Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

The use of intraperitoneal chemotherapy for advanced ovarian cancer - The experience of a tertiary referral centre.

Background: Platinum-based chemotherapy is the backbone of the medical management of ovarian cancer. The dose, route and timing of treatment are ongoing areas of debate. Intraperitoneal (IP) chemotherapy is an alternative delivery method treatment to the conventional intravenous (IV) route for patients with epithelial ovarian cancer, with efficacy supported by Level 1 evidence.

Establishing the core elements of a frailty at the front door model of care using a modified real-time Delphi technique.

Background: Innovations in models of care for older adults living with frailty presenting to the emergency department (ED) have become a key priority for clinicians, researchers and policymakers due to the deleterious outcomes older adults experience due to prolonged exposure to such an environment. This study aimed to develop a set of expert consensus-based statements underpinning operational design, outcome measurement and evaluation of a Frailty at the Front Door (FFD) model of care for older adults within an Irish context.

Methods: A modified real-time Delphi method was used.

Feasibility of Microlearning for Improving the Self-Efficacy of Cancer Patients Managing Side Effects of Chemotherapy.

Lung cancer patients have a high symptom burden that negatively affects their quality of life. Increasing patient self-efficacy to deal with treatment side effects can ameliorate their symptom burden. Education programs can help enhance patient self-efficacy by giving patients more control over their condition through increased disease literacy.

Qualitative study of international key informants' perspectives on the current and future state of healthcare quality measurement and feedback.

Objectives: The aim of this study is to explore the current and future state of quality measurement and feedback and identify factors influencing measurement feedback systems, including the barriers and enablers to their effective design, implementation, use and translation into quality improvement.

Design: This qualitative study used semistructured interviews with key informants. A deductive framework analysis was conducted to code transcripts to the Theoretical Domains Framework (TDF).

Interventions for improving executive functions in children with foetal alcohol spectrum disorder (FASD): A systematic review.

Background: The consequences for children born with birth defects and developmental disabilities encompassed by foetal alcohol spectrum disorder (FASD) are profound, affecting all areas of social, behavioural and cognitive functioning. Given the strong evidence for a core deficit in executive functioning, underpinned by impaired self-regulation skills, there has been a growing focus on the development of interventions that enhance or support the development of executive functions (EFs).

Objectives: The primary objective of this review is to synthesise the evidence for structured psychological interventions that explicitly aim to improve EF in children.

An investigation of the utility of the Australian Guide to the Diagnosis of Fetal Alcohol Spectrum Disorder in young children.

Background: Early diagnosis of children with fetal alcohol spectrum disorder (FASD) assists in implementing critical early support. The challenge lies in having a diagnostic process that enables valid and reliable assessment of domains of functioning in young children, with the added complexity that many children will also have co-occurring exposure to childhood adversity that is likely to impact these domains.

Methods: The aim of this study was to test a diagnostic assessment of FASD in young children using the Australian Guide to the Diagnosis of FASD.

Older age should not be a barrier to testing for somatic variants in homologous recombination DNA repair-related genes in patients with high-grade serous ovarian carcinoma.

Background: Somatic pathogenic variants (PVs) in homologous recombination DNA repair (HR)-related genes found in high-grade serous ovarian carcinomas (HGSC) are not well-characterised in older patients (≥70 years). This may reflect low testing rates in older patients.

Methods: Data from 1210 HGSC patients in AACR Project GENIE and 324 patients in an independent dataset INOVATe were analysed.

Mainstream genetic testing for high-grade ovarian, tubal and peritoneal cancers: A tertiary referral centre experience.

Background: Fifteen percent of ovarian, tubal, and peritoneal (OTP) invasive epithelial cancers are linked to an underlying heritable pathogenic variant (PV) in the BRCA1/2 cancer susceptibility genes. Identifying a PV has management implications for an affected individual and relatives. Cancer team-facilitated genetic testing (mainstreaming) aims to provide equitable systematic access to genetic testing for appropriate patients.

Measurement that matters: A systematic review and modified Delphi of multidisciplinary colorectal cancer quality indicators.

Aim: To develop a priority set of quality indicators (QIs) for use by colorectal cancer (CRC) multidisciplinary teams (MDTs).

Methods: The review search strategy was executed in four databases from 2009-August 2019. Two reviewers screened abstracts/manuscripts.

A Systematic Review of Electronic Medical Record Driven Quality Measurement and Feedback Systems.

Historically, quality measurement analyses utilize manual chart abstraction from data collected primarily for administrative purposes. These methods are resource-intensive, time-delayed, and often lack clinical relevance. Electronic Medical Records (EMRs) have increased data availability and opportunities for quality measurement.

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.

Associations and mitigations: an analysis of the changing risk factor landscape for chronic kidney disease in primary care using national general practice level data.

Objectives: Early recognition of chronic kidney disease (CKD) should be achieved by every modern healthcare system. The objective of this study was to investigate CKD risk factor trends in England using general practice level data.

Design: Observational analysis of data at practice level for all general practices in England.

The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer.

Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after diagnosis, but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load.

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

Background: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.

Methods: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively).

The Relationship Between Sensory Processing and Attachment Patterns: A Scoping Review.

Clinicians and researchers have observed that sensory processing and attachment difficulties frequently co-occur; however, little is known about which sensory processing and attachment patterns are interrelated across populations. To review evidence of empirical relationships between sensory processing and attachment patterns across the life span. Using the Arksey and O'Malley framework, four databases were searched up to June 2021 for studies that investigated relationships between sensory processing and attachment patterns.

A review of Australian Government funding of parenting intervention research.

Objectives: Parenting is central to children's optimal development and accounts for a substantial proportion of the variance in child outcomes, including up to 40% of child mental health. Parenting is also one of the most modifiable, proximal, and direct factors for preventing and treating a range of children's problems and enhancing wellbeing. To determine the effectiveness of new approaches to parenting intervention, and to evaluate how to optimise reach and uptake, sufficient funding must be allocated for high quality research.

Policies are Needed to Increase the Reach and Impact of Evidence-Based Parenting Supports: A Call for a Population-Based Approach to Supporting Parents, Children, and Families.

Parents can be essential change-agents in their children's lives. To support parents in their parenting role, a range of programs have been developed and evaluated. In this paper, we provide an overview of the evidence for the effectiveness of parenting interventions for parents and children across a range of outcomes, including child and adolescent mental and physical health, child and adolescent competencies and academic outcomes, parental skills and competencies, parental wellbeing and mental health, and prevention of child maltreatment and family violence.