Effects of cognitive behavioral therapy for insomnia on subjective and objective measures of sleep and cognition

Study Objectives: To assess the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on subjective and objective sleep, sleep-state misperception as well as self-reported and objective cognitive performance. Methods: We performed a randomized controlled trial with a treatment group and a wait-list control group to assess changes in insomnia symptoms after CBTi (8 sessions/3 months) in 62 participants with chronic insomnia. To this end, we conducted a multimodal investigation of sleep and cognition including subjective measures of sleep difficulties (Insomnia Severity Index (ISI), sleep diaries) and cognitive functioning (Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire), objective assessments of sleep (polysomnography recording, cognition (attention and working memory tasks), and sleep-state misperception measures, collected at baseline and at 3-months post-randomization. At 6 months post-randomization, we collected similar data from the wait-list group after CBTi. We also assessed ISI one year after CBTi in both groups. Our main analysis investigated changes in sleep and cognition after 3 months (treatment versus wait-list group). In secondary analyses, we pooled data from both groups to observe changes after CBTi. Results: ISI score was reduced and self-reported sleep quality improved after CBTi (treatment group at 3 months and pooled groups after CBTi). Sleep misperception in sleep onset latency and sleep duration decreased after CBTi. In contrast, objective sleep, objective and subjective cognitive functioning did not improve after CBTi. Conclusions: We showed that CBTi has a beneficial effect on variables pertaining to the subjective perception of sleep, which is a central feature of insomnia. However, we observed no significant effect of CBTi on measures of cognitive functioning.

P055 Brain-Immune Axis Regulation is Responsive to Cognitive Behavioral and Mindfulness-Based Stress Reduction in Crohn’s Disease

Background Crohn’s disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the pituitary-hypophysis-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month period of Cognitive Behavioral and Mindfulness-Based Stress Reduction (COBMINDEX) impacts their inflammatory process. Methods Circulating inflammatory markers (IFN-α, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-18, IL-23, and IL-33) and a wide range of psychological parameters were measured before (T1) and after (T2) COBMINDEX in CD patients. Inflammatory parameters were also compared to age- and sex-matched healthy controls (HCs) at T1, and to wait-list CD patients (at T1 and T2) who were followed for 3 months but did not receive COMBINDEX. Psychological symptoms were assessed by two questionnaires: the Perceived Stress Scale PSS4, and the Brief Symptom Inventory of psychological distress with Global Severity Index GSI. Statistical significance was assessed using Spearman correlation. Results CD patients (N=100, mean age 33.6 ± 13 years, 69% female, Harvey-Bradshaw Index mean 31± 55) exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by higher serum levels of interleukin (IL)-6 (mean 4.084± 8.4) and IL-18 (mean 302.09± 286) shown in Figure 1. Notably, IL-18 levels correlated with a higher stress score and a lower wellbeing score in CD patients (Figure 2). COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 (0.32, p<0.05) and INFα (0.36, p<0.05) and correlated negatively with those of MCP-1 (-0.34, p<0.05). Finally, baseline inflammatory markers of CD patients predicted COBMINDEX efficacy, as changes in HBI were negatively correlated with cytokines levels of IFNa (p=0.046), IFNg (p=0.03), IL-10 (p=0.002), IL-23 (p=0.025), IL33 (p=0.009) and IL12p70 (p=0.037) at T1 in the COBMINDEX group, but not in the wait-list group. In addition, basal levels of circulating cortisol at T1 negatively correlated with changes in GSI (-0.33, p<0.05) between T1 and T2 in the COBMINDEX group, but not in the wait-list group. Conclusion Our results show that CD patients have a characteristic immunological profile that correlates with psychological stress and disease activity, and predicts COBMINDEX outcomes. We suggest that COBMINDEX induces stress resilience in CD patients, which not only impacts their well-being, but also their disease-associated inflammatory process.

