Service Needs of Parent Caregivers of Adolescents and Young Adults with Incurable Cancer: A Scoping Review.

Adolescent and Young Adult (AYA) oncology is an internationally recognized established subspecialty in cancer care. Dedicated programs tailored to local environments endeavor to address unique medical, psychological, cognitive, and social needs that historically, health services have been challenged to meet. In recent years there has been a growing appreciation of the challenges facing AYA with incurable cancer and their parent caregivers. While health care professionals recognize the importance of parents' involvement in the care trajectory, there is less understanding of the services needed for support. This scoping review set out to identify and describe evidence available to better understand the services and approaches required from hospital teams to address the needs of parent caregivers and to identify gaps in knowledge to inform areas for further research. The question guiding this review is: What are the service needs of parent carers of AYA with incurable cancer. Using the Arksey and O'Malley scoping review framework, 1009 studies were identified from a broad search of relevant online databases, gray literature, and reference lists of published studies. After removing duplicates and ineligible studies, 492 abstracts were screened. Of these, 421 were ineligible, and 71 articles underwent full-text review. Eight studies were included in the final review. No single study was focused exclusively on parent caregivers of AYA with incurable cancer, demonstrating a paucity of quantitative and qualitative evidence to inform practice and a need for further research in the field.

AYA 'Can-Sleep' programme: protocol for a stepped-care, cognitive behavioural therapy-based approach to the management of sleep difficulties in adolescents and young adults with cancer.

BACKGROUND: Sleep problems are reported in up to 50% of adolescents and young adults (AYA) with cancer. Cognitive behavioural therapy for insomnia (CBTi) is considered the gold-standard treatment. In the AYA population, CBTi is associated with improvements in insomnia, daytime sleepiness, fatigue and quality of life. In adults, stepped-care interventions can improve accessibility to CBTi. This study aims to evaluate the acceptability and feasibility of a stepped-care CBTi programme in AYA with cancer. METHODS AND ANALYSIS: AYA (target N = 80) aged 16-25 with a diagnosis of cancer will be screened using the Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS). When sleep difficulties are identified by the ISI and/or ESS, they will be screened for obstructive sleep apnoea and restless leg syndrome and referred to a sleep service if indicated. The remainder with sleep difficulties will be offered a stepped-care sleep programme including CBT self-management and coaching (first step). Participants will then be rescreened at 5 weeks, and those with ongoing sleep difficulties will be offered individualised CBT (second step). Recruitment and retention rates, adherence to intervention and time taken to deliver screening and intervention will be collected to assess the feasibility of the programme. AYA and clinicians will complete evaluation surveys to assess the acceptability of the AYA Can-Sleep programme. DISCUSSION: We seek to contribute to the evidence base regarding screening and treatment of sleep difficulties in the AYA population by implementing the AYA Can-Sleep programme and determining its feasibility and acceptability as an approach to care in an Adolescent & Young Adult Cancer Service.

A Descriptive Cohort Study of Adolescent and Young Adult Decedents Known to an Australian Comprehensive Cancer Center.

In Australia, cancer is the second leading cause of death in adolescents and young adults (AYA). In an audit of 76 AYA decedents known to a comprehensive cancer center, most were male (63%), and most had a parent as primary carer (78%). Median age at diagnosis was 21 years (range: 15-27). Median time from diagnosis to first palliative care consultation was 9 months, and from first palliative care review to death, 4 months. Location of death was hospital (41%), home (24%), and palliative care unit (16%). Eleven (65%) of 17 patients who wished to die at home achieved this.

An Exploratory Study into the Experience of Health Care Professionals Caring for Adolescents and Young Adults with Incurable Cancer.

Adolescents and young adults 15 to 25 years of age with incurable cancer are a unique patient group. There is growing evidence of the emotionally taxing nature of this work, yet limited understanding of the health care professional experience across professional disciplines. This exploratory study, comprising in-depth semistructured interviews, undertaken at a major cancer center in Melbourne, Australia, describes the challenges facing health care professionals and the factors enabling them to deliver care with greater confidence. The findings provide a platform for further research with key recommendations to enhance the delivery of care to young people with a life-limiting cancer diagnosis.

The transition of human estrogen sulfotransferase from generalist to specialist using directed enzyme evolution.

Broad specificity is believed to be a property of primordial enzymes that diverged during natural protein evolution to produce highly specific and efficient enzymes. Human estrogen sulfotransferase (SULT1E1) is a broad-specificity enzyme that detoxifies a variety of chemicals, including estrogens, by the transfer of sulfate. To study the molecular basis for the broad specificity of this enzyme and to investigate the process of SULT1E1 specialization, we have adopted a directed enzyme evolution approach. Using two iterative rounds of evolution, we generated SULT1E1 mutants with increased thermostability and narrower specificity from the broadly specific wild-type enzyme. To identify mutants with enhanced specificity, we developed an unbiased screening assay to assess sulfate transfer to three different acceptors in parallel. Such an assay enabled the isolation of SULT1E1 mutants with enhanced or wild-type activity toward an estrogen acceptor and significantly reduced activity for phenol or coumarin type of acceptors, leading to up to 3 orders of magnitude increase in specificity. We found that mutations conferring novel specificity are located in the vicinity of the active site and thus may play a direct role in reshaping the acceptor-binding site. Finally, such mutations resulted in reduced SULT1E1 thermostability, revealing a trade-off between SULT1E1 thermostability and acquisition of novel function.

The molecular basis for the broad substrate specificity of human sulfotransferase 1A1.

Cytosolic sulfotransferases (SULTs) are mammalian enzymes that detoxify a wide variety of chemicals through the addition of a sulfate group. Despite extensive research, the molecular basis for the broad specificity of SULTs is still not understood. Here, structural, protein engineering and kinetic approaches were employed to obtain deep understanding of the molecular basis for the broad specificity, catalytic activity and substrate inhibition of SULT1A1. We have determined five new structures of SULT1A1 in complex with different acceptors, and utilized a directed evolution approach to generate SULT1A1 mutants with enhanced thermostability and increased catalytic activity. We found that active site plasticity enables binding of different acceptors and identified dramatic structural changes in the SULT1A1 active site leading to the binding of a second acceptor molecule in a conserved yet non-productive manner. Our combined approach highlights the dominant role of SULT1A1 structural flexibility in controlling the specificity and activity of this enzyme.

Interplay of metagenomics and in vitro compartmentalization.

In recent years, the application of approaches for harvesting DNA from the environment, the so-called, 'metagenomic approaches' has proven to be highly successful for the identification, isolation and generation of novel enzymes. Functional screening for the desired catalytic activity is one of the key steps in mining metagenomic libraries, as it does not rely on sequence homology. In this mini-review, we survey high-throughput screening tools, originally developed for directed evolution experiments, which can be readily adapted for the screening of large libraries. In particular, we focus on the use of in vitro compartmentalization (IVC) approaches to address potential advantages and problems the merger of culture-independent and IVC techniques might bring on the mining of enzyme activities in microbial communities.