Current Recommendations for Patient-Reported Outcome Measures Assessing Domains of Quality of Life in Neurofibromatosis Clinical Trials.

OBJECTIVE: To review and recommend patient-reported outcome (PRO) measures assessing multidimensional domains of quality of life (QoL) to use as clinical endpoints in medical and psychosocial trials for children and adults with neurofibromatosis (NF) type 1, NF2, and schwannomatosis. METHODS: The PRO working group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration used systematic methods to review, rate, and recommend existing self-report and parent-report PRO measures of generic and disease-specific QoL for NF clinical trials. Recommendations were based on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility. RESULTS: The highest-rated generic measures were (1) the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales for NF clinical trials for children or for children through adults, (2) the Functional Assessment of Cancer Therapy-General for adult medical trials, and (3) the World Health Organization Quality of Life-BREF for adult psychosocial trials. The highest-rated disease-specific measures were (1) the PedsQL NF1 Module for NF1 trials, (2) the NF2 Impact on Quality of Life Scale for NF2 trials, and (3) the Penn Acoustic Neuroma Quality of Life Scale for NF2 trials targeting vestibular schwannomas. To date, there are no disease-specific tools assessing multidimensional domains of QoL for schwannomatosis. CONCLUSIONS: The REiNS Collaboration currently recommends these generic and disease-specific PRO measures to assess multidimensional domains of QoL for NF clinical trials. Additional research is needed to further evaluate the use of these measures in both medical and psychosocial trials.

Effects of a mind-body program on symptoms of depression and perceived stress among adults with neurofibromatosis type 2 who are deaf: A live-video randomized controlled trial.

INTRODUCTION: Neurofibromatosis type 2 (NF2) is a rare, progressive and incurable genetic disorder associated with progressive hearing loss and eventual deafness. As a group, patients with NF report high levels of stress and depressive symptoms. However, no studies have explored improvement in these symptoms after psychosocial interventions. We have previously shown that a mind-body program tailored to adults with NF2 who are deaf (the Relaxation Response and Resiliency Program for Deaf NF2, d3RP-NF2) improves quality of life and resiliency over and above a Health Enhancement program when both are delivered via live-video and assisted by Communication Access Realtime Translation (CART). Here we tested the effects of the programs on depression and perceived stress. METHODS: Forty-five patients with NF2 and significant hearing loss were randomized to the d3RP-NF2 or Health-Enhancement program and completed measures of depression (PHQ-9) and perceived stress (PSS-10) at baseline, post-intervention, and six-month follow-up. RESULTS: Patients randomized to the d3RP-NF2 program, but not to the control condition, experienced significant decreases on both measures from baseline to post-test, which were maintained at follow-up (within group tests). However, improvements following the d3RP-NF2 program was not significantly higher than those observed in the control group (between group tests). CONCLUSION: Results provide the first evidence of improvement in symptoms of depression and perceived stress among deaf patients living with NF2 who participate in a virtual mind-body program.

"Cooling of the mind": Assessing the relevance of mindfulness training among people living with HIV using alcohol and other substances in South Africa.

RATIONALE: "Thinking too much" is a cultural idiom of distress identified across sub-Saharan Africa, including among people living with HIV (PLWH), which is associated with depression, substance use, and HIV medication nonadherence. Despite the relevance of mindfulness training to address thinking too much, improve HIV-related outcomes, and reduce substance use, efforts to adapt mindfulness training for this context and underserved populations more broadly have been limited. OBJECTIVE: We explored in this context: (a) the experience of thinking too much among PLWH struggling with adherence and substance use; (b) the appropriateness of mindfulness training to address thinking too much; and (c) potential barriers and facilitators to implementing mindfulness training. METHOD: We conducted semi-structured interviews with patients (n = 19) and providers (n = 11) at two clinics in a peri-urban area of Cape Town. Guided by the ADAPT-ITT model, we included an experiential mindfulness practice and participants shared their observations and descriptions of the intervention in the local language (isiXhosa). RESULTS: Participants found mindfulness relevant, culturally salient, and appropriate for refocusing the mind. Findings provide unique language offered by participants to tailor mindfulness training in the future (e.g., "hearing your veins," "cooling of the mind"). Participants identified potential implementation barriers, including lack of privacy, and facilitators to guide future adaptations. CONCLUSIONS: More research is needed to adapt and increase access to mindfulness training in resource-limited settings globally, while also maintaining treatment integrity and fidelity.

Pain Catastrophizing and Limiting Behavior Mediate the Association Between Anxiety and Postconcussion Symptoms.

BACKGROUND: Despite growing evidence that anxiety is critical in the development and maintenance of postconcussion symptoms after mild traumatic brain injury (mTBI), little is known about potential mechanisms through which anxiety may affect these symptoms. OBJECTIVE: To test the strength and reliability of cognitive (pain catastrophizing) and behavioral (limiting behaviors) pathways mediating the relationship between anxiety and postconcussion symptoms among patients with mTBI. METHOD: Patients with mTBI (N = 57) completed self-report measures of anxiety, postconcussion symptoms, pain catastrophizing, and limiting behavior. After preliminary simple-mediation models (for pain catastrophizing and limiting behavior separately), we ran a multiple-mediation model (pathways modeled simultaneously). Bootstrapping with 10,000 resampling iterations assessed mediation reliability. RESULTS: In preliminary simple mediation models, both pain catastrophizing (ß = 0.24, 95% confidence interval [CI] = 0.03-0.44, P = 0.02) and limiting behaviors (ß = 0.14, 95% CI = 0.03-0.26, P = 0.01) partially mediated the relationship between anxiety and postconcussion symptoms. In the multiple mediation model, pain catastrophizing was a less reliable but numerically stronger mediator (ß = 0.19, 95% CI = -0.01 to 0.38; P = 0.05) and explained more variance in postconcussion symptoms (R2 = 0.41) than limiting behavior (ß = 0.10, 95% CI = 0.02-0.21, P = 0.03; R2 = 0.22), although mediators did not significantly differ in strength (ß = 0.08, 95% CI = -0.16 to 0.32; P = 0.49). Results provide novel evidence for the role of pain catastrophizing and limiting behaviors in explaining the association between anxiety and postconcussion symptoms. Addressing both factors may improve the recovery trajectory of individuals with mTBI. Emphasizing limiting behavior may yield more consistent and reliable effects. CONCLUSION: Results support developing interventions to directly target anxiety, for pain catastrophizing, and for activity engagement despite symptoms, to decrease symptom severity among patients with mTBI.

Cultivating resiliency in patients with neurofibromatosis 2 who are deafened or have severe hearing loss: a live­video randomized control trial.

INTRODUCTION: Patients with NF2 who are deaf or have significant hearing loss face numerous and unique challenges which lead to poor quality of life, and thus may benefit from resiliency programs. METHODS: We performed secondary data analyses on a single blind, randomized controlled trial of an 8 week mind-body resiliency program (the Relaxation Response and Resiliency program for Deaf NF2; d3RP-NF2) versus a health education control (Health Enhancement Program for Deaf NF2;dHEP-NF2) which showed improvement in quality of life (Funes in JAMA 2019, https://doi.org/10.1007/s11060-019-03182-3). Here we report on improvements in resiliency factors (i.e. optimism, gratitude, perceived social support, mindfulness, and perceived coping abilities) assessed at baseline, post-test and 6-month follow-up. Both programs were delivered via Skype using Communication Access Real-Time Translation. RESULTS: Patients who were randomized to the d3RP-NF2 program exhibited significant improvements from baseline to post-program in gratitude (Mdifference = 4.04, 95% CI 1.58-6.50; p = 0.002), perceived social support (Mdifference = 16.36, 95% CI 9.20-23.51; p < 0.001), mindfulness (Mdifference = 4.02, 95% CI 1.10-6.94; p = 0.008), perceived coping (Mdifference = 15.25, 95% CI 10.21-20.28; p < 0.001), and a non-significant trend of improvement in optimism (Mdifference = 1.15, 95% CI -0.14-12.44; p = 0.079). These improvements were all maintained through the 6-month follow up. Improvements in perceived coping (Mdifference = 12.34, 95% CI 4.75-19.93; p = 0.002), social support (Mdifference = 13.11, 95% CI 2.19-24.03; p = 0.02), and gratitude (Mdifference = 4.59, 95% CI 0.83-8.36; p = 0.018) were over and above the changes observed in those randomized to dHEP-NF2. CONCLUSION: The d3RP-NF2 sustainably improves multiple dimensions of resiliency. Promoting resiliency may be of utmost importance for this uderserved population.

First report of quality of life in adults with neurofibromatosis 2 who are deafened or have significant hearing loss: results of a live-video randomized control trial.

PURPOSE: To test the feasibility, acceptability, and preliminary efficacy of a mind-body program for patients with neurofibromatosis 2 (NF2) who are deaf or have significant hearing loss (d3RP-NF2) against an attention placebo control (dHEP-NF2) in a single-blind randomized control trial. Both were delivered using Communication Access Real-Time Translation and live group videoconferencing. METHODS: Forty-five adults with NF2 were randomized. Co-primary outcomes were physical quality of life (QoL) and psychological QoL and secondary outcomes were social QoL and environmental QoL, all measured with the World Health Organization Quality of Life Abbreviated Instrument (WHOQOL-BREF). Assessments were conducted at baseline, post-treatment, and six-month follow-up. RESULTS: Forty-one participants (91%) completed the intervention, and 29 (64%) completed the six-month follow up. Participants in the d3RP-NF2 showed significantly greater improvements from baseline to post-treatment on physical QoL (14.79, 95% CI 5.41-24.18; p ≤ 0.001), psychological QoL (18.77, 95% CI 7.09-30.44, p ≤ 0.001), and environmental QoL (13.25, 95% CI 1.10-25.39, p = 0.03) compared to the dHEP-NF2. Social QoL also significantly increased in the d3RP-NF2 (16.32, 95% CI 6.66-25.97, p = 0.001), but improvement was not beyond the dHEP-NF2. Gains in QoL were clinically meaningful and maintained at the 6-month follow-up for d3RP-NF2 participants across all QoL domains. There were more treatment responders in the d3RP-NF2 compared to the dHEP-NF2. CONCLUSIONS: The d3RP-NF2 was well accepted, highly feasible, and resulted in sustained improvements in QoL in patients with NF2 who are deaf or have significant hearing loss.

Results of a feasibility randomized controlled trial (RCT) of the Toolkit for Optimal Recovery (TOR): a live video program to prevent chronic pain in at-risk adults with orthopedic injuries.

BACKGROUND: Orthopedic injuries are the leading cause of hospital admissions in the USA, and many of these patients transition into chronic pain. Currently, there are no evidence-based interventions targeting prevention of chronic pain in patients with orthopedic injuries. We iteratively developed a four-session intervention "The Toolkit for Optimal Recovery" (TOR) which we plan to subsequently test for efficacy in a phase III hybrid efficacy-effectiveness multi-site clinical trial. In order to prevent methodological weaknesses in the subsequent trial, we conducted a feasibility pilot to evaluate the TOR delivered via secure live video versus usual care (UC) in patients with orthopedic injuries from an urban, level I trauma clinic, who screen in as at risk for chronic pain and disability. We tested the feasibility of recruitment, acceptability of screening, and randomization methods; acceptability of the intervention, treatment adherence, and treatment fidelity; satisfaction with the intervention; feasibility of the assessment process at all time points; acceptability of outcome measures for the definitive trial; and within-treatment effect sizes. METHODS: We aimed to recruit 50-60 participants, randomize, and retain them for ~ 4 months. Assessments were done electronically via REDCap at baseline, post-intervention (approximately 5 weeks after baseline), and 3 months later. We followed procedures we intend to implement in the full-scale hybrid efficacy-effectiveness trial. RESULTS: We recruited 54 participants and found that randomization and data collection procedures were generally acceptable. The majority of participants were white, educated, and employed. Warm hand-off referrals were more effective than research assistants directly approaching patients for participation without their providers' engagement. Feasibility of recruitment, acceptability of screening, and randomization were good. Satisfaction with the program, adherence to treatment sessions, and treatment fidelity were all high. There were no technical issues associated with the live video delivery of the TOR. There was minimal missing data and outcome measures were deemed appropriate. Effect sizes for improvement after participation in TOR were moderate to large. There were many lessons learned for future trials. CONCLUSIONS: This study provided evidence of the feasibility of the planned hybrid efficacy-effectiveness trial design when implemented at our home institution. Establishing feasibility of the intervention and study procedures at other trauma centers with more diverse patient populations and different clinical practices is required before a multi-site phase III efficacy-effectiveness trial. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03405610. Registered on January 28, 2018-retrospectively registered.

Preventing Chronic Emotional Distress in Stroke Survivors and Their Informal Caregivers.

BACKGROUND/OBJECTIVE: Chronic emotional distress (e.g., depression, anxiety, post-traumatic stress) is common after stroke and interdependent between patients and their informal caregivers. We measured stroke survivors', caregivers', and neurocritical care nurses' views of primary drivers of distress during the stroke experience, and needs and preferences for the structure, topics, mode of delivery, and timing of an intervention to promote emotional recovery. METHODS: We conducted semi-structured interviews with 24 patient-caregiver dyads within the Neuroscience Intensive Care Unit (Neuro-ICU). Additionally, we conducted two focus groups with 15 nurses. Interviews and focus groups were audio-recorded, transcribed, and coded using NVivo 11 (QSR International) software. RESULTS AND CONCLUSIONS: The challenges and impacts of stroke most commonly reported by dyads were: uncertainty about future health, fear of recurrent strokes, negative emotions, and role changes post-stroke. Dyads and nurses agreed that resiliency skills such as mindfulness/focusing on the present, problem solving, gratitude/optimism, self-care, interpersonal communication and developing a supportive team of family, friends, and medical staff are beneficial to optimize recovery. The potential barrier to intervention delivery was accessibility, due to challenges of time and travel to appointments. Participants agreed that starting the intervention at hospitalization and continuing via live video after discharge is an ideal delivery modality. Stroke survivors, caregivers, and Neuro-ICU nurses believe that a resiliency skills-based intervention to prevent chronic emotional distress is necessary and urgent. This qualitative study provides valuable information on the challenges faced by dyads, intervention topics to prioritize, and strategies to maximize feasibility, acceptability, and effect.

Mind-Body Treatment for International English-Speaking Adults With Neurofibromatosis via Live Videoconferencing: Protocol for a Single-Blind Randomized Controlled Trial.

BACKGROUND: Neurofibromatoses (NF) are rare genetic conditions associated with substantial psychosocial burden and impaired quality of life (QoL). We developed the first NF-tailored mind-body program (the Relaxation Response Resiliency Program for NF) and adapted it for delivery via live videoconferencing to decrease participation barriers and increase its reach. In a pilot randomized controlled trial (RCT), we found that the Relaxation Response Resiliency Program for NF had excellent feasibility and acceptability when delivered via live videoconferencing; furthermore, the Relaxation Response Resiliency Program for NF showed proof of concept in improving QoL compared with an NF-tailored health education control program (the Health Enhancement Program for NF). A fully powered trial is needed to ascertain the efficacy and durability of the Relaxation Response Resiliency Program for NF delivered via secure live videoconferencing among geographically diverse patients. OBJECTIVE: The objective of this study is to evaluate the efficacy of the Relaxation Response Resiliency Program for NF versus the Health Enhancement Program for NF, both delivered in groups via secure live videoconferencing, among geographically diverse patients with NF across the United States and internationally. Here we describe the protocol, manualized treatments, evaluation plan, and study design. METHODS: This is a single-blind RCT. Patients are told that they will be randomized to one of the two stress management programs (stress management program 1: the Relaxation Response Resiliency Program for NF and stress management program 2: the Health Enhancement Program for NF). Patients are recruited from NF-specific national and international foundations and NF clinics across the United States through study ads and a video of participants who have completed the program as part of the pilot study or ongoing trial. Interested participants are screened for eligibility via secure live videoconferencing (self-reported stress and difficulties coping, no change in antidepressant medication within the past 3 months, no psychotherapy within the past 3 months, no major upcoming surgeries within the next 12 months, English speaking, and able to complete questionnaires online and participate in live video interventions) and consent obtained before participation. Both programs are manualized comprising 8 sessions delivered via secure live videoconferencing by trained clinical psychologists. Primary outcomes are physical health QoL and psychological health QoL. Secondary outcomes are social relationship QoL, environment QoL, and psychosocial and resiliency variables. Outcomes are assessed at baseline, posttraining, and 6- and 12-month follow-ups. RESULTS: The trial is ongoing. Thus far, we have recruited 55 patients and aim to recruit a total of 224. Recruitment will close in May 2020; we plan to complete data analyses by June 2021. CONCLUSIONS: This trial will answer key questions about the efficacy and durability of the Relaxation Response Resiliency Program for NF via live videoconferencing with English-speaking adults with NF worldwide. If found efficacious, this program can be readily implemented through national and international NF foundations and NF-specific clinics. The virtual model of delivery has extensive applications for patients in rural areas, those with disability or illness that precludes travel to clinics, and those with rare diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT03406208; https://clinicaltrials.gov/ct2/show/NCT03406208 (Archived by WebCite at http://www.webcitation.org/72ZoTDQ6h). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/11008.

What Factors Are Associated With Disability After Upper Extremity Injuries? A Systematic Review.

BACKGROUND: Psychosocial factors are key determinants of health after upper extremity injuries. However, a systematic review is needed to understand which psychosocial factors are most consistently associated with disability and how the language, conceptualization, and types of measures used to assess disability impact these associations in upper extremity injuries. QUESTIONS/PURPOSES: (1) What factors are most consistently associated with disability after upper extremity injuries in adults? (2) What are the trends in types of outcome measures and conceptualization of disability in patients' upper extremity injuries? METHODS: We searched multiple electronic databases (PubMED, OVIDSP, PsycInfo, Google Scholar, ISI Web of Science) between January 1, 1996, and December 31, 2016, using terms related to the "upper extremity", "outcome measurement", and "impairment, psychological, social or symptomatic" variables. We included all studies involving adult patients with any musculoskeletal injury and excluded those that did not use patient-reported outcome measures. We identified and screened 9339 studies. Of these, we retained 41 studies that involved conditions ranging from fractures to soft tissue injuries in various regions of the arm. We conducted quality assessment using a 10-item validated checklist and a five-tier strength of evidence assessment. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria and registered the review before performing our search (PROSPERO: CRD42017054048). None of the authors received any funding to perform this work. RESULTS: Disability after upper extremity injury was most consistently associated with depression (21 cohorts), catastrophic thinking (13 cohorts), anxiety (11 cohorts), pain self-efficacy (eight cohorts), and pain interference (seven cohorts). Social and demographic factors were also associated with disability. Measures of impairment such as ROM and injury severity were least associated with disability. There has been a gradual increase in use of region or condition-specific patient-reported outcome measures and measures of psychological, social, and symptomatic factors over a period since the introduction of the World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) around 2000. Approximately 17% of studies (n = 454 of 2628) had instances of unclear, conflicting, or inappropriate terminology and 11% of studies (n = 257 of 2628) involved misrepresentations of outcome measures related to disability. CONCLUSIONS: Psychologic and social factors are most consistently associated with disability than factors related to impairment. Further research involving the assessment of depression, anxiety, and coping strategies in cohorts with specific injuries may support decision-making regarding the provision of emotional support and psychologic therapies during recovery. Using the WHO ICF framework to conceptualize disability is key in increasing strength of evidence and allowing accurate comparisons of research in this field. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Early Risk and Resiliency Factors Predict Chronic Posttraumatic Stress Disorder in Caregivers of Patients Admitted to a Neuroscience ICU.

OBJECTIVES: Informal caregivers-that is, close family and friends providing unpaid emotional or instrumental care-of patients admitted to ICUs are at risk for posttraumatic stress disorder. As a first step toward developing interventions to prevent posttraumatic stress disorder in ICU caregivers, we examined the predictive validity of psychosocial risk screening during admission for caregiver posttraumatic stress disorder at 3 and 6 months post hospitalization. DESIGN: An observational, prospective study. PARTICIPANTS: Ninety-nine caregivers were recruited as part of a longitudinal research program of patient-caregiver dyads in a neuroscience ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Caregiver posttraumatic stress disorder symptoms were assessed during admission (baseline), 3 months, and 6 months post hospitalization. We 1) characterized prevalence of clinically significant symptoms at each time point 2); calculated sensitivity and specificity of baseline posttraumatic stress disorder screening in predicting posttraumatic stress disorder at 3 and 6 months; and 3) used recursive partitioning to select potential baseline factors and examine the extent to which they helped predict clinically significant posttraumatic stress disorder symptoms at each time point. Rates of caregiver posttraumatic stress disorder remained relatively stable over time (16-22%). Screening for posttraumatic stress disorder at baseline predicted posttraumatic stress disorder at 3 and 6 months with moderate sensitivity (75-80%) and high specificity (92-95%). Screening for posttraumatic stress disorder at baseline was associated with caregiver anxiety, mindfulness (i.e., ability to be aware of one's thoughts and feelings in the moment), and bond with patient. Furthermore, baseline posttraumatic stress disorder screening was the single most relevant predictor of posttraumatic stress disorder at 3 and 6 months, such that other baseline factors did not significantly improve predictive ability. CONCLUSIONS: Screening neuroscience ICU caregivers for clinically significant posttraumatic stress disorder symptoms during admission is the single most important way to identify the majority of those likely to suffer from chronic posttraumatic stress disorder following discharge. Addressing early posttraumatic stress disorder symptoms and their psychosocial correlates during admission may help prevent chronic posttraumatic stress disorder in these at-risk caregivers.