A dual-acting DNASE1/DNASE1L3 biologic prevents autoimmunity and death in genetic and induced lupus models.

A defining feature of systemic lupus erythematosus (SLE) is loss of tolerance to self-DNA, and DNASE1L3 deficiency, the main enzyme responsible for chromatin degradation in blood, is also associated with SLE. This association includes an ultra-rare pediatric population with DNASE1L3 deficiency who develop SLE, adult patients with loss of function variants of DNASE1L3 who are at a higher risk for SLE, and patients with sporadic SLE who have neutralizing autoantibodies to DNASE1L3. To mitigate the pathogenic effects of inherited and acquired DNASE1L3 deficiencies, we engineered a long-acting enzyme biologic with dual DNASE1/DNASE1L3 activity that is resistant to DNASE1 and DNASE1L3 inhibitors. Notably, we found that the biologic prevented the development of lupus in Dnase1-/-/Dnase1L3-/- double knockout mice and rescued animals from death in pristane-induced lupus. Finally, we confirmed that the human isoform of the enzyme biologic was not recognized by autoantibodies in SLE and efficiently degrades genomic and mitochondrial cell free DNA, as well as microparticle DNA, in SLE plasma. Our findings suggest that autoimmune diseases characterized by aberrant DNA accumulation, such as SLE, can be effectively treated with a replacement DNASE tailored to bypass pathogenic mechanisms, both genetic and acquired, that restrict DNASE1L3 activity.

Does gender moderate resiliency variables and posttraumatic stress symptoms in informal caregivers of neurocritical care patients? An exploratory study.

We examined gender differences between resiliency factors (i.e. mindfulness, self-efficacy, coping, intimate care, and caregiver preparedness) and posttraumatic stress symptoms (PTSS) in informal caregivers of patients in the neuroscience intensive care unit (Neuro-ICU). Ninety-two informal caregivers were enrolled during patients' hospitalization and completed resiliency measures at baseline, and a PTSS measure at baseline, 3 and 6 months. We conducted five ANCOVAs to explore gender and resiliency on PTSS. No significant main effects of gender on PTSS were observed across time points. However, main effects were seen for resiliency on PTSS at baseline for informal caregivers with high (vs. low) mindfulness, coping, and self-efficacy. Gender moderated the association between mindfulness and PTSS (i.e. high mindfulness at baseline was associated with lower PTSS in males compared to females at 3 months) and intimate care and PTSS (high intimate care at baseline was associated with lower PTSS in males than females at 6 months; high intimate care at baseline for females was associated with lower PTSS at 6 months than females with low intimate care). Overall, we observed associations among informal caregivers' gender, resiliency, and PTSS, with males particularly benefitting from mindfulness and intimate care. These findings hold value for future inquiry into gender differences in this population with possible clinical implications.

Resiliency outcomes after participation in an asynchronous web-based platform for adults with neurofibromatosis: The NF-Web study.

The purpose of this study was to analyze secondary resiliency and user experience outcomes from a novel, 8-week website-based mind-body intervention (NF-Web) for adults (18+) with neurofibromatosis (NF1, NF2, and schwannomatosis), a genetic, neurocutaneous disorder characterized by nerve sheath tumors of the central and peripheral nervous system. The study design was a secondary data analysis of a single-arm, early feasibility pilot study (September 2020-May 2021) for adults with NF (N = 28). Across participants, the mean age was 46 (SD = 13.67) and included 22 females and 6 males. Participants completed baseline and posttest assessments (t-tests), as well as exit interviews (exploratory rapid data analysis). Results demonstrated that participation was associated with pre-to-post improvements in gratitude, coping, and mindfulness (p < .05). Exit interviews indicated participant enjoyment and that many would recommend NF-Web to a friend. Participants found the website easy to navigate and enjoyed NF-Web's video format. Many found transcripts useful if they had hearing differences or if English was their second language. NF-Web demonstrated initial signals of improvement in resiliency outcomes and positive user experience. Future pilot RCTs will explore these changes by NF type.

"When Will All of This End?": A 65-Year-Old Man With Amyotrophic Lateral Sclerosis and Psychiatric Distress.

