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)

The Impact of Strategy to Real Time Chat Process : A Qualitative Multi-Method Study in the E-commerce Context

While retail e-commerce keeps on clicking the examination of its strategic business and operations requirements for success emerges as crucial. In terms of achieving competitive advantage, no longer is it sustainable for e-retailers to solely focus on traditional dimensions of providing high quality and low cost for their target customers. As a substitute, they must adapt to the ever-changing competitive environment by endowing customers novel ways to interact with the website before, during and after the purchasing decision. One such way is real time chat, which is quickly becoming one of the most desired methods of contact between customers and websites. Although many e-retailers acknowledge the relevance of real time human-to-human contact, and the utilization of the real time chat in enriching the websites and consumers’ shopping experiences, the strategic and operational value that chat generates to the business itself it is still not explored by academic scholars.This forms the basis for our study.Purpose –This thesis aims to describe and explain the main business and operations strategies that determine the design of real time chat in B2C e-commerce companies. The paper used models and theories from strategic management namely strategic orientation, and strategic typologies. CSFs were derived from combining concepts from strategy, operations management, information systems and e-commerce disciplines while service delivery systems literature from service operations management literature. Design/methodology/approach–Using anabductive approach a cross-sectional study was conducted using a qualitative multi-methodology. The data was collected through semi-structured interviews with four B2C e-commerce firms from the Nordic and Western European regions. Further, the data collection was enriched through observation and document analysis using real time chat logs. The data was then analyzed using the theoretical frame of reference to provide a strong theoretical base for our findings.Findings–The study established links between strategy, operations and service delivery systems with respect to real time chat. Particularly the combination of orientation with the Miles &amp; Snow model (1978) informed the various strategic options a firm has. Furthermore, when combined with the perspectives on operationsstrategy informed how real time chat can be used while also taking into consideration the resources, product category and industry of the firm. The derived e-commerce service operations strategy CSFs despite being unique for each of the studied firms showed three recurring factors that were common to them. These were service provision, customer acceptance/focus and flexibility. Synthesizing all perspectives helped in developing a model that provides an overview of B2C e-commerce firms can align strategy, operations and service delivery systems with respect to real time chat. Originality/value–The thesis contributes to adding knowledge to the under researched area of real time chat in B2C e-commerce settings. It also synthesizes disparate concepts of strategy, operations and service delivery systems and develops a guideline in helping firms using real time chat to improve their existing service process efficiencies. Concurrently the paper also serves as an evaluative tool for firms that are considering real time chat implementation to understand the various aspects that influence it and help them to better plan and design the service process

The Impact of Strategy to Real Time Chat Process : A Qualitative Multi-Method Study in the E-commerce Context

While retail e-commerce keeps on clicking the examination of its strategic business and operations requirements for success emerges as crucial. In terms of achieving competitive advantage, no longer is it sustainable for e-retailers to solely focus on traditional dimensions of providing high quality and low cost for their target customers. As a substitute, they must adapt to the ever-changing competitive environment by endowing customers novel ways to interact with the website before, during and after the purchasing decision. One such way is real time chat, which is quickly becoming one of the most desired methods of contact between customers and websites. Although many e-retailers acknowledge the relevance of real time human-to-human contact, and the utilization of the real time chat in enriching the websites and consumers’ shopping experiences, the strategic and operational value that chat generates to the business itself it is still not explored by academic scholars.This forms the basis for our study.Purpose –This thesis aims to describe and explain the main business and operations strategies that determine the design of real time chat in B2C e-commerce companies. The paper used models and theories from strategic management namely strategic orientation, and strategic typologies. CSFs were derived from combining concepts from strategy, operations management, information systems and e-commerce disciplines while service delivery systems literature from service operations management literature. Design/methodology/approach–Using anabductive approach a cross-sectional study was conducted using a qualitative multi-methodology. The data was collected through semi-structured interviews with four B2C e-commerce firms from the Nordic and Western European regions. Further, the data collection was enriched through observation and document analysis using real time chat logs. The data was then analyzed using the theoretical frame of reference to provide a strong theoretical base for our findings.Findings–The study established links between strategy, operations and service delivery systems with respect to real time chat. Particularly the combination of orientation with the Miles &amp; Snow model (1978) informed the various strategic options a firm has. Furthermore, when combined with the perspectives on operationsstrategy informed how real time chat can be used while also taking into consideration the resources, product category and industry of the firm. The derived e-commerce service operations strategy CSFs despite being unique for each of the studied firms showed three recurring factors that were common to them. These were service provision, customer acceptance/focus and flexibility. Synthesizing all perspectives helped in developing a model that provides an overview of B2C e-commerce firms can align strategy, operations and service delivery systems with respect to real time chat. Originality/value–The thesis contributes to adding knowledge to the under researched area of real time chat in B2C e-commerce settings. It also synthesizes disparate concepts of strategy, operations and service delivery systems and develops a guideline in helping firms using real time chat to improve their existing service process efficiencies. Concurrently the paper also serves as an evaluative tool for firms that are considering real time chat implementation to understand the various aspects that influence it and help them to better plan and design the service process

Fluoride in the Environment and Its Metabolism in Humans

Not AvailableFluorine is widely dispersed in nature and is estimated to be the 13th most abundant element on our planet (Mason and Moore 1982). It is the most electronegative of all chemical elements, and as a result, it never exists in elemental form, but rather combines with other elements; fluoride compounds represent about 0.06–0.09% of the content of the earth’s crust (Wedephol 1974). Fluoride is distributed universally throughout soils, plants, and animals, and is assumed to be an essential element in animals, including humans. Fluoride has an important role in bone mineralization and formation of dental enamels. Fluoride, when consumed in inadequate quantities (less than 0.5 ppm), causes health problems such as dental caries, lack of formation of dental enamel, and reduced bone mineralization, especially among children (WHO 1996). In contrast, when fluoride is consumed in excess (more than 1 ppm), health problems may result, which equally affect the young and old (WHO 1996). At higher fluoride concentrations, metabolic processes are affected in humans, and overexposed individuals may suffer from skeletal or dental fluorosis, non-skeletal manifestations, or combinations of these maladies (Susheela et al. 1993). The incidence and severity of fluorosis depends upon the fluoride concentration in air, soil or water, and the degree of exposure to these levels.Not Availabl

Not Available

Not AvailableFluorine is widely dispersed in nature and is estimated to be the 13th most abundant element on our planet (Mason and Moore 1982). It is the most electronegative of all chemical elements, and as a result, it never exists in elemental form, but rather combines with other elements; fluoride compounds represent about 0.06–0.09% of the content of the earth’s crust (Wedephol 1974). Fluoride is distributed universally throughout soils, plants, and animals, and is assumed to be an essential element in animals, including humans. Fluoride has an important role in bone mineralization and formation of dental enamels. Fluoride, when consumed in inadequate quantities (less than 0.5 ppm), causes health problems such as dental caries, lack of formation of dental enamel, and reduced bone mineralization, especially among children (WHO 1996). In contrast, when fluoride is consumed in excess (more than 1 ppm), health problems may result, which equally affect the young and old (WHO 1996). At higher fluoride concentrations, metabolic processes are affected in humans, and overexposed individuals may suffer from skeletal or dental fluorosis, non-skeletal manifestations, or combinations of these maladies (Susheela et al. 1993). The incidence and severity of fluorosis depends upon the fluoride concentration in air, soil or water, and the degree of exposure to these levels.Not Availabl