Participants’ perspectives of feasibility of a novel group treatment for people with cognitive communication difficulties following acquired brain injury

Purpose: To determine whether treatment was acceptable to participants and perceived as beneficial by exploring the experiences of people with cognitive communication difficulties following acquired brain injury who participated in a novel, group, communication, project-based treatment. The purpose of the treatment was to improve participants’ communication skills and quality of life, by focusing group activity towards the production of a project and by incorporating individualised communication goals into group sessions. Methods: Twenty-one people with acquired brain injury recruited from community settings participated in project-based treatment, which comprised one individual and nine group sessions (of 2-3 people) over six weeks. Structured interviews were conducted post-treatment as part of a broader assessment battery. Interviews were transcribed verbatim and analysed using content analysis to identify codes, categories and themes. Results: Themes identified from the analysis centred around the treatment experience (general experience; group experience; project experience; working on goals) and benefit of treatment (communicative benefit; other benefits; emotional effects; meeting others; something to do). These themes were consistent with the treatment being perceived as acceptable and having initial efficacy for the participant group. Conclusion: The qualitative data presented here provide positive feasibility findings (acceptability and initial efficacy) of project-based treatment for people with acquired brain injury. The results highlight the value of incorporating participants’ views in assessing feasibility in developing novel interventions

Technology and its role in rehabilitation for people with cognitive-communication disability following a traumatic brain injury (TBI)

© 2017 Taylor & Francis Group, LLC. Purpose: To review the literature on communication technologies in rehabilitation for people with a traumatic brain injury (TBI), and: (a) determine its application to cognitive-communicative rehabilitation, and b) develop a model to guide communication technology use with people after TBI. Method: This integrative literature review of communication technology in TBI rehabilitation and cognitive-communication involved searching nine scientific databases and included 95 studies. Results: Three major types of communication technologies (assistive technology, augmentative and alternative communication technology, and information communication technology) and multiple factors relating to use of technology by or with people after TBI were categorized according to: (i) individual needs, motivations and goals; (ii) individual impairments, activities, participation and environmental factors; and (iii) technologies. While there is substantial research relating to communication technologies and cognitive rehabilitation after TBI, little relates specifically to cognitive-communication rehabilitation. Conclusions: Further investigation is needed into the experiences and views of people with TBI who use communication technologies, to provide the ‘user’ perspective and influence user-centred design. Research is necessary to investigate the training interventions that address factors fundamental for success, and any impact on communication. The proposed model provides an evidence-based framework for incorporating technology into speech pathology clinical practice and research

Prenatal stress, the placenta and maternal microbial transmission; implications for health and disease

There is an extensive amount of epidemiological evidence showing that prenatal maternal distress (PNMD) is a risk factor for a wide range of poor obstetric and neonatal outcomes, as well as an increased risk for the development of metabolic, immune and nervous system disorders in affected children later in life. Whilst many epidemiology studies have supported these associations, the biological mechanisms linking maternal prenatal distress with adverse outcomes remains understudied, particularly in human cohorts. One potential mechanism, known as the glucocorticoid hypothesis proposes that fetal overexposure to stress-induced maternal cortisol during critical windows of development increases the risk of adverse outcomes in the offspring. At the core of this hypothesis is the placenta, which expresses the enzyme 11beta hydroxysteroid dehydrogenase type 2 (HSD11B2), which ultimately controls the amount of cortisol a fetus is exposed to. Prenatal stress has been shown to reduce the placental expression of this enzyme; however the molecular mechanisms through which this occurs have not been well examined. More recently, the transmission of a suboptimal stressed maternal microbiota is emerging as an alternative mechanism that may mediate the impact of prenatal stress on infant development. However this has not yet been examined in a clinical population. We first utilized an in vitro placenta model, JEG-3 cells, to examine the effects of stress on the placental expression of HSD11B2. JEG-3 cells were cultured with exogenous cortisol and interleukin-1 beta (IL-1β), two potential biological mediators of prenatal stress. This study showed both cortisol and IL-1β can reduce HSD11B2 expression, an effect that could be prevented by co-treatment with a histone deacetylase inhibitor. Having established that cortisol can directly affect the expression of HSD11B2, we moved on to our first clinical study to examine this question in a clinical population by examining the impact of prenatal distress on placental gene expression and infant outcomes. A cohort of 121 pregnant women receiving antenatal care at Cork University Maternity Hospital (CUMH) completed the Perceived stressed scale (PSS), State Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) in late pregnancy and donated placental biopsies at the time of birth. This study identified a significant reduction in HSD11B2 mRNA along with an increase in the glucocorticoid receptor (NR3C1) in placentae from high distressed pregnancies. Additionally prenatal distress was associated with a number of adverse outcomes including delivering via Caesarean section, reduced Apgar scores and reduced birth temperature, supporting a role for placental glucocorticoid signalling in the relationship between prenatal distress and adverse outcomes. Having reported that stress impacts molecular placental signals and birth outcomes, we moved on to complete the SMArTI (Stressed Microbial Transfer to the Infant) study, a more detailed pregnancy cohort to examine the impact prenatal distress on the maternal and infant microbiome. This study yielded a final cohort off 111 nulliparous pregnant women that were recruited from the IMPROvED consortium at CUMH. Women enrolled in SMArTI completed distress questionnaires and provided saliva and fecal samples in the second and/or third trimester of pregnancy. Vaginal swabs, placenta samples and newborn hair were acquired at birth and infant fecal samples were subsequently collected across the first 5 months of life. We first used this cohort to further examine and validate the relationship between prenatal distress, placental glucocorticoid genes and infant outcomes. We found this relationship to be dependent on the timing of distress, type of distress and infant sex. Most notably we observed second trimester maternal anxiety correlated with reduced birthweight in female infants, a relationship mediated by placental FK506-bind protein 51 (FKBP51) mRNA expression. We finally used the SMArTI cohort to examine, for the first time, the impact of PNMD on the maternal and infant microbiome, using 16S rRNA gene sequencing. Reduced diversity of the maternal gut microbiome in the second trimester was associated with second trimester distress, most substantially with maternal depressive symptoms, an effect that was no longer apparent by the third trimester. The third trimester gut microbiome appeared relatively resistant to change with only modest alterations observed in women who had high second trimester cortisol. Of interest, third trimester distress had no effect on the third trimester gut microbiome, highlighting the experience of distress specifically in the second trimester as an important window of vulnerability. Reduced diversity of the vaginal microbiome, just prior to delivery, was associated with second trimester cortisol, with no alterations linked third trimester distress. When examining the infant gut microbiome we found increased diversity across the first 5 months of life to be associated with second trimester stress with corresponding decreases to the important Bifidobacteriaceae and Lactobacillaceae family. In conclusion, this thesis indicates the experience of PNMD influences key placental genes involved in glucocorticoid signalling in the placentae. The timing of maternal distress and infant sex are important factors in this relationship. Of particular interest we find placental FKBP51 to mediate a relationship between maternal anxiety and infant birthweight, demonstrating a direct role for placental glucocorticoid signalling underlying the relationship between prenatal distress and infant outcomes. The work presented in this thesis is the first of its kind to prospectively examine the influence of PNMD on the maternal gut, vaginal and infant gut microbiome. Stress-induced alterations in the maternal gut microbiome may contribute to adverse obstetric and birth outcomes albeit via a mechanism other than transmission of a suboptimal maternal microbiota during birth. Taken together, our results identify the second trimester as an especially vulnerable period to stress exposures and implicate the placenta and microbiome in mediating these effects. Counteracting the impact of stress during this critical time window may have important obstetric implications. Additionally understanding the consequence of the altered infant gut microbiome as a result of prenatal distress warrants further investigation

Setting and achieving individualised social communication goals for people with acquired brain injury (ABI) within a group treatment

Background and Aims: Cognitive-communication disorders are common following an acquired brain injury (ABI). Remediation should involve individualised goal setting, yet few reports describe the effectiveness of setting communication goals in a group setting. This paper aims to describe a process for setting and achieving goals for people with ABI. Methods and Procedures: Twenty-one participants with ABI participated in a group treatment (triads and dyads) over 6 weeks (20 hours in total). Specific social communication goals were set using Goal Attainment Scaling (GAS) with the participant and their communication partner. Goals targeted strategy use that accounted for existing cognitive abilities. The participant and their communication partner evaluated the goals post-treatment and 6-8 weeks later. Data was analysed using Friedman’s Test to identify achievement of GAS goals. Outcomes and Results: Twenty participants recalled goals independently post-treatment. Significant improvement post-treatment on GAS goals was rated by both the participant (p<0.001) and their communication partner (p<0.001). This improvement was maintained at follow-up. No significant differences in ratings were found between participants and their communication partners at either time point. Conclusions and implications: Individualised social communication goals can be set and achieved for people with ABI in group treatment, even when participants are several years post-injury. GAS offers a method for structuring and quantifying goal progress. Involving communication partners and cognitive strategies were effective in improving communication

Maternal distress in late pregnancy alters obstetric outcomes and the expression of genes important for placental glucocorticoid signalling

The experience of maternal distress in pregnancy is often linked with poorer obstetric outcomes for women as well as adverse outcomes for offspring. Alterations in placental glucocorticoid signalling and subsequent increased fetal exposure to cortisol have been suggested to underlie this relationship. In the current study, 121 pregnant women completed the Perceived Stress Scale, State Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale in the third trimester of pregnancy. Placental samples were collected after delivery. Maternal history of psychiatric illness and miscarriage were significant predictors of poorer mental health in pregnancy. Higher anxiety was associated with an increase in women delivering via elective Caesarean Section, and an increase in bottle-feeding. Birth temperature was mildly reduced among infants of women with high levels of depressive symptomology. Babies of mothers who scored high in all stress (cumulative distress) measures had reduced 5-min Apgar scores. High cumulative distress reduced the expression of placental HSD11B2 mRNA and increased the expression of placental NR3C1 mRNA. These data support a role for prenatal distress as a risk factor for altered obstetric outcomes. The alterations in placental gene expression support a role for altered placental glucocorticoid signalling in the relationship between maternal prenatal distress and adverse outcomes

Content Analysis of Tweets by People with Traumatic Brain Injury (TBI): Implications for Rehabilitation and Social Media Goals

In this Twitter research, 6874 tweets of six adults with traumatic brain injury (TBI) were analyzed qualitatively and quantitatively using content classification [1], inductive coding of content themes, socio-linguistic analysis, and computational analysis in KH Coder. The results reflected that participants used Twitter for: (i) supporting others, including people with TBI; (ii) discussing society and culture, popular issues, news, and personal interests; (iii) connecting with others; (iv) sharing their experiences of life after TBI; (v) knowledge via exchanging information; and (vii) advocacy. ‘Emotional expression’, and ‘connection’ were common threads running across themes. Attending to the expressions of people with TBI on Twitter provides important insights into their lived experiences and could inform the development of user-centered cognitive-communication and social participation goals for people with TBI

Recommendations for the Design and Implementation of Virtual Reality for Acquired Brain Injury Rehabilitation: Systematic Review

Background: Virtual reality (VR) is increasingly being used for the assessment and treatment of impairments arising from acquired brain injuries (ABIs) due to perceived benefits over traditional methods. However, no tailored options exist for the design and implementation of VR for ABI rehabilitation and, more specifically, traumatic brain injury (TBI) rehabilitation. In addition, the evidence base lacks systematic reviews of immersive VR use for TBI rehabilitation. Recommendations for this population are important because of the many complex and diverse impairments that individuals can experience. Objective: This study aims to conduct a two-part systematic review to identify and synthesize existing recommendations for designing and implementing therapeutic VR for ABI rehabilitation, including TBI, and to identify current evidence for using immersive VR for TBI assessment and treatment and to map the degree to which this literature includes recommendations for VR design and implementation. Methods: This review was guided by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). A comprehensive search of 11 databases and gray literature was conducted in August 2019 and repeated in June 2020. Studies were included if they met relevant search terms, were peer-reviewed, were written in English, and were published between 2009 and 2020. Studies were reviewed to determine the level of evidence and methodological quality. For the first part, qualitative data were synthesized and categorized via meta-synthesis. For the second part, findings were analyzed and synthesized descriptively owing to the heterogeneity of data extracted from the included studies. Results: In the first part, a total of 14 papers met the inclusion criteria. Recommendations for VR design and implementation were not specific to TBI but rather to stroke or ABI rehabilitation more broadly. The synthesis and analysis of data resulted in three key phases and nine categories of recommendations for designing and implementing VR for ABI rehabilitation. In the second part, 5 studies met the inclusion criteria. A total of 2 studies reported on VR for assessment and three for treatment. Studies were varied in terms of therapeutic targets, VR tasks, and outcome measures. VR was used to assess or treat impairments in cognition, balance, and anxiety, with positive outcomes. However, the levels of evidence, methodological quality, and inclusion of recommendations for VR design and implementation were poor. Conclusions: There is limited research on the use of immersive VR for TBI rehabilitation. Few studies have been conducted, and there is limited inclusion of recommendations for therapeutic VR design and implementation. Future research in ABI rehabilitation should consider a stepwise approach to VR development, from early co-design studies with end users to larger controlled trials. A list of recommendations is offered to provide guidance and a more consistent model to advance clinical research in this area

A Web-Based Service Delivery Model for Communication Training After Brain Injury: Protocol for a Mixed Methods, Prospective, Hybrid Type 2 Implementation-Effectiveness Study.

BackgroundAcquired brain injuries (ABIs) commonly cause cognitive-communication disorders, which can have a pervasive psychosocial impact on a person's life. More than 135 million people worldwide currently live with ABI, and this large and growing burden is increasingly surpassing global rehabilitation service capacity. A web-based service delivery model may offer a scalable solution. The Social Brain Toolkit is an evidence-based suite of 3 web-based communication training interventions for people with ABI and their communication partners. Successful real-world delivery of web-based interventions such as the Social Brain Toolkit requires investigation of intervention implementation in addition to efficacy and effectiveness.ObjectiveThe aim of this study is to investigate the implementation and effectiveness of the Social Brain Toolkit as a web-based service delivery model.MethodsThis is a mixed methods, prospective, hybrid type 2 implementation-effectiveness study, theoretically underpinned by the Nonadoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework of digital health implementation. We will document implementation strategies preemptively deployed to support the launch of the Social Brain Toolkit interventions, as well as implementation strategies identified by end users through formative evaluation of the Social Brain Toolkit. We will prospectively observe implementation outcomes, selected on the basis of the NASSS framework, through quantitative web analytics of intervention use, qualitative and quantitative pre- and postintervention survey data from all users within a specified sample frame, and qualitative interviews with a subset of users of each intervention. Qualitative implementation data will be deductively analyzed against the NASSS framework. Quantitative implementation data will be analyzed descriptively. We will obtain effectiveness outcomes through web-based knowledge tests, custom user questionnaires, and formal clinical tools. Quantitative effectiveness outcomes will be analyzed through descriptive statistics and the Reliable Change Index, with repeated analysis of variance (pretraining, posttraining, and follow-up), to determine whether there is any significant improvement within this participant sample.ResultsData collection commenced on July 2, 2021, and is expected to conclude on June 1, 2022, after a 6-month sample frame of analytics for each Social Brain Toolkit intervention. Data analysis will occur concurrently with data collection until mid-2022, with results expected for publication late 2022 and early 2023.ConclusionsEnd-user evaluation of the Social Brain Toolkit's implementation can guide intervention development and implementation to reach and meet community needs in a feasible, scalable, sustainable, and acceptable manner. End user feedback will be directly incorporated and addressed wherever possible in the next version of the Social Brain Toolkit. Learnings from these findings will benefit the implementation of this and future web-based psychosocial interventions for people with ABI and other populations.Trial registrationAustralia and New Zealand Clinical Trials Registry ACTRN12621001170819; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621001170819, Australia and New Zealand Clinical Trials Registry ACTRN12621001177842; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621001177842, Australia and New Zealand Clinical Trials Registry ACTRN12621001180808; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621001180808.International registered report identifier (irrid)DERR1-10.2196/31995

Implementation of Web-Based Psychosocial Interventions for Adults With Acquired Brain Injury and Their Caregivers: Systematic Review.