Patients with amyotrophic lateral sclerosis (ALS) are impacted both physically and psychiatrically during their illness. Emotional distress (ie, anxiety, depression, stress) is common in patients diagnosed with ALS, as prognosis is poor and there are very few effective treatments. The progression of symptoms is unpredictable, and all cases are terminal. Neuropsychiatric symptoms are also increasingly recognized as part of ALS symptomatology. There are currently no empirically supported interventions or best practices for adjustment to ALS. This case presents both the psychological and pharmacologic aspects of caring for a patient with ALS. Psychotherapy utilized a cognitive behavioral therapy-informed approach, and pharmacotherapy was tailored to the specific needs of the patient. We explore how these approaches impacted our patient, as well as how ALS-specific challenges presented throughout the course of treatment.

The impact of a virtual mind-body program on resilience factors among international English-speaking adults with neurofibromatoses: secondary analysis of a randomized clinical trial.

PURPOSE: To test the effects of the Relaxation Response Resiliency Program - Neurofibromatosis (3RP-NF), a mind-body resilience program for people with NF, on resilience factors from baseline to post-treatment and 6- and 12-month follow-up. METHODS: This is a secondary analysis of a fully powered randomized clinical trial (RCT) of 3RP-NF and health education control (HEP-NF). We recruited adults with NF1, NF2, or schwannomatosis who reported stress or difficulty coping with NF symptoms. Both conditions received 8 weekly 90-minute group sessions; 3RP-NF focused on building resilience skills. We measured resilience factors via the Measure of Current Status-A (adaptive coping), Cognitive and Affective Mindfulness Scale-Revised (mindfulness), Gratitude Questionnaire-6 (gratitude), Life Orientation Test Optimism Scale (optimism), and Medical Outcomes Study Social Support Survey (perceived social support) at baseline, post-intervention, and 6- and 12-month follow-up. We used linear mixed models with completely unstructured covariance across up to four repeated measurements (baseline, post-treatment, and 6- and 12-month follow-up) to investigate treatment effects on resilience factors. RESULTS: We enrolled 228 individuals (Mage=42.7, SD = 14.6; 74.5% female; 87.7% White; 72.8% NF1, 14.0% NF2, 13.2% schwannomatosis). Within groups, both 3RP-NF and HEP-NF showed statistically significant improvements in all outcomes across timepoints. 3RP-NF showed significantly greater improvement in adaptive coping compared to HEP-NF from baseline to post-intervention and baseline to 6 months (Mdifference= 0.29; 95% CI 0.13-0.46; p < 0.001; Mdifference= 0.25; 95% CI 0.07-0.33; p = 0.005); there were no other between-group differences amongst the remaining resilience factors. CONCLUSION: 3RP-NF showed promise in sustainably improving coping abilities amongst people with NF. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03406208. Registration submitted December 6, 2017, first patient enrolled October 2017.

Effect of Mind-Body Skills Training on Quality of Life for Geographically Diverse Adults With Neurofibromatosis: A Fully Remote Randomized Clinical Trial.

