Feasibility and acceptability of an acceptance and commitment therapy intervention for caregivers of adults with Alzheimer's disease and related dementias.

BACKGROUND: Caregivers of patients with Alzheimer's disease or a related dementia (ADRD) report high levels of distress, including symptoms of anxiety and depression, caregiving burden, and existential suffering; however, those with support and healthy coping strategies have less stress and burden. Acceptance and Commitment Therapy (ACT) aims to foster greater acceptance of internal events while promoting actions aligned with personal values to increase psychological flexibility in the face of challenges. The objective of this single-arm pilot, Telephone Acceptance and Commitment Therapy Intervention for Caregivers (TACTICs), was to evaluate the feasibility, acceptability, and preliminary effects of an ACT intervention on ADRD caregiver anxiety, depressive symptoms, burden, caregiver suffering, and psychological flexibility. METHODS: ADRD caregivers ≥21 years of age with a Generalized Anxiety Disorder Scale (GAD-7) score ≥ 10 indicative of moderate or higher symptoms of anxiety were enrolled (N = 15). Participants received a telephone-based ACT intervention delivered by a non-licensed, bachelor's-prepared trained interventionist over 6 weekly 1-h sessions that included engaging experiential exercises and metaphors designed to increase psychological flexibility. The following outcome measures were administered at baseline (T1), immediately post-intervention (T2), 3 months post-intervention (T3), and 6 months post-intervention (T4): anxiety symptoms (GAD-7; primary outcome); secondary outcomes of depressive symptoms (Patient Health Questionnaire-9), burden (Zarit Burden Interview), suffering (The Experience of Suffering measure), psychological flexibility/experiential avoidance (Acceptance and Action Questionnaire-II), and coping skills (Brief COPE). RESULTS: All 15 participants completed the study and 93.3% rated their overall satisfaction with their TACTICs experience as "completely satisfied." At T2, caregivers showed large reduction in anxiety symptoms (SRM 1.42, 95% CI [0.87, 1.97], p < 0.001) that were maintained at T3 and T4. At T4, psychological suffering (SRM 0.99, 95% CI [0.41, 1.56], p = 0.0027) and caregiver burden (SRM 0.79, 95% CI [0.21, 1.37], p = 0.0113) also decreased. CONCLUSIONS: Despite a small sample size, the 6-session manualized TACTICs program was effective in reducing anxiety, suggesting that non-clinically trained staff may be able to provide an effective therapeutic intervention by phone to maximize intervention scalability and reach. TRIAL REGISTRATION: Institutional Review Board (IRB) protocol #1904631305 version 05-14-2019. Recruitment began 06-14-2019 and was concluded on 12-09-2019. Recruitment began 06-14-2019 and was concluded on 12-09-2019.

Acceptance and commitment therapy for breast cancer survivors with fear of cancer recurrence: A 3-arm pilot randomized controlled trial.

BACKGROUND: Fear of cancer recurrence (FCR) has a profound negative impact on quality of life (QOL) for many cancer survivors. Breast cancer survivors (BCS) are particularly vulnerable, with up to 70% reporting clinically significant FCR. To the authors' knowledge, evidence-based interventions for managing FCR are limited. Acceptance and commitment therapy (ACT) promotes psychological flexibility in managing life's stressors. The current study examined the feasibility and preliminary efficacy of group-based ACT for FCR in BCS. METHODS: Post-treatment BCS (91 patients with stage I-III disease) with clinical FCR randomly were assigned to ACT (6 weekly 2-hour group sessions), survivorship education (SE; 6 weekly 2-hour group sessions), or enhanced usual care (EUC; one 30-minute group coaching session with survivorship readings). FCR severity (primary outcome) and avoidant coping, anxiety, post-traumatic stress, depression, QOL, and other FCR-related variables (secondary outcomes) were assessed at baseline (T1), after the intervention (T2), 1 month after the intervention (T3), and 6 months after the intervention (T4) using intent-to-treat analysis. RESULTS: Satisfactory recruitment (43.8%) and retention (94.5%) rates demonstrated feasibility. Although each arm demonstrated within-group reductions in FCR severity over time, only ACT produced significant reductions at each time point compared with baseline, with between-group differences at T4 substantially favoring ACT over SE (Cohen d for effect sizes, 0.80; P < .001) and EUC (Cohen d, 0.61; P < .01). For 10 of 12 secondary outcomes, only ACT produced significant within-group reductions across all time points. By T4, significant moderate to large between-group comparisons favored ACT over SE and EUC with regard to avoidant coping, anxiety, depression, QOL, and FCR-related psychological distress. CONCLUSIONS: Group-based ACT is a feasible and promising treatment for FCR and associated outcomes in BCS that warrants testing in larger, fully powered trials.

Abbreviated dignity therapy for adults with advanced-stage cancer and their family caregivers: Qualitative analysis of a pilot study.

OBJECTIVE: Dignity therapy (DT) is designed to address psychological and existential challenges that terminally ill individuals face. DT guides patients in developing a written legacy project in which they record and share important memories and messages with those they will leave behind. DT has been demonstrated to ease existential concerns for adults with advanced-stage cancer; however, lack of institutional resources limits wide implementation of DT in clinical practice. This study explores qualitative outcomes of an abbreviated, less resource-intensive version of DT among participants with advanced-stage cancer and their legacy project recipients. METHOD: Qualitative methods were used to analyze postintervention interviews with 11 participants and their legacy recipients as well as the created legacy projects. Direct content analysis was used to assess feedback from the interviews about benefits, barriers, and recommendations regarding abbreviated DT. The legacy projects were coded for expression of core values.ResultFindings suggest that abbreviated DT effectively promotes (1) self-expression, (2) connection with loved ones, (3) sense of purpose, and (4) continuity of self. Participants observed that leading the development of their legacy projects promoted independent reflection, autonomy, and opportunities for family interaction when reviewing and discussing the projects. Consistent with traditional DT, participants expressed "family" as the most common core value in their legacy projects. Expression of "autonomy" was also a notable finding.Significance of resultsAbbreviated DT reduces resource barriers to conducting traditional DT while promoting similar benefits for participants and recipients, making it a promising adaptation warranting further research. The importance that patients place on family and autonomy should be honored as much as possible by those caring for adults with advanced-stage cancer.

Development and preliminary validation of the Brief Self-Compassion Inventory.

Research and clinical interest in self-compassion has grown due to its associations with physical and mental health benefits. Widely used measures of self-compassion have conceptual and psychometric limitations that warrant attention. The purpose of this project was to develop a new self-compassion measure, the Brief Self-Compassion Inventory (BSCI), and test its psychometric properties. We developed items for the BSCI based on theory, prior research, and expert and cancer patient feedback. The BSCI was then tested with adults diagnosed with breast, gastrointestinal, lung, or prostate cancer (N = 404). Confirmatory factor analysis suggested a unidimensional structure, and internal consistency reliability was excellent. Construct validity of the BSCI was established through its correlations with psychological variables hypothesized to be related to self-compassion, such as mindfulness, acceptance of cancer, and other coping strategies. Furthermore, measurement invariance testing of the BSCI indicated that it could be used across patients of varying genders, cancer types, and stages of illness. In conclusion, the 5-item BSCI was determined to be psychometrically sound and suitable for use with adults of varying genders, cancer types, and stages of disease. The measure warrants testing with other medical and nonclinical populations.

Symptom Treatment Preferences of Cancer Survivors: Does Fatigue Level Make a Difference?

