Adherence to treatment guideline recommendations for Parkinson's disease in Japan: A longitudinal analysis of a nationwide medical claims database between 2008 and 2016.

BackgroundAdherence to the 2011 Japanese guidelines for treatment of Parkinson's disease (PD) in real-life practice is unknown.MethodsIn this retrospective longitudinal observational study, we examined patterns and trends in anti-PD drug prescriptions in 20,936 patients (≥30 years of age with newly diagnosed PD [International Classification of Diseases-Tenth code G20 or PD Hoehn and Yahr scale 1-5] and one or more prescriptions) using nationwide registry data between 2008 and 2016. Data are presented as descriptive statistics.ResultsHalf (49.6%) of the patients received levodopa (L-dopa) monotherapy, followed by non-ergot dopamine agonists (DA) prescribed as monotherapy (8.3%) or with L-dopa (8.1%). Consistent with the guidelines, 75% of patients were prescribed within 13 days of initial diagnosis; L-dopa monotherapy was the most prescribed drug in patients ≥70 years of age, whereas non-ergot DA monotherapy was more likely to be prescribed than L-dopa in patients between 30 and 50 years of age. Inconsistent with the guidelines, L-dopa monotherapy was the most prescribed drug in patients between 51 and 69 years of age. Over the course of 4 years of treatment, the prescription rate of L-dopa monotherapy and non-ergot DA monotherapy decreased by 63.7% and 44.1%, respectively, whereas that of L-dopa and non-ergot DA combination therapy increased by 103.7%. Combination therapy with L-dopa, non-ergot DA, and monoamine oxidase-B inhibitors was gradually increased at a later stage.ConclusionThese results highlight that the state of PD treatment in Japan adheres to most of the recommendations in the 2011 national guidelines, but also precedes the 2018 guidelines

Syntactic Comprehension in Patients with Amyotrophic Lateral Sclerosis

Recent neuropsychological studies of patients with amyotrophic lateral sclerosis (ALS) have demonstrated that some patients have aphasic symptoms, including impaired syntactic comprehension. However, it is not known if syntactic comprehension disorder is related to executive and visuospatial dysfunction. In this study, we evaluated syntactic comprehension using the Syntax Test for Aphasia (STA) auditory comprehension task, frontal executive function using the Frontal Assessment Battery (FAB), visuospatial function using Raven’s Coloured Progressive Matrices (RCPM), and dementia using the Hasegawa Dementia Scale-Revised (HDS-R) in 25 patients with ALS. Of the 25 patients, 18 (72%) had syntactic comprehension disorder (STA score < IV), nine (36%) had frontal executive dysfunction (FAB score < 14), six (24%) had visuospatial dysfunction (RCPM score < 24), and none had dementia (HDS-R score < 20). Nine of the 18 patients with syntactic comprehension disorder (50%) passed the FAB and RCPM. Although sample size was small, these patients had a low STA score but normal FAB and RCPM score. All patients with bulbar onset ALS had syntactic comprehension disorder. These results indicate that it might be necessary to assess syntactic comprehension in patients with bulbar onset ALS. The implications of these findings are discussed in relation to the pathological continuum of ALS

Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients.

OBJECTIVE:Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS. DESIGN:A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial. METHODS:The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing. RESULTS:Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence. CONCLUSIONS:BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment. TRIAL REGISTRATION:UMIN Clinical Trials UMIN000008527

Correction: Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients

<p>Correction: Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients</p

The results of primary efficacy analysis I on Limb Norris Scale total score.

<p>In 1^st endpoint analysis, the group of BRC treatment tended to be recovered compared to the group of placebo treatment. Moreover, in 2^nd endpoint analysis, the group of BRC was significantly recovered in Limb Norris Scale total score compared to the group of placebo (p < 0.2).</p