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Summary: A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na+ channel (ENaC), yielding increased Na+ reabsorption and airway dehydration. We use a non-invasive self-referencing Na+-selective microelectrode technique to measure Na+ transport across individual folds of distal airway surface epithelium preparations from CFTR−/− (CF) and wild-type (WT) swine. We show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na+ transport that are unaffected by the ENaC blocker amiloride. However, in the presence of the cyclic AMP (cAMP)-elevating agents forskolin+IBMX (isobutylmethylxanthine), folds of WT tissues secrete large amounts of Na+, while CFTR−/− tissues absorb small, but potentially important, amounts of Na+. In cAMP-stimulated conditions, amiloride inhibits Na+ absorption in CFTR−/− tissues but does not affect secretion in WT tissues. Our results are consistent with the hypothesis that ENaC-mediated Na+ absorption may contribute to dehydration of CF distal airways.

A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na

BackgroundClose contact casting (CCC) may offer an alternative to open reduction and internal fixation (ORIF) surgery for unstable ankle fractures in older adults.ObjectivesWe aimed to (1) determine if CCC for unstable ankle fractures in adults aged over 60 years resulted in equivalent clinical outcome compared with ORIF, (2) estimate cost-effectiveness to the NHS and society and (3) explore participant experiences.DesignA pragmatic, multicentre, equivalence randomised controlled trial incorporating health economic evaluation and qualitative study.SettingTrauma and orthopaedic departments of 24 NHS hospitals.ParticipantsAdults aged over 60 years with unstable ankle fracture. Those with serious limb or concomitant disease or substantial cognitive impairment were excluded.InterventionsCCC was conducted under anaesthetic in theatre by surgeons who attended training. ORIF was as per local practice. Participants were randomised in 1 : 1 allocation via remote telephone randomisation. Sequence generation was by random block size, with stratification by centre and fracture pattern.Main outcome measuresFollow-up was conducted at 6 weeks and, by blinded outcome assessors, at 6 months after randomisation. The primary outcome was the Olerud–Molander Ankle Score (OMAS), a patient-reported assessment of ankle function, at 6 months. Secondary outcomes were quality of life (as measured by the European Quality of Life 5-Dimensions, Short Form questionnaire-12 items), pain, ankle range of motion and mobility (as measured by the timed up and go test), patient satisfaction and radiological measures. In accordance with equivalence trial US Food and Drug Administration guidance, primary analysis was per protocol.ResultsWe recruited 620 participants, 95 from the pilot and 525 from the multicentre phase, between June 2010 and November 2013. The majority of participants, 579 out of 620 (93%), received the allocated treatment; 52 out of 275 (19%) who received CCC later converted to ORIF because of loss of fracture reduction. CCC resulted in equivalent ankle function compared with ORIF at 6 months {OMAS 64.5 points [standard deviation (SD) 22.4 points] vs. OMAS 66.0 points (SD 21.1 points); mean difference –0.65 points, 95% confidence interval (CI) –3.98 to 2.68 points; standardised effect size –0.04, 95% CI –0.23 to 0.15}. There were no differences in quality of life, ankle motion, pain, mobility and patient satisfaction. Infection and/or wound problems were more common with ORIF [29/298 (10%) vs. 4/275 (1%)], as were additional operating theatre procedures [17/298 (6%) vs. 3/275 (1%)]. Malunion was more common with CCC [38/249 (15%) vs. 8/274 (3%);p p = 0.002; medial: 3/274 (1%) vs. 18/248 (7%);p 95% from NHS perspective and 85% from societal perspective). Experiences of treatments were similar; both groups endured the impact of fracture, uncertainty regarding future function and the need for further interventions.LimitationsAssessors at 6 weeks were necessarily not blinded. The learning-effect analysis was inconclusive because of limited CCC applications per surgeon.ConclusionsCCC provides a clinically equivalent outcome to ORIF at reduced cost to the NHS and to society at 6 months.Future workLonger-term follow-up of trial participants is under way to address concerns over potential later complications or additional procedures and their potential to impact on ankle function. Further study of the patient factors, radiological fracture patterns and outcomes, treatment responses and prognosis would also contribute to understanding the treatment pathway.Trial registrationCurrent Controlled Trials ISRCTN04180738.FundingThe National Institute for Health Research Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 75. See the NIHR Journals Library website for further project information. This report was developed in association with the National Institute for Health Research Oxford Biomedical Research Unit funding scheme. The pilot phase was funded by the AO Research Foundation.

Background\ud Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery.\ud \ud Methods/Design\ud This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud and Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment.\ud \ud Discussion\ud This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013.

Introduction Clinical practice should be informed by high quality evidence, of which randomised controlled trials (RCTs) are considered the gold standard. Surgical trials are inherently difficult with potential problems around clinical equipoise and participant acceptability. This is often most true with trial designs comparing operative and non-operative treatments. It is hoped that research activity can be maximised by collaborating in (a) the identification of research questions and (b) involvement in clinical trials. Development of the national research networks can be utilised to provide support for research endeavours within the orthopaedic trauma community. Aims To identify and prioritise the research questions felt to be of most importance by the orthopaedic trauma community. Research studies will be considered for questions given the highest priority. Methods A Delphi approach was used to determine consensus between the faculty members of the AOUK. A two round process was used to elicit the research questions and then to rank them in order of priority. Results 217 members of the AOUK Long Bone Faculty were asked to submit research questions, predominantly consultant orthopaedic surgeons. A 22% response rate generated 147 questions. These were collated and the most frequent 24 sent back out for ranking by mean scores. A 55% response to this second round identified 10 top questions. Literature searches for these 10 looked at current knowledge of the subject, completed and ongoing research projects. We also looked at the advantages and disadvantages of undertaking a study and the most appropriate methodology. Conclusion The response rates demonstrated a clear interest in developing a collaborative research strategy. This can be enhanced by utilising the support of the National Institute of Health Research Clinical Research Networks (NIHR CRN).

Summary The aim of this study was to test the feasibility of using peripherally inserted central catheters (PICCs) in older people to enable fluid optimisation. Fourteen patients were randomised to three groups: (i) usual care, insertion of short peripheral intravenous cannulae and normal fluid prescription; (ii) PICC insertion and normal fluid prescription; (iii) PICC insertion and guided fluid prescription based on measurements of central venous pressure (CVP). A range of outcome measures were undertaken, plus two focus groups with ward staff and an interview with the research nurse to ascertain views concerning the implementation of the study. Descriptive findings identified that PICC use in this group of patients was extremely difficult. The practical issues affecting the feasibility of this study were: (i) the physical and psychological frailty of the patients, proxy consent, difficulties measuring outcomes, unsuccessful PICC placement due to aged veins, intolerance to lines; (ii) staff concerns relating to patient vulnerability, competent use of new technology, limited resources and work capacity. Most aspects of the trial were made more difficult due to the frailty of the patient group.

We investigated whether, in the management of stable paediatric fractures of the forearm, flexible casts that can be removed at home are as clinically effective, cost-effective and acceptable to both patient and parent as management using a cast conventionally removed in hospital. A single-centre randomised controlled trial was performed on 317 children with a mean age of 9.3 years (2 to 16). No significant differences were seen in the change in Childhood Health Assessment Questionnaire index score (p = 0.10) or EuroQol 5-Dimensions domain scores between the two groups one week after removal of the cast or the absolute scores at six months. There was a significantly lower overall median treatment cost in the group whose casts were removed at home (£150.88 (sem 1.90) vs £251.62 (sem 2.68); p < 0.001). No difference was seen in satisfaction between the two groups (p = 0.48). Cite this article: Bone Joint J 2013;95-B:1714–20.

The problem of how to retain experienced nurses within a given specialist field impacts on both nurses and managers. This article explores the development of a new clinical role which gives experienced E and F grade nurses the opportunity for personal and professional growth. Within the new role, 50% of the nurse's time is devoted to ward-based clinical work and the other 50% to developing an area of clinical practice or research, as is the case with some clinical nurse specialists. There is flexibility over the area of specialist interest to reflect the needs of the service and the expertise and interests of the individual, and there is also flexibility in relation to the clinical commitment which increases opportunities for job shares. This development has arisen from an organizational culture which recognizes the need for more flexible job classifications and work rules. This new model for practice also represents a new model for management. In fostering self-reliance within the workforce it enables all parties to work towards a shared vision which Is mutually beneficial for nurses, managers, the organization and, most importantly, the patient.

INTRODUCTION: There are increasing numbers of older persons sustaining ankle fractures. This injury often results in a degree of functional limitation, particularly in older patients. There is currently limited research into factors associated with mobility outcomes. DESIGN: Observational cohort study. SETTING: Hospital Trauma Department, UK. PARTICIPANTS: Persons aged 60 years or over who sustained an unstable ankle fracture with no established peripheral arterial disease pre-injury. METHODS: This study investigated the association between ankle-brachial pressure index (ABPI) and extended timed 'up and go' (TUG) measures. Associations between TUG outcomes and age, pre-morbid functional mobility (Olerud-Molander Ankle Score) and fracture severity (number of malleoli injured) were also explored. ANALYSIS: Complete cases (n=76; 84% of cohort) were entered into univariate and multivariate linear regression. RESULTS: No association was found between ABPI and TUG at 6 months in unadjusted and adjusted analyses. Pre-morbid functional mobility (B=-0.34, 95% confidence interval (CI) -0.45 to -0.23, p