BACKGROUND: More than 135 million people worldwide live with acquired brain injury (ABI) and its many psychosocial sequelae. This growing global burden necessitates scalable rehabilitation services. Despite demonstrated potential to increase the accessibility and scalability of psychosocial supports, digital health interventions are challenging to implement and sustain. The Nonadoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) framework can offer developers and researchers a comprehensive overview of considerations to implement, scale, and sustain digital health interventions. OBJECTIVE: This systematic review identified published, peer-reviewed primary evidence of implementation outcomes, strategies, and factors for web-based psychosocial interventions targeting either adults with ABI or their formal or informal caregivers; evaluated and summarized this evidence; synthesized qualitative and quantitative implementation data according to the NASSS framework; and provided recommendations for future implementation. Results were compared with 3 hypotheses which state that complexity (dynamic, unpredictable, and poorly characterized factors) in most or all NASSS domains increases likelihood of implementation failure; success is achievable, but difficult with many complicated domains (containing multiple interacting factors); and simplicity (straightforward, predictable, and few factors) in most or all domains increases the likelihood of success. METHODS: From a comprehensive search of MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, speechBITE, and neuroBITE, we reviewed primary implementation evidence from January 2008 to June 2020. For web-based psychosocial interventions delivered via standard desktop computer, mobile phone, tablet, television, and virtual reality devices to adults with ABI or their formal or informal caregivers, we extracted intervention characteristics, stakeholder involvement, implementation scope and outcomes, study design and quality, and implementation data. Implementation data were both narratively synthesized and descriptively quantified across all 7 domains (condition, technology, value proposition, adopters, organization, wider system, and their interaction over time) and all subdomains of the NASSS framework. Study quality and risk of bias were assessed using the 2018 Mixed Methods Appraisal Tool. RESULTS: We identified 60 peer-reviewed studies from 12 countries, including 5723 adults with ABI, 1920 carers, and 50 health care staff. The findings aligned with all 3 hypotheses. CONCLUSIONS: Although studies were of low methodological quality and insufficient number to statistically test relationships, the results appeared consistent with recommendations to reduce complexity as much as possible to facilitate implementation. Although studies excluded individuals with a range of comorbidities and sociocultural challenges, such simplification of NASSS domain 1 may have been necessary to advance intervention value propositions (domain 3). However, to create equitable digital health solutions that can be successfully implemented in real-world settings, it is recommended that developers involve people with ABI, their close others, and health care staff in addressing complexities in domains 2 to 7 from the earliest intervention design stages. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020186387; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186387. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1177/20552076211035988

Romidepsin induces caspase-dependent cell death in human neuroblastoma cells

Neuroblastoma is the most common extracranial pediatric solid tumor, arising from the embryonic sympathoadrenal lineage of the neural crest, and is responsible for 15% of childhood cancer deaths. Although survival rates are good for some patients, those children diagnosed with high-risk neuroblastoma have survival rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge and the development of novel therapeutic strategies is essential. Given that there is widespread epigenetic dysregulation in neuroblastoma, epigenetic pharmacotherapy holds promise as a therapeutic approach. In recent years, histone deacetylase (HDAC) inhibitors, which cause selective activation of gene expression, have been shown to be potent chemotherapeutics for the treatment of a wide range of cancers. Here we examined the ability of the FDA-approved drug Romidepsin, a selective HDAC1/2 inhibitor, to act as a cytotoxic agent in neuroblastoma cells. Treatment with Romidepsin at concentrations in the low nanomolar range induced neuroblastoma cell death through caspase-dependent apoptosis. Romidepsin significantly increased histone acetylation, and significantly enhanced the cytotoxic effects of the cytotoxic agent 6-hydroxydopamine, which has been shown to induce cell death in neuroblastoma cells through increasing reactive oxygen species. Romidepsin was also more potent in MYCN-amplified neuroblastoma cells, which is an important prognostic marker of poor survival. This study has thus demonstrated that the FDA-approved chemotherapeutic drug Romidepsin has a potent caspase-dependent cytotoxic effect on neuroblastoma cells, whose effects enhance cell death induced by other cytotoxins, and suggests that Romidepsin may be a promising chemotherapeutic candidate for the treatment of neuroblastoma