The Hand and Wrist: AntImicrobials and Infection (HAWAII) trial.

BACKGROUND: Hand trauma, comprising injuries to both the hand and wrist, affects over five million people per year in the NHS, resulting in 250 000 operations each year. Surgical site infection (SSI) following hand trauma surgery leads to significant morbidity. Triclosan-coated sutures may reduce SSI in major abdominal surgery but have never been tested in hand trauma. Feasibility needs to be ascertained before a definitive trial can be delivered in hand trauma. METHODS: A multicentre feasibility RCT of antimicrobial sutures versus standard sutures involving adults undergoing surgery for hand trauma to evaluate feasibility for a definitive trial. Secondary objectives were incidence of SSI in both groups, hand function measured with patient-reported outcome measures, health-related quality of life and change in employment. Randomization was performed on a 1:1 basis, stratified by age of the patient and whether the injury was open or closed, using a secure, centralized, online randomization service. Participants were blinded to allocation. RESULTS: 116 participants were recruited and randomized (60 intervention, 56 control). Of 227 screened, most were eligible (89.5 per cent), and most who were approached agreed to be included in the study (84.7 per cent). Retention was low: 57.5 per cent at 30 days, 52 per cent at 90 days and 45.1 per cent at 6 months. Incidence of SSI was >20 per cent in both groups. Hand function deteriorated after injury but recovered to near pre-injury levels during the study period. CONCLUSIONS: Risk of SSI after hand trauma is high. A definitive RCT of antimicrobial sutures in hand trauma surgery is feasible, if retention is improved. TRIAL REGISTRATION: ISRCTN10771059.

Flexibility and resistance exercises versus usual care for improving pain and function after distal radius fracture in adults aged 50 years or over: protocol for the WISE randomised multicentre feasibility trial.

BACKGROUND: Distal radius fractures represent about 1 in 5 of all fractures treated in UK hospitals. Most distal radius fractures occur in women aged 50 years or over after a fall. Distal radius fractures are managed using splints or casting, some are also treated with surgical fixation. Patients often experience long-term muscle weakness of the hand and arm that may impact their ability to do daily activities such as personal hygiene, routine household chores and food preparation. We propose a structured and tailored flexibility and resistance exercise programme for the hand and arm supplemented with behaviour change strategies to help perform daily exercise. The main aim of our study is to assess the feasibility of conducting a definitive randomised controlled trial. METHODS: This study is a multicentre, parallel-group individually randomised feasibility trial. We will recruit a minimum of 72 adults aged 50 years or over with distal radius fracture treated surgically or non-surgically from at least three UK National Health Service (NHS) hospitals. They will be randomised 1:1:1 to receive usual care, usual care and independent exercise with a single therapy session or usual care and supervised exercise with three therapy sessions over 12 weeks. Our primary feasibility objectives are (1) patient engagement assessed by recruitment, (2) acceptability of the interventions assessed by adherence and patient and clinician experience and (3) retention of participants in the trial. Outcome measures will be assessed at baseline, 3 months and at 6 months after randomisation. A qualitative sub-study will explore the experiences of the trial participants and therapists delivering the exercises. DISCUSSION: A definitive trial will be considered feasible without major modifications if our progression criteria are met. If successful, the findings will inform the design of a future definitive RCT to evaluate the clinical and cost-effectiveness of the WISE exercise programme. TRIAL REGISTRATION: ISRCTN12290145 .

Low iodine diet advice and differentiated thyroid cancer treatment: A historic exploration in three UK centres.

BACKGROUND AND AIMS: Patients with differentiated thyroid cancer are often advised to follow a low iodine diet (LID) one to two weeks before radioiodine remnant ablation (RRA). We describe treatment practices and ablation success rates in centres (C1, C2, C3) in the UK with different approaches to LID advice. METHODS: Historic cohort of patients with differentiated thyroid cancer treated with RRA in 2015/16 in C1 (n = 50, 1-week LID), C2 (n = 59, 2-week LID) and C3 (n = 108, no LID advice). Response to RRA was stratified as excellent, indeterminate, or incomplete by the adapted American Thyroid Association Dynamic Risk Stratification Score. RESULTS: There was little difference in age, sex and staging between centres, but the percentage receiving 1.1 GBq vs higher administered activities differed (C1:22%, C2:44%, C3:15%, p < 0.001). Excellent response was recorded for: C1:48%, C2:36%, C3:49% (p = 0.61). Differences in RRA preparation and outcome assessment at C3 precluded comparison across all centres. Adjusted odds ratio for excellent response at C2 vs C1 was 0.57 (95%CI: 0.25,1.32), p = 0.19. CONCLUSIONS: There was no evidence that advising a LID for 2-weeks before RRA improves outcomes compared to 1-week. For definitive recommendations on LIDs prior to RRA, a prospective multi-centre study with a more homogenous approach to patient management or, randomised controlled trial, is needed.

Heat shock enhances NGF-induced neurite elongation which is not mediated by Hsp25 in PC12 cells.

Neuronal differentiation and neurite outgrowth are key processes during development of the nervous system. Understanding the regulation of neurite outgrowth stimulated by neurotrophins is crucial to developing therapies to promote axon regeneration after injury or in neurodegenerative diseases. Treatment of PC12 cells with nerve growth factor (NGF) stimulates them to extend neurites and differentiate into a sympathetic neuron-like phenotype. In this study we found that exposure of PC12 cells to 42 degrees C for 1 h significantly enhanced NGF-induced neurite elongation, but not branching. This heat shock treatment led to induction of heat shock protein 25 (Hsp25) and Hsp70. The morphological changes induced by NGF were accompanied by increased Hsp25 mRNA levels, in addition to elevation in Hsp25 protein expression and phosphorylation, without a concomitant increase in Hsp70. A possible role for Hsp25 in NGF-stimulated neurite outgrowth was investigated. However, quantification of NGF-induced neurite elongation and branching revealed that neither of these features were altered in PC12 cells which stably overexpressed human Hsp27 (to mimic heat shock induction of Hsp25). Similarly, knockdown of Hsp25 using siRNA had no effect on NGF-induced neurite outgrowth. Inhibition of p38 MAPK signalling with SB202190 blocked phosphorylation of Hsp25 without affecting NGF-induced neurite outgrowth or the heat shock-dependent enhancement of elongation. These findings indicate that Hsp25 is not required for NGF-induced neurite outgrowth in PC12 cells and is not responsible for the heat shock-enhancement of NGF-induced neurite elongation. Instead, inhibition of MEK1/2 with U0126 partially reduced the heat shock-enhancement of NGF-stimulated neurite elongation.

Functionality of NGF-protected PC12 cells following exposure to 6-hydroxydopamine.

6-Hydroxydopamine (6-OHDA) is often used in models of Parkinson's disease since it can selectively target and kill dopaminergic cells of the substantia nigra. In this study, pre-treatment of PC12 cells with nerve growth factor (NGF) inhibited apoptosis and necrosis by 6-OHDA, including caspase activity and lactate dehydrogenase release. Notably, cells exposed to 6-OHDA in the presence of NGF were subsequently capable of proliferation (when replated without NGF), or neurite outgrowth (with continued presence of NGF). Following 7 days growth in the presence of NGF, expression of betaIII tubulin and tyrosine hydroxylase and increased intracellular catecholamines was detectable in PC12 cells, features characteristic of functional dopaminergic neurons. NGF-pre-treated PC12 cells retained expression of betaIII-tubulin and tyrosine hydroxylase, but not catecholamine content following 6-OHDA exposure. These data indicate that NGF-protected cells maintained some aspects of functionality and were subsequently capable of proliferation or differentiation.