Use of Actigraphy for a Rat Behavioural Sleep Study

Previous studies of animal behavioural sleep is mainly divided into two study types, observation by video recording or counts by sensor, both of which require a complex environment and procedure. An actigraph unit is a commercially available product which can provide non-invasive monitoring human rest/activity cycles. The goal of this study was to evaluate whether actigraphy can be applied for analysing behavioural sleep in rats, since no reports have described utilization of the actigraphy unit for monitoring sleep of small animals. The actigraph unit was held on the chest of eight male rats by a loose elastic belt. The rats spent two days in a normal condition, followed by two days of sleep deprivation. Total counts measured by the actigraph could be clearly divided into two phases, sleep phase and awake phase, when the rats were kept in the normal cage. Next, the rats were moved into the sleep-deviation cage, and the total counts were significantly higher during daytime, indicating the successful induction of sleep deprivation. These results showed that the actigraphy unit monitored rest/activity cycles of rats, which will contribute to making sleep behaviour experiments easier

A Pilot Study on the Efficacy of Continuous Positive Airway Pressure on the Manifestations of Ménière's Disease in Patients with Concomitant Obstructive Sleep Apnea Syndrome.

ObjectivesTo evaluate the effect of continuous positive airway pressure (CPAP) therapy on Ménière's disease patients with concomitant obstructive sleep apnea syndrome (OSAS), since recent reports suggest OSAS may cause dysfunction of the vestibular system.Study designProspective study using CPAP administered to patients diagnosed with "Definite Ménière's disease" according to the guidelines of the American Academy of Otolaryngology--Head and Neck Surgery and combined with OSAS.SettingUniversity hospital.MethodsTwenty consecutive patients, 14 male and 6 female with active, unilateral, cochleovestibular Ménière's disease refractory to medical management who also had concurrent OSAS as defined by International Classification of Sleep Disorders, Second Edition were selected to undergo solitary CPAP therapy. Audiometric testing, caloric testing, and DHI survey were conducted before and after CPAP therapy and compared to assess effectiveness of CPAP therapy as utilized for treatment of Ménière's disease.ResultsAlthough caloric testing did not show significant difference, audiometric testing and results of dizziness handicap inventory were significantly improved (p < 0.05) after CPAP therapy only, without standard treatment for Ménière's disease.ConclusionRecent reports have suggested that OSAS may cause dysfunction of the vestibular system. We investigated whether standard therapy for OSAS would be of benefit in the management of vertigo and hearing loss in Ménière's disease patients. Our study cohort demonstrated significant improvement in both DHI and audiometric testing following solitary CPAP therapy for OSAS. Solitary CPAP therapy may become a new effective treatment strategy for Ménière's disease patients with OSAS, not just only for control of dizziness and vertigo but also for potential benefit of hearing

A Pilot Study on the Efficacy of Continuous Positive Airway Pressure on the Manifestations of Ménière's Disease in Patients with Concomitant Obstructive Sleep Apnea Syndrome

OBJECTIVE: To evaluate the effect of continuous positive airway pressure (CPAP) therapy on Ménière's disease patients with concomitant obstructive sleep apnea syndrome (OSAS), since recent reports suggest OSAS may cause dysfunction of the vestibular system. STUDY DESIGN: Prospective study using CPAP administered to patients diagnosed with “Definite Ménière's disease” according to the guidelines of the American Academy of Otolaryngology— Head and Neck Surgery and combined with OSAS. SETTING: University hospital. METHODS: Twenty consecutive patients, 14 male and 6 female with active, unilateral, cochleovestibular Ménière's disease refractory to medical management who also had concurrent OSAS as defined by International Classification of Sleep Disorders, Second Edition were selected to undergo solitary CPAP therapy. Audiometric testing, caloric testing, and DHI survey were conducted before and after CPAP therapy and compared to assess effectiveness of CPAP therapy as utilized for treatment of Ménière's disease. RESULTS: Although caloric testing did not show significant difference, audiometric testing and results of dizziness handicap inventory were significantly improved (p < 0.05) after CPAP therapy only, without standard treatment for Ménière's disease. CONCLUSIONS: Recent reports have suggested that OSAS may cause dysfunction of the vestibular system. We investigated whether standard therapy for OSAS would be of benefit in the management of vertigo and hearing loss in Ménière's disease patients. Our study cohort demonstrated significant improvement in both DHI and audiometric testing following solitary CPAP therapy for OSAS. Solitary CPAP therapy may become a new effective treatment strategy for Ménière's disease patients with OSAS, not just only for control of dizziness and vertigo but also for potential benefit of hearing. CITATION: Nakayama M, Masuda A, Ando KB, Arima S, Kabaya K, Inagaki A, Nakamura Y, Suzuki M, Brodie H, Diaz RC, Murakami S. A pilot study on the efficacy of continuous positive airway pressure on the manifestations of Ménière's disease in patients with concomitant obstructive sleep apnea syndrome. J Clin Sleep Med 2015;11(10):1101–1107

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II\ue2\u80\u93IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56\uc2\ub76 [SEM 4\uc2\ub75] vs 68\uc2\ub73 [4\uc2\ub75]; rank-based treatment difference \ue2\u88\u9211\uc2\ub77, 95% CI \ue2\u88\u9224\uc2\ub73 to 0\uc2\ub796; p=0\uc2\ub70698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals