Evaluation of vardenafil for the treatment of subjective tinnitus: a controlled pilot study

<p>Abstract</p> <p>Background</p> <p>Vardenafil (Levitra^®) represents a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor, which is established for treatment of various diseases. There are several unpublished reports from patients stating that vardenafil has a considerable therapeutic effect on their concomitant tinnitus. This pilot study was conducted to specifically assess the effect of vardenafil in patients with chronic tinnitus.</p> <p>Methods</p> <p>This trial was based on a prospective, randomized, double-blind, placebo-controlled, parallel group design. Fourty-two consecutive subjects with mon- or binaural chronic tinnitus received 10 mg vardenafil (N = 21) or matching placebo tablets (N = 21) administered orally twice a day over a period of 12 weeks. Clinical examination and data acquisition took place at each visit: at baseline, after 4 weeks, after 12 weeks (end of treatment with study medication), and at non-medicated follow-up after 16 weeks. Assessment of clinical effectiveness was based on a standardized tinnitus questionnaire (TQ), the Short Form 36 health survey (SF-36), audiometric measurements (mode, pitch and loudness of tinnitus; auditory thresholds) and biomarkers of oxidative stress in patients' blood (malondialdehyde, protein carbonyl, homocysteine and total antioxidative status). Therapeutic efficacy was evaluated by comparison of subjective and objective parameters with baseline data between both treatment groups (ANCOVA).</p> <p>Results</p> <p>Vardenafil had no superior efficacy over placebo in the treatment of chronic tinnitus during this study. The primary efficacy criterion 'TQ total score' failed to demonstrate significant improvement compared to placebo. Subjective reports of TQ subscales and general quality of life areas (SF-36), objective audiometric examinations as well as investigated biomarkers for oxidative stress did not reveal any significant treatment effects. The safety profile was favorable and consistent with that in other vardenafil studies.</p> <p>Conclusion</p> <p>Although hypoxia and ischemia play a special role in the pathogenesis of tinnitus, the PDE5-inhibitor-induced increase of nitric oxide-mediated vasodilatation exerted no specific influence on tinnitus symptomatology. Considering the unclear risk of rarely associated hearing impairment, systemic application of vardenafil or other PDE5 inhibitors prove to be not appropriate for therapy of chronic tinnitus.</p

The clinical impact of pain neuroscience continuing education on physical therapy outcomes for patients with low back and neck pain.

ObjectivesResearch suggests that attendance by physical therapists at continuing education (CE) targeting the management of low back pain (LBP) and neck pain does not result in positive impacts on clinical outcomes. The aim of this study was to determine if therapists attending a self-paced 3-hour online Pain Neuroscience Education (PNE) program was associated with any observed changes to patient outcomes and also clinical practice.MethodsParticipants were 25 different physical therapists who treated 3,705 patients with low back pain (LBP) or neck pain before and after they had completed an online PNE CE course. Change in outcomes measures of pain and disability at discharge were compared for the patients treated before and after the therapist training. Clinical practice patterns of the therapists, including total treatment visits, duration of care, total units billed, average units billed per visit, percentage of 'active' billing units and percentage of 'active and manual' billing units, were also compared for the patient care episodes before and after the therapist training.ResultsThere was no significant difference for change in pain scores at discharge for patients treated after therapist CE training compared to those treated before regardless of the condition (LBP or neck pain). However, patients with LBP who were treated after therapist CE training did report greater improvement in their disability scores. Also after CE training, for each episode of care, therapists tended to use less total visits, billed fewer units per visit, and billed a greater percentage of more 'active' and 'active and manual' billing units.DiscussionAttending an online 3-hour CE course on PNE resulted in improved disability scores for patients with LBP, but not for those with neck pain. Changes in clinical behavior by the therapists included using less visits, billing fewer total units, and shifting to more active and manual therapy interventions. Further prospective studies with control groups should investigate the effect of therapist CE on patient outcomes and clinical practice

rAAV Gene Therapy in a Canavan\u27s Disease Mouse Model Reveals Immune Impairments and an Extended Pathology Beyond the Central Nervous System

Aspartoacylase (AspA) gene mutations cause the pediatric lethal neurodegenerative Canavan disease (CD). There is emerging promise of successful gene therapy for CD using recombinant adeno-associated viruses (rAAVs). Here, we report an intracerebroventricularly delivered AspA gene therapy regime using three serotypes of rAAVs at a 20-fold reduced dose than previously described in AspA(-/-) mice, a bona-fide mouse model of CD. Interestingly, central nervous system (CNS)-restricted therapy prolonged survival over systemic therapy in CD mice but failed to sustain motor functions seen in systemically treated mice. Importantly, we reveal through histological and functional examination of untreated CD mice that AspA deficiency in peripheral tissues causes morphological and functional abnormalities in this heretofore CNS-defined disorder. We demonstrate for the first time that AspA deficiency, possibly through excessive N-acetyl aspartic acid accumulation, elicits both a peripheral and CNS immune response in CD mice. Our data establish a role for peripheral tissues in CD pathology and serve to aid the development of more efficacious and sustained gene therapy for this disease