Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Anti-inflammatory Components from Functional Foods for Obesity

Obesity, defined as excessive fat accumulation that may impair health, has been described throughout human history, but it has now reached epidemic proportions with the WHO estimating that 39% of the world’s adults over 18 years of age were overweight or obese in 2016. Obesity is a chronic low-grade inflammatory state leading to organ damage with an increased risk of common diseases including cardiovascular and metabolic disease, non-alcoholic fatty liver disease, osteo-arthritis and some cancers. This inflammatory state may be influenced by adipose tissue hypoxia and changes in the gut microbiota. There has been an increasing focus on functional foods and nutraceuticals as treatment options for obesity as drug treatments are limited in efficacy. This chapter summarises the importance of anthocyanin-containing fruits and vegetables, coffee and its components, tropical fruit and food waste as sources of phytochemicals for obesity treatment. We emphasise that preclinical studies can form the basis for clinical trials to determine the effectiveness of these treatments in humans

Sustainable wineries through waste valorisation: A review of grape marc utilisation for value-added products

Grapes are one of the most cultivated fruits worldwide, with one third of total production used in winemaking. Both red and white winemaking processes result in substantial quantities of solid organic waste, such as grape marc (pomace) and stalks, which requires suitable disposal. Grape marc accounts for approximately 10-30% of the mass of grapes crushed and contains unfermented sugars, alcohol, polyphenols, tannins, pigments, and other valuable products. Being a natural plant product rich in lignocellulosic compounds, grape marc is also a promising feedstock for renewable energy production. However, despite grape marc having such potential, advanced technologies to exploit this have not been widely adopted in wineries and allied industries. This review covers opportunities beyond traditional composting and animal feed, and examines value-added uses via the extraction of useful components from grape marc, as well as thermochemical and biological treatments for energy recovery, fuel or beverage alcohol production, and specialty novel products and applications such as biosurfactants and environmental remediation. New advances in relevant technology for each of these processes are discussed, and future directions proposed at both individual producer and regional facility scales, including advanced processing techniques for integrated ethanol production followed by bioenergy generation from the spent marc.Richard A. Muhlack, Ravichandra Potumarthi, David W. Jeffer

Models for predicting wine fermentation kinetics

Fermentation of grape juice by yeast is a critical stage in industrial wine production. However, the kinetics of the process are poorly understood due to the extreme conditions present during such fermentations. Problematic fermentations occur regularly and result in significant cost as a result of wasted tank capacity and low value of the final degraded product. Control of the fermentation process is important to avoid 'stuck fermentations' (a stuck fermentation is a fermentation that has stopped before all the available sugar in the wine has been converted to alcohol and CO2) and clearly, the fermentation unit operation strongly influences the aesthetic endcharacteristics of the wine. A variety of models have been proposed to predict the dynamic behaviour (kinetics) of the process. Two traditional and simple biochemical models (Monod kinetics and the Gompertz model) are predominantly employed and these were investigated in this work. The primary aim of this study was to determine the ability of both models to predict fermentation behaviour when fitted to data from early stages of fermentation. Initially, the Monod and Gompertz models were fitted to sugar consumption data for laboratory scale wine fermentations using least squares regression. The model produced a reasonable qualitative fit for the kinetic (growth and production) data with a root-mean-squared error (RMS) of 21 g/L or less in each case. Both models were then fitted to sugar consumption data from twenty two industrial fermentations over a varying number of time steps following the initial measurement in each data set. The number of time steps required to produce an RMS error less than 20 g/L was 8 days in 19 cases using the Monod model. However, the Gompertz model (successful in 18 cases) generally required 2 – 4 fewer time steps (days). No correlation was found between the number of time steps required or the regressed parameters and the volume of fermentation. The values of the regressed Monod parameters maximum growth rate (μm), the Monod constant (KS) and the yield coefficient (YX/S) lay between 0.1 – 1.0 day-1, 200 – 1000 g/L and 0.01 – 0.10 g cell X/g substrate (assumed to be sugar content) S in most cases, with deviations loosely correlated to the use of Semillon grapes. Both models exhibited promise for use in industry alongside traditional winemaking techniques, depending upon the specific goals and requirements of each individual winery. Rigorous error analysis was not possible due to a lack of supplied experimental uncertainty data and this will be investigated in future work.Brian O'Neill, Torbjorn van Heeswijck and Richard Muhlackhttp://www.chemeca2011.com

Gasification of grape marc in a circulating fluidised bed

Philip J. van Eyk, Richard A. Muhlack and Peter J. Ashmanhttp://www.mech.uq.edu.au/conferences/ACS2009/index.ht

Modelling the mass transfer process of malvidin-3-glucoside during simulated extraction from fresh grape solids under wine-like conditions

Extraction of grape components is a key consideration for red winemaking. The impact of changing process variables on mass transfer properties of anthocyanins from fresh pre-fermentative red grape solids under forced convective conditions was explored using the dominant red grape anthocyanin, malvidin-3-glucoside (M3G) as a model solute. A two level full factorial design was implemented to investigate effects of temperature, sugar and ethanol on mass transfer properties. Factor levels were chosen to simulate conditions found at various points during the maceration and fermentation steps of the red winemaking process. A rigorous mathematical model was developed and applied to experimental extraction curves, allowing the separation of mass transport properties in liquid and solid phases in a wine-like system, for the first time. In all cases, the coefficient of determination exceeded 0.92, indicating good agreement between experimental and mathematically-solved M3G concentrations. For the conditions studied, internal mass transfer was found to limit M3G extraction and changes to the liquid phase composition and temperature influence the distribution constant. Surface response models of mass transfer parameters were developed to allow future simulations of fermentation scenarios aimed at maximising the extraction potential of M3G.Patrick C. Setford, David W. Jeffery, Paul R. Grbin and Richard A. Muhlac

Factors affecting extraction and evolution of phenolic compounds during red wine maceration and the role of process modelling

Background, The overall quality of red wine is well known to be influenced markedly by various phenolic compounds that are extracted from the grape solids during maceration. The concentration and composition of phenolics then impact the flavour and mouthfeel of wines. Scope and Approach, This review analyses the available literature on specific process variables that influence the diffusive mass transfer and evolution of phenolic compounds during red wine maceration. These variables are discussed in terms of techniques and strategies used by winemakers to influence the extractive behaviour of phenolic compounds and control their concentration in the finished wine. Mathematical models used to describe extraction and evolution phenomena in wine are also examined and the potential for future models to predict phenolic behaviour is discussed. Key Findings and Conclusions, The impact of various winemaking techniques aimed at improving the extraction of phenolic compounds during red winemaking, as well as the subsequent reactions that take place following extraction, are qualitatively well understood. Mathematically, many of these techniques can be described in terms of their changing process variables such as temperature, solvent conditions and sold-liquid contact. Despite this, non-steady state models for mass transport or reaction kinetics of phenolic compounds in wine fermentation are currently unavailable in published literature. Further research into the production of global models capable of accurately describing this behaviour would be a significant advancement for industry and would aid in the development of adaptive process control technologies for red wine phenolic composition.Patrick C. Setford, David W. Jeffery, Paul R. Grbin and Richard A. Muhlac