Melatonin as a potential therapy for sepsis : a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis

This article is protected by copyright. All rights reserved. This study was funded by the Chief Scientist Office, NHS Scotland. We would like to thank all the volunteers who gave up their time and blood to take part in the study and the data monitoring committee and staff of the intensive care unit for their support. In addition, thanks to Dr Malachy Columb for performing Page's trend test for us and to Annette Fearnley at Nu-Pharm Ltd for her advice.Peer reviewedPublisher PD

Parents’ and children's views of wider genomic testing when used as part of newborn screening to identify cystic fibrosis

Newborn bloodspot screening (NBS) is currently undergoing a ‘revolution’ (Spiekerkoetter et al., 2023). The development of new therapies (Vockley et al., 2023) and the piloting of whole genome sequencing in healthy newborns (e.g. Newborn Genomes Programme, UK, BabySeq USA) are challenging NBS practice and policy, as well as the Wilson & Jungner criteria (Wilson & Jungner, 1968) that underpin them (Andermann et al., 2008; Rahimzadeh et al., 2022; Vears et al., 2023). The capacity to screen for large numbers of variants simultaneously and generate data with potential relevance across the life course, and for family members beyond the screened infant, has prompted widespread discussion of the benefits (e.g., early identification and treatment of screened conditions) and harms (e.g., identification of variants of unknown clinical significance) that such high throughput screening programmes bring (Bick et al., 2022; Remec et al., 2021; Spiekerkoetter et al., 2023; Tluczek et al., 2022)

Stakeholder views of the proposed introduction of next generation sequencing into the cystic fibrosis screening protocol in England

The project aimed to gather, analyze and compare views of stakeholders on the proposed UK cystic fibrosis (CF) screening protocol incorporating next generation sequencing (NGS). The study design was based on principles of Q-methodology with a willingness to pay exercise. Par-ticipants were recruited from 12 CF centers in the UK. Twenty-eight adults with experience of CF (parents of children with CF [n=21], parents of children with CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS)/CF Screen Positive – Inconclusive Diag-nosis (CFSPID), an uncertain outcome [n=3] and adults with CF [n=4]), and nine health profes-sionals involved in caring for children with CF. Parents and health professionals expressed a preference for a sensitive approach to NGS. This was influenced by the importance participants placed on not missing any children with CF via screening and the balance of harm between missing a case of CF compared to picking up more children with an uncertain outcome (CRMS/CFSPID). Given the preference for a sensitive approach, the need for adequate explana-tions about potential outcomes including uncertainty (CFSPID) at the time of screening was em-phasized. More research is needed to inform definitive guidelines for managing children with an uncertain outcome following CF screening

Exercise as an Airway Clearance Technique in people with Cystic Fibrosis (ExACT-CF):rationale and study protocol for a randomised pilot trial

BACKGROUND: Chest physiotherapy is an established cornerstone of care for people with cystic fibrosis (pwCF), but is often burdensome. Guidelines recommend at least one chest physiotherapy session daily, using various airway clearance techniques (ACTs). Exercise (with huffs and coughs) may offer an alternative ACT, however the willingness of pwCF to be randomised into a trial needs testing. The 'ExACT-CF: Exercise as an Airway Clearance Technique in people with Cystic Fibrosis' trial will test the feasibility of recruiting pwCF to be randomised to continue usual care (chest physiotherapy) or replace it with exercise ACT (ExACT) for 28-days. Secondary aims include determining the short-term clinical impact (and safety) of stopping routine chest physiotherapy and replacing it with ExACT, and effects on physical activity, sleep, mood, quality of life and treatment burden, alongside preliminary health economic measures and acceptability.METHODS: Multi-centre, two-arm, randomised (1:1 allocation using minimisation), pilot trial at two sites. Fifty pwCF (≥10 years, FEV 1 &gt;40% predicted, stable on Elexacaftor/Tezacaftor/Ivacaftor (ETI)) will be randomised to an individually-customised ExACT programme (≥once daily aerobic exercise of ≥20-minutes duration at an intensity that elicits deep breathing, with huffs and coughs), or usual care. After baseline assessments, secondary outcomes will be assessed after 28-days, with additional home lung function and exacerbation questionnaires at 7, 14 and 21-days, physical activity and sleep monitoring throughout, and embedded qualitative and health-economic components. Feasibility measures include recruitment, retention, measurement completion, adverse events, interviews exploring the acceptability of trial procedures, and a trial satisfaction questionnaire. DISCUSSION: Co-designed with the UK CF community, the ExACT-CF pilot trial is the first multi-centre RCT to test the feasibility of recruiting pwCF stable on ETI into a trial investigating ExACT. This pilot trial will inform the feasibility, design, management, likely external validity for progression to a main phase randomised controlled trial.REGISTRATION: Clinicaltrials.gov ( NCT05482048).</p

