Morning light treatment for traumatic stress: The role of amygdala reactivity study protocol.

BACKGROUND: Exposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye. METHODS: In this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment. DISCUSSION: Morning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

Real-World Performance of High-Flux Dialyzers in Patients With Hypoalbuminemia.

There is little research on factors that influence the choice of dialyzer in patients undergoing hemodialysis. In patients at risk for poorer outcomes, including those with hypoalbuminemia, understanding how this choice impacts clinical parameters could inform patient management. The objective of this real-world analysis was to evaluate the use and performance of four single-use (i.e., nonreuse [NR]), high-flux Optiflux dialyzers with varying surface areas (F160NR [1.5 m2], F180NR [1.7 m2], F200NR [1.9 m2], and F250NR [2.5 m2]) in patients (N = 271) with baseline hypoalbuminemia (≤3.5 g/dl) receiving hemodialysis at a medium-sized dialysis organization. Thrice weekly, in-center dialysis was delivered for 6 months without adjustments to the hemodialysis prescription. Larger dialyzers were more frequently used in men, patients with higher body mass indices, and those with diabetes. Increases in serum albumin from baseline (month 1) to month 6 (p < 0.05) were observed with all dialyzer sizes. A mean increase in hemoglobin of 0.31 g/dl was also observed (p < 0.001). Among patients exhibiting increased serum albumin levels (n = 177), reductions in the neutrophil-to-lymphocyte ratio, a marker of inflammation, were observed (mean: 0.90; p < 0.001). These results support the use of high-flux dialyzers in patients with hypoalbuminemia.

Associations between Self-Reported Daily Affect Ratings and Sleep Duration during the First Two Weeks of Antidepressant Therapy.

Background: In the context of a randomized controlled trial evaluating the efficacy of augmenting fluoxetine treatment in young adults with major depressive disorder (MDD) using a modified repeated partial sleep deprivation protocol contrasting 2 weeks of restricted time in bed (i.e., 6 h TIB) to no time in bed restriction (i.e., 8 h TIB) the study examines whether sleep duration and the timing of repeated partial sleep deprivation predicts patient-reported affect ratings. Participants: Participants included 58 young adults with DSM-IV-diagnosed MDD. Methods: Daily ratings of affect and sleep were collected during the first 2 weeks of initiating fluoxetine treatment, yielding 630 person-days. Actigraphy monitoring was employed to assess compliance with time in bed condition. Results: Negative affect ratings and positivity ratios in the morning were more improved among participants assigned to the 6 h TIB condition compared to the 8 h TIB group. Participants whose bedtime was delayed by 2-h nightly demonstrated the most significant improvement in negative affect and positivity ratio during the first 2 weeks of fluoxetine therapy. Moreover, the trajectory of morning negative affect ratings in the first 2 weeks was predictive of remission after 4 weeks of fluoxetine therapy. Conclusions: These findings suggest that monitoring changes in daily affect may be a valuable marker of early treatment response in young adults with MDD.

Telemedicine versus face-to-face delivery of cognitive behavioral therapy for insomnia: a randomized controlled noninferiority trial.

STUDY OBJECTIVES: In a randomized controlled noninferiority trial, we compared face-to-face and telemedicine delivery (via the AASM SleepTM platform) of cognitive-behavioral therapy (CBT) for insomnia for improving insomnia/sleep and daytime functioning at posttreatment and 3-month follow-up. A secondary objective compared the modalities on treatment credibility, satisfaction, and therapeutic alliance. METHODS: A total of 65 adults with chronic insomnia (46 women, 47.2 ± 16.3 years of age) were randomized to 6 sessions of CBT for insomnia delivered individually via AASM SleepTM (n = 33, CBT-TM) or face-to-face (n = 32, CBT-F2F). Participants completed sleep diaries, the Insomnia Severity Index (ISI), and daytime functioning measures at pretreatment, posttreatment, and 3-month follow-up. Treatment credibility, satisfaction, and therapeutic alliance were compared between treatment modalities. The ISI was the primary noninferiority outcome. RESULTS: Based on a noninferiority margin of four points on the ISI and, after adjusting for confounders, CBT-TM was noninferior to CBT-F2F at posttreatment (ß = 0.54, SE = 1.10, 95% CI = 1.64 to 2.72) and follow-up (ß = 0.34, SE = 1.10, 95% CI = 1.83 to 2.53). Daytime functioning measures, except the physical composite scale of the SF-12, were significantly improved at posttreatment and follow-up, with no difference between treatment formats. CBT-TM sessions were, on average, nearly 10 min shorter, yet participant ratings of therapeutic alliance were similar to CBT-F2F. CONCLUSIONS: Telemedicine delivery of CBT for insomnia is not inferior to face-to-face for insomnia severity and yields similar improvements on other sleep and daytime functioning outcomes. Further, telemedicine allows for more efficient treatment delivery while not compromising therapeutic alliance. CLINICAL TRIAL REGISTRATION NUMBER: NCT03293745.

