A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity.

Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI(-/-) and KtyII(-/-)(K8) mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation

Improving follow-up care for long term survivors of childhood cancer: A new model of care

Childhood cancer survivors are at risk of treatment-related health complications including second cancers and late mortality, requiring surveillance and management. Using a mixed-methods, multi-perspective approach, this body of work aimed to develop a new model of care for optimal follow-up of survivors. In Chapter 2, I outlined key survivorship issues including survivors' long-term medical (e.g. second cancers, cardiac complications, infertility) and psychosocial (poor quality of life, vocational challenges) needs. In Chapter 3, I systematically reviewed the international literature showing that follow-up care engagement improves survivors' knowledge about their cancer history, increases surveillance and late effects detected, and decreases emergency department visits and hospitalisations. In an audit of all 11 Australian and New Zealand survivorship clinics (Chapter 4), I interviewed 19 lead oncologists and nurse consultants who shared their perceived strengths and challenges of current binational survivorship practices. This audit revealed no clearly endorsed model of care, inadequate funding and staffing, and inconsistent practices binationally. I explored predictors of general practitioners (GPs) participation in qualitative research (Chapter 5), based on my experiences recruiting 51 GPs for interviews investigating their role in delivering childhood cancer survivorship care. In Chapter 6, I explored families' confidence in GPs, and GPs' confidence in caring for this population. Many families lacked confidence in GPs to deliver childhood cancer survivorship care. GPs were willing and confident in delivering follow-up care, yet this appeared to be contingent upon increased - and prescriptive - communication between primary and tertiary providers. In a mixed-method study of 633 survivors (Chapter 7), I explored survivor-reported barriers to accessing follow-up care and preferences for the delivery of care. Most survivors preferred an oncologist-led model and reported logistical (e.g. distance, costs) and personal (e.g. wanting to 'get on' with life) barriers to care. Based on the findings of these studies, I proposed a new nurse-led, distance-delivered, intervention called 'Re-engage'. In Chapter 8, I described Re-engage, which aims to empower disengaged survivors (i.e. not receiving cancer-related care). Innovative solutions such as Re-engage are needed to promote engagement in follow-up care and help survivors to live to their fullest potential

Sleep disturbances in childhood cancer survivors [letter to the editor]

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The psychosocial experiences and needs of children undergoing surgery and their parents: a systematic review

Introduction:Surgery in children can be difficult for patients and parents. We aimed to summarize pediatric patients' and parents' psychosocial experiences and needs in surgery.Method:We used the Ovid search engine and screened 877 abstracts across three databases to extract data on pediatric patients' and parents' surgical experiences.Results:Our search yielded 11 eligible studies representing 1,307 children undergoing surgery and their parents. Children's adverse experiences included psychological and behavioral changes before, during, and after surgery (e.g., anxiety, eating disturbances). Parents commonly experienced psychological distress. Children's needs related to medical and health care services, whereas parents had high information needs.Discussion:Children's adverse experiences can negatively affect medical outcomes. Children's experiences are inextricably linked to their parents' and can become negatively affected by their parents' adverse experiences. Patients and parents with previous hospitalizations and surgeries had worse surgical experiences, highlighting further research in the context of chronic illness

Strategies to facilitate shared decision-making about pediatric oncology clinical trial enrollment:: a systematic review

Objective: we conducted a systematic review to identify the strategies that have been recommended in the literature to facilitate shared decision-making regarding enrolment in pediatric oncology clinical trials.Methods: we searched seven databases for peer-reviewed literature, published 1990–2017. Of 924 articles identified, 17 studies were eligible for the review. We assessed study quality using the ‘Mixed-Methods Appraisal Tool’. We coded the results and discussions of papers line-by-line using nVivo software. We categorized strategies thematically.Results: five main themes emerged: 1) decision-making as a process, 2) individuality of the process; 3) information provision, 4) the role of communication, or 5) decision and psychosocial support. Families should have adequate time to make a decision. HCPs should elicit parents’ and patients’ preferences for level of information and decision involvement. Information should be clear and provided in multiple modalities. Articles also recommended providing training for healthcare professionals and access to psychosocial support for families.Conclusion: high quality, individually-tailored information, open communication and psychosocial support appear vital in supporting decision-making regarding enrollment in clinical trials. These data will usefully inform future decision-making interventions/tools to support families making clinical trial decisions.Practice implications: a solid evidence-base for effective strategies which facilitate shared decision-making is needed

Pediatric surgery for childhood cancer: Lasting experiences and needs of children and parents

Objective: surgery for pediatric cancer presents many stresses on patients and families. The authors aimed to understand the long-term impact of childhood cancer surgery on survivors and parents.Methods: the study recruited participants from 11 Australia/New Zealand hospitals for telephone interviews. The authors used descriptive statistics to analyse participants’ quantitative distress ratings and conducted thematic analysis of shared surgical experiences and needs.Results: of 32 participants (n=17 survivors, n=15 parents), survivors’ mean age at surgery was 6.9 (SD=5.17) and parents’ children were 2.1 years old (SD=1.41) at time of surgery. Survivors had surgery on average 15.2 years ago (SD=6.72) and parents’ children 11.5 years ago (SD=3.94). Parents and survivors rated surgery as highly distressing. Preoperatively, survivors recalled experiencing fear and pain mainly associated with preoperative procedures. Postoperatively, survivors reported immobility and some lasting behavioral disturbances. Parents described pre- and intraoperative anxiety and stress and some lasting postoperative psychological disturbances. Experiences appeared toimprove with clear/consistent communication from hospital staff, proximity to hospital, and with support for parents and children postoperatively.Conclusions: surgical treatment for childhood cancer can have a lasting impact for survivors and parents. Better information provision may improve families’ surgical experience whilst reducing anxiety, distress and physical discomfort