Acceptability and Impact of Group Interpersonal Therapy (IPT-G) on Kenyan Adolescent Mothers Living with HIV: A Qualitative Analysis

Background Task shifting is a well-tested implementation strategy, within low- and middle-income countries (LMICs), that addresses the shortage of trained mental health personnel. Task sharing can increase access to care for patients with mental illnesses. In Kenya, community health workers [CHWs are a combination of community health assistants (CHAs) and community health volunteers (CHVs)], have played a crucial role in this front. In our study, we seek to assess the acceptability and feasibility of IPT-G delivered by CHWs among depressed postpartum adolescents (PPAs) living with HIV.Method Twenty-four PPAs were administered IPT-G by trained CHWs from two health centers. A two-arm study design (IPT-G intervention and treatment as usual) with an intent to treat was used to assess acceptability and feasibility of IPT-G. Participants who scored >10 on Edinburgh postnatal depression scale (EPDS) and who were 6–12 weeks postpartum were eligible for the study using purposeful sampling. Participants were equally distributed into two groups: one group for intervention and another for wait-list group. This was achieved by randomly allocating numerical numbers and separating those with odd numbers (intervention group) and even numbers (wait-list group). Focus group discussions (FGDs) and in-depth interviews ascertained the experience and perceptions of the postpartum adolescents and the CHWs. In addition to weekly face-to-face continuous supportive supervision for CHWs, phone calls, short messages services, and WhatsApp instant messaging services were also utilized.Results The CHWs found the intervention useful for their own knowledge and skill-set. On participation, 21out of the 24 adolescents attended all sessions. Most of the adolescents reported improvement in their interpersonal relationships with reduced distress and lessening of HIV-related stigma. Primary health care workers embraced the intervention by availing space for sessions. Conclusion Our study demonstrates possible benefits of task shifting in addressing mental health problems within low-resource settings in Kenya and group IPT is demonstrated to be both acceptable and feasible by health workers and adolescents receiving care.

Retreat Intervention Effectiveness for Female Survivors of Child Sexual Abuse

Purpose: Childhood sexual abuse (CSA) is a widespread issue that can have detrimental effects on adult well-being. As demand for CSA treatment is high, it is important for clinicians to understand what forms of interventions are effective. Method: This quasi-experimental study examined the effectiveness of a 4-day retreat intervention for 986 adult female CSA survivors. Multilevel growth curve modeling was used to analyze treatment group effects, and paired-sample t tests were used for the wait-list group. Results: The intervention significantly reduced post-traumatic stress disorder symptoms (Cohen’s d = 0.69) and increased life satisfaction (Cohen’s d = 0.98), social support (Cohen’s d = 0.20), and coping self-efficacy (Cohen’s d = 1.14); these changes were maintained 1-year postintervention. The wait-list group did not report statistically significant changes across time. Discussion: Findings suggest retreat interventions may be a promising form of CSA treatment and encourage more empirical work on retreat interventions across diverse samples and settings.

Baseline imbalance about depressive symptoms may overestimate the effectiveness of mindfulness-based cognitive therapy for anxiety disorders.

We read the article by Ninomiya et al. with great interest and appreciate the author's efforts to analyze the effect of primary mindfulness-based cognitive therapy (MBCT) in patients with anxiety disorder in secondary-care settings, compared with a waiting-list group. However, we have concerns about baseline imbalance of depressive symptoms that may influence the conclusion of the trial. Comorbid major depressive disorder can have caused an underestimation of anxiety symptoms in the waiting-list group and distort effectiveness of MBCT. The wait-list group had more severe depressive symptoms than the intervention group, about 7 points more in the Center for Epidemiologic Studies Depression Scale (CES-D) scores, and that group might have more major depressive disorder. Indeed, the rate of antidepressant use in the wait-list group was 25% higher than the intervention group. It is well known that major depressive disorder is associated with cognitive errors and underestimation of self-report outcomes. Baseline imbalance of depressive symptoms may therefore weaken the conclusion of the study, because all outcome measures were self-report questionnaires. The authors should acknowledge the limitation and provide information about the diagnosis of major depressive disorder.

