The problems associated with the pharmacological treatment of the later stages of Parkinson’s disease(PD)remain those seen over many years.These centre on a loss of drug effect(‘wearing off’)with disease progressio...The problems associated with the pharmacological treatment of the later stages of Parkinson’s disease(PD)remain those seen over many years.These centre on a loss of drug effect(‘wearing off’)with disease progression,the occurrence of dyskinesia,notably with L-dopa use and the appearance of non-motor symptoms that are largely refractory to dopaminergic medication.Treatment strategies in late PD have been dominated by the use of drug combinations and the subtle manipulation of drug dosage.However,change is occurring as the understanding of the basis of motor complications and fluctuations and non-motor symptoms improves.New pharmacological options are expanding with the advent of longer acting versions of existing dopaminergic drugs,new drug delivery systems and the introduction of non-dopaminergic agents able to manipulate motor function both within the basal ganglia and in other brain regions.Non-dopaminergic agents are also being investigated for the treatment of dyskinesia and for the relief of non-motor symptoms.However,while therapy continues to improve,the treatment of late stage PD remains problematic with non-motor symptoms dominating the unmet need in this patient group.展开更多
Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations...Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations,while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD.All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of‘OFF’periods.However,data suggest that despite their efficacy in reducing the number and duration of‘OFF’periods,these strategies still do not prevent‘OFF’periods in the middle to late stages of PD,thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation.Why these emergent‘OFF’periods still occur is unknown.In this review,we analyse the potential reasons for their persistence.The contribution of drug-and device-related involvement,and the problems related to site-specific drug delivery are analysed.We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent‘OFF’periods unresponsive to dopaminergic therapy delivered via CDD.展开更多
Social innovation(SI)continues to raise interest among scholars and policymakers,as a potential panacea for social disenfranchisement and civic dysfunction.What is troubling is diverse perspectives of SI abound,creati...Social innovation(SI)continues to raise interest among scholars and policymakers,as a potential panacea for social disenfranchisement and civic dysfunction.What is troubling is diverse perspectives of SI abound,creating inconsistencies in methodological approaches which confound theory development.This paper clarifies that discussion by considering the locus of initiation and locus of benefit as informing characteristics that differentiate grounded social innovation from other types of well-recognized socially beneficent endeavors.The notion of‘from community e for community’is presented to aid understanding of the unique nature of authentically grounded social innovation.This paper is significant as it presents a practical approach to help researchers and practitioners consider where opportunities for targeted policy support,institutional involvement,and agency action can aid community development and wellbeing.展开更多
文摘The problems associated with the pharmacological treatment of the later stages of Parkinson’s disease(PD)remain those seen over many years.These centre on a loss of drug effect(‘wearing off’)with disease progression,the occurrence of dyskinesia,notably with L-dopa use and the appearance of non-motor symptoms that are largely refractory to dopaminergic medication.Treatment strategies in late PD have been dominated by the use of drug combinations and the subtle manipulation of drug dosage.However,change is occurring as the understanding of the basis of motor complications and fluctuations and non-motor symptoms improves.New pharmacological options are expanding with the advent of longer acting versions of existing dopaminergic drugs,new drug delivery systems and the introduction of non-dopaminergic agents able to manipulate motor function both within the basal ganglia and in other brain regions.Non-dopaminergic agents are also being investigated for the treatment of dyskinesia and for the relief of non-motor symptoms.However,while therapy continues to improve,the treatment of late stage PD remains problematic with non-motor symptoms dominating the unmet need in this patient group.
文摘Continuous drug delivery(CDD)is used in moderately advanced and late-stage Parkinson’s disease(PD)to control motor and non-motor fluctuations(‘OFF’periods).Transdermal rotigotine is indicated for early fluctuations,while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD.All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD.A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of‘OFF’periods.However,data suggest that despite their efficacy in reducing the number and duration of‘OFF’periods,these strategies still do not prevent‘OFF’periods in the middle to late stages of PD,thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation.Why these emergent‘OFF’periods still occur is unknown.In this review,we analyse the potential reasons for their persistence.The contribution of drug-and device-related involvement,and the problems related to site-specific drug delivery are analysed.We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent‘OFF’periods unresponsive to dopaminergic therapy delivered via CDD.
文摘Social innovation(SI)continues to raise interest among scholars and policymakers,as a potential panacea for social disenfranchisement and civic dysfunction.What is troubling is diverse perspectives of SI abound,creating inconsistencies in methodological approaches which confound theory development.This paper clarifies that discussion by considering the locus of initiation and locus of benefit as informing characteristics that differentiate grounded social innovation from other types of well-recognized socially beneficent endeavors.The notion of‘from community e for community’is presented to aid understanding of the unique nature of authentically grounded social innovation.This paper is significant as it presents a practical approach to help researchers and practitioners consider where opportunities for targeted policy support,institutional involvement,and agency action can aid community development and wellbeing.
