Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders.

Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A 'pathway' driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the 'gene-environment neuroscience interaction'. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench-to-bedside scientific discovery agenda with ongoing clinician and patient engagement. WHAT THIS PAPER ADDS: Precision medicine has predominantly focused on genetic risk factors. The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied. A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented. The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.

Patterns and Predictors of Healthcare Use among Adolescent and Young Adult Cancer Survivors versus a Community Comparison Group.

Healthcare use (HCU) during survivorship can mitigate adolescent and young adult (AYA) cancer survivors' (aged 15-39 years) risk of medical and psychosocial late effects, but this is understudied. We surveyed 93 Australian AYA post-treatment cancer survivors (Mage = 22.0 years, SD = 3.5; 55.9% female) and a comparison sample of 183 non-matched AYAs (Mage = 19.7, SD = 3.2; 70.5% female) on their HCU, medication use, depression/anxiety, and general functioning. Relative to our comparison AYAs, a higher proportion of our survivor group reported medical HCU (community-delivered: 65.6% versus 47.0%, p = 0.003; hospital-delivered: 31.2% versus 20.3%, p = 0.044) and mental HCU (53.8% vs. 23.5%; p < 0.0001) in the past six months. A higher proportion of our survivors reported taking medications within the past six months than our comparison AYAs (61.3% vs. 42.1%, p = 0.003) and taking more types (p < 0.001). Vitamin/supplement use was most common followed by psychotropic medications. Our survivor group reported lower depression (p = 0.001) and anxiety symptoms (p = 0.003), but similar work/study participation (p = 0.767) to our comparison AYAs. Across groups, psychological distress was associated with higher mental HCU (p = 0.001). Among survivors, those who were female, diagnosed with brain/solid tumors and who had finished treatment more recently reported greater HCU. Future research should establish whether this level of HCU meets AYAs' survivorship needs.

How physically active do Australian and New Zealander childhood cancer survivors perceive themselves? A report from the ANZCHOG survivorship study.

PURPOSE: Childhood cancer survivors are at risk of treatment late-effects. Physical activity represents a necessary complementary therapy and modifiable risk-factor across all ages for many cardio-metabolic late-effects. This study assessed perceived physical activity in Australian and New Zealander childhood cancer survivors. METHODS: We recruited parents of survivors aged <16 years, and adult survivors of childhood cancer aged ≥16 years, ≥5 years since diagnosis, with age-matched controls for comparison. We compared perceived moderate-vigorous physical activity between survivors and controls, using regression to identify associations with physical activity. RESULTS: We recruited 914 participants (570 childhood cancer survivors and 344 age-matched controls). Parents of survivors perceived more moderate-vigorous physical activity than child controls (248 ± 218, 95% Confidence Interval (CI) = 218-280 vs 185 ± 214 min/week, 95% CI = 144-225, p = 0.036), with no perceived difference between adult survivors and controls (125 ± 152, 95% CI = 108-140 vs 160 ± 201 min/week, 95% CI = 132-187, p = 0.477). Twenty-seven percent of child survivors (vs. 14.5% controls) and 30% of adult survivors (vs. 39.4% controls) met recommendations. Adult survivors who received radiotherapy (OR = 0.585, 95% CI = 0.343-0.995, p = 0.048) or not completed university (OR = 1.808, 95% CI = 1.071-3.053, p = 0.027) were less likely to meet recommendations. CONCLUSIONS: Over two-thirds of Australian and New Zealander childhood cancer survivors across all ages are perceived to not meet physical activity recommendations. Adult survivors who had radiotherapy or did not complete university appeared at-risk for low physical activity. PRACTICAL IMPLICATIONS: Physical activity is important for everyone, but critical among childhood cancer survivors due to increased late cardio-metabolic risks. Monitoring survivors' perceived but also objectively measured physical activity as complementary to routine care is warranted, to provide education and motivate survivors to take control of their health.

Dietary intake and diet quality in children receiving treatment for cancer.

This narrative synthesis aims to examine the dietary intake, diet quality, and dietary preferences of pediatric cancer patients during cancer treatment. Thirteen studies were eligible for review. Studies mostly investigated nutrient intake, with 7 reporting on children's food intake. There was consensus among studies, which reported suboptimal fruit and vegetable intake and a preference for savory, carbohydrate-based foods. Results suggest that pediatric cancer patients consume a limited variety of foods, with a high intake of noncore foods. Future research should aim to examine dietary food data against dietary guidelines to assess adequacy and variety within core food groups.

The Role of Primary Care Physicians in Childhood Cancer Survivorship Care: Multiperspective Interviews.

BACKGROUND: Primary care physicians (PCPs) are well placed to provide holistic care to survivors of childhood cancer and may relieve growing pressures on specialist-led follow-up. We evaluated PCPs' role and confidence in providing follow-up care to survivors of childhood cancer. SUBJECTS, MATERIALS, AND METHODS: In Stage 1, survivors and parents (of young survivors) from 11 Australian and New Zealand hospitals completed interviews about their PCPs' role in their follow-up. Participants nominated their PCP for an interview for Stage 2. In Stage 2, PCPs completed interviews about their confidence and preparedness in delivering childhood cancer survivorship care. RESULTS: Stage 1: One hundred twenty survivors (36% male, mean age: 25.6 years) and parents of young survivors (58% male survivors, survivors' mean age: 12.7 years) completed interviews. Few survivors (23%) and parents (10%) visited their PCP for cancer-related care and reported similar reasons for not seeking PCP-led follow-up including low confidence in PCPs (48%), low perceived PCP cancer knowledge (38%), and difficulty finding good/regular PCPs (31%). Participants indicated feeling "disconnected" from their PCP during their cancer treatment phase. Stage 2: Fifty-one PCPs (57% male, mean years practicing: 28.3) completed interviews. Fifty percent of PCPs reported feeling confident providing care to childhood cancer survivors. PCPs had high unmet information needs relating to survivors' late effects risks (94%) and preferred a highly prescriptive approach to improve their confidence delivering survivorship care. CONCLUSION: Improved communication and greater PCP involvement during treatment/early survivorship may help overcome survivors' and parents' low confidence in PCPs. PCPs are willing but require clear guidance from tertiary providers. IMPLICATIONS FOR PRACTICE: Childhood cancer survivors and their parents have low confidence in primary care physicians' ability to manage their survivorship care. Encouraging engagement in primary care is important to promote holistic follow-up care, continuity of care, and long-term surveillance. Survivors'/parents' confidence in physicians may be improved by better involving primary care physicians throughout treatment and early survivorship, and by introducing the concept of eventual transition to adult and primary services. Although physicians are willing to deliver childhood cancer survivorship care, their confidence in doing so may be improved through better communication with tertiary services and more appropriate training.

Feasibility, acceptability, and safety of the Recapture Life videoconferencing intervention for adolescent and young adult cancer survivors.

OBJECTIVE: Online psychological therapies provide a way to connect adolescent and young adult (AYA) cancer survivors to evidence-based support. We aimed to establish the feasibility, acceptability, and safety of Recapture life, a six-session group-based online cognitive-behavioural intervention, led by a facilitator, for AYAs in the early post-treatment period. METHODS: A randomised-controlled trial compared Recapture Life to an online peer-support group control and a waitlist control. Participants could nominate a support person. Acceptability was assessed using study opt-in and retention rates, participant-reported benefits/burdens of participation, and group facilitator burden. We also assessed the feasibility (eg, frequency/impact of technological difficulties) and psychological safety (ie, occurrence of clinically concerning distress) of the program. RESULTS: Sixty-one participants took part (45 AYAs, 51.1% female; 19 support people). The opt-in rate was 30%, the enrolment rate was 87%, and 75% of participants took part in ≥5/6 sessions. AYAs reported high benefit and low burden of participation. Overall, 95 online group sessions were conducted; few required rescheduling by group facilitators (3%), but many took place outside of office hours (~90 hours). It took 40 days on average to create online groups, but established weekly sessions commenced quickly (M = 4.0 minutes). Technological difficulties were common but had a low impact on intervention delivery. Although 54% of AYAs returned a clinically concerning distress screen at some point, none reflected acute mental health risks. CONCLUSIONS: The data largely indicate that Recapture Life is an acceptable, feasible, and safe model of evidence-based psychological support for AYAs during early survivorship, which nevertheless experienced common challenges in online/AYA intervention delivery.

Nutritional interventions for survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors are at a higher risk of developing health conditions such as osteoporosis, and cardiovascular disease than their peers. Health-promoting behaviour, such as consuming a healthy diet, could lessen the impact of these chronic issues, yet the prevalence rate of health-protecting behaviour amongst survivors of childhood cancer is similar to that of the general population. Targeted nutritional interventions may prevent or reduce the incidence of these chronic diseases. OBJECTIVES: The primary aim of this review was to assess the efficacy of a range of nutritional interventions designed to improve the nutritional intake of childhood cancer survivors, as compared to a control group of childhood cancer survivors who did not receive the intervention. Secondary objectives were to assess metabolic and cardiovascular risk factors, measures of weight and body fat distribution, behavioural change, changes in knowledge regarding disease risk and nutritional intake, participants' views of the intervention, measures of health status and quality of life, measures of harm associated with the process or outcomes of the intervention, and cost-effectiveness of the intervention SEARCH METHODS: We searched the electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 3), MEDLINE/PubMed (from 1945 to April 2013), and Embase/Ovid (from 1980 to April 2013). We ran the search again in August 2015; we have not yet fully assessed these results, but we have identified one ongoing trial. We conducted additional searching of ongoing trial registers - the International Standard Randomised Controlled Trial Number register and the National Institutes of Health register (both screened in the first half of 2013) - reference lists of relevant articles and reviews, and conference proceedings of the International Society for Paediatric Oncology and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (both 2008 to 2012). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared the effects of a nutritional intervention with a control group which did not receive the intervention in this review. Participants were childhood cancer survivors of any age, diagnosed with any type of cancer when less than 18 years of age. Participating childhood cancer survivors had completed their treatment with curative intent prior to the intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and extracted data from each identified study, using a standardised form. We assessed the validity of each identified study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE criteria to assess the quality of each trial. MAIN RESULTS: Three RCTs were eligible for review. A total of 616 participants were included in the analysis. One study included participants who had been treated for acute lymphoblastic leukaemia (ALL) (275 participants). Two studies included participants who had all forms of paediatric malignancies (266 and 75 participants). All participants were less than 21 years of age at study entry. The follow-up ranged from one month to 36 months from the initial assessment. All intended outcomes were not evaluated by each included study. All studies looked at different interventions, and so we were unable to pool results. We could not rule out the presence of bias in any of the studies.There was no clear evidence of a difference in calcium intake at one month between those who received the single, half-day, group-based education that focused on bone health, and those who received standard care (mean difference (MD) 111.60, 95% confidence interval (CI) -258.97 to 482.17; P = 0.56, low quality evidence). A regression analysis, adjusting for baseline calcium intake and changes in knowledge and self-efficacy, showed a significantly greater calcium intake for the intervention as compared with the control group at the one-month follow-up (beta coefficient 4.92, 95% CI 0.33 to 9.52; P = 0.04). There was statistically significant higher, self-reported milk consumption (MD 0.43, 95% CI 0.07 to 0.79; P = 0.02, low quality evidence), number of days on calcium supplementation (MD 11.42, 95% CI 7.11 to 15.73; P < 0.00001, low quality evidence), and use of any calcium supplementation (risk ratio (RR) 3.35, 95% CI 1.86 to 6.04; P < 0.0001, low quality evidence), with those who received this single, face-to-face, group-based, health behaviour session.There was no clear evidence of a difference in bone density Z-scores measured with a dual-energy X-ray absorptiometry (DEXA) scan at 36 months follow-up (MD -0.05, 95% CI -0.26 to 0.16; P = 0.64, moderate quality evidence) between those who received calcium and vitamin D supplementation combined with nutrition education and those who received nutrition education alone. There was also no clear evidence of a difference in bone mineral density between the intervention and the control group at the 12-month (median difference -0.17, P = 0.99) and 24-month follow-up (median difference -0.04, P = 0.54).A single multi-component health behaviour change intervention, focusing on general healthy eating principles, with two telephone follow-ups brought about a 0.17 lower score on the four-point Likert scale of self-reported junk food intake compared with the control group (MD -0.17, 95% CI -0.33 to -0.01; P = 0.04, low quality evidence); this result was statistically significant. There was no clear evidence of a difference between the groups in the self-reported use of nutrition as a health protective behaviour (MD -0.05, 95% CI -0.24 to 0.14; P = 0.60, low quality evidence). AUTHORS' CONCLUSIONS: Due to a paucity of studies, and the heterogeneity of the studies included in this review, we are unable to draw conclusions regarding the effectiveness of nutritional interventions for use with childhood cancer survivors. Although there is low quality evidence for the improvement in health behaviours using health behaviour change interventions, there remains no evidence as to whether this translates into an improvement in dietary intake. There was also no evidence that the studies reduced the risk of cardiovascular and metabolic disorders in childhood cancer survivors, although no evidence of effect is not the same as evidence of no effect. This review highlights the need for further well designed trials to be implemented in this population.

A study protocol for Truce: a pragmatic controlled trial of a seven-week acceptance and commitment therapy program for young people who have a parent with cancer.