Importance: Neurofibromatoses (NF; NF1, NF2, and schwannomatosis) are hereditary tumor predisposition syndromes with a risk for poor quality of life (QOL) and no evidence-based treatments. Objective: To compare a mind-body skills training program, the Relaxation Response Resiliency Program for NF (3RP-NF), with a health education program (Health Enhancement Program for NF; HEP-NF) for improvement of quality of life among adults with NF. Design, Setting, and Participants: This single-blind, remote randomized clinical trial randomly assigned 228 English-speaking adults with NF from around the world on a 1:1 basis, stratified by NF type, between October 1, 2017, and January 31, 2021, with the last follow-up February 28, 2022. Interventions: Eight 90-minute group virtual sessions of 3RP-NF or HEP-NF. Main Outcomes and Measures: Outcomes were collected at baseline, after treatment, and at 6-month and 1-year follow-up. The primary outcomes were physical health and psychological domain scores of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). Secondary outcomes were the social relationships and environment domain scores of the WHOQOL-BREF. Scores are reported as transformed domain scores (range, 0-100, with higher scores indicating higher QOL). Analysis was performed on an intention-to-treat basis. Results: Of 371 participants who underwent screening, 228 were randomized (mean [SD] age, 42.7 [14.5] years; 170 women [75%]), and 217 attended 6 or more of 8 sessions and provided posttest data. Participants in both programs improved from baseline to after treatment in primary outcomes of physical health QOL score (3RP-NF, 5.1; 95% CI, 3.2-7.0; P < .001; HEP-NF, 6.4; 95% CI, 4.6-8.3; P < .001) and psychological QOL score (3RP-NF, 8.5; 95% CI, 6.4-10.7; P < .001; HEP-NF, 9.2; 95% CI, 7.1-11.2; P < .001). Participants in the 3RP-NF group showed sustained improvements after treatment to 12 months; posttreatment improvements for the HEP-NF group diminished (between-group difference for physical health QOL score, 4.9; 95% CI, 2.1-7.7; P = .001; effect size [ES] = 0.3; and psychological QOL score, 3.7; 95% CI, 0.2-7.6; P = .06; ES = 0.2). Results were similar for secondary outcomes of social relationships and environmental QOL. There were significant between-group differences from baseline to 12 months in favor of the 3RP-NF for physical health QOL score (3.6; 95% CI, 0.5-6.6; P = .02; ES = 0.2), social relationships QOL score (6.9; 95% CI, 1.2-12.7; P = .02; ES = 0.3), and environmental QOL score (3.5; 95% CI, 0.4-6.5; P = .02; ES = 0.2). Conclusions and Relevance: In this randomized clinical trial of 3RP-NF vs HEP-NF, benefits from 3RP-NF and HEP-NF were comparable after treatment, but at 12 months from baseline, 3RP-NF was superior to HEP-NF on all primary and secondary outcomes. Results support the implementation of 3RP-NF in routine care. Trial Registration: ClinicalTrials.gov Identifier: NCT03406208.

Resilient together-ALS: leveraging the NDD transdiagnostic framework to develop an early dyadic intervention for people with amyotrophic lateral sclerosis and their informal care-partners.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and eventual death, usually within 3-5 years. An ALS diagnosis is associated with substantial emotional distress for both the affected person and their family care-partners which impairs the ability to engage in important conversations about long term care planning, negatively impacts ALS symptoms for the patient, and quality of life for both patient and care-partner. Here we 1) discuss published works identified by the authors about psychosocial interventions for the ALS population, 2) identify a lack of early, dyadic interventions to support psychosocial needs of people with ALS and care-partners; 3) describe the Neurodegenerative Diseases (NDD) framework for early dyadic intervention development and 4) propose an adaptation of an evidence-based early dyadic psychosocial intervention, Recovering Together, for the unique needs of people with ALS and their care-partners (Resilient Together-ALS; RT-ALS) using the NDD framework. Future work will use stakeholder feedback to optimize the intervention for subsequent efficacy testing.

A roadmap for early psychosocial support in palliative care for people impacted by ALS-reducing suffering, building resiliency, and setting the stage for delivering timely transdiagnostic psychosocial care.

This commentary describes the current state of psychosocial care for people with amyotrophic lateral sclerosis and their caregivers. We provide recommendations for developing a roadmap for future research based on existing literature and our group's clinical and research experience to inform next steps to expand evidence-based psychosocial care for people with amyotrophic lateral sclerosis and their caregivers, with potential implications for a range of advanced illnesses.

This article talks about psychosocial care for people with amyotrophic lateral sclerosis and the loved ones who take care of them (caregivers). We talk about gaps in current psychosocial care and offer ideas about research to help develop care options for people with amyotrophic lateral sclerosis and their caregivers. It is possible that this work could also guide the development of psychosocial care for people with other advanced illnesses and their caregivers.

Occurrence and Severity of Suicidal Ideation in Adults With Neurofibromatosis Participating in a Mind-Body RCT.

BACKGROUND: Emotional distress can lead to suicidal ideation and potentially suicide completion, yet there is very little literature on suicidal ideation in individuals with a diagnosis of neurofibromatosis (NF; NF1, NF2, and schwannomatosis). OBJECTIVE: To examine the baseline occurrence, severity, and clinical correlates of suicidal ideation in adults with NF. METHOD: Individuals with NF (N = 220) completed assessments measuring depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), perceived stress (Perceived Stress Scale-10), pain (Graded Chronic Pain Scale and PROMIS Pain Interference Short Form 8a), and general quality of life (World Health Organization Quality of Life-Brief version) before beginning a two-arm, single-blind randomized control trial of a live-video mind-body program for stress management and resiliency. RESULTS: Nineteen percent (n = 42) of the individuals experienced suicidal ideation (ie, >0; ideation present several days or greater). More individuals with NF2 experienced suicidal ideation compared with those with NF1 or schwannomatosis. All of the clinical variables except pain intensity were significantly correlated ( P < 0.01) with greater suicidal ideation. Suicidal ideation in individuals with NF was comparable to or higher than that in other medical populations (eg, cancer, dermatological, neurologic). Depression and poor psychological quality of life significantly increased the risk for suicidal ideation. CONCLUSION: Suicidal ideation was relatively prevalent in individuals with NF seeking participation in a mind-body randomized controlled trial. NF clinicians should be prepared to discuss these concerns and provide resources when suicidal ideation is present. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT03406208).