Genetic testing for the risk of developing late effects among survivors of childhood cancer : consumer understanding, acceptance, and willingness to pay

Background: Genetic testing to determine cancer survivors' risk of developing late effects from their cancer treatment will be increasingly used in survivorship care. This 2-stage study with 64 survivors of childhood cancer and their parents investigated the preferences and acceptability of testing among those who may be at risk of developing late effects. Methods: The first stage (Stage 1) identified the most commonly perceived benefits and concerns regarding genetic testing for the risk of late effects among 24 participants. In Stage 2, during interviews, 20 survivors (55% of whom were female; mean age, 26.0 years [range, 18-39 years]; standard deviation [SD], 0.80) and 20 parents (55% of whom were male; mean age of child survivor, 14.2 years [range, 10-19 years]; SD, 0.79) rated the 7 most common benefits and concerns from those identified in Stage 1. Interviews were transcribed verbatim and analyzed. Decisional balance ratios were calculated by dividing the participants' average concerns scores with the average benefits scores. Results: Genetic testing for late effects was highly acceptable: 95% of participants leaned toward testing, and the majority (65.9%) would pay up to Australian $5000. The majority (97.2%) reported it was acceptable to wait for up to 6 months to receive results, and to be offered testing immediately after treatment or when the survivor reached adulthood (62.9%). Survivors and parents had a highly positive decisional balance (Mean (M), 0.5 [SD, 0.38] and M, 0.5 [SD, 0.39], respectively), indicating that perceived benefits outweighed concerns. Conclusions: Although to our knowledge clinical efficacy has yet to be clearly demonstrated, survivors and parents described positive interest in genetic testing for the risk of developing late effects. Perceived benefits outweighed harms, and the majority of participants would be willing to pay, and wait, for testing.10 page(s

"Forewarned and forearmed" : long-term childhood cancer survivors' and parents' information needs and implications for survivorship models of care

Objective: This mixed-method study assessed 1) survivors' and parents' information needs; and 2) associations between unmet information needs and clinical and socio-demographic characteristics. Methods: Stage 1: CCS and parents of CCS, >5years post-diagnosis completed a questionnaire on information needs, overall health and perceived risk. Predictors for unmet information needs were assessed by multivariable regression. Stage 2: participants were interviewed in-depth on these topics. Results: Questionnaires were completed by 485 participants comprising 322 survivors (mean age: 26.7years, SD = 7.9; time since diagnosis: 19.7years, SD = 8.8) and 163 parents (child age: 12.9years, SD = 2.4; time since diagnosis: 9.7years, SD = 2.3), and complemented by 70 interviews. Survivors reported unmet information needs about late effects (57.5%) and parents for fertility issues (62.5%). Survivors had more unmet needs for medical information whereas parents had significantly more regarding sexual issues and lifestyle. Being a parent (p = 0.001), dissatisfaction with follow-up care (p = 0.003), lower overall health (p = 0.014), higher perceived risk of late effects (p < 0.001), and greater anxiety/depression (p < 0.001) were significantly associated with more unmet needs. Conclusion: Unmet information needs were common for survivors and parents of CCS. Practice implications: Future efforts towards tailoring information on potential late effects, healthy lifestyles and follow-up care may help to address unmet information needs.9 page(s

Interactive video games to improve pediatric procedural pain and anxiety: a systematic review and meta-analysis

Background: procedural pain and anxiety in children can be poorly controlled, leading to significant short and long-term sequelae such as longer procedure times or future healthcare avoidance. Caregiver anxiety can exacerbate these effects. We aimed to evaluate the effect of interactive video game interventions on children’s procedural pain and anxiety, including the effect of different types of video games on those outcomes. Methods: we conducted a systematic review and meta-analysis of the effectiveness of interactive video games compared to standard care in children (0-18 years) undergoing painful procedures. We searched the databases MEDLINE, Embase and PsycInfo. We conducted random-effects meta-analysis using ‘R’ of children’s procedural pain and anxiety, and caregivers’ anxiety. Results: of 2,185 studies screened, 36 were eligible (n=3,406 patients). Studies commonly involved venous access (33%) or day surgery (31%). Thirty-four studies were eligible for meta-analyses. Interactive video games appear to reduce children’s procedural pain (standardised mean difference = -0.43, 95% CI -0.67, -0.20) and anxiety (SMD = 0.61, 95% CI -0.88, -0.34), and caregivers’ procedural anxiety (SMD = -0.31, 95% CI -0.58, -0.04). We observed no difference between preparatory and distracting games, or between virtual reality and non-virtual reality games. We also observed no difference between interactive video games compared to standard care for most medical outcomes (e.g. procedure length), except a reduced need for restraint. Studies reported minimal adverse effects and typically had high intervention acceptability and satisfaction. Conclusions: our findings support introducing easily available video games such as distraction-based conventional video games into routine practice, to minimise paediatric procedural pain and child/caregiver anxiety