Insomnia as a Moderator of Response to Time in Bed Restriction for Augmenting Antidepressant Treatment: A Preliminary Investigation.

BACKGROUND: There are complex, bidirectional associations between major depressive disorder and insomnia. In the present study, we evaluated insomnia as a moderator of response to antidepressant therapy in the context of a sleep manipulation (time in bed restriction) for major depressive disorder. METHODS: Fifty-eight adults with major depressive disorder received 8 weeks of fluoxetine 20-40 mgs and were randomized to 8 hr time in bed (8h TIB) or 6 hr time in bed (6h TIB) for the first 2 weeks (participants in the 6h TIB condition were further randomized to a delayed bedtime (Late Bedtime) or advanced rise time (Early Rise Time) group). Insomnia was assessed at baseline using the Insomnia Severity Index. Depression symptom severity was determined by the clinician-rated 17-item Hamilton Rating Scale for Depression (HAMD-17), completed weekly. RESULTS: A group by time interaction was observed whereby HAMD-17 scores were higher for participants assigned to the 6h TIB group (without insomnia, weeks 3 through 7; with insomnia from week 3 through 6, ps < .05) relative to participants without insomnia assigned to the 8h TIB group. There were no differences in HAMD-17 scores for participants with insomnia in the 6h TIB group relative to the 8h TIB group. CONCLUSION: These preliminary findings suggest that response to fluoxetine may be hindered by TIB restriction in individuals without insomnia. Individuals with insomnia respond similarly to fluoxetine regardless of whether their TIB is restricted. Limitations include exclusive use of self-report measures to categorize insomnia, and small sample sizes in several of the subgroups.

Moving Towards Wellness: Physical activity practices, perspectives, and preferences of users of outpatient mental health service.

OBJECTIVE: This study assessed the beliefs, barriers and preferences for physical activity (PA) among users of outpatient mental health (MH) services. Outpatient discussions with MH providers were also evaluated. METHOD: Between September-December 2014, patient advisors approached adult and family members in an academic MH clinic's waiting room on high volume patient visit days during peak clinic hours; 83% participated in the survey. Analyses were restricted to MH services users (n=295). RESULTS: Fully 84% of respondents reported a link between PA and their mood or anxiety level and 85% wanted to be more active. Less than half currently met US PA guidelines (≥150min/week). Most (52%) reported their mood limited their involvement in PA. Only 37% reported their MH providers regularly discussed PA with them. Beliefs about the benefits of physical activity (p<0.0001), mood limiting their ability to be physically active (p=0.03), and wanting to be more physically active (p=0.02) were significant predictors of PA (min/week) in the multivariate linear regression model. CONCLUSIONS: Most MH outpatients may need and want assistance in increasing PA. Patient-centered research could inform the development of PA programs in MH settings.

Relationships between circadian measures, depression, and response to antidepressant treatment: A preliminary investigation.

Few studies have examined relationships between circadian rhythms and unipolar major depressive disorder. Further, no study to date has examined circadian markers as predictors of response to depression treatment. In the present study, we examined associations between circadian timing and its alignment with sleep and depression severity in 30 adults with major depressive disorder who completed a randomized controlled trial of two weeks of time in bed (TIB) restriction administered adjunctive to fluoxetine, with a focus on sex differences. Thirty adults with major depressive disorder received 8 weeks of fluoxetine 20-40 mgs and were randomized to 8h TIB or 6h TIB for the first 2 weeks. Participants in the 6h TIB condition were further randomized to a delayed bedtime or advanced risetime group. Circadian measures included dim light melatonin onset (DLMO) and the difference between DLMO and midsleep point (i.e., phase angle difference). Depression was assessed using the Hamilton Rating Scale for Depression. For females, a phase delay after 2 weeks of fluoxetine and the experimental TIB manipulation was associated with a poorer response to fluoxetine, and depression severity was negatively correlated with phase angle difference, whereas males showed a positive correlation between depression severity and phase angle difference.

Dialysis Catheter-Related Bloodstream Infections: A Cluster-Randomized Trial of the ClearGuard HD Antimicrobial Barrier Cap.

BACKGROUND: The rate of bloodstream infections (BSIs) is disproportionately high in hemodialysis (HD) patients with central venous catheters (CVCs) versus those with permanent accesses, contributing to poorer outcomes, such as increased rates of death and hospitalizations. STUDY DESIGN: 12-month, prospective, cluster-randomized, multicenter, open-label trial. SETTING & PARTICIPANTS: 40 Fresenius Medical Care North America dialysis facilities were matched and paired by positive blood culture rate and number of patients with CVCs and then cluster-randomized with 20 in each study group. 2,470 patients participated in the study (1,245, intervention group; 1,225, control group), accruing approximately 350,000 CVC-days. INTERVENTION: Use of ClearGuard HD Antimicrobial Barrier Caps versus use of standard CVC caps; assigned at the facility level. OUTCOME: Primary end point was positive blood culture rate as an indicator of BSI rate. MEASUREMENTS: Positive blood cultures, hospital admissions for BSI, hospitalization-days for BSI, intravenous antibiotic starts, and CVC-days. RESULTS: Baseline positive blood culture rates were similar (P=0.8) between groups. Use of ClearGuard HD caps for 12 months was associated with a 56% lower BSI rate versus use of standard CVC caps (0.26 vs 0.59/1,000 CVC-days, respectively; P=0.01). When considering sustained use (defined as last 6 months of the study), the intervention versus the control was associated with a 69% lower BSI rate (0.22 vs 0.72/1,000 CVC-days, respectively; P=0.01), 43% fewer hospital admissions for BSI (0.28 vs 0.48/1,000 CVC-days, respectively; P=0.04), and 51% fewer hospitalization days for BSI (2.42 vs 4.94/1,000 CVC-days, respectively; P=0.04). No device-related adverse events were reported. LIMITATIONS: Study was open label; patients occasionally received HD at nonresearch facilities; patients did not receive the intervention when hospitalized. CONCLUSIONS: The findings show that use of ClearGuard HD Antimicrobial Barrier Caps, when compared with standard CVC caps, significantly lowers rates of catheter-related BSIs and hospital admissions for BSI in HD patients using CVCs.

Effects of Restricted Time in Bed on Antidepressant Treatment Response: A Randomized Controlled Trial.

OBJECTIVE: Antidepressant response onset is delayed in individuals with major depressive disorder (MDD). This study compared remission rates and time to remission onset for antidepressant medication delivered adjunctively to nightly time in bed (TIB) restriction of 6 hours or 8 hours for the initial 2 weeks. METHODS: Sixty-eight adults with DSM-IV-diagnosed MDD (mean ± SD age = 25.4 ± 6.6 years, 34 women) were recruited from September 2009 to December 2012 in an academic medical center. Participants received 8 weeks of open-label fluoxetine 20-40 mg and were randomized to 1 of 3 TIB conditions for the first 2 weeks: 8-hour TIB (n = 19); 6-hour TIB with a 2-hour bedtime delay (late bedtime, n = 24); or 6-hour TIB with a 2-hour rise time advance (early rise time, n = 25). Clinicians blinded to TIB condition rated symptom severity weekly. Symptom severity, remission rates, and remission onset as rated by the 17-item Hamilton Depression Rating Scale were the primary outcomes. RESULTS: Mixed effects models indicated lower depression severity for the 8-hour TIB compared to the 6-hour TIB group overall (F8, 226.9 = 2.1, P < .05), with 63.2% of 8-hour TIB compared to 32.6% of 6-hour TIB subjects remitting by week 8 (χ²1 = 4.9, P < .05). Remission onset occurred earlier for the 8-hour TIB group (hazard ratio = 0.43; 95% CI, 0.20-0.91; P < .03), with no differences between 6-hour TIB conditions. CONCLUSIONS: Two consecutive weeks of nightly 6-hour TIB does not accelerate or improve antidepressant response. Further research is needed to determine whether adequate sleep opportunity is important to antidepressant treatment response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01545843.

Outcomes among patients receiving in-center, self-care hemodialysis.

Modalities of renal replacement therapy are categorized into incenter hemodialysis and home therapies. A subset of hemodialysis patients referred to as in-center self-care hemodialysis (ICSCHD) receive patient training as if they were going home but instead perform their dialysis in-center with minimal staff support. Preliminary data suggests ICSCHD is associated with better outcomes than traditional in-center hemodialysis. We looked at ICSCHD patients initiating maintenance dialysis from April 1, 2011 to March 30, 2014 and compared them at a 1:2 ratio to propensity-score matched controls from surrounding facilities within the same catchment area. The median follow-up was 14 months. Patients on ICSCHD had lower mortality rate (0.02 vs 0.07 per patient year; p <0.05), fewer hospitalization events (0.82 vs. 1.70 per patient year; p = 0.008) and fewer missed treatments (1.1% vs 3.8% of all treatments; p = 0.005) than matched controls. We concluded that patients on ICSCHD had lower mortality rates and fewer hospital days than well-matched controls and spent more time on dialysis and missed fewer treatments. Establishing a facility-wide.

The Glycemic Indices in Dialysis Evaluation (GIDE) study: Comparative measures of glycemic control in diabetic dialysis patients.

The validity of hemoglobin A1c (HgbA1c) is undergoing increasing scrutiny in the advanced CKD/ESRD (chronic kidney disease/end-stage renal disease) population, where it appears to be discordant from other glycemic indices. In the Glycemic Indices in Dialysis Evaluation (GIDE) Study, we sought to assess correlation of HgbA1c with casual glucose, glycated albumin, and serum fructosamine in a large group of diabetic patients on dialysis. From 26 dialysis facilities in the United States, 1758 diabetic patients (hemodialysis = 1476, peritoneal dialysis = 282) were enrolled in the first quarter of 2013. The distributions of HgbA1c and the other glycemic indices were analyzed. Intra-patient coefficients of variation and correlations among the four glycemic indices were determined. Patients with low HgbA1c values were both on higher erythropoietin (ESA) doses and more anemic. Serum glucose exhibited the highest intra-patient variability over a 3-month period; variability was modest among the other glycemic indices, and least with HgbA1c. Statistical analyses inclusive of all glycemic markers indicated modest to strong correlations. HgbA1c was more likely to be in the target range than glycated albumin or serum fructosamine, suggesting factors which may or may not be directly related to glycemic control, including anemia, ESA management, and iron administration, in interpreting HgbA1c values. These initial results from the GIDE Study clarify laboratory correlations among glycemic indices and add to concerns about reliance on HgbA1c in patients with diabetes and advanced kidney disease.

Depressive affect and hospitalization risk in incident hemodialysis patients.

BACKGROUND AND OBJECTIVES: Recent studies demonstrated an association between depressive affect and higher mortality risk in incident hemodialysis patients. This study sought to determine whether an association also exists with hospitalization risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All 8776 adult incident hemodialysis patients with Medical Outcomes Study Short Form 36 survey results treated in Fresenius Medical Care North America facilities in 2006 were followed for 1 year from the date of survey, and all hospitalization events lasting >24 hours were tracked. A depressive affect score was derived from responses to two Medical Outcomes Study Short Form 36 questions ("down in the dumps" and "downhearted and blue"). A high depressive affect score corresponded with an average response of "some of the time" or more frequent occurrence. Cox and Poisson models were constructed to determine associations of depressive affect scores with risk for time to first hospitalization and risk for hospitalization events, as well as total days spent in the hospital, respectively. RESULTS: Incident patients with high depressive affect score made up 41% of the cohort and had a median (interquartile range) hospitalization event rate of one (0, 3) and 4 (0, 15) total hospital days; the values for patients with low depressive affect scores were one (0, 2) event and 2 (0, 11) days, respectively. For high-scoring patients, the adjusted hazard ratio for first hospitalization was 1.12 (1.04, 1.20). When multiple hospital events were considered, the adjusted risk ratio was 1.13 (1.02, 1.25) and the corresponding risk ratio for total hospital days was 1.20 (1.07, 1.35). High depressive affect score was generally associated with lower physical and mental component scores, but these covariates were adjusted for in the models. CONCLUSIONS: Depressive affect in incident hemodialysis patients was associated with higher risk of hospitalization and more hospital days. Future studies are needed to investigate the effect of therapeutic interventions to address depressive affect in this high-risk population.

Sickle trait in African-American hemodialysis patients and higher erythropoiesis-stimulating agent dose.

