A Randomized Phase 3 Study Comparing P2B001 to its Components (Low-Dose Extended-Release Rasagiline and Pramipexole) and to Optimized Doses of Marketed Extended-Release Pramipexole in Early Parkinson's Disease.

Background: There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity.

Objectives: The objective was to determine if P2B001 (a fixed, low-dose, extended-release [ER] combination of pramipexole 0.6 mg and rasagiline 0.

Exploiting common senses: sensory ecology meets wildlife conservation and management.

Multidisciplinary approaches to conservation and wildlife management are often effective in addressing complex, multi-factor problems. Emerging fields such as conservation physiology and conservation behaviour can provide innovative solutions and management strategies for target species and systems. Sensory ecology combines the study of 'how animals acquire' and process sensory stimuli from their environments, and the ecological and evolutionary significance of 'how animals respond' to this information.

Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials.

Background: Parkinson's disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life.

Objective: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes.

Methods: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12.

Author Correction to: Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease.

An Online First version of this article was made available online at http://link.springer.com/journal/40263/onlineFirst/page/1 on 12 March 2018.

Pooled Analyses of Phase III Studies of ADS-5102 (Amantadine) Extended-Release Capsules for Dyskinesia in Parkinson's Disease.

Background: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRI) is a recent US FDA-approved treatment for dyskinesia in PD patients. ADS-5102 is a high-dose, ER formulation of amantadine, administered orally once daily at bedtime, that achieves high plasma drug concentrations throughout the day.

Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea.

Importance: Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study.

Objectives: To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD).

Angling into the Future: Ten Commandments for Recreational Fisheries Science, Management, and Stewardship in a Good Anthropocene.

A new geological epoch, the "Anthropocene", has been defined as the period in which humans have had substantial geological and ecological influence on the planet. A positive future for this epoch can be referred to as the "good Anthropocene" and would involve effective management strategies and changes in human behavior that promote the sustainability and restoration of ecosystems. Recreational fisheries hold significant social, cultural, and economic value and can generate many benefits when managed sustainably and thus be an integral part of a "good Anthropocene".

A randomized trial of a low-dose Rasagiline and Pramipexole combination (P2B001) in early Parkinson's disease.

Background: Rasagiline and pramipexole act to improve striatal dopaminergic transmission in PD via distinct and potentially synergistic mechanisms. We performed a placebo-controlled study to determine whether 2 doses of a novel slow-release, low-dose combination of rasagiline and pramipexole (P2B001) are effective and have a good safety profile in patients with early untreated PD.

Methods: Previously untreated patients with early PD were randomized (1:1:1) to once-daily treatment with P2B001 (0.

Oxidative ecology of paternal care in wild smallmouth bass, .

Physiologically, oxidative stress is considered a homeostatic imbalance between reactive oxygen species production and absorption. From an ecological perspective, oxidative stress may serve as an important constraint to life-history traits, such as lifespan, reproduction and the immune system, and is gaining interest as a potential mechanism underlying life-history trade-offs. Of late, there has been much interest in understanding the role of oxidative stress in the ecology of wild animals, particularly during challenging periods such as reproduction.

Optimizing extended-release carbidopa/levodopa in Parkinson disease: Consensus on conversion from standard therapy.

Purpose Of Review: To help clinicians optimize the conversion of a patient's Parkinson disease pharmacotherapy from immediate-release carbidopa/levodopa (IR CD/LD) to an extended-release formulation (ER CD/LD).

Recent Findings: Eleven movement disorders specialists achieved consensus positions on the modification of trial-based conversion guidelines to suit individual patients in clinical practice.

Summary: Because the pharmacokinetics of ER CD/LD differ from those of IR CD/LD, modification of dosage and dosing frequency are to be expected.

The Chemistry of a Non-Interacting Vicinal Frustrated Phosphane/Borane Lewis Pair.

The dimesitylphosphinocyclopentene/HB(C F ) -derived vicinal trans-1,2-P/B frustrated Lewis pair (FLP) 4 shows no direct phosphane-borane interaction. Toward some reagents it behaves similar to an intermolecular FLP; it cleaves dihydrogen, deprotonates terminal alkynes, and adds to organic carbonyl compounds including CO . It shows typical intramolecular FLP reaction modes (cooperative 1,1-additions) to mesityl azide, to carbon monoxide, and to NO.

Aminoxyl Radicals of B/P Frustrated Lewis Pairs: Refinement of the Spin-Hamiltonian Parameters by Field- and Temperature-Dependent Pulsed EPR Spectroscopy.

