Evaluation of Possible Effects of a Potassium Channel Modulator on Temporal Processing by Cochlear Implant Listeners

Temporal processing by cochlear implant listeners is degraded and is affected by auditory deprivation. The fast-acting Kv3.1 potassium channel is important for sustained temporally accurate firing and is also susceptible to deprivation, the effects of which can be partially restored in animals by the molecule AUT00063. We report the results of a randomised placebo-controlled double-blind study on psychophysical tests of the effects of AUT00063 on temporal processing by CI listeners. The study measured the upper limit of temporal pitch, gap detection, and discrimination of low rates (centred on 120 pps) for monopolar pulse trains presented to an apical electrode. The upper limit was measured using the optimally efficient midpoint comparison (MPC) pitch-ranking procedure; thresholds were obtained for the other two measures using an adaptive procedure. Twelve CI users (MedEl and Cochlear) were tested before and after two periods of AUT00063 or placebo in a within-subject crossover study. No significant differences occurred between post-drug and post-placebo conditions. This absence of effect occurred despite high test-retest reliability for all three measures, obtained by comparing performance on the two baseline visits, and despite the demonstrated sensitivity of the measures to modest changes in temporal processing obtained in other studies from our laboratory. Hence, we have no evidence that AUT00063 improves temporal processing for the doses and patient population employed

Supervised exercise training as an adjunctive therapy for venous leg ulcers: study protocol for a randomised controlled trial

Background: Venous leg ulcers are common, chronic wounds that are painful and reduce quality of life. Compression therapy is known to assist in the healing of venous leg ulceration. Supervised exercise training that targets an improvement in calf muscle pump function might be a useful adjunctive therapy for enhancing ulcer healing and other aspects of physical and mental health. However, the evidence of exercise for individuals with venous ulcers is sparse. Here, we describe the protocol for a study that aims to assess the feasibility of undertaking a randomised controlled trial of a supervised exercise programme in people who are receiving compression for venous ulceration. Methods/Design: This is a randomised, controlled, assessor-blinded, two-centre, feasibility trial with two parallel groups. Eighty adults who are receiving lower-limb compression for a venous leg ulcer will be randomly assigned to receive usual care (compression only) or usual care plus a 12-week supervised exercise programme. Participants in the exercise group will be invited to undertake three, 60-minute sessions of supervised exercise each week, and each session will involve a combination of treadmill walking, upright cycling and strength and flexibility exercises for the lower limbs. Participants will be assessed before randomisation and 3, 6 and 12 months after randomisation. Primary outcomes include rates of recruitment, retention and adherence. Secondary outcomes include time to ulcer healing, proportion of participants healed, percentage and absolute change in ulcer size, health-related quality of life (EQ-5D-5L and VEINES-QOL/Sym), lower-limb cutaneous microvascular function (laser Doppler flowmetry coupled with iontophoresis) and physical fitness (30-second sit-to-stand test, chair sit and reach test, 6-minute walk test and ankle range of motion). The costs associated with the exercise programme and health-care utilisation will be calculated. We will also complete interviews with a sub-sample of participants to explore their experiences of having a venous ulcer and the acceptability of the exercise intervention and study procedures. Discussion: Data from this study will be used to refine the supervised exercise programme, investigate the acceptability of the intervention and study design and determine the most appropriate outcome measures, thereby providing estimates of the factors needed to design an adequately powered trial across several centres

Do varicose veins affect quality of life? Results of an international population-based study.

PURPOSE: This study assessed the impact of varicose veins (VV) on quality of life (QOL) and patient-reported symptoms. METHODS: A cross-sectional population-based study was held in 166 general practices and 116 specialist clinics for venous disorders of the leg in Belgium, Canada (Quebec), France, and Italy. Study subjects included a sample of 259 reference patients without VV (CEAP class 0 or 1) and 1054 patients with VV who were classified as having VV alone (367; 34.8%), VV with edema (125; 11.9%), VV with skin changes (431; 40.9%), VV with healed ulcer (100; 9.5%), and VV with active ulcer (31; 2.9%). The main outcome measure was generic and disease-specific QOL, as measured by means of the Short-Form Health Survey-36 (SF-36) and the VEINES-QOL scale, and patient-reported symptoms as measured by the VEINES-SYM scale. RESULTS: In patients with VV, age-standardized mean SF-36 physical (PCS) and mental (MCS) scores were 45.6 and 46.1 in men and 44.2 and 43.2 in women, respectively, compared with population norms of 50. PCS scores decreased according to increasing severity of concomitant venous disease, with the lowest mean scores of 37.3 and 35.5 found in patients with VV and active ulcer. However, adjusted analyses showed no statistically significant differences between patients with VV alone and patients without VV for PCS (0.0), MCS (1.0), VEINES-QOL (-0.1), or VEINES-SYM (0.0) scores. In comparison with patients without VV, the largest differences were seen in patients with VV and edema (PCS, VEINES-QOL, and VEINES-SYM score differences of -1.8, -2.5, and -2.9, respectively) and in patients with VV and ulceration (differences of -3.3, -3.4, and -2.7, respectively). The high prevalence of major symptoms of venous disorders in patients in CEAP class 0 or 1 being treated for venous disorders (76.1% of patients had heaviness, aching legs, or swelling) might have contributed to the impairment of QOL in the reference group. CONCLUSION: Results indicate that impairment in physical QOL in patients with VV is associated with concomitant venous disease, rather than the presence of VV per se. Findings concerning QOL in patients with VV can only be reliably interpreted when concomitant venous disease is taken into account. In patients with VV alone, the objectives of cosmetic improvement and the improvement of QOL should be considered separately

The influence of venous thromboembolism on quality of life and severity of chronic venous disease.

BACKGROUND: It is not known whether burden-of-illness differs in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. OBJECTIVE: To compare severity of disease and quality of life in chronic venous disease patients with and without prior venous thromboembolism. PATIENTS AND METHODS: The VEINES Study population is an international cohort of 1531 outpatients with chronic venous disease in Belgium, France, Italy and Canada. Clinical severity of chronic venous disease graded using the seven-category 'CEAP' scale, and quality of life using standardized generic (SF-36) and venous disease-specific (VEINES-QOL/Sym) questionnaires were compared in patients with and without venous thromboembolism. Multivariable analyses with adjustment for known confounders were used to examine associations between venous thromboembolism and quality of life. RESULTS: One hundred and fifty-one (10%) patients had prior venous thromboembolism. These patients had more severe chronic venous disease than those without venous thromboembolism (P <0.0001), including a higher frequency of healed or active ulcers (29% vs. 7%, respectively). Multivariable analyses controlling for age, sex, country, education, body mass index, years of chronic venous disease and comorbid conditions demonstrated that prior venous thromboembolism was an independent predictor of poorer generic quality of life (SF-36 Mental Component Summary score, P=0.047; SF-36 Physical Component Summary score, P=0.012) and venous disease-specific quality of life (VEINES-QOL, P = 0.0002; VEINES-Sym, P=0.009). CONCLUSIONS: Disease severity is worse and quality of life poorer in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. Our findings support the need for further research of interventions to prevent and treat the long-term complications of venous thromboembolism