BACKGROUND: Cancer-related fatigue (CRF) is among the most prevalent symptoms in cancer survivors and often co-occurs with other symptoms. However, little is known about survivors' preferences for treating CRF and associated symptoms. OBJECTIVE: The aim of this study was to examine cancer survivors' interest in learning skills to manage CRF and associated symptoms and their interest in various nonpharmacologic interventions and modalities. These outcomes were compared between survivors with high and normal fatigue. METHODS: Breast, gastrointestinal, lung, and prostate cancer survivors (N = 338) completed a 1-time survey, including a Patient-Reported Outcomes Measurement Information System fatigue measure and a checklist assessing interest in learning skills to manage CRF and associated symptoms as well as interest in nonpharmacologic interventions and modalities. RESULTS: Many cancer survivors reported interest in learning skills to manage CRF (range, 35%-78%) and associated symptoms (range, 13%-48%). Compared with survivors with normal fatigue (n = 180), highly fatigued survivors (n = 158; Patient-Reported Outcomes Measurement Information System fatigue T score ≥ 55) were more likely to report interest in learning skills to manage various symptoms, self-compassion training, and programs offered individually and in person. Interest in other interventions and modalities did not vary by fatigue level. CONCLUSIONS: Many cancer survivors, especially those with high fatigue, report interest in learning symptom management skills. Given survivors' high level of interest in complementary and integrative health interventions, future research should continue to assess their impact on symptoms and functioning. IMPLICATIONS FOR PRACTICE: Nurses can offer a menu of evidence-based options for symptom management, given survivors' diverse preferences. Nurses can also provide psychoeducation regarding their preferred treatments.

Effects of mindfulness-based interventions on fatigue in cancer survivors: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis was designed to determine the efficacy of mindfulness-based interventions (MBIs) in improving fatigue-related outcomes in adult cancer survivors. Randomized controlled trials (RCTs) were identified from PubMed, MEDLINE, PsycINFO, CINAHL, Web of Science, and EMBASE databases and reference lists of included studies. Separate random-effects meta-analyses were conducted for fatigue and vitality/vigor. Twenty-three studies reporting on 21 RCTs (N = 2239) met inclusion criteria. MBIs significantly reduced fatigue compared to controls at post-intervention (g = 0.60, 95 % CI [0.36, 0.83]) and first follow-up (g = 0.42, 95 % CI [0.20, 0.64]). Likewise, MBIs significantly improved vitality/vigor at post-intervention (g = 0.39, 95 % CI [0.25, 0.52]) and first follow-up (g = 0.35, 95 % CI [0.03, 0.67]). The evidence grade was low due to risk of bias, substantial heterogeneity, and publication bias among studies. MBIs show promise in improving fatigue and vitality/vigor in cancer survivors. More rigorous trials are needed to address current gaps in the evidence base.

Mindfulness Training Supports Quality of Life and Advance Care Planning in Adults With Metastatic Cancer and Their Caregivers: Results of a Pilot Study.

BACKGROUND: Emotional distress often causes patients with cancer and their family caregivers (FCGs) to avoid end-of-life discussions and advance care planning (ACP), which may undermine quality of life (QoL). Most ACP interventions fail to address emotional barriers that impede timely ACP. AIM: We assessed feasibility, acceptability, and preliminary effects of a mindfulness-based intervention to facilitate ACP for adults with advanced-stage cancer and their FCGs. DESIGN: A single-arm pilot was conducted to assess the impact of a 6-week group mindfulness intervention on ACP behaviors (patients only), QoL, family communication, avoidant coping, distress, and other outcomes from baseline (T1) to post-intervention (T2) and 1 month later (T3). PARTICIPANTS: Eligible patients had advanced-stage solid malignancies, limited ACP engagement, and an FCG willing to participate. Thirteen dyads (N = 26 participants) enrolled at an academic cancer center in the United States. RESULTS: Of eligible patients, 59.1% enrolled. Attendance (70.8% across 6 sessions) and retention (84.6% for patients; 92.3% for FCGs) through T3 were acceptable. Over 90% of completers reported high intervention satisfaction. From T1 to T3, patient engagement more than doubled in each of 3 ACP behaviors assessed. Patients reported large significant decreases in distress at T2 and T3. Family caregivers reported large significant improvements in QoL and family communication at T2 and T3. Both patients and FCGs reported notable reductions in sleep disturbance and avoidant coping at T3. CONCLUSIONS: The mindfulness intervention was feasible and acceptable and supported improvements in ACP and associated outcomes for patients and FCGs. A randomized trial of mindfulness training for ACP is warranted. The study is registered at ClinicalTrials.gov with identifier NCT02367508 ( https://clinicaltrials.gov/ct2/show/NCT02367508 ).