Solution Focused brief therapy In post-stroke Aphasia (SOFIA Trial): protocol for a feasibility randomised controlled trial

Background: Around a quarter of people post stroke will experience aphasia, a language disability. Having aphasia places someone at risk of becoming depressed and isolated. There is limited evidence for effective interventions to enhance psychological well-being for this client group. A potential intervention is Solution Focused Brief Therapy (SFBT), which supports a person to build meaningful, achievable change through focusing on a person’s skills and resources rather than their deficits. The SOFIA Trial aims to explore the acceptability of SFBT to people with varying presentations of aphasia, including severe aphasia, and to assess the feasibility of conducting a future definitive trial investigating clinical and cost effectiveness. Methods: The trial is a single-blind, randomised, wait-list controlled feasibility trial with nested qualitative research and pilot economic evaluation comparing SFBT plus usual care to usual care alone. The study will recruit 32 participants with aphasia who are ≥6 months post stroke. All participants will be assessed on psychosocial outcome measures at baseline, three, and six months post randomisation by assessors blinded to treatment allocation. Participants will be randomly assigned to intervention group (start intervention immediately post randomisation) or wait-list group (start intervention six months post randomisation). Wait-list group will additionally be assessed nine months post randomisation. The intervention consists of up to six SFBT sessions delivered over three months by speech and language therapists. Participants and therapists will also take part in in-depth interviews exploring their experiences of the study. The pilot economic evaluation will use the EQ-5D-5L measure and an adapted Client Service Receipt Inventory. People with aphasia have been involved in designing and monitoring the trial. Discussion: Given the high levels of depression and isolation, there is a need to investigate effective interventions that enhance the psychological wellbeing of people with aphasia. Trial registration: ClinicalTrials.gov NCT03245060 10/08/2017.

SOlution Focused brief therapy In post-stroke Aphasia (SOFIA Trial): protocol for a feasibility randomised controlled trial

Background: Around a quarter of people post stroke will experience aphasia, a language disability. Having aphasia places someone at risk of becoming depressed and isolated. There is limited evidence for effective interventions to enhance psychological well-being for this client group. A potential intervention is Solution Focused Brief Therapy (SFBT), which supports a person to build meaningful, achievable change through focusing on a person’s skills and resources rather than their deficits. The SOFIA Trial aims to explore the acceptability of SFBT to people with varying presentations of aphasia, including severe aphasia, and to assess the feasibility of conducting a future definitive trial investigating clinical and cost effectiveness. Methods: The trial is a single-blind, randomised, wait-list controlled feasibility trial with nested qualitative research and pilot economic evaluation comparing SFBT plus usual care to usual care alone. The study will recruit 32 participants with aphasia who are ≥6 months post stroke. All participants will be assessed on psychosocial outcome measures at baseline, three, and six months post randomisation by assessors blinded to treatment allocation. Participants will be randomly assigned to intervention group (start intervention immediately post randomisation) or wait-list group (start intervention six months post randomisation). Wait-list group will additionally be assessed nine months post randomisation. The intervention consists of up to six SFBT sessions delivered over three months by speech and language therapists. Participants and therapists will also take part in in-depth interviews exploring their experiences of the study. The pilot economic evaluation will use the EQ-5D-5L measure and an adapted Client Service Receipt Inventory. People with aphasia have been involved in designing and monitoring the trial. Discussion: Given the high levels of depression and isolation, there is a need to investigate effective interventions that enhance the psychological wellbeing of people with aphasia. Trial registration: ClinicalTrials.gov NCT03245060 10/08/2017.

Efficacy and Safety of the Traditional Herbal Medicine, Gamiguibi-tang, in Patients With Cancer-Related Sleep Disturbance: A Prospective, Randomized, Wait-List-Controlled, Pilot Study

Background: Sleep disturbance is the second most bothersome symptom in patients with cancer, and it can significantly impair their quality of life. The aim of this study was to investigate the efficacy and safety of the traditional herbal medicine Gamiguibi-tang (GGBT) in patients with cancer-related sleep disturbance. Methods: We conducted a prospective, randomized, wait-list-controlled, open-label pilot clinical trial on cancer-related sleep disturbance. Patients with cancer experiencing poor sleep quality with a Pittsburgh Sleep Quality Index of at least 6 were randomly assigned to the GGBT and wait-list groups to receive GGBT and conventional care, respectively, for 2 weeks. The primary endpoint was the Insomnia Severity Index (ISI) score. Fatigue, depression, and cognitive impairment were assessed as the secondary endpoints by using the Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), and Montreal Cognitive Assessment (MoCA). Results: Thirty participants who met the eligibility criteria were enrolled. Sleep disturbance assessed using the ISI improved significantly more in the GGBT group than in the wait-list group (−5.5 ± 4.4 vs 0.1 ± 1.1, P < .001). Fatigue level determined using the BFI also improved significantly more in the GGBT group than in the wait-list group (−0.8 ± 0.8 vs 0.0 ± 0.3, P = .002). The BDI and MoCA scores showed no significant changes. Adverse events were reported in two patients in the GGBT group and consisted of mild dyspepsia and mild edema. Conclusion: GGBT may be a potential treatment option for cancer-related sleep disturbance. Further research is needed to investigate the efficacy and safety of GGBT.

Prospective Randomized Wait-List Control Trial Of IV Iron Sucrose In Older Anemic Adults With Serum Ferritin Of 20-200ng/Ml

Background Anemia is a common problem in older adults. Approximately one third of anemic adults 65 years and older have unexplained anemia of the elderly (UAE) as no clear cause can be identified. The Partnership for Anemia: Clinical and Translational Trials in the Elderly (PACTTE), an NIH funded consortium to perform interventional trials in this population, conducted a randomized prospective wait-list control study of the value of IV iron sucrose (IS). PACTTE consists of eight clinical sites (seven university based and one community based) and one data coordinating center. We hypothesized that UAE patients (pts) with moderate serum ferritin levels and no bleeding would benefit from iron repletion. Methods Pts 65 years and older with UAE, hemoglobin (Hb) values between 9 g/dL and 11.5 g/dL (in women) and 12.7 g/dL (in men) inclusive, serum ferritin levels between 20 and 200 ng/mL, and negative stool cards for occult blood, were randomized to receive 5 weekly doses of 200 mg of intravenous iron sucrose (Venofer®, Luitpold Pharmaceuticals), either immediately (immediate group) or to watch and wait (wait list group) for a 12 week waiting period. After 12 weeks, the wait-list control received IV Iron. The primary outcome was the difference in change in 6 minute walk test (6MWT) distance, from baseline to week 12 between the two groups. Secondary outcome measures included erythroid response, cognitive function, self-report function (FACT-An), quality of life (SF-36), and frailty (Fried Frailty Index). We targeted enrollment of 84 patients to provide 85% power to detect 50 meters difference in 6MWT distance. Results 43 pts were formally screened and 19 pts enrolled with a mean age of 78.5 years. 9 pts were randomized to the immediate group and 10 to the wait list group. The study was stopped due to poor accrual both related to strict eligibility and problems identifying pts to be screened. Baseline hematologic and demographic characteristics of the immediate and wait-list groups were similar except for a few variables such as lower serum iron (55.3 vs 84.5 mcg/dL, p=0.006) and transferrin saturation (12.4% vs 27.4%, p=0.015) in the immediate group. However, serum ferritin was similar (79 ng/mL in immediate and 53 ng/mL in wait-list, p=0.21). There was no significant difference in the primary outcome: at week 12, the immediate intervention group had a mean increase of 8.05± 55.48 meters on the 6MWT and the wait list group had a mean decline of 11.45±49.46 meters walked (p=0.44). Hb rose 0.39 g/dL ± 0.46 in the immediate intervention group compared to a mean decline of 0.39 ± 0.85 in the wait list group (p=0.026). Anemia symptoms improved by the FACT-An in the immediate group compared to the wait list group (+7.3 ±10.4 vs. -1.3 ±8.2, p=0.03). There were no significant differences in other secondary outcomes. Two patients in the immediate intervention group and 1 patient in the wait list group experienced grade 1 or grade 2 possibly or probably related treatment adverse events. One patient in each group experienced a serious adverse event, considered unlikely to be related to the study drug. Discussion The study was hampered by difficulty in recruitment. Future studies of older adults with UAE likely will require more sites, less stringent eligibility, and methods to screen and stimulate interest among eligible community dwelling subjects and their physicians. Nevertheless, the improvements in symptoms and hemoglobin from IV iron, in this limited sample justify further evaluation of IV iron in UAE with low to normal iron stores if recruitment barriers can be overcome. Disclosures: Off Label Use: IV iron with venofer is off label and given for unexplained anemia with low to normal iron stores.