Clinical importance of cystic fibrosis-related diabetes

AbstractThe prevalence of cystic fibrosis-related diabetes (CFRD) and glucose intolerance (IGT) has risen dramatically over the past 20 years as survival has increased for people with cystic fibrosis (CF). Diabetes is primarily caused by pancreatic damage, which reduces insulin secretion, but glucose tolerance is also modified by factors that alter insulin resistance, such as intercurrent illness and infection. CFRD not only causes the symptoms and micro and macrovascular complications seen in type 1 and type 2 diabetes in the general population, but also is associated with accelerated pulmonary decline and increased mortality. Pulmonary effects are seen some years before the diagnosis of CFRD, implying that impaired glucose tolerance may be detrimental.Current practice is to screen for changes in glucose tolerance by regular measurement of fasting blood glucose, by oral glucose tolerance test or a combination of these approaches with symptom review and measurement of HbA1C. Treatment is clearly indicated for those with CFRD and fasting hyperglycaemia to control symptoms and reduce complications. As nutrition is critical in people with CF to maintain body mass and lung function, blood glucose should be controlled in CFRD by adjusting insulin doses to the requirements of adequate food intake and not by calorie restriction. It is less clear whether blood glucose control will have clinical benefits in the management of patients with CFRD without fasting hyperglycaemia or with impaired glucose tolerance and further studies are required to establish the best treatment for this patient group

Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis

AbstractBackgroundPulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)≥8 mmol L−1 (airway threshold), and are associated with acquisition of respiratory infection.MethodsTo determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry.ResultsAG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5–3 mmol L−1-vs.-0.5–1 mmol L−1, p<0.0001) when BG was ≥8 mmol L−1-vs.-<8 mmol L−1. Daily time with BG≥8 mmol L−1 was CFRD (49±25%), CF-NGT (6±5%), healthy volunteers (1±3%), p<0.0001. Staphylococcus aureus growth increased at ≥0.5 mmol L−1 (p=0.006) and Pseudomonas aeruginosa growth above 1–4 mmol L−1 glucose (p=0.039).ConclusionsBG≥8 mmol L−1 predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent ∼ 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD

Notes towards a history of Khoi literature

This article puts forward a revisionist history of Khoi literature, and also presents a number of translated Khoi narratives that have not been available in English before. Compared to the large volume of Bushman literature and scholarship, there has been very little Khoi literature and engagement with it, and an argument is presented to account for this gap in South African cultural history. Until now, the major source of Khoi literature was Wilhelm Bleek’s Reynard the Fox in South Africa (1864), and this text is critically interrogated as a limiting version of Khoi orature. An alternative corpus of Khoi narratives is presented that was originally published in Leonard Schultze’s Aus Namaland und Kalahari (1907).Web of Scienc

Practicing physiotherapy in Danish private practice: an ethical perspective.

Despite an increasingly growth of professional guidelines, textbooks and research about ethics in health care, awareness about ethics in Danish physiotherapy private practice seen vague. This article explores how physiotherapists in Danish private practice, from an ethical perspective, perceive to practice physiotherapy. The empirical data consists of interviews with twenty-one physiotherapists. The interviews are analysed from a hermeneutic approach, inspired by Ricoeur's textual interpretation of distanciation. The analysis follows three phases: naïve reading, structural analysis and comprehensive analysis. Four main themes are constructed: Beneficence as the driving force; Disciplining the patient through the course of physiotherapy; Balancing between being a trustworthy professional and a businessperson; The dream of a code of practice. Private practice physiotherapy is embedded in a structural frame directed by both political and economical conditions that shape the conditions for practicing physiotherapy. It means that beneficence in practice is a balance between the patient, the physiotherapists themselves and the business. Beneficence towards the patient is expressed as an implicit demand. Physiotherapeutic practice is expressed as being an integration of professionalism and personality which implies that the physiotherapists also have to benefit themselves. Private practice seems to be driven by a paternalistic approach towards the patient, where disciplining the patient is a crucial element of practice, in order to optimise profit. Physiotherapists wish for a more beneficent practice in the future by aiming at bridging 'to be' and 'ought to be'

We need timely access to mental health data: implications of the Goldacre review

The Goldacre review, published in April, 2022, 1 is a landmark evaluation of the use, availability, and safety of National Health Service (NHS) data across all four nations of the UK. The review underscores the necessary role of data in driving health-care improvement and innovation, and the potential risks inherent in using data routinely contributed by health service users. The review recommends a radical overhaul in NHS data curation, access, and analysis, and, crucially, argues that substantial new resources must be marshalled to make this aspiration a reality

Islet transplantation from a nationally funded UK centre reaches socially deprived groups and improves metabolic outcomes

Acknowledgements We thank the transplant nurses involved with the Scottish Islet Transplant Programme (T. McGilvray, J. Davidson, M. Phillips and C. Jansen) for help with participant assessment. We thank the Scottish National Blood Transfusion Services including the Histocompatibility and Immunogenetics Team for HLA typing and antibody screening, and the Tissue and Cells Team (A. Timpson, L. Fraser, L. Irvine and P. Henry) for islet isolation and product release testing. We acknowledge the Departments of Transplantation, Diabetes and Interventional Radiology at NHS Lothian for all aspects of patient care and the organ procurement programme. We thank J. Shaw and A. Brooks from the Department of Regenerative Medicine for Diabetes at the University of Newcastle for advice regarding CGMS. C-peptide assays were performed by the NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay Laboratory. Funding: The Scottish Islet Transplant Programme is funded by the National Services Division. This research was funded by Diabetes UK (Biomedical and Psychosocial Outcomes of Islet Transplantation; Grant no. BDA 06/0003362), Diabetes Research and Wellness Foundation, Diabetes Foundation, Juvenile Diabetes Research Foundation and the Royal Infirmary Diabetes Treatment Trust Fund. Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Peer reviewedPublisher PD

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis:a randomised, double-blind, placebo-controlled, phase 2b trial

Background: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods: We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (&lt;70 vs ≥70%), age (&lt;18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings: Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation: Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials