Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: study protocol for a randomised controlled trial.

BACKGROUND: Children with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain. METHODS/DESIGN: This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05. DISCUSSION: This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20

Saying it as it is: Experiences of Gypsies and Travellers caring for family members living with dementia

The aim of this study is to increase the understanding of some of the challenges that Gypsy and Traveller carers experience when caring for loved ones who are living with dementia

Pathways to prevention: protocol for the CAP (Climate and Preventure) study to evaluate the long-term effectiveness of school-based universal, selective and combined alcohol misuse prevention into early adulthood

Background: Alcohol use and associated harms are among the leading causes of burden of disease among young people, highlighting the need for effective prevention. The Climate and Preventure (CAP) study was the first trial of a combined universal and selective school-based approach to preventing alcohol misuse among adolescents. Initial results indicate that universal, selective and combined prevention were all effective in delaying the uptake of alcohol use and binge drinking for up to 3 years following the interventions. However, little is known about the sustainability of prevention effects across the transition to early adulthood, a period of increased exposure to alcohol and other drug use. This paper describes the protocol for the CAP long-term follow-up study which will determine the effectiveness of universal, selective and combined alcohol misuse prevention up to 7 years post intervention, and across the transition from adolescence into early adulthood. Methods: A cluster randomized controlled trial was conducted between 2012 and 2015 with 2190 students (mean age: 13.3 yrs) from 26 Australian high schools. Participants were randomized to receive one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). The positive effect of the interventions on alcohol use at 12-, 24- and 36-month post baseline have previously been reported. This study will follow up the CAP study cohort approximately 5- and 7-years post baseline. The primary outcome will be alcohol use and related harms. Secondary outcomes will be cannabis use, alcohol and other drug harms including violent behavior, and mental health symptomatology. Analyses will be conducted using multi-level, mixed effects models within an intention-to-treat framework. Discussion: This study will provide the first ever evaluation of the long-term effectiveness of combining universal and selective approaches to alcohol prevention and will examine the durability of intervention effects into the longer-term, over a 7-year period from adolescence to early adulthood

KSU Men\u27s Ensemble, KSU Community & Alumni Choir and KSU Chamber Singers, Illumination

KSU School of Music presents Illumination with KSU Men\u27s Ensemble, The Kennesaw State University Community and Alumni Choir and KSU Chamber Singers featuring John Rutter\u27s Gloria!https://digitalcommons.kennesaw.edu/musicprograms/1249/thumbnail.jp

The global impact of adverse childhood experiences on criminal behavior: A cross-continental study

Background: Adverse Childhood Experiences (ACEs) have been associated with a greater risk of later criminal offending. However, existing research in this area has been primarily conducted in Western developed countries and cross-cultural studies are rare. Objectives: This study examined the relationship between ACEs and criminal behaviors in young adults living in 10 countries located across five continents, after accounting for sex, age, and cross-national differences. Participants and setting: In total, 3797 young adults aged between 18 and 20 years (M = 18.97; DP = 0.81) were assessed locally in community settings within the 10 countries.Method: The ACE Questionnaire was used to assess maltreatment and household dysfunction during childhood and a subset of questions derived from the Deviant Behavior Variety Scale (DBVS) was used to determine past-year criminal variety pertaining to 10 acts considered crime across participating countries. Results: Physical and sexual abuse, physical neglect, and household substance abuse were related to criminal variety, globally, and independently across sexes and countries ranked differently in the United Nations Human Development Index (HDI). In addition, three out of five experiences of household dysfunction were related to criminal variety, but subsequent analyses indicate that some forms of household dysfunction only hold statistical significance among males or females, or in countries ranking lower in the HDI. Conclusions: This research strengthens the finding that there are cross-cultural mechanisms perpetuating the cycle of violence. It also indicates that forms of household dysfunction have an impact on criminal behavior that is shaped by gender and the country's levels of social well-being.info:eu-repo/semantics/publishedVersio

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse