Hard-to-treat childhood cancers are those where standard treatment options do not exist and the prognosis is poor. Healthcare professionals (HCPs) are responsible for communicating with families about prognosis and complex experimental treatments. We aimed to identify HCPs’ key challenges and skills required when communicating with families about hard-to-treat cancers and their perceptions of communication-related training.

We interviewed Australian HCPs who had direct responsibilities in managing children/adolescents with hard-to-treat cancer within the past 24 months. Interviews were analyzed using qualitative content analysis.

We interviewed 10 oncologists, 7 nurses, and 3 social workers. HCPs identified several challenges for communication with families including: balancing information provision while maintaining realistic hope; managing their own uncertainty; and nurses and social workers being underutilized during conversations with families, despite widespread preferences for multidisciplinary teamwork. HCPs perceived that making themselves available to families, empowering them to ask questions, and repeating information helped to establish and maintain trusting relationships with families. Half the HCPs reported receiving no formal training for communicating prognosis and treatment options with families of children with hard-to-treat cancers. Nurses, social workers, and less experienced oncologists supported the development of communication training resources, more so than more experienced oncologists.

Resources are needed which support HCPs to communicate with families of children with hard-to-treat cancers. Such resources may be particularly beneficial for junior oncologists and other HCPs during their training, and they should aim to prepare them for common challenges and foster greater multidisciplinary collaboration.

To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).

Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.

pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).

Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.

To determine the association between in-vivo spectroscopy metabolite data, the local connectome, and markers of initial injury severity (I.e., history of loss of consciousness; LoC) in traumatic brain injury (TBI), in a heterogenous sample of Veterans and non-Veterans with a history of remote mild-to-moderate TBI (I.e., >6 months).

Participants with complete PRESS magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) data (N = 41) were sampled from a larger multisite study of chronic mild-to-moderate TBI (Nmiid = 38; Nmoderate = 3; 54% with LoC; 46% with multiple TBI). The sample was predominantly male (76%) with ages ranging from 23-59 (M = 36.9, SD = 10.1), with 98% holding at least a high school degree (M = 14.5 years of education, SD = 2.4). Fully tissue-and-relaxation-corrected metabolite concentration estimates in the dorsal anterior cingulate (30x30x30mm voxel) were modeled using Osprey 2.4.0. Total creatine (tCr), total choline (tCho), total N-acetylaspartate (tNAA), glutamate/glutamine (Glx), and myo-inositol (mI) were analyzed. Logistic regression was used to measure the association between metabolites and history of TBI with LoC. Correlational connectometry using the normalized spin distribution function was performed for metabolites associated with LoC, to characterize the local connectome associated with metabolites of interest, controlling for age and sex, and correcting for multiple comparisons (FDR < .050 with 4000 permutations). A profile approach was used to interpret diffusion metrics, contrasting quantitative anisotropy (QA) with fractional anisotropy (FA). Local connectome tracks were then clustered to identify the larger white matter tract.

Glx (p = .008) and tCr (p = .032) were significantly associated with history of TBI with LoC. Increased Glx was associated with increased QA in 11,001 tracks, accounting for 1.4% of the total white matter tracks in the brain. 90% of tracks were identified in bilateral cingulum (33%), bilateral thalamic (13%), bilateral corticospinal (13%), corpus callosum (12%), left arcuate fasciculus (9%), left frontoparietal aslant tracts (6%), and bilateral inferior fronto-occipital fasciculus (4%) tracts. In contrast, FA was not associated with Glx. The same pattern emerged for tCr, with 10,542 tracks identified predominantly in bilateral cingulum (29%), corpus callosum (21%), bilateral corticospinal (15%), bilateral corticostriatal (7%), bilateral medial lemniscus (7%), left cortico-pontine (3%), left thalamic (2%), and bilateral superior longitudinal fasciculus (2%) tracts. Post-hoc exploratory analyses of mean QA across regions of cingulum found that increased QA was associated with self-report measures of headache intensity, fatigue, and perceived change in executive functioning.

Results provided evidence that multimodal imaging can identify subtle markers of initial TBI severity years after injury. Neurometabolite concentrations were associated with diffuse changes in the local connectome; the pattern of discrepancy between FA and QA was suggestive of reduced potential for neuroplasticity. Exploratory analyses further indicated that variability in white matter density in the cingulum, an important connection for limbic regions, was associated with a range of problems commonly reported in clinical settings, which may be informative for diagnosis and treatment planning.

Mental fatigue, ‘brain fog’, and difficulties maintaining engagement are commonly reported issues in a range of neurological and psychiatric conditions. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory or visual domains. However, with this approach, discrete target stimuli may exogenously capture attention to aid detection, thereby masking deficits in the ability to endogenously sustain attention over time.

To address this, we developed the Continuous Temporal Expectancy Task (CTET) where individuals continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690 ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020 ms or longer). As such, sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration. Using the CTET, we assessed stroke survivors with unilateral right hemisphere damage (N = 14), a cohort in which sustained attention deficits have been extensively reported.

Stroke survivors had overall lower target detection accuracy compared with neurologically healthy age-matched older controls (N = 18). Critically, stroke survivors performance was characterised by significantly steeper within-block performance decrements, which occurred within short temporal windows (˜3 ½ min), and were restored by the break periods between blocks.

These findings suggest that continuous temporal monitoring taxes sustained attention processes to capture clinical deficits in this capacity over time, and outline a precise measure of the endogenous processes hypothesised to underpin sustained attention deficits following right hemisphere stroke.

With one in ten young people being affected by ill mental health and stigma regularly cited as a factor affecting access to early intervention services, focussing resources on school based stigma reduction strategies seems prudent. ‘Headucate’, a student society, designed a 50 minute workshop which aims to increase mental health literacy and decrease stigma.

Repeated, cross sectional surveys were carried out at three time points; 1) immediately before (n=77), 2) Immediately after (n=81) and 3) three months post workshop (n=73). The surveys were paper based versions of the Reported Intended Behaviours Score (RIBS) and Mental Health Knowledge Scale (MAKS) utilising a social distance scale.

Four year 10 classed (pupils aged 14-15) were recruited. Post hoc t-tests were carried out when one-way ANOVAS were significant.

Disorder knowledge (from MAKS) and intended contact (from RIBS) significantly increased between time points one and two (p<0.01 and <0.004 respectively) but then decreased.

Analysis of the question pertaining to knowing where to access help showed a statistically significant increase (p<0.001) between time points one and two and then a decrease at time three, albeit to a higher value than at time point one (3.45 compared to 3.13, P=0.088).

Headucate workshops offer a low resource option which is well accepted by students. Like other school based stigma reduction strategies, a dramatic increase was seen between immediately before and after indicating that the workshop resonates with the pupils, but there was little sustained change in attitudes.

Against a backdrop of poor mental health education in UK schools a group of students from Norwich Medical School have formed a student society called ‘Headucate’ in order to create, deliver and evaluate an educational intervention for adolescents, initially to be delivered in Norfolk schools.

To create an educational intervention that:

• Is the length of a standard lesson

• Is age appropriate and acceptable

• Contains appropriate signposting

• Contains content that challenges common myths and replaces them with knowledge

• Contains content that encourages empathy and understanding towards those with mental illnesses

• Is easily delivered in the same way each time so that its effectiveness can be evaluated

To create an intervention effective at tackling stigma and empowering adolescents to recognise signs of poor mental health and access services appropriately.

Lesson plan created after consultation with psychiatrists, a psychologist, a GP, a university outreach professional, a teacher and secondary school age children, then trialled and revised.

Interactive workshop produced with 5 sections.

1. 1) Myth vs Fact activity that dispels prevalent myths

2. 2) Scenario based activity to demonstrate that mental health is a spectrum

3. 3) An interactive presentation covering the most common mental illnesses and their symptoms

4. 4) An activity focusing on talking to those with mental illnesses, furthering the scenario from the previous activity

5. 5) A question and answer session. Every student leaves with a leaflet containing appropriate signposting.

We have created an educational intervention ready to be delivered and evaluated.

GXR, a selective α2A-adrenergic agonist, is a non-stimulant treatment for ADHD (approved in the USA for children and adolescents and in Canada for children).

To assess the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD.

To evaluate the efficacy (symptom and function) and safety of GXR for the treatment of ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo (NCT01244490).

Patients (6–17 years) were randomly assigned at baseline to dose-optimized GXR (6–12 years, 1–4 mg/day; 13–17 years, 1–7 mg/day), ATX (10–100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure is change from baseline in ADHD-Rating Scale-version IV (ADHD-RS-IV). Key secondary measures were defined as Clinical Global Impressions-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs.

Of 338 patients randomized, 272 (80.5%) completed the study. Placebo-adjusted differences in least squares (LS) mean in ADHD-RS-IV total score, percent improvement versus placebo for CGI-I, placebo-adjusted differences in LS mean change from baseline in WFIRS-P score (family and learning and school domains) are shown in the Table. The most common TEAEs for GXR were somnolence, headache, and fatigue; 8 (7%) TEAEs were severe.

GXR was effective and well tolerated in children and adolescents with ADHD.

Mental health education is not compulsory in the UK therefore adolescents have very varied experiences despite half of people with mental health illnesses reporting having experienced symptoms by 14 years old. University students are ideal for delivering a relaxed, educational intervention aimed at this age group, providing an opportunity to for them to learn necessary tools for recognising signs of poor mental health and tackle associated stigma.

To expand Headucate's membership, including other disciplines within the University of East Anglia (UEA) and provide core training enabling members to deliver a school-based educational intervention

Recruitment of members has been a multifaceted approach utilising social media sites such as Facebook and the Headucate website, and oncampus events and ‘awareness campaigns’ including several successful evening talks and lectures.

Three training sessions, which include ‘Introduction to Mental Health’, ‘Workshop run-through’ and ‘Child Protection’, have been developed for all members wishing to partake in the delivery of workshops.

We have recruited approximately 300 members since summer 2012; 70 fully paid members in 2012/13 academic year and currently 45 paid members for 2013/14.

A total of 18 members are fully trained and ready to deliver workshops within schools and 17 other members have just one training session remaining.

We are looking forward to delivering our first workshops in October and building on a successful first year. We are confident we can provide workshops for approximately 600 children per year.

The symptoms of many mental illnesses often begin during high school. Interventions to improve mental health awareness amongst adolescents may lead to improved outcomes. in the UK unfortunately many schools do not fulfil this need and mental health education is not a compulsory part of the curriculum.

To develop and measure the effectiveness of and educational intervention designed to raise awareness and empower adolescents to recognise signs of poor mental health and access services appropriately.

Evaluate the effectiveness of the intervention through baseline and follow up surveys.

Students at Norwich Medical School collaborated with teachers, psychiatrists and general practitioners to design an educational intervention that aims to tackle stigma and raise awareness of mental health conditions among 13-14 year olds in the hope that they can access services when needed, support those around them and look after their mental health. To evaluate effectiveness of the intervention, a knowledge, attitudes and practices survey that utilises a social distance scale that has been adapted for this age group and will be used to gather baseline and follow up data after six months.

We have developed a one-hour educational intervention delivered by medical students, that uses a variety of teaching techniques to raise awareness of mental health issues. We will start implementation in January 2013 so will have baseline effectiveness results shortly after.

Headucate has the potential to fill an important gap in effectively raising awareness of mental health issues in schools.

GXR, a selective α2A-adrenergic agonist, is a non-stimulant ADHD treatment approved in the USA for children and adolescents, and in Canada for children.

To evaluate long-term maintenance of efficacy of GXR in children and adolescents with ADHD who respond to an initial open-label, short-term trial.

To determine if there is a higher rate of treatment failure for placebo vs GXR during the double-blind randomised-withdrawal phase (RWP) (NCT01081145).

Patients (6–17 years) meeting DSM-IV-TR criteria for ADHD, baseline ADHD Rating Scale-IV (ADHD-RS-IV) ≥32 and Clinical Global Impressions-Severity (CGI-S) ratings ≥4 were enrolled. Following 7-week dose optimization and 6-week maintenance periods on open-label GXR (1–7 mg/day), eligible patients entered a 26-week, double-blind, RWP with GXR or placebo. The primary endpoint was rate of treatment failure (≥50% increase in ADHD-RS-IV total score and ≥2-point increase in CGI-S at two consecutive visits, compared to the RWP baseline). The key secondary endpoint was time-to-treatment failure. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs.

Of 528 patients enrolled, 316 (60.0%) entered the RWP. At study end, 49.3% (GXR) and 64.9% (placebo) (95%CI; −26.6, −4.5, p<0.01) of patients had relapsed (Figure). Time-to-treatment failure was 56 days (placebo) versus 218 days (GXR), p=0.003. During the RWP, the most common GXR TEAEs (≥5% patients) were headache, somnolence and nasopharyngitis.

GXR demonstrated long-term maintenance of efficacy versus placebo in children and adolescents with ADHD.