Q-band and X-band pulsed electron paramagnetic resonance spectroscopic methods (EPR) in the solid state were employed to refine the parameters characterizing the anisotropic interactions present in six nitroxide radicals prepared by N,N addition of NO to various borane-phosphane frustrated Lewis pairs (FLPs). The EPR spectra are characterized by the g-anisotropy as well as by nuclear hyperfine coupling between the unpaired electron and the 11B/10B, 14N and 31P nuclear magnetic moments. It was previously shown that continuous-wave spectra measured at X-band frequency (9.

The Efficacy Profile of Rotigotine During the Waking Hours in Patients With Advanced Parkinson's Disease: A Post Hoc Analysis.

Objectives: Transdermal delivery of rotigotine maintains stable plasma concentrations for 24 hours. Three phase 3 studies of rotigotine as add-on to levodopa in advanced Parkinson's disease showed a significant reduction in "off" time from baseline to end of maintenance (EoM). However, detailed analyses over the range of a day have not yet been performed.

Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials.

Background: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours.

Objective: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting.

Posterior Reversible Encephalopathy Syndrome Secondary to CSF Leak and Intracranial Hypotension: A Case Report and Literature Review.

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical neuroradiological condition characterized by insidious onset of neurological symptoms associated with radiological findings indicating posterior leukoencephalopathy. PRES secondary to cerebrospinal fluid (CSF) leak leading to intracranial hypotension is not well recognized etiology of this condition. Herein, we report a case of PRES that occurred in the setting of CSF leak due to inadvertent dural puncture.

Impact of 6-month earlier versus postponed initiation of rotigotine on long-term outcome: post hoc analysis of patients with early Parkinson's disease with mild symptom severity.

Objective: Investigate impact of 6-month earlier versus postponed initiation of rotigotine in patients with early Parkinson's disease (PD) with mild symptom severity.

Background: Long-term benefit of rotigotine in early-PD has been demonstrated: SP702 (NCT00594165) and SP716 (NCT00599196) were long-term, open-label extensions of double-blind, placebo-controlled studies of 6-month maintenance; rotigotine was well tolerated for up to 6 years, and demonstrated efficacy (Unified Parkinson's Disease Rating Scale [UPDRS] II + III below baseline) for ∼ 2 years (SP702) and ∼ 4 years (SP716).

Methods: Post hoc analysis of patients at Hoehn and Yahr 1-2; groups defined by treatment received in 6-month double-blind studies: 'Rotigotine-Rotigotine' received rotigotine (n = 221), 'Placebo-Rotigotine' received placebo (n = 125).

Solid-state EPR strategies for the structural characterization of paramagnetic NO adducts of frustrated Lewis pairs (FLPs).

Anisotropic interactions present in three new nitroxide radicals prepared by N,N addition of NO to various borane-phosphane frustrated Lewis pairs (FLPs) have been characterized by continuous-wave (cw) and pulsed X-band EPR spectroscopies in solid FLP-hydroxylamine matrices at 100 K. Anisotropic g-tensor values and (11)B, (14)N, and (31)P hyperfine coupling tensor components have been extracted from continuous-wave lineshape analyses, electron spin echo envelope modulation (ESEEM), and hyperfine sublevel correlation spectroscopy (HYSCORE) experiments with the help of computer simulation techniques. Suitable fitting constraints are developed on the basis of density functional theory (DFT) calculations.

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

Importance: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.

Objective: To examine whether CoQ10 could slow disease progression in early PD.

A randomized study of rotigotine dose response on 'off' time in advanced Parkinson's disease.

Background: Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of 'off' time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established.

Objective: This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h.

Rasagiline adjunct therapy in patients with Parkinson's disease: post hoc analyses of the PRESTO and LARGO trials.

Background: Rasagiline was safe and effective when used as adjunct therapy with levodopa in patients with moderate-to-advanced Parkinson's disease (PD) in the phase III PRESTO and LARGO studies.

Objective: To assess clinical effects of rasagiline 1 mg/day on cardinal PD symptoms and motor fluctuations in defined patient subgroups using pooled data from PRESTO and LARGO.

Methods: Both double-blind, randomized, and placebo-controlled studies included PD patients with motor fluctuations despite optimized therapy with levodopa, with or without concomitant dopamine agonists (DA) or catechol-O-methyltransferase inhibitor (COMT-I) treatment.

A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease.

Objective: To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD).

Methods: A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39).

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.

Purpose: This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD).

Methods: Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed.

Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience.

Background: The long-term efficacy of pyridostigmine, a reversible acetyl cholinesterase inhibitor, in the treatment of postural orthostatic tachycardia syndrome (POTS) patients remains unclear. We report our retrospective, single-center, long-term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients.

Methods: This retrospective study included an extensive review of electronic charts and data collection in regards to patient demographics, orthostatic parameters, side-effect profile, subjective response to therapy, as well as laboratory studies recorded at each follow-up visit to our institution's Syncope and Autonomic Disorders Center.