Animal models of fatigue in major depressive disorder.

Fatigue is common in a host of neurological and psychiatric disorders including depression and often continues unabated even after primary symptoms of disease are treated. Its high estimated prevalence combined with the lack of effective medicines has engaged the preclinical research community to search for fatigue models. The present review briefly summarizes the most common animal models that have been brought forward along with some of the associated pharmacological validation data. Like all preclinical models, these models have issues that need to be appreciated in the generation and interpretation of data for the purposes of translation to human disease; specifically, there are deficiencies in construct validity, a lack of medicines that effectively address residual fatigue symptoms, and difficulties in defining specificity with respect to drug effects on fatigue per se. Nonetheless, existing animal models of fatigue arguably serve the valuable purpose of encouraging research in this large area of unmet medical need. Data from these models are predicted to engender human experimentation and the further development of improved model systems.

Inquiries into the Biological Significance of Transmembrane AMPA Receptor Regulatory Protein (TARP) γ-8 Through Investigations of TARP γ-8 Null Mice§.

Transmembrane AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor regulatory protein (TARP) γ-8 is an auxiliary protein associated with some AMPA receptors. Most strikingly, AMPA receptors associated with this TARP have a relatively high localization in the hippocampus. TARP γ-8 also modifies the pharmacology and trafficking of AMPA receptors. However, to date there is little understanding of the biological significance of this auxiliary protein. In the present set of studies we provide a characterization of the differential pharmacology and behavioral consequences of deletion of TARP γ-8 by comparing the wild type (WT) and γ-8 -/- (knock-out, KO) mouse. KO mice were mildly hyperactive in a locomotor arena but not in other environments compared to WT mice. Additionally, the KO mice demonstrated enhanced locomotor stimulatory effects of both d-amphetamine and phencyclidine. Marble-burying and digging behaviors were dramatically reduced in KO mice. In another assay that can detect anxiety-like phenotypes, the elevated plus maze, no differences were observed in overall movement or open arm entries. In the forced-swim assay, KO mice displayed decreases in immobility time like the antidepressant imipramine and the AMPA receptor potentiator, LY392098. In KO mice, the antidepressant-like effects of LY392098 were prevented whereas the effects of imipramine were unaffected. Convulsions were induced by pentylenetetrazole, N-methyl-D-aspartate, and by kainic acid. However, in KO mice, kainic acid produced less tonic convulsions and lethality. KO mice had reduced levels of norepinephrine in hippocampus and cerebellum but not in hypothalamus or prefrontal cortex, decreased levels of cAMP in hippocampus, and increased levels of acetylcholine in the hypothalamus and prefrontal cortex. KO mice displayed decreased turnover of dopamine and increased histamine turnover in multiple brain areas In contrast, serotonin and its metabolites were not significantly affected by deletion of the γ-8 protein. Of a large panel of plasma lipids, only two monoacylglycerols (1OG and 2OG) were marginally but nonsignificantly altered in WT vs KO mice. Overall, the data suggest genetic inactivation of this specific population of AMPA receptors results in modest changes in behavior characterized by a mild hyperactivity which is condition dependent and a marked reduction in digging and burying behaviors. Despite deletion of TARP γ-8, chemoconvulsants were still active. Consistent with their predicted pharmacological actions, the convulsant effects of kainate and the antidepressant-like effects of an AMPA receptor potentiator (both acting upon AMPA receptors) were reduced or absent in KO mice.