The Recovering Together study protocol: A single-blind RCT to prevent chronic emotional distress in patient-cargiver dyads in the Neuro-ICU.

INTRODUCTION: Patients admitted to the Neuroscience Intensive Care Unit (Neuro-ICU) with acute neurological illnesses (ANI; e.g., stroke, tumor, TBI) and their informal caregivers experience high rates of anxiety, depression, and posttraumatic stress. To address this need, we previously developed the Recovering Together (RT) dyadic intervention to help prevent chronic emotional distress in both patients and caregivers. Currently, we are conducting a fully-powered, single-blind randomized clinical trial (RCT) to evaluate the efficacy of RT versus an attention matched health education control. Here, we describe the protocol and current status of this RCT. METHODS: We aim to recruit 194 at risk patient-caregiver dyads from the Neuro-ICU at MGH. Eligible dyads include patients diagnosed with ANI, cognitively intact, at least one partner endorses emotional distress (on Hospital Anxiety and Depression Scale), English speaking, age 18 or older. Dyads are randomized to the intervention (RT-1) or control condition (RT-2) (both six sessions). RT-1 teaches resiliency (e.g., coping, mindfulness) and interpersonal skills. RT-2 provides education on health-related topics (e.g., stress, self-care, adhering to medical recommendations). Blinded research assistants collect measures at baseline, post-intervention, and three months follow-up. We will conduct mixed linear, mediation, and actor-partner interdependence models to examine changes in dyads' outcomes across time. RESULTS: We have recruited 41 dyads and aim to recruit 194 total. DISCUSSION: If successful, we plan to test RT in a large-scale, multisite hybrid effectiveness-implementation study in Neuro-ICUs across the country. Enhancing psychosocial supports for patients and families could improve health outcomes, healthcare efficiency, and the culture of these units.

Catalysis-Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass.

Biallelic ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency induces vascular/soft tissue calcifications in generalized arterial calcification of infancy (GACI), and low bone mass with phosphate-wasting rickets in GACI survivors (autosomal hypophosphatemic rickets type-2). ENPP1 haploinsufficiency induces early-onset osteoporosis and mild phosphate wasting in adults. Both conditions demonstrate the unusual combination of reduced accrual of skeletal mineral, yet excess and progressive heterotopic mineralization. ENPP1 is the only enzyme that generates extracellular pyrophosphate (PPi), a potent inhibitor of both bone and heterotopic mineralization. Life-threatening vascular calcification in ENPP1 deficiency is due to decreased plasma PPi; however, the mechanism by which osteopenia results is not apparent from an understanding of the enzyme's catalytic activity. To probe for catalysis-independent ENPP1 pathways regulating bone, we developed a murine model uncoupling ENPP1 protein signaling from ENPP1 catalysis, Enpp1T238A mice. In contrast to Enpp1asj mice, which lack ENPP1, Enpp1T238A mice have normal trabecular bone microarchitecture and favorable biomechanical properties. However, both models demonstrate low plasma Pi and PPi, increased fibroblast growth factor 23 (FGF23), and by 23 weeks, osteomalacia demonstrating equivalent phosphate wasting in both models. Reflecting findings in whole bone, calvarial cell cultures from Enpp1asj mice demonstrated markedly decreased calcification, elevated transcription of Sfrp1, and decreased nuclear ß-catenin signaling compared to wild-type (WT) and Enpp1T238A cultures. Finally, the decreased calcification and nuclear ß-catenin signaling observed in Enpp1asj cultures was restored to WT levels by knockout of Sfrp1. Collectively, our findings demonstrate that catalysis-independent ENPP1 signaling pathways regulate bone mass via the expression of soluble Wnt inhibitors such as secreted frizzled-related protein 1 (SFRP1), whereas catalysis dependent pathways regulate phosphate homeostasis through the regulation of plasma FGF23. © 2022 American Society for Bone and Mineral Research (ASBMR).

