Publications by authors named "Alex Gibson"

31 Publications

Averting a public health crisis in England's coastal communities: a call for public health research and policy.

J Public Health (Oxf) 2021 May 13. Epub 2021 May 13.

Plymouth Institute of Health and Care Research (PIHR), University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK.

Coastal communities have received little attention in the public health literature, perhaps because our mental maps tend to associate socio-economic deprivation and health inequalities with inner cities. Mapping a range of key health indicators at small area level, this paper reveals a distinct core-periphery pattern in disease prevalence, with coastal communities experiencing a high burden of ill health across almost all conditions included in the Quality and Outcomes Framework dataset. Other sources suggest poor outcomes for children and young people living in coastal areas. Low rates of participation in higher education contrast with high rates of hospitalisation for self-harm, alcohol and substance use. Reflecting a shift in the distribution of children living in poverty since the 1990s, this may be an early indicator of a future public health crisis in these communities. Exploring reasons for the health challenges facing the periphery, this perspective piece calls for more public health research that can accommodate the complex and interlinked problems facing coastal communities and a more concerted effort to align public health with economic, education, local government and transport policies at the national level.
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http://dx.doi.org/10.1093/pubmed/fdab130DOI Listing
May 2021

Chronic low back pain.

Skeletal Radiol 2020 05;49(5):819-820

Imaging Department, Royal National Orthopaedic Hospital NHS Trust, Stanmore, UK.

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http://dx.doi.org/10.1007/s00256-019-03311-zDOI Listing
May 2020

Chronic low back pain.

Skeletal Radiol 2020 05;49(5):805-807

Imaging Department, Royal National Orthopaedic Hospital NHS Trust, Stanmore, UK.

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http://dx.doi.org/10.1007/s00256-019-03310-0DOI Listing
May 2020

Advanced glycosylated end products restrain the osteogenic differentiation of the periodontal ligament stem cell.

J Dent Sci 2019 Jun 16;14(2):146-151. Epub 2019 Apr 16.

School of Dentistry, College of Oral Medicine, Taipei Medical University, Taiwan.

Background/purpose: Many studies have confirmed that periodontal disease interacts with diabetes. The aim of this study was to examine whether the advanced glycosylated end products (AGEs), which are generated by diabetics, have important effects on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs).

Materials And Methods: In this study PDLSCs were isolated from the periodontal ligaments of extracted third molar teeth. The subjects were divided into two groups, which included the normal control group (N-PDLSCs) and the AGEs-stimulating group (A-PDLSCs). Changes of receptor of AGEs (RAGE) and cumulative ROS in PDLSCs were monitored by western blot and flow cytometry, respectively.

Results: In the study AGEs noticeably inhibited the osteogenic differentiation of PDLSCs, with significant lower calcification nodules detected in A-PDLSCs ( < 0.01). RAGE expression level and ROS accumulation in A-PDLSCs were clearly higher than those in N-PDLSCs ( < 0.01).

Conclusion: Our conclusions were that AGEs may cause the apoptosis of stem cells, which could lead to the disorder of bone differentiation function of PDLSCs.
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http://dx.doi.org/10.1016/j.jds.2019.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562104PMC
June 2019

The National Health Service (NHS) in 'crisis': the role played by a shift from horizontal to vertical principles of equity.

Health Econ Policy Law 2020 01 2;15(1):1-17. Epub 2018 Aug 2.

School of Law, Criminology and Government, University of Plymouth, Drake Circus, Plymouth, UK.

Explanations of the state of 'crisis' in the English National Health Service (NHS) generally focus on the overall level of health care funding rather than the way in which funding is distributed. Describing systematic patterns in the way different areas are experiencing crisis, this paper suggests that NHS organisations in older, rural and particularly coastal areas are more likely to be 'failing' and that this is due to the historic underfunding of such areas. This partly reflects methodological and technical shortcomings in NHS resource allocation formulae. It is also the outcome of a philosophical shift from horizontal (equal access for equal needs) to vertical (unequal access to equalise health outcomes) principles of equity. Insofar as health inequalities are determined by factors well beyond health care, we argue that this is an ineffective approach to addressing health inequalities. Moreover, it sacrifices equity in access to health care by failing to adequately fund the health care needs of older populations. The prioritisation of vertical over horizontal equity also conflicts with public perspectives on the NHS. Against this background, we ask whether the time has come to reassert the moral and philosophical case for the principle of equal access for equal health care need.
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http://dx.doi.org/10.1017/S1744133118000361DOI Listing
January 2020

Variation in referral and access to new psychological therapy services by age: an empirical quantitative study.