Measuring quality in community nursing: A mixed methods study

AbstractBackgroundHigh-quality nursing care is crucial for patients with complex conditions and co-morbidities living at home, but such care is largely invisible to health planners and managers. Nursing care quality in acute settings is typically measured using a range of different quality measures; however, little is known about how service quality is measured in community nursing.ObjectiveTo establish which quality indicators are selected for community nursing; how these are selected and applied; and their usefulness to service users (patients and/or carers), commissioners and provider staff.DesignA mixed-methods study comprising three phases:1)A national survey of ‘Commissioning for Quality and Innovation’ indicators applied to community nursing care in 2014/2015. Data were analysed descriptively using SPSS 20.0.2)In-depth case study in five sites. Qualitative data were collected through observations, interviews, focus groups and documents. Thematic analysis was conducted using QSR NVivo 10.Findings from the first two phases were synthesised using a theoretical framework to examine how local and distal contexts affecting care provision impacted on selection and application of quality indicators for community nursing.3)Validity testing the findings and associated draft good practice guidance through a series of stakeholder engagement events held in venues across England.SettingThe national survey was conducted by telephone and e-mail. Each case study site comprised a Clinical Commissioning Group (CCG) and its associated provider of community nursing services.ParticipantsSurvey: 145 (68.7%) CCGs across England.Case study: NHS England national and regional quality leads (n=5); commissioners (n=19); provider managers (n=32); registered community nurses (n=45); adult patients (n=14) receiving care in their own homes and/or carers (n=7).FindingsA wide range of indicators was used nationally, with a major focus on organisational processes.Lack of nurse and service user involvement in indicator selection processes impacted negatively on their application and perceived usefulness. Indicator data collection was hampered by problematic IT software and connectivity and inter-organisational system incompatibility. Frontline staff considered indicators designed for acute settings inappropriate for use in community settings. Indicators did not reflect aspects of care such as time spent, kindness and respect, highly valued by frontline staff and service user participants.Workshop delegates (commissioners, provider managers, frontline staff and service users, n=242) endorsed the findings and draft good practice guidance.LimitationsOn-going service re-organisation during the study period affected access to participants in some sites. Limited available data precluded in-depth documentary analysis.ConclusionsCurrent quality indicators for community nursing are of limited use:Commissioners and provider managers should ensure that service users and frontline staff are involved in identifying and selecting indicators.Difficulties with connectivity and compatibility should be resolved before rolling new IT packages out into practice.Quality measures designed for acute settings should not be applied in community settings without modification.A mix of qualitative and quantitative methods should be used to determine service qualityFuture workResearch investigating appropriate modifications and associated costs of administering quality indicator schemes in integrated care settings.Funding detailsThe study was funded by the NIHR Health Service and Delivery Research programme

A refresh of the top 10 research priorities in cystic fibrosis

In 2018 we published the James Lind Alliance (JLA) top 10 priorities for clinical research in cystic fibrosis (CF), chosen jointly by the patient and clinical communities. These priorities have led to new research funding. To establish whether priorities have changed with novel modulator therapies, we undertook an online international update through a series of surveys and a workshop. Patients and clinicians (n=1417) chose the refreshed top 10 from 971 new research questions (suggested by patients and clinicians) and 15 questions from 2018. We are working with the international community to promote research based on these refreshed top 10 priorities

Evidence review of the potential wider impacts of climate change mitigation options: agriculture, forestry, land use and waste sectors

A report prepared for Scottish Government. Greenhouse gas (GHG) mitigation is a central policy objective in Scotland. The Climate Change (Scotland) Act 2009 sets an interim 42% reduction target for 2020 and an 80% target for 2050 across all sectors of society (1990 baseline). As a priority policy area, it has become vital to better understand the co-benefits and adverse impacts arising from mitigation actions on our environment, economy and society. Integrated assessment is key in prioritising environmental actions, reducing adverse impacts and enhancing positive co-effects. This report aims to summarise evidence on the wider impacts (WI) of GHG mitigation options (MO) in the Agriculture, land use, land use change and forestry sectors (ALULUCF) and those related waste management. The key findings of the review, are a summary of the wider impacts and an overview of the challenges in quantifying and monetising these impacts

How can we relieve gastrointestinal symptoms in people with cystic fibrosis? An international qualitative survey

Introduction Relieving gastrointestinal (GI) symptoms was identified as a ‘top ten’ priority by our James Lind Alliance Priority Setting Partnership in cystic fibrosis (CF). We conducted an online survey to find out more about the effect of GI symptoms in CF.Methods We co-produced an online survey distributed to the CF community via web-based platforms. The survey consisted of open and closed questions designed to help us learn more about the effects of GI symptoms for people with CF (pwCF). We analysed the data using descriptive statistics and thematic analysis. We promoted the survey via social media and web-based platforms which allowed respondents from any country to take part. Our participants came from the CF community, including: adults and children with CF, parents and close family of pwCF and healthcare professionals (HCPs) working with pwCF.Results There were 276 respondents: 90 (33%) pwCF, 79 (29%) family, 107 (39%) HCPs. The most commonly reported symptoms by lay respondents were stomach cramps/pain, bloating and a ‘combination of symptoms’. The top three symptoms that HCPs said were reported to them were reduced appetite, bloating and constipation. Almost all (94% (85/90)) HCPs thought medications helped to relieve GI symptoms but only 58% (82/141) of lay respondents agreed.Conclusions Our survey has shown that GI symptoms among our participants are prevalent and intrude on daily lives of pwCF. There is a need for well-designed clinical studies to provide better evidence for management of GI symptoms and complications