Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis

This is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. METHODS: We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. RESULTS: Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. CONCLUSION: These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications.Funding: Medtronic funded the development of the model, including consulting fees to physicians and health economic specialists, sponsored a medical writer and reviewed the manuscript. The funders provided input on the study design, decision to publish, and preparation of the manuscript. HTA Consulting provided support in the form of salaries for authors [TF], and staff resources to support evidence review and synthesis. They did not have any additional role in the study design and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section

Funding sustainable mobility and liveability: are the current scheme appraisal procedures appropriate?

The CREATE project is concerned with transport policies in cities and how these have evolved over time in response to changing challenges and priorities. In particular it examines how cities have succeeded in limiting the growth and extent of road traffic congestion by reducing reliance on the private car for day-to-day mobility. One of the project's propositions is the existence of a 3-Stage “Transport Policy Evolution Cycle” spread over 50+ years, which gradually shifts the policy emphasis and investments priorities from catering for road traffic growth to building a liveable and healthy city, through developing streets as ‘places’. This report identifies how 'Stage 3' cities assess the benefits of their major transport initiatives in terms the city policy objectives, looking at a set of 10 relevant impacts: number/length of trips made, trip quality,time use in transport, personal security, street liveability, time spent in places, health/wellbeing, community severance, equity/social inclusion, and visual blight. We then focus on how 'Stage 1' and 'Stage 3' cities make investment decisions to prioritise the deployment of sustainability measures and then fund and finance their development Master Plans

Designing Engaging Learning Experiences in Programming

In this paper we describe work to investigate the creation of engaging programming learning experiences. Background research informed the design of four fieldwork studies to explore how programming tasks could be framed to motivate learners. Our empirical findings from these four field studies are summarized here, with a particular focus upon one – Whack a Mole – which compared the use of a physical interface with the use of a screen-based equivalent interface to obtain insights into what made for an engaging learning experience. Emotions reported by two sets of participant undergraduate students were analyzed, identifying the links between the emotions experienced during programming and their origin. Evidence was collected of the very positive emotions experienced by learners programming with a physical interface (Arduino) in comparison with a similar program developed using a screen-based equivalent interface. A follow-up study provided further evidence of the motivation of personalized design of programming tangible physical artefacts. Collating all the evidence led to the design of a set of ‘Learning Dimensions’ which may provide educators with insights to support key design decisions for the creation of engaging programming learning experiences

Quantum theory's last challenge

Quantum mechanics is now 100 years old and still going strong. Combining general relativity with quantum mechanics is the last hurdle to be overcome in the "quantum revolution".Comment: (9 pages, LaTex) This is the preprint version of an article that appeared in the issue 6813 (volume 408) of Nature, as part of a 3-article celebration of the 100th anniversary of Planck's solution of the black-body-radiation proble

A phenomenological description of quantum-gravity-induced space-time noise

I propose a phenomenological description of space-time foam and discuss the experimental limits that are within reach of forthcoming experiments.Comment: 10 pages, LaTex, 1 figure. Short paper, omitting most technical details. More detailed analysis was reported in gr-qc/010400

A Trial Installation of High Voltage Composite Cross-arms

Four high voltage composite cross-arms have been installed as part of a non-energised trial taking place in the Scottish Highlands. The non-cylindrical geometry of their two main structural members offers improved mechanical strength-to-weight ratio compared to cylindrically-shaped insulators of similar cross-sectional area. The instrumentation system aims to monitor mechanical performance through the use of embedded strain gauges and a combination of a load cell, accelerometer and inclinometer at the cross-arm nose. An industrial data capture and control platform is used to capture sensor outputs and store them until retrieval. Networked cameras with local storage capabilities are used to capture video recordings of the cross-arms. The trial has helped establish handling, transportation and installation procedures. The first results from the instrumentation system indicate the resilience of the cross-arms to winds reaching up to 151 mph (243 km/h) while no irregularities regarding snow and ice accretion have been observed

Rapid generation of chromosome-specific alphoid DNA probes using the polymerase chain reaction

Non-isotopic in situ hybridization of chromosome-specific alphoid DNA probes has become a potent tool in the study of numerical aberrations of specific human chromosomes at all stages of the cell cycle. In this paper, we describe approaches for the rapid generation of such probes using the polymerase chain reaction (PCR), and demonstrate their chromosome specificity by fluorescence in situ hybridization to normal human metaphase spreads and interphase nuclei. Oligonucleotide primers for conserved regions of the alpha satellite monomer were used to generate chromosome-specific DNA probes from somatic hybrid cells containing various human chromosomes, and from DNA libraries from sorted human chromosomes. Oligonucleotide primers for chromosome-specific regions of the alpha satellite monomer were used to generate specific DNA probes for the pericentromeric heterochromatin of human chromosomes 1, 6, 7, 17 and X directly from human genomic DNA

Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace