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1.  Parkinson's Impulse‐Control Scale for the Severity Rating of Impulse‐Control Behaviors in Parkinson's Disease: A Semistructured Clinical Assessment Tool 
Abstract
Background
Impulse‐control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug‐related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician‐rated severity scale for the assessment of syndromal and subsyndromal forms of impulse‐control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome).
Methods
The Parkinson's Impulse‐Control Scale (PICS), the first PD‐specific, semistructured interview to cover the full range of PD‐related ICBs, is described along with initial evidence on its clinimetric properties including interrater reliability, discriminant validity and sensitivity to change. A convenience sample of PD patients with ICBs and those without were administered a semistructured interview (n = 92).
Results
The scale distinguished between those with and without clinically detected ICBs and between patients with syndromal ICD and subsyndromal ICB (receiver operating characteristic areas under the curve, 92%–95%). Cutoff values were suggested, and substantial agreement was reported on weighted kappa (Κ) values for clinician‐clinician rating of severity (Κ = 0.92). Significant improvements were detected on the scale after a randomized controlled trial of cognitive‐behavioral therapy and medication adjustment (t[22] = 5.47; P < 0.001).
Conclusions
The PICS appears to be a reliable measure of the full range of PD ICBs with good levels of interrater reliability. It may provide a useful measure to assess the severity of ICBs and monitor change in clinical and research settings; although, given the specialized centers used for recruitment of this sample, further psychometric evaluation is required.
doi:10.1002/mdc3.12316
PMCID: PMC5053221  PMID: 27774496
impulse‐control disorder; Parkinson's disease; severity; rating; carer
2.  A pharmacoeconomic approach to assessing the costs and benefits of air quality interventions that improve health: a case study 
BMJ Open  2016;6(6):e010686.
Objective
This paper explores the use of pharmacoeconomic methods of valuation to health impacts resulting from exposure to poor air quality. In using such methods, interventions that reduce exposure to poor air quality can be directly compared, in terms of value for money (or cost-effectiveness), with competing demands for finite resources, including other public health interventions.
Design
Using results estimated as part of a health impact assessment regarding a West Yorkshire Low Emission Zone strategy, this paper quantifies cost-saving and health-improving implications of transport policy through its impact on air quality.
Data source
Estimates of health-related quality of life and the National Health Service (NHS)/Personal Social Services (PSS) costs for identified health events were based on data from Leeds and Bradford using peer-reviewed publications or Office for National Statistics releases.
Population
Inhabitants of the area within the outer ring roads of Leeds and Bradford.
Main outcomes measures
NHS and PSS costs and quality-adjusted life years (QALYs).
Results
Averting an all-cause mortality death generates 8.4 QALYs. Each coronary event avoided saves £28 000 in NHS/PSS costs and generates 1.1 QALYs. For every fewer case of childhood asthma, there will be NHS/PSS cost saving of £3000 and a health benefit of 0.9 QALYs. A single term, low birthweight birth avoided saves £2000 in NHS/PSS costs. Preventing a preterm birth saves £24 000 in NHS/PSS costs and generates 1.3 QALYs. A scenario modelled in the West Yorkshire Low Emission Zone Feasibility Study, where pre-EURO 4 buses and HGVs are upgraded to EURO 6 by 2016 generates an annual benefit of £2.08 million and a one-off benefit of £3.3 million compared with a net present value cost of implementation of £6.3 million.
Conclusions
Interventions to improve air quality and health should be evaluated and where improvement of population health is the primary objective, cost-effectiveness analysis using a NHS/PSS costs and QALYs framework is an appropriate methodology.
doi:10.1136/bmjopen-2015-010686
PMCID: PMC4916570  PMID: 27329439
4.  Predicting outcomes after blunt chest wall trauma: development and external validation of a new prognostic model 
Critical Care  2014;18(3):R98.
Introduction
Blunt chest wall trauma accounts for over 15% of all trauma admissions to Emergency Departments worldwide. Reported mortality rates vary between 4 and 60%. Management of this patient group is challenging as a result of the delayed on-set of complications. The aim of this study was to develop and validate a prognostic model that can be used to assist in the management of blunt chest wall trauma.
Methods
There were two distinct phases to the overall study; the development and the validation phases. In the first study phase, the prognostic model was developed through the retrospective analysis of all blunt chest wall trauma patients (n = 274) presenting to the Emergency Department of a regional trauma centre in Wales (2009 to 2011). Multivariable logistic regression was used to develop the model and identify the significant predictors for the development of complications. The model’s accuracy and predictive capabilities were assessed. In the second study phase, external validation of the model was completed in a multi-centre prospective study (n = 237) in 2012. The model’s accuracy and predictive capabilities were re-assessed for the validation sample. A risk score was developed for use in the clinical setting.
Results
Significant predictors of the development of complications were age, number of rib fractures, chronic lung disease, use of pre-injury anticoagulants and oxygen saturation levels. The final model demonstrated an excellent c-index of 0.96 (95% confidence intervals: 0.93 to 0.98).
Conclusions
In our two phase study, we have developed and validated a prognostic model that can be used to assist in the management of blunt chest wall trauma patients. The final risk score provides the clinician with the probability of the development of complications for each individual patient.
doi:10.1186/cc13873
PMCID: PMC4095687  PMID: 24887537
5.  Trial of CBT for impulse control behaviors affecting Parkinson patients and their caregivers 
Neurology  2013;80(9):792-799.
Objective:
To test the effects of a novel cognitive-behavioral therapy (CBT)–based intervention delivered by a nurse therapist to patients with Parkinson disease (PD) with clinically significant impulse control behaviors (ICB).
Methods:
This was a randomized controlled trial comparing up to 12 sessions of a CBT-based intervention compared to a waiting list control condition with standard medical care (SMC). A total of 27 patients were randomized to the intervention and 17 to the waiting list. Patients with a Mini-Mental State Examination score of <24 were excluded. The coprimary outcomes were overall symptom severity and neuropsychiatric disturbances in the patients and carer burden and distress after 6 months. Secondary outcome measures included depression and anxiety, marital satisfaction, and work and social adjustment in patients plus general psychiatric morbidity and marital satisfaction in carers.
Results:
There was a significant improvement in global symptom severity in the CBT intervention group vs controls, from a mean score consistent with moderate to one of mild illness-related symptoms (χ2 = 16.46, p < 0.001). Neuropsychiatric disturbances also improved significantly (p = 0.03), as did levels of anxiety and depression and adjustment. Measures of carer burden and distress showed changes in the desired direction in the intervention group but did not change significantly. General psychiatric morbidity did improve significantly in the carers of patients given CBT.
Conclusions:
This CBT-based intervention is the first to show efficacy in ICB related to PD in terms of patient outcomes. The hoped-for alleviation of carer burden was not observed. The study demonstrates the feasibility and potential benefit of a psychosocial treatment approach for these disturbances at least in the short term, and encourages further larger-scale clinical trials.
Classification of evidence:
The study provides Class IV evidence that CBT plus SMC is more effective than SMC alone in reducing the severity of ICB in PD, based upon Clinical Global Impression assessment (χ2 = 16.46, p < 0.001): baseline to 6-month follow-up, reduction in symptom severity CBT group, 4.0–2.5; SMC alone group, 3.7–3.5.
doi:10.1212/WNL.0b013e3182840678
PMCID: PMC3598451  PMID: 23325911
6.  The DNA sequence of the human X chromosome 
Ross, Mark T. | Grafham, Darren V. | Coffey, Alison J. | Scherer, Steven | McLay, Kirsten | Muzny, Donna | Platzer, Matthias | Howell, Gareth R. | Burrows, Christine | Bird, Christine P. | Frankish, Adam | Lovell, Frances L. | Howe, Kevin L. | Ashurst, Jennifer L. | Fulton, Robert S. | Sudbrak, Ralf | Wen, Gaiping | Jones, Matthew C. | Hurles, Matthew E. | Andrews, T. Daniel | Scott, Carol E. | Searle, Stephen | Ramser, Juliane | Whittaker, Adam | Deadman, Rebecca | Carter, Nigel P. | Hunt, Sarah E. | Chen, Rui | Cree, Andrew | Gunaratne, Preethi | Havlak, Paul | Hodgson, Anne | Metzker, Michael L. | Richards, Stephen | Scott, Graham | Steffen, David | Sodergren, Erica | Wheeler, David A. | Worley, Kim C. | Ainscough, Rachael | Ambrose, Kerrie D. | Ansari-Lari, M. Ali | Aradhya, Swaroop | Ashwell, Robert I. S. | Babbage, Anne K. | Bagguley, Claire L. | Ballabio, Andrea | Banerjee, Ruby | Barker, Gary E. | Barlow, Karen F. | Barrett, Ian P. | Bates, Karen N. | Beare, David M. | Beasley, Helen | Beasley, Oliver | Beck, Alfred | Bethel, Graeme | Blechschmidt, Karin | Brady, Nicola | Bray-Allen, Sarah | Bridgeman, Anne M. | Brown, Andrew J. | Brown, Mary J. | Bonnin, David | Bruford, Elspeth A. | Buhay, Christian | Burch, Paula | Burford, Deborah | Burgess, Joanne | Burrill, Wayne | Burton, John | Bye, Jackie M. | Carder, Carol | Carrel, Laura | Chako, Joseph | Chapman, Joanne C. | Chavez, Dean | Chen, Ellson | Chen, Guan | Chen, Yuan | Chen, Zhijian | Chinault, Craig | Ciccodicola, Alfredo | Clark, Sue Y. | Clarke, Graham | Clee, Chris M. | Clegg, Sheila | Clerc-Blankenburg, Kerstin | Clifford, Karen | Cobley, Vicky | Cole, Charlotte G. | Conquer, Jen S. | Corby, Nicole | Connor, Richard E. | David, Robert | Davies, Joy | Davis, Clay | Davis, John | Delgado, Oliver | DeShazo, Denise | Dhami, Pawandeep | Ding, Yan | Dinh, Huyen | Dodsworth, Steve | Draper, Heather | Dugan-Rocha, Shannon | Dunham, Andrew | Dunn, Matthew | Durbin, K. James | Dutta, Ireena | Eades, Tamsin | Ellwood, Matthew | Emery-Cohen, Alexandra | Errington, Helen | Evans, Kathryn L. | Faulkner, Louisa | Francis, Fiona | Frankland, John | Fraser, Audrey E. | Galgoczy, Petra | Gilbert, James | Gill, Rachel | Glöckner, Gernot | Gregory, Simon G. | Gribble, Susan | Griffiths, Coline | Grocock, Russell | Gu, Yanghong | Gwilliam, Rhian | Hamilton, Cerissa | Hart, Elizabeth A. | Hawes, Alicia | Heath, Paul D. | Heitmann, Katja | Hennig, Steffen | Hernandez, Judith | Hinzmann, Bernd | Ho, Sarah | Hoffs, Michael | Howden, Phillip J. | Huckle, Elizabeth J. | Hume, Jennifer | Hunt, Paul J. | Hunt, Adrienne R. | Isherwood, Judith | Jacob, Leni | Johnson, David | Jones, Sally | de Jong, Pieter J. | Joseph, Shirin S. | Keenan, Stephen | Kelly, Susan | Kershaw, Joanne K. | Khan, Ziad | Kioschis, Petra | Klages, Sven | Knights, Andrew J. | Kosiura, Anna | Kovar-Smith, Christie | Laird, Gavin K. | Langford, Cordelia | Lawlor, Stephanie | Leversha, Margaret | Lewis, Lora | Liu, Wen | Lloyd, Christine | Lloyd, David M. | Loulseged, Hermela | Loveland, Jane E. | Lovell, Jamieson D. | Lozado, Ryan | Lu, Jing | Lyne, Rachael | Ma, Jie | Maheshwari, Manjula | Matthews, Lucy H. | McDowall, Jennifer | McLaren, Stuart | McMurray, Amanda | Meidl, Patrick | Meitinger, Thomas | Milne, Sarah | Miner, George | Mistry, Shailesh L. | Morgan, Margaret | Morris, Sidney | Müller, Ines | Mullikin, James C. | Nguyen, Ngoc | Nordsiek, Gabriele | Nyakatura, Gerald | O’Dell, Christopher N. | Okwuonu, Geoffery | Palmer, Sophie | Pandian, Richard | Parker, David | Parrish, Julia | Pasternak, Shiran | Patel, Dina | Pearce, Alex V. | Pearson, Danita M. | Pelan, Sarah E. | Perez, Lesette | Porter, Keith M. | Ramsey, Yvonne | Reichwald, Kathrin | Rhodes, Susan | Ridler, Kerry A. | Schlessinger, David | Schueler, Mary G. | Sehra, Harminder K. | Shaw-Smith, Charles | Shen, Hua | Sheridan, Elizabeth M. | Shownkeen, Ratna | Skuce, Carl D. | Smith, Michelle L. | Sotheran, Elizabeth C. | Steingruber, Helen E. | Steward, Charles A. | Storey, Roy | Swann, R. Mark | Swarbreck, David | Tabor, Paul E. | Taudien, Stefan | Taylor, Tineace | Teague, Brian | Thomas, Karen | Thorpe, Andrea | Timms, Kirsten | Tracey, Alan | Trevanion, Steve | Tromans, Anthony C. | d’Urso, Michele | Verduzco, Daniel | Villasana, Donna | Waldron, Lenee | Wall, Melanie | Wang, Qiaoyan | Warren, James | Warry, Georgina L. | Wei, Xuehong | West, Anthony | Whitehead, Siobhan L. | Whiteley, Mathew N. | Wilkinson, Jane E. | Willey, David L. | Williams, Gabrielle | Williams, Leanne | Williamson, Angela | Williamson, Helen | Wilming, Laurens | Woodmansey, Rebecca L. | Wray, Paul W. | Yen, Jennifer | Zhang, Jingkun | Zhou, Jianling | Zoghbi, Huda | Zorilla, Sara | Buck, David | Reinhardt, Richard | Poustka, Annemarie | Rosenthal, André | Lehrach, Hans | Meindl, Alfons | Minx, Patrick J. | Hillier, LaDeana W. | Willard, Huntington F. | Wilson, Richard K. | Waterston, Robert H. | Rice, Catherine M. | Vaudin, Mark | Coulson, Alan | Nelson, David L. | Weinstock, George | Sulston, John E. | Durbin, Richard | Hubbard, Tim | Gibbs, Richard A. | Beck, Stephan | Rogers, Jane | Bentley, David R.
Nature  2005;434(7031):325-337.
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
doi:10.1038/nature03440
PMCID: PMC2665286  PMID: 15772651
7.  An evaluation of a multidisciplinary team for intermediate care at home 
Abstract
Background
The implementation of the National Health Service Plan for the UK will see an expansion of services for intermediate care. Such services are usually targeted at older people and aim to: prevent ‘avoidable’ admissions to acute inpatient care; facilitate the timely discharge of patients from acute inpatient care; promote patient rehabilitation. A range of services might fall under the banner of intermediate care. They are usually delivered in patients' homes or in non-acute institutions. This paper describes an evaluation of a multidisciplinary Rapid Response Team (RRT). This service aimed to provide a home based alternative to care previously provided in an acute hospital bed which was acceptable to patients and carers and which maintained clinical care standards. The service was provided for the population of Hereford, a rural town in the middle of England.
Methods
A mixed-method descriptive design using quantitative and qualitative techniques was used to monitor: the characteristics of service users, the types and amounts of care received, any ‘adverse’ events arising from that care, and the acceptability of the service to patients and carers. A collaborative approach involving key stakeholders allowed appropriate data to be gathered from patient case notes, RRT staff, local health and social care providers, and patients and their carers. A suite of self-completed questionnaires was, therefore, designed to capture study data on patients and activities of care, and workshops and semi-structured interview schedules used to obtain feedback from users and stakeholders.
Results
Service users (231) were elderly (mean age 75.9), from three main diagnostic categories (respiratory conditions 19.0%, heart/stroke 16.2%, falls 13.4%), with the majority (57.0%) having both medical and social care needs. All patients received care at home (mean duration 5.6 days) with only 5.7% of patients having to be re-admitted to acute care. Overall, patients and carers had positive attitudes to the new service but some expressed concerns about their ability to influence the choice of care option (24.1% and 25.0% of patients and carers, respectively), whilst 22.7% of carers were concerned about the quality of information about care.
Conclusions
Both the nature of schemes for intermediate care, and the policy context in which they are introduced, mean that pragmatic methodologies are often required to evaluate their impacts. Unfortunately, this need for pragmatism can then mean that it is difficult to reach definitive conclusions about the merits of schemes. However, the findings of this evaluation suggest that the Rapid Response Team provided an ‘acceptable’ alternative to an extended period of care in an acute setting. Such schemes may have relevance beyond the NHS of the UK as a means of providing a more appropriate and cost efficient match between patients' needs for care, the types of care provided, and the place in which care is provided.
PMCID: PMC1393274  PMID: 16773151
intermediate care; early hospital discharge; evaluation

Results 1-7 (7)