels (EMM -60.1 mg/dL, 95% CI -91.3 to -28.9 mg/dL) more than participants in the control group (EMM -6.2 mg/dL, 95% CI -46.0 to 33.6 mg/dL; P=.01). Dropout was 8% (1/12) and 46% (6/13) for the intervention and control groups, respectively (P=.07). CONCLUSIONS: Individuals with type 2 diabetes improved their glycemic control and lost more weight after being randomized to a very low-carbohydrate ketogenic diet and lifestyle online program rather than a conventional, low-fat diabetes diet online program. Thus, the online delivery of these very low-carbohydrate ketogenic diet and lifestyle recommendations may allow them to have a wider reach in the successful self-management of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01967992; https://clinicaltrials.gov/ct2/show/NCT01967992 (Archived by WebCite at http://www.webcitation.org/6o0fI9Mkq).