Orthopedic Providers' Preferences for Education and Training on Psychosocial Clinical Research Initiatives: A Qualitative Investigation.

INTRODUCTION: Psychosocial factors (e.g., depression, anxiety) increase risk for chronic pain, disability, and other health complications following acute orthopedic traumatic injury. Orthopedic providers lack skills to address these factors. Education around psychosocial factors of recovery and psychosocial clinical and research initiatives could address this gap. The purpose of this study was to understand orthopedic trauma providers' preferences for the design and distribution of educational materials to facilitate psychosocial initiative implementation. METHODS: We conducted live-video, semi-structured focus groups with outpatient orthopedic trauma providers across three Level 1 Trauma Centers, using a hybrid inductive-deductive approach to analyze qualitative data and extract themes and subthemes characterizing providers' recommendations for appropriate psychosocial education. RESULTS: Four themes described providers' recommendations for receiving educational materials: (1) provide foundational knowledge and tools about psychosocial factors; (2) provide information regarding a psychosocial initiative's purpose and procedures; (3) leverage educational materials to maximize buy-in to psychosocial clinical research initiatives; and (4) deliver information concisely, clearly, and electronically. CONCLUSION: Orthopedic providers recommended ways to optimize design and dissemination of education on psychosocial care. Optimizing knowledge of psychosocial factors and clinical and research initiatives facilitates providers' ability to appropriately target the often-underdressed psychosocial component of recovery in orthopedics.

Together from the start: A transdiagnostic framework for early dyadic interventions for neurodegenerative diseases.

BACKGROUND: Neurodegenerative diseases (NDDs) are increasingly prevalent and radically alter the lives of individuals and their informal care partners (together called a dyad). As symptoms progress, dyads are at risk for elevated emotional distress and declines in relationship functioning and quality of life. Psychosocial interventions delivered to dyads early after diagnosis have successfully prevented chronic emotional distress across several chronic illnesses including cancer and acute brain injury. Dyads with NDD could benefit from such interventions, however, they are limited. Because NDDs have symptom profiles that are distinct from other chronic illnesses, they require a unique framework and interventions. Given the limited dyadic interventions and unified symptoms across NDDs, a transdiagnostic framework may help to enhance scalability and efficiency. To address this problem, we developed a transdiagnostic framework that cuts across NDD physical and emotional diagnoses to inform cost-effective and sustainable NDD dyadic interventions. METHODS: To develop this framework, we conducted: (1) a narrative review on dyadic adjustment and existent dyadic interventions for those with NDDs, and (2) integrated findings to develop our NDD transdiagnostic framework for dyadic interventions early after diagnosis. RESULTS: Findings revealed no existent dyadic interventions for NDDs delivered shortly after diagnosis. Among available interventions, all were delivered later in disease progression, thereby focusing on dyadic challenges at more advanced stages. In addition, although research emphasized the influence of individual, dyadic, and contextual factors on dyads' early adjustment to NDDs, no conceptual model has been developed. Informed by theory and current research, we introduce an NDD transdiagnostic framework for couples' early biopsychosocial adjustment. This framework includes NDD specific: contextual factors, illness-related factors, individual and dyadic stressors, adaptive coping strategies, and dyads' resources. CONCLUSIONS: Our NDD transdiagnostic framework can be used to inform early dyadic psychosocial interventions that cut across all NDDs. This approach has important implications for implementation and scalability.

Identification of ENPP1 Haploinsufficiency in Patients With Diffuse Idiopathic Skeletal Hyperostosis and Early-Onset Osteoporosis.

