Working with the patient and clinical community to deliver clinical research in cystic fibrosis. James Lind CF Phase II

This is a protocol which sets out the aims, objectives and commitments of the second phase of the James Lind Alliance Priority Setting Partnership in Cystic Fibrosis and the basic roles and responsibilities of the partners therein. The James Lind Alliance Priority Setting Partnership in cystic fibrosis was carried out in 2016 using a robust and widely accepted methodology to develop the top 10 questions for clinical research in CF, through discussions with both the clinical and patient community. We now aim to explore four of the top ten questions from this process and develop them into a series of testable hypotheses for clinical research. Where the hypothesis will be tested in a clinical trial, we will develop a PICO question for each hypothesis (Population, Intervention, Comparator & Outcome). We will use online surveys and focus groups to achieve our aim

A novel role for Hedgehog in T-cell receptor signaling: implications for development and immunity

The Hedgehog (Hh) signaling pathway is a key regulator of both embryonic development and homeostasis of adult tissues, including thymus and blood. In the thymus, Hh signals for differentiation, survival and proliferation in the early stages of T cell development, before TCR gene rearrangement. Our recent data has shown that Hh signaling also modulates T cell receptor (TCR) signal strength in more mature T lineage cells. We showed that constitutive activation of the Hh pathway in thymocytes (by transgenic expression of the transcriptional activator form of Gli2) decreased TCR signal strength with profound consequences for the thymus--allowing self-reactive T cells to escape deletion and altering T cell CD4/CD8 lineage decisions. In contrast, in the Sonic Hh deficient thymus, TCR signaling was increased, again influencing both TCR repertoire selection and CD4/8 lineage commitment. In peripheral T cells, the transcriptional changes induced by activation of the Hh signaling pathway lead to reduced T cell activation. Hh signaling also attenuated ERK phosphorylation and proliferation in mature T cells on TCR ligation. Modulation of TCR signal strength by Hh pathway activation has importance for immunity as the presence or absence of Hh in the environment in which a T cell is activated would shape the immune response

Working with the patient and clinical community to deliver clinical research in cystic fibrosis: James Lind CF Phase II

This is a protocol which sets out the aims, objectives and commitments of the second phase of the James Lind Alliance Priority Setting Partnership in Cystic Fibrosis and the basic roles and responsibilities of the partners therein. The James Lind Alliance Priority Setting Partnership in cystic fibrosis was carried out in 2016 using a robust and widely accepted methodology to develop the top 10 questions for clinical research in CF, through discussions with both the clinical and patient community.We now aim to explore four of the top ten questions from this process and develop them into a series of testable hypotheses for clinical research. Where the hypothesis will be tested in a clinical trial, we will develop a PICO question for each hypothesis (Population, Intervention, Comparator & Outcome). We will use online surveys and focus groups to achieve our aim

Cystic Fibrosis James Lind Alliance Priority Setting Partnership PROTOCOL [updated 13 July 2016]

The purpose of this protocol is to set out the aims, objectives and commitments of the Cystic Fibrosis Priority Setting Partnership (PSP) and the basic roles and responsibilities of the partners therein

Cystic Fibrosis James Lind Alliance Priority Setting Partnership PROTOCOL [5 February 2016]

The purpose of this protocol is to set out the aims, objectives and commitments of the Cystic Fibrosis Priority Setting Partnership (PSP) and the basic roles and responsibilities of the partners therein

A systematic review to identify how the current clinical trials landscape reflects the James Lind Alliance top 10 research priorities for cystic fibrosis

This is a protocol to describe the methodology for a systematic review of clinical trials registries to identify intervention trials in the treatment of CF and map them to priorities for CF research

Industry influence in healthcare harms patients: myth or maxim?

Healthcare is a major global industry accounting for a significant proportion of government spending. Drug and medical device manufacturers are publicly traded companies with a responsibility to their shareholders to maximise profits by increasing sales. In order to achieve this, industry exerts influence over every part of healthcare including academic research, medical education, clinical guideline development, physician prescribing and through direct interactions with patients. In contrast, healthcare services seek to provide effective, safe and evidence-based treatments. This article examines interactions with industry across these domains and seeks to identify mutually beneficial relationships and potential conflict leading to patient harms. Case studies are used to illustrate these interactions. There is no single solution for improving healthcare’s relationship with industry, although increased transparency has raised awareness of this issue. We briefly discuss some successful interventions that have been tried at national and regulatory level. While industry influence is widespread in healthcare and this has benefits for shareholders, healthcare practitioners have an ethical obligation to prioritise their patients’ best interests. Industry interactions with healthcare professionals have a valid role in product development and distribution, but industry sponsorship of healthcare education and practice, guideline development or regulatory decision-making can have harmful consequences for patients. Healthcare practitioners need to carefully consider these issues when deciding whether to collaborate with industry

A systematic review to identify how the current clinical trials landscape reflects the James Lind Alliance top 10 research priorities for cystic fibrosis

This is a protocol to describe the methodology for a systematic review of clinical trials registries to identify intervention trials in the treatment of CF and map them to priorities for CF research

Infection prevention and control in cystic fibrosis: a systematic review of interventions

Introduction: Cystic fibrosis is a life-limiting genetic condition characterized by recurrent pulmonary infection. Acquisition of infection can occur from environmental reservoirs, person-to-person transmission and from the healthcare environment. Primary prevention of infections through infection prevention and control measures is an important strategy in cystic fibrosis care.Areas covered: Here we present a systematic review of the evidence base around infection prevention and control in cystic fibrosis. We found 36 studies and 7 guidelines that met our inclusion criteria. Strategies covered include cohort segregation, individual segregation, hand hygiene, facemasks, combination strategies, equipment strategies, and adherence. Quality of evidence overall was deemed low or very low. Most guideline recommendations have little or no evidence to support them.Expert opinion: Although low quality, there is an abundance of evidence suggesting segregation is beneficial in reducing pathogen spread. Undertaking high-quality studies may, therefore, be ethically challenging. Large-scale registry studies may provide a better strategy for answering questions on the efficacy of infection control policy. With the rise of antibiotic resistance, effective eradication of cystic fibrosis pathogens is becoming more difficult so primary prevention through infection control will become increasingly important over the coming years

Cystic Fibrosis James Lind Alliance Priority Setting Partnership PROTOCOL [5 February 2016]

The purpose of this protocol is to set out the aims, objectives and commitments of the Cystic Fibrosis Priority Setting Partnership (PSP) and the basic roles and responsibilities of the partners therein