Br J Gen Pract 2017 Jul 5;67(660):e453-e459. Epub 2017 Jun 5.

Clinical Trials and Population Studies, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth.

Background: Older people with common mental health problems (CMHPs) are known to have reduced rates of referral to psychological therapy.

Aim: To assess referral rates to the Improving Access to Psychological Therapies (IAPT) services, contact with a therapist, and clinical outcome by age.

Design And Setting: Empirical research study using patient episodes of care from South West of England IAPT services.

Method: By analysing 82 513 episodes of care (2010-2011), referral rates and clinical improvement were compared with both total population and estimated prevalence in each age group using IAPT data. Probable recovery of those completing treatment was calculated for each group.

Results: Estimated prevalence of CMHPs peaks in 45-49-year-olds (20.59% of population). The proportions of patients identified with CMHPs being referred peaks at 20-24 years (22.95%) and reduces with increase in age thereafter to 6.00% for 70-74-year-olds. Once referred, the proportion of those attending first treatment increases with age between 20 years (57.34%) and 64 years (76.97%). In addition, the percentage of those having a clinical improvement gradually increases from the age of 18 years (12.94%) to 69 years (20.74%).

Conclusion: Younger adults are more readily referred to IAPT services. However, as a proportion of those referred, probabilities of attending once, attending more than once, and clinical improvement increase with age. It is uncertain whether optimum levels of referral have been reached for young adults. It is important to establish whether changes to service configuration, treatment options, and GP behaviour can increase referrals for middle-aged and older adults.
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http://dx.doi.org/10.3399/bjgp17X691361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565877PMC
July 2017

Inequity in cardiovascular care in the English National Health Service (NHS): a scoping review of the literature.

Health Soc Care Community 2018 05 16;26(3):259-272. Epub 2016 Oct 16.

School of Geosciences, University of Edinburgh, Edinburgh, UK.

There is a general understanding that socioeconomically disadvantaged people are also disadvantaged with respect to their access to NHS care. Insofar as considerable NHS funding has been targeted at deprived areas, it is important to better understand whether and why socioeconomic variations in access and utilisation exist. Exploring this question with reference to cardiovascular care, our aims were to synthesise and evaluate evidence relating to access to and/or use of English NHS services around (i) different points on the care pathway (i.e. presentation, primary management and specialist management) and (ii) different dimensions of inequality (socioeconomic, age- and gender-related, ethnic or geographical). Restricting our search period from 2004 to 2016, we were concerned to examine whether, compared to earlier research, there has been a change in the focus of research examining inequalities in cardiac care and whether the pro-rich bias reported in the late 1990s and early 2000s still applies today. We conducted a scoping study drawing on Arksey & O'Malley's framework. A total of 174 studies were included in the review and appraised for methodological quality. Although, in the past decade, there has been a shift in research focus away from gender and age inequalities in access/use and towards socioeconomic status and ethnicity, evidence that deprived people are less likely to access and use cardiovascular care is very contradictory. Patterns of use appear to vary by ethnicity; South Asian populations enjoying higher access, black populations lower. By contrast, female gender and older age are consistently associated with inequity in cardiovascular care. The degree of geographical variation in access/use is also striking. Finally, evidence of inequality increases with stage on the care pathway, which may indicate that barriers to access arise from the way in which health professionals are adjudicating health needs rather than a failure to seek help in the first place.
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http://dx.doi.org/10.1111/hsc.12384DOI Listing
May 2018

A qualitative study of diverse providers' behaviour in response to commissioners, patients and innovators in England: research protocol.

BMJ Open 2016 05 13;6(5):e010680. Epub 2016 May 13.

School of Government, Plymouth University, Plymouth, UK.

Introduction: The variety of organisations providing National Health Service (NHS)-funded services in England is growing. Besides NHS hospitals and general practitioners (GPs), they include corporations, social enterprises, voluntary organisations and others. The degree to which these organisational types vary, however, in the ways they manage and provide services and in the outcomes for service quality, patient experience and innovation, remains unclear. This research will help those who commission NHS services select among the different types of organisation for different tasks.

Research Questions: The main research questions are how organisationally diverse NHS-funded service providers vary in their responsiveness to patient choice, NHS commissioning and policy changes; and their patterns of innovation. We aim to assess the implications for NHS commissioning and managerial practice which follow from these differences.

Methods And Analysis: Systematic qualitative comparison across a purposive sample (c.12) of providers selected for maximum variety of organisational type, with qualitative studies of patient experience and choice (in the same sites). We focus is on NHS services heavily used by older people at high risk of hospital admission: community health services; out-of-hours primary care; and secondary care (planned orthopaedics or ophthalmology). The expected outputs will be evidence-based schemas showing how patterns of service development and delivery typically vary between different organisational types of provider.

Ethics, Benefits And Dissemination: We will ensure informants' organisational and individual anonymity when dealing with high profile case studies and a competitive health economy. The frail elderly is a key demographic sector with significant policy and financial implications. For NHS commissioners, patients, doctors and other stakeholders, the main outcome will be better knowledge about the relative merits of different kinds of healthcare provider. Dissemination will make use of strategies suggested by patient and public involvement, as well as DH and service-specific outlets.
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http://dx.doi.org/10.1136/bmjopen-2015-010680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874134PMC
May 2016

Does Spinal Fusion and Scoliosis Correction Improve Activity and Participation for Children With GMFCS level 4 and 5 Cerebral Palsy?

Medicine (Baltimore) 2015 Dec;94(49):e1907

From the Spinal Deformity Unit, Royal National Orthopaedic Hospital, Stanmore, UK.

Spinal fusion is used to treat scoliosis in children with cerebral palsy (CP). Following intervention, the WHO considers activity and participation should be assessed to guide intervention and assess the effects. This study assesses whether spinal fusion for scoliosis improves activity and participation for children with severe CP.Retrospective cohort study of 70 children (39M:31F) with GMFCS level 4/5 CP and significant scoliosis. Thirty-six underwent observational and/or brace treatment as the sole treatment for their scoliosis, and 34 underwent surgery. Children in the operative group were older and had worse scoliosis than those in the observational group. Questionnaire and radiographic data were recorded over a 2-year period. The ASKp was used to measure activity and participation.In the observational group, Cobb angle and pelvic obliquity increased from 51 (40-90) and 10 (0-30) to 70 (43-111) and 14 (0-37). Mean ASKp decreased from 16.3 (1-38) to 14.2 (1-36). In the operative group, Cobb angle and pelvic obliquity decreased from 81 (50-131) and 14 (1-35) to 38 (10-76) and 9 (0-24). Mean ASKp increased from 10.5 (0-29) to 15.9 (3-38). Spinal-related pain correlated most with change in activity and participation in both groups. There was no difference in mobility, GMFCS level, feeding or communication in either group before and after treatment.In children with significant scoliosis and CP classified within GMFCS levels 4 and 5, spinal fusion was associated with an improvement in activity and participation, whereas nonoperative treatment was associated with a small reduction. Pain should be carefully assessed to guide intervention.
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http://dx.doi.org/10.1097/MD.0000000000001907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008467PMC
December 2015

A Preliminary Study to Assess Whether Spinal Fusion for Scoliosis Improves Carer-assessed Quality of Life for Children With GMFCS Level IV or V Cerebral Palsy.

J Pediatr Orthop 2016 Apr-May;36(3):299-304

The Royal National Orthopaedic Hospital, Stanmore, London, UK.

Background: Scoliosis affects 50% of children with Gross Motor Function Classification System (GMFCS) level IV or V cerebral palsy (CP). In children with complex neurodisability following intervention, the WHO considers quality of life (QoL) should be assessed to aid decision-making and assess the effects. This study assesses whether scoliosis surgery improves carer-assessed QoL for children with severe CP.

Methods: Retrospective review of 33 children (16 male:17 female) with GMFCS level IV/V CP and significant scoliosis. Fifteen underwent observational treatment during childhood, and 18 underwent surgery. Questionnaire and radiographic data were recorded over a 2-year period. The carer-completed Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire was used to assess QoL.

Results: In the observational group, Cobb angle and pelvic obliquity increased from 46 (40 to 60) and 8 degrees (0 to 28) to 62 (42 to 94) and 12 degrees (1 to 35). Mean CPCHILD score decreased from 50 (30 to 69) to 48 (27 to 69) (P<0.05). In the operative group, Cobb angle and pelvic obliquity decreased from 78 (52 to 125) and 14 degrees (1 to 35) to 44 (16 to 76) and 9 degrees (1 to 24). Mean CPCHILD score increased from 45 (20 to 60) to 58 (37 to 76) (P<0.05). Change in pain, and not presence of associated impairments, was the most significant factor affecting QoL changes for children in both groups. There was no difference in mobility, GMFCS level, feeding, or communication in either group before and after treatment.

Conclusions: Nonoperative treatment for children with GMFCS level IV/V CP and a significant scoliosis was associated with a small decrease in carer-assessed QoL over 2 years. Spinal fusion was associated with an increase in QoL. Change in pain was the most significant factor affecting QoL changes, and is therefore an important factor to consider when deciding upon surgery.

Level Of Evidence: Level III-therapeutic retrospective study.
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http://dx.doi.org/10.1097/BPO.0000000000000447DOI Listing
November 2016

A retrospective review to assess whether spinal fusion and scoliosis correction improved activity and participation for children with Angelman syndrome.

Dev Neurorehabil 2016 Oct 30;19(5):315-20. Epub 2014 Dec 30.

a The Royal National Orthopaedic Hospital , Stanmore , UK.

Objective: This study investigates outcome of scoliosis treatment for 11 children with Angelman syndrome (AS), with particular focus on activity, participation and the musculoskeletal factors that may affect these outcomes.

Methods: Retrospective review of medical records, radiographs and questionnaires administered to caregivers of 11 children (8M:3F) with AS and scoliosis. Six underwent observational treatment during childhood and five underwent spinal fusion. The Activities Scale for Kids (ASKp) questionnaire was used to measure activity and participation. Questionnaire and radiographic data were recorded over a 2 year period.

Results: In the observational group, scoliosis increased from 31° to 46°. Mean ASKp decreased from 13.8 to 11.9 (p = 0.06). In the operative group, scoliosis decreased from 68° to 29°. Mean ASKp increased from 11.4 to 15.9 (p < 0.01). There was also a reduction in spinal-related pain and mean number of hospital admissions for chest infection. However, there was a 60% major complication rate. There was no difference in mobility, GMFCS level, feeding or communication in either group before or after treatment.

Conclusion: In children with significant scoliosis and AS, spinal fusion was associated with a small improvement in activity and participation, reduction in pain and a decrease in frequency of severe chest infections. Non-operative treatment resulted in progression of scoliosis during childhood and decrease in activity.
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http://dx.doi.org/10.3109/17518423.2014.980524DOI Listing
October 2016

Acute care: The real reason for 'failing' hospitals.

Health Serv J 2013 Mar;123(6343):20-2

Plymouth University.

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March 2013

A Resin-linker-vector approach to radiopharmaceuticals containing 18F: application in the synthesis of O-(2-[18F]-fluoroethyl)-L-tyrosine.

Chemistry 2013 Jan 19;19(5):1720-5. Epub 2012 Dec 19.

Department of Chemistry, University of Southampton, Southampton, Hampshire, SO17 1BJ, UK.

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide (18)F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [(18)F]-fluoride ion. Three model linker-vector molecules 7a-c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8a-c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8a,b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4-fluorobutyl)phenylcarbamic acid tert-butyl ester (9) in NMR kinetic studies and gave superior radiochemical yields (RCY≈60%) of the (18) F-labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[(18)F]-fluoroethyl)-L-tyrosine ([(18) F]-FET), delivering protected [(18) F]-FET in >90% RCY. Acid deprotection gave [(18)F]-FET in an overall RCY of 41% from the RLV.
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http://dx.doi.org/10.1002/chem.201202474DOI Listing
January 2013

The medicalisation of health inequalities and the English NHS: the role of resource allocation.

Health Econ Policy Law 2013 Apr 4;8(2):167-83. Epub 2012 Sep 4.

Faculty of Health, Education and Society, University of Plymouth, Plymouth, UK.

Tackling health inequalities (HI) has become a key policy objective in England in recent years. Yet, despite the wide-ranging policy response of the 1997-2010 Labour Government, socio-economic variations in health continued to widen. In this paper, we seek to explore why. We propose that a meta-narrative has emerged in which the health problems facing England's most deprived areas, and the solution to those problems, have increasingly come to be linked to levels of National Health Service (NHS) funding. This has been, in part, a response to key shortcomings in previous rounds of resource allocation. The very significant sums of money allocated with respect to 'health inequalities' reflects and reinforces the belief that the NHS can and should play a central role in promoting health equity. This medicalisation of HI focuses attention on the role of individual risk factors that lend themselves to medical management, but effectively sidelines the macroprocesses of social inequality, legitimising the kind of society that neo-liberal government has produced in the United Kingdom - one in which health (like other assets) has become a matter of individual and not collective responsibility.
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http://dx.doi.org/10.1017/S1744133112000126DOI Listing
April 2013

General practitioner commissioning consortia and budgetary risk: evidence from the modelling of 'fair share' practice budgets for mental health.

J Health Serv Res Policy 2011 Apr;16(2):95-101

Faculty of Health, 1School of Computing and Mathematics, University of Plymouth, Plymouth, UK.

Objectives: To contribute to current policy debates regarding the devolution of commissioning responsibilities to locally-based consortia of general practices in England by assessing the potential magnitude and significance of budgetary risk for commissioning units of different sizes.

Methods: Predictive distributions of practice-level mental health care resource needs (used by the Department of Health to set 'fair-share' practice budgets) are aggregated to a range of hypothetical, but spatially-contiguous, consortia serving populations of up to 400,000 patients. The resulting joint distributions describe the extent to which the legitimate mental health needs of consortia populations are likely to vary. Budgetary risk is calculated as the likelihood that a consortia's resource needs will, in any given year, exceed its allocation (taken as the mean of its predictive distribution) by more than 1%, 3%, 5% or 10%. The relationship between population size and budgetary risk is then explored.

Results: If between 500 and 600 consortia are created in England (serving 87,000 to 104,000 patients) then, in order to meet the legitimate mental health needs of their patients, each year around 15 to 26 consortia will overspend by at least 5%, and one or two by at least 10%. The budgetary risk faced by consortia serving smaller/larger populations can be read off the graphs provided.

Conclusions: Unless steps are taken to mitigate budgetary risk, the devolution of decision-making and introduction of fixed budgets is likely to result in significant financial instability. It will be difficult to reconcile the policy objectives of devolved commissioning, best met through relatively small and fully accountable consortia, with the need for financial stability, which is best met by pooling risk across larger populations.
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http://dx.doi.org/10.1258/jhsrp.2010.010086DOI Listing
April 2011

Computed tomographic artifact suggesting cervical facet subluxation.

Spine (Phila Pa 1976) 2011 Jul;36(15):E1038-41

AO Spine Reference Center, Queensland University of Technology, Brisbane, Queensland, Australia.

Study Design: A case report with review of the literature on the cause of computed tomographic (CT) artifacts and recommendations for identification of such artifacts.

Objective: To describe the presentation of a patient with a CT scan suggesting a cervical facet dislocation that ultimately proved to be artifactual.

Summary Of Background Data: CT scanning is routinely used in the detection of cervical spine injuries. This technique has a reported sensitivity of 98%, although specificity has proved more difficult to estimate. CT artifacts such as the case reported here is a significant cause of a decrease in specificity for this technique.

Methods: A 30-year-old woman with a history of a cervical fracture developed severe neck pain without neurologic deficit after trauma to the back of her neck. CT scans were obtained and reviewed at a local secondary level hospital. A cervical fracture dislocation was diagnosed and cervical spinal injury protocols were initiated and the patient transferred to authors', tertiary level institution for surgical management. A repeat CT scan showed her cervical spine to be in normal alignment.

Results: A movement artifact in the patient's original CT scans was misinterpreted as a unilateral facet fracture subluxation at C5-C6. There are two clues that in hindsight indicate that this finding was artifactual; an ill-defined tracheal margin in contrast with the sharply defined margin above and below the level of the artifact and a double bone margin seen on axial sections at the level of the artifact.

Conclusion: Motion artifacts are an important cause in the reduction in specificity of CT scans and can be easily missed. It is important to be aware of the indicators of motion artifacts to reduce the risk of unnecessary treatments.
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http://dx.doi.org/10.1097/BRS.0b013e3181fec3afDOI Listing
July 2011

Setting health care capitations through diagnosis-based risk adjustment: a suitable model for the English NHS?

Health Policy 2011 Jul 19;101(2):133-9. Epub 2010 Nov 19.

Faculty of Health, University of Plymouth, Drake Circus, Plymouth, PL4 8AA, United Kingdom.

The English system of health resource allocation has been described as the apotheosis of the area-level approach to setting health care capitations. However, recent policy developments have changed the scale at which commissioning decisions are made (and budgets allocated) with important implications for resource allocation. Doubts concerning the legitimacy of applying area-based formulae used to distribute resources between Primary Care Trusts (PCTs) to the much smaller scale required by Practice Based Commissioning (PBC) led the English Department of Health (DH) to introduce a new approach to setting health care budgets. To this end, practice-level allocations for acute services are now calculated using a diagnosis-based capitation model of the kind used in the United States and several other systems of competitive social health insurance. The new Coalition Government has proposed that these budgets are directly allocated to