Achieving consensus on priority items for paediatric palliative care outcome measurement: Results from a modified Delphi survey, engagement with a children’s research involvement group and expert item generation

BACKGROUND: There is no validated outcome measure for use in children’s palliative care outside sub-Saharan Africa. Stakeholders must be involved in the development of such measures to ensure face and content validity. AIM: To gain expert stakeholder consensus on items for inclusion in a paediatric palliative care outcome measure to establish face and content validity. DESIGN: This study was conducted in two phases following Rothrock and COSMIN guidance on patient-reported outcome measure development. Phase 1: Three-round modified Delphi survey to establish consensus on priority items. Phase 2: Item generation meeting with key stakeholders to develop initial measure versions. A young person’s advisory group was also consulted on priority outcomes. SETTING AND PARTICIPANTS: Delphi survey: Parents and professionals with experience of caring for a child with a life-limiting condition. Young person’s advisory group: young people age 10–20 years. Item generation meeting: bereaved parents, academics and clinicians. RESULTS: Phase 1: Delphi survey (n = 82). Agreement increased from Kendall’s W = 0.17 to W = 0.61, indicating movement towards consensus. Agreement between professional and parent ranking was poor (Cohen’s kappa 0.13). Professionals prioritised physical symptoms, whereas parents prioritised psychosocial and practical concerns. Advisory group: Children (n = 22) prioritised items related to living a ‘normal life’ in addition to items prioritised by adult participants. Phase 2: Five age/developmental stage appropriate child and proxy-reported versions of C-POS, containing 13 items, were drafted. CONCLUSIONS: This study highlights the importance and feasibility of involving key stakeholders in PROM item generation, as important differences were found in the priority outcomes identified by children, parents and professionals

Design and Administration of Patient-Centred Outcome Measures: The Perspectives of Children and Young People with Life-Limiting or Life-Threatening Conditions and Their Family Members

BACKGROUND: Self-reported health data from children with life-limiting conditions is rarely collected. To improve acceptability and feasibility of child and family-centred outcome measures for children, they need to be designed in a way that reflects preferences, priorities and abilities. OBJECTIVES: The aim was to identify preferences for patient-reported outcome measure design (recall period, response format, length, administration mode) to improve the feasibility, acceptability, comprehensibility and relevance of a child and family-centred outcome measure, among children with life-limiting conditions and their family members. METHOD: A semi-structured qualitative interview study seeking the perspectives of children with life-limiting conditions, their siblings and parents on measure design was conducted. Participants were purposively sampled and recruited from nine UK sites. Verbatim transcripts were analysed using framework analysis. RESULTS: A total of 79 participants were recruited: 39 children aged 5–17 years (26 living with a life-limiting condition; 13 healthy siblings) and 40 parents (of children aged 0–17 years). Children found a short recall period and a visually appealing measure with ten questions or fewer most acceptable. Children with life-limiting conditions were more familiar with using rating scales such as numeric and Likert than their healthy siblings. Children emphasised the importance of completing the measure alongside interactions with a healthcare professional to enable them to talk about their responses. While parents assumed that electronic completion methods would be most feasible and acceptable, a small number of children preferred paper. CONCLUSIONS: This study demonstrates that children with life-limiting conditions can engage in communicating preferences regarding the design of a patient-centred outcome measure. Where possible, children should be given the opportunity to participate in the measure development process to enhance acceptability and uptake in clinical practice. Results of this study should be considered in future research on outcome measure development in children

Widening socio-economic inequalities in oral cancer incidence in Scotland, 1976–2002

Oral cancer incidence was investigated among 10 857 individuals using Scottish Cancer Registry data. Since 1980 the incidence of oral cancer among males in Scotland has significantly increased, the rise occurring almost entirely in the most deprived areas of residence

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC

Safety and Adherence to Intermittent Pre-Exposure Prophylaxis (PrEP) for HIV-1 in African Men Who Have Sex with Men and Female Sex Workers

Background Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). Methods/Principal Findings MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a onemonth recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63–92] for daily dosing and 55% [IQR:28–78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14–50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Conclusions/Significance Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens</p

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe.

Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (&lt;50%), fair (50%-75%) or consensus (≥75%). A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval &gt;2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials

The relationship between team ability and home advantage in the English football league system

The existence of home advantage (HA) has been found in a variety of team sports including football. There is a paucity of research on the relationship between team ability and HA in domestic football leagues and the findings of previous studies are inconclusive. Using longitudinal data from the top four football divisions in England, this study investigates the influence of team ability on the HA of teams. The data collected for this study spans 24 seasons from 1995/96 to 2018/19 and includes 48,864 matches from the English Premier League (n=9,120), the Championship (n=13,248), League One (n=13,248) and League Two (n=13,248). Team ability was interpreted in two ways: (1) the division in which teams play; and, (2) their league table position within each division. For both the divisional and positional analysis, HA was calculated as the ratio of home points to total points achieved by teams in each season under review. Evidence of a statistically significant HA was found in all four divisions and for teams of all abilities within each division. Small but statistically significant differences in HA were observed between divisions and between high, moderate and low ability teams within divisions