Homozygous ENPP1 mutations are associated with autosomal recessive hypophosphatemic rickets type 2 (ARHR2), severe ossification of the spinal ligaments, and generalized arterial calcification of infancy type 1. There are a limited number of reports on phenotypes associated with heterozygous ENPP1 mutations. Here, we report a series of three probands and their families with heterozygous and compound heterozygous ENPP1 mutations. The first case (case 1) was a 47-year-old male, diagnosed with early-onset osteoporosis and low-normal serum phosphate levels, which invoked suspicion for hypophosphatemic rickets. The second and third cases were 77- and 54-year-old females who both presented with severe spinal ligament ossification and the presumptive diagnosis of diffuse idiopathic skeletal hyperostosis (DISH). Upon workup, fibroblast growth factor 23 (FGF23) was noted to be relatively high in case 2 and serum phosphorous was low-normal in case 3, and the diagnoses of X-linked hypophosphatemic rickets (XLH) and ARHR2 were considered. Genetic testing for genes related to congenital hypophosphatemic rickets was therefore performed, revealing heterozygous ENPP1 variants in cases 1 and 2 (case 1, c.536A>G, p.Asn179Ser; case 2, c.1352A>G, p.Tyr451Cys) and compound heterozygous ENPP1 variants in case 3 constituting the same variants present in cases 1 and 2 (c.536A>G, p.Asn179Ser and c.1352A>G, p.Tyr451Cys). Several in silico tools predicted the two variants to be pathogeneic, a finding confirmed by in vitro biochemical analysis demonstrating that the p.Asn179Ser and p.Tyr451Cys ENPP1 variants possessed a catalytic velocity of 45% and 30% compared with that of wild-type ENPP1, respectively. Both variants were therefore categorized as pathogenic loss-of-function mutations. Our findings suggest that ENPP1 mutational status should be evaluated in patients presenting with the diagnosis of idiopathic DISH, ossification of the posterior longitudinal ligament (OPLL), and early-onset osteoporosis. © 2022 American Society for Bone and Mineral Research (ASBMR).

Mindfulness is inversely associated with psychological symptoms in long-term cardiac arrest survivors.

Identifying correlates of psychological symptoms in cardiac arrest (CA) survivors is a major research priority. In this longitudinal survey study, we evaluated associations between mindfulness, baseline psychological symptoms, and 1-year psychological symptoms in long-term CA survivors. We collected demographic and CA characteristics at baseline. At both timepoints, we assessed posttraumatic stress symptoms (PTS) through the PTSD Checklist-5 (PCL-5) and depression and anxiety symptoms through the Patient Health Questionnaire-4 (PHQ-4). At follow-up, we assessed mindfulness through the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R). We used adjusted linear regression to predict 1-year PCL-5 and PHQ-4 scores, with particular consideration of the CAMS-R as a cross-sectional correlate of outcome. We included 129 CA survivors (mean age: 52 years, 52% male, 98% white). At 1-year follow-up, in adjusted models, CAMS-R (ß: -0.35, p < 0.001) and baseline PCL-5 scores (ß: 0.56, p < 0.001) were associated with 1-year PCL-5 scores. CAMS-R (ß: -0.34, p < 0.001) and baseline PHQ-4 scores were associated with 1-year PHQ-4 scores (ß: 0.37, p < 0.001). In conclusion, mindfulness was inversely associated with psychological symptoms in long-term CA survivors. Future studies should examine the longitudinal relationship of mindfulness and psychological symptoms after CA.

Understanding the interplay between lifestyle factors and emotional distress for hemorrhagic stroke survivors and their informal caregivers: Protocol for a mixed methods dyadic natural history study.

Emotional distress (depression, anxiety, and PTS) and unhealthy lifestyle factors (e.g., smoking, alcohol consumption, poor diet, limited physical activity, medication adherence) are common in hemorrhagic stroke (HS) survivors and may increase risk for recurrence, morbidity, and mortality. Emotional distress and unhealthy lifestyle factors tend to be interdependent between survivors and their informal caregivers (e.g., family and friends who provide unpaid care; together called dyads), such that one partner's lifestyle and coping behaviors influence the other's behaviors, yet no research has closely examined this relationship in HS dyads over time. We will conduct a mixed methods study to quantitatively and qualitatively understand the longitudinal relationship between emotional distress and lifestyle factors across time in this population (HS dyads) to identify treatment targets to prevent emotional distress chronicity and stroke recurrence. In aim 1, we will assess emotional distress (i.e., depression, anxiety, and PTS) and lifestyle factors (smoking, alcohol consumption, poor diet, limited physical activity medication adherence/blood pressure control) in dyads of survivors of HS and their caregivers (N = 80), at three separate time points (hospitalization in the Neuro-ICU, 1, and 3 months later). We hypothesize that 1) lifestyle factors and emotional distress will be interrelated within and across time for both survivors and caregivers, and 2) lifestyle factors and emotional distress will be interdependent between survivors and caregivers. We also aim to explore the nuanced interplay between lifestyle factors and emotional distress and gain in depth information on barriers and facilitators for a dyadic intervention to optimize lifestyle behaviors and emotional functioning in HS dyads. Eligible patients will be adults who have a caregiver also willing to participate. Patients will be referred for study participation by the nursing team who will ensure that they are cognitively able to meaningfully participate. Multilevel dyadic modeling (i.e., actor-partner interdependence model; APIM) with distinguishable dyads will be used to determine influences of these factors onto each other over time. In Aim 2, we will conduct live video qualitative dyadic interviews (N = 20 or until theme saturation) at all time points from the same participants with and without emotional distress and at least one lifestyle risk factor, to understand the nuanced relationships between emotional distress and lifestyle behaviors, and barriers and facilitators to engagement in a skills-based psychosocial intervention. Interviews will be analyzed using inductive and deductive approaches. The present study is currently ongoing. So far, we enrolled 2 participants. Recruitment will end October 2022 with plans to analyze data by December 2022. The findings from this study will be used to further develop psychosocial interventions and inform novel treatments for survivors of HS and their informal caregivers.

Emotional distress in neuro-ICU survivor-caregiver dyads: The recovering together randomized clinical trial.

OBJECTIVE: Emotional distress is common in both survivors and their informal caregivers following admission to a neuroscience intensive care unit (Neuro-ICU) and can negatively affect their individual recovery and quality of life. Neuro-ICU survivor-caregiver dyads can influence each other's emotional distress over time, but whether such influence emerges during dyadic treatment remains unknown. The present study involved secondary data analysis of Neuro-ICU dyads enrolled in a randomized clinical trial of a dyadic resiliency intervention, Recovering Together (RT), versus a health education attention placebo control to test dyadic similarities in emotional distress before and after treatment. METHOD: Data were collected from 58 dyads following Neuro-ICU admission. Emotional distress (depression, anxiety, and posttraumatic stress) was assessed at baseline, 6 weeks (postintervention), and 12 weeks later. Nonindependence within survivor-caregiver dyads was examined (i.e., correlations between cross-sectional symptoms and changes in symptoms over time); mutual influence of emotional functioning over time (i.e., "partner effects") was examined using cross-lagged path analyses. RESULTS: There were strong, positive cross-sectional correlations between survivor and caregiver distress at postintervention and follow-up and between changes in survivor and caregiver distress from baseline to postintervention and postintervention to follow-up. There were no partner effects. CONCLUSIONS: Neuro-ICU survivors and their informal caregivers show similar changes in emotional distress after treatment. These findings highlight the potential benefits of intervening on both survivor and caregiver distress following Neuro-ICU admission. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Early feasibility testing of a web-based mind-body resiliency program for adults with neurofibromatosis: The NF-Web study.

Objectives: We aimed to test early feasibility, acceptability, and signals of improvement after the 8-week individually delivered asynchronous, web-based mind-body program (NF-Web) modeled after the synchronous group-based live video program (Relaxation Response Resiliency Program for NF; 3RP-NF). Methods: Two cohorts (cohort 1 n = 14, cohort 2 n = 14) completed baseline and posttest (feasibility markers, t-tests). Results: Enrolled participants (N = 28; 80% of those eligible) completed baseline (N = 28; 100% of sample) and posttests (N = 25; 89.3%). Video lesson (58.0%) and homework (70.9%) completion were fair to good. Satisfaction (M = 8.85/10; SD = 2.35), credibility (M = 7.07/10; SD = 1.44), and expectancy (M = 6.68/10; SD = 2.10) were good to excellent. Participation was associated with statistically significant pre-to-post positive changes in quality of life (QoL; Physical, Psychological, Social, and Environmental,; p < 0.05) and emotional distress (depression, anxiety, and stress; p < 0.05). Pain intensity and interference did not improve significantly (p > 0.05) after participation. Conclusions: NF-Web demonstrates initial feasibility, acceptability, and signals of improvement. Results support future trials to ascertain efficacy. Innovation: Web-based programs may be valuable for individuals with rare illness who prefer to learn skills on their own timeline, have barriers to live video participation, and who also have apprehensions about interacting with others during treatment.