African Americans require higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait and other hemoglobinopathy traits on anemia in dialysis patients has not been adequately evaluated. We performed a cross-sectional study of a large cohort of adult African-American hemodialysis patients in the United States to determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing. Laboratory and clinical data were obtained over 6 months in 2011. Among 5319 African-American patients, 542 (10.2%) patients had sickle cell trait, and 129 (2.4%) patients had hemoglobin C trait; no other hemoglobinopathy traits were present. Sickle cell trait was more common in this cohort than the general African-American population (10.2% versus 6.5%-8.7%, respectively, P<0.05). Among 5002 patients (10.3% sickle cell trait and 2.4% hemoglobin C trait) receiving ESAs, demographic and clinical variables were similar across groups, with achieved hemoglobin levels being nearly identical. Patients with hemoglobinopathy traits received higher median doses of ESA than patients with normal hemoglobin (4737.4 versus 4364.1 units/treatment, respectively, P=0.02). In multivariable analyses, hemoglobinopathy traits associated with 13.2% more ESA per treatment (P=0.001). Within subgroups, sickle cell trait patients received 13.2% (P=0.003) higher dose and hemoglobin C trait patients exhibited a similar difference (12.9%, P=0.12). Sensitivity analyses using weight-based dosing definitions and separate logistic regression models showed comparable associations. Our findings suggest that the presence of sickle cell trait and hemoglobin C trait may explain, at least in part, prior observations of greater ESA doses administered to African-American dialysis patients relative to Caucasian patients.

Exercise for adolescents with depressive disorders: a feasibility study.

Objectives. Adolescence is associated with increased depressive symptoms and decreased aerobic exercise, yet the relationship between exercise and clinical depression among adolescents requires further examination. This study assessed the feasibility of a 12-week intervention designed to increase exercise for adolescents with depressive disorders: Will a teenager with depression exercise? Methods. Participants were 13 adolescents with depression reporting low levels of aerobic exercise. They completed a 12-week intervention (15 supervised exercise sessions and 21 independent sessions). Exercise was measured through the aerobic exercise Questionnaire, actigraphy, and heart-rate monitoring. Depression was measured with the Children's Depression Rating Scale, Revised, and Quick Inventory of Depressive Symptomatology, Self-Report. Results. All participants who started the intervention completed the protocol, attending all supervised exercise sessions. Actigraphy verified 81% adherence to the protocol's independent sessions. Analysis of secondary outcomes showed a significant increase in exercise levels and a significant decrease in depression severity. Initially, ten participants were overweight or obese, and three were healthy weight. After 12 weeks of exercise, the number of participants in the healthy-weight category doubled. Conclusions. Adolescents suffering from depression can complete a rigorous protocol requiring structured increases in aerobic exercise. Participants showed significant increases in exercise, and significant decreases in depressive symptoms.

Abandoning peracetic acid-based dialyzer reuse is associated with improved survival.

BACKGROUND AND OBJECTIVES: Higher mortality risk reported with reuse versus single use of dialyzers is potentially related to reuse reagents that modify membrane surface characteristics and the blood-membrane interface. A key mechanism may involve stimulation of an inflammatory response. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a prospective crossover design, laboratory markers and mortality from 23 hemodialysis facilities abandoning reuse with peracetic acid mixture were tracked. C-reactive protein (CRP), white blood cell (WBC) count, albumin, and prealbumin were measured for 2 consecutive months before abandoning reuse and subsequently within 3 and 6 months on single use. Survival models were utilized to compare the 6-month period before abandoning reuse (baseline) and the 6-month period on single use of dialyzers after a 3-month "washout period." RESULTS: Patients from baseline and single-use periods had a mean age of approximately 63 years; 44% were female, 54% were diabetic, 60% were white, and the mean vintage was approximately 3.2 years. The unadjusted hazard ratio for death was 0.70 and after case-mix adjustment was 0.74 for single use compared with reuse. Patients with CRP≥5 mg/L during reuse (mean CRP=26.6 mg/ml in April) declined on single use to 20.2 mg/L by August and 20.4 mg/L by November. WBC count declined slightly during single use, but nutritional markers were unchanged. CONCLUSIONS: Abandonment of peracetic-acid-based reuse was associated with improved survival and lower levels of inflammatory but not nutritional markers. Further study is needed to evaluate a potential link between dialyzer reuse, inflammation, and mortality.