BACKGROUND: This paper presents the rationale and study protocol for a pragmatic controlled effectiveness trial of Truce, a prevention-based selective intervention targeting the significant mental health needs of young people who have a parent with cancer. METHODS/DESIGN: Truce is a seven week, facilitated, face-to-face group program. The design is a 2 groups (intervention vs control) x 3 (pre-treatment vs post-treatment vs 2 month follow-up) repeated measures. Allocation to groups will be dependent upon recruitment; when groups have sufficient numbers, they will be assigned to the intervention condition, but participants recruited without a viable group will be assigned to the wait-list control condition. Eligible participants are young people aged 14 to 22 years who have a parent diagnosed with cancer within the last 5 years. Wait-list controls are offered the opportunity to participate in the program once they have completed their follow-up questionnaires. The target sample size is 65 participants in each condition. The primary hypothesis is that participants in the intervention will show significant reductions in distress and increases in psychological well-being relative to participants in the wait-list control group, and these effects will continue through two-month follow-up. Mixed-models analysis of variance will be used to measure differences between the two conditions. Secondary analyses will focus on variables which may relate to the effectiveness of the intervention: ACT-related concepts of experiential avoidance and mindfulness, family functioning, unmet needs and demographic variables. We will also assess program fidelity and satisfaction. DISCUSSION: The development and evaluation of a manualised intervention for young people with a parent with cancer responds to a gap in the provision of empirically-based psychological support for this vulnerable group. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12615000761561. Registered 22(nd) July 2015.

Online parent-targeted cognitive-behavioural therapy intervention to improve quality of life in families of young cancer survivors: study protocol for a randomised controlled trial.

BACKGROUND: Due to advances in multimodal therapies, most children survive cancer. In addition to the stresses of diagnosis and treatment, many families are now navigating the challenges of survivorship. Without sufficient support, the ongoing distress that parents experience after their child's cancer treatment can negatively impact the quality of life and psychological wellbeing of all family members. METHODS/DESIGN: The 'Cascade' (Cope, Adapt, Survive: Life after C AncEr) study is a three-arm randomised controlled trial to evaluate the feasibility and efficacy of a new intervention to improve the quality of life of parents of young cancer survivors. Cascade will be compared to a peer-support group control and a 6-month waitlist control. Parents (n = 120) whose child (under 16 years of age) has completed cancer treatment in the past 1 to 12 months will be recruited from hospitals across Australia. Those randomised to receive Cascade will participate in four, weekly, 90-minute online group sessions led live by a psychologist. Cascade involves peer discussion on cognitive-behavioural coping skills, including behavioural activation, thought challenging, mindfulness and acceptance, communication and assertiveness skills training, problem-solving and goal-setting. Participants randomised to peer support will receive four, weekly, 90-minute, live, sessions of non-directive peer support. Participants will complete measures at baseline, directly post-intervention, one month post-intervention, and 6 months post-intervention. The primary outcome will be parents' quality of life. Secondary outcomes include parent depression, anxiety, parenting self-agency, and the quality of life of children in the family. The child cancer survivor and all siblings aged 7 to 15 years will be invited to complete self-report quality of life measures covering physical, emotional, social and school-related domains. DISCUSSION: This article reviews the empirical rationale for group-based, online cognitive-behavioural therapy in parents of children who have recently finished cancer treatment. The potential challenges of delivering skills-based programs online are highlighted. Cascade's videoconferencing technology has the potential to address the geographic and psychological isolation of families after cancer treatment. Teaching parents coping skills as they resume their normal lives after their child's cancer may see long-term benefits for the quality of life of the family as a whole. TRIAL REGISTRATION: ACTRN12613000270718 (registered 6 March 2013).

Paediatric oncology patient preference for oral nutritional supplements in a clinical setting.

PURPOSE: Oral nutrition supplements are commonly used to increase the nutrient intake of children who are undergoing treatment for cancer. However, little research has been conducted systematically examining preferences for oral supplements in this population. This study aims to address a gap in the literature by examining taste preferences of oral nutrition supplements routinely recommended for children undergoing treatment for cancer. METHODS: Twenty-one children undergoing treatment for cancer and 38 healthy control subjects participated in an acute double-blinded feeding trial. A variety of energy drinks, available both commercially and in the hospital, were sampled. Patients rated the taste of the drinks on a 10-cm coloured analogue scale. RESULTS: A commercially-based drink (Moove™) rated the highest in the blinded and branded tests for the treatment (mean rating out of 10, 6.44±2.69 and 7.26±2.33, respectively) and control groups (mean rating, 7.61±1.91 and 7.70±2.32, respectively). Taste ratings were significantly higher for commercially available supplements over the hospital-prepared supplements, (p=0.041), with no main effect for tasting condition (i.e. blinded versus branded, p=0.902). There was a statistically significant trend such that ratings, when the brand that was known decreased for hospital supplements, while ratings for commercially available supplements increased (p=0.014). CONCLUSION: Fresh milk-based supplements were the preferred type of oral nutrition supplement in a cohort of paediatric oncology patients. The data also suggest that commercially available products are more likely to be accepted than hospital-prepared supplements. This pilot study supports the need for further research in the area of oral nutrition supplements for paediatric oncology patients as a way of determining a reliable way to estimate preferences and therefore maximise compliance. Results from this research could be also used as the basis for designing research to study the effects of flavour fatigue and long-term compliance with oral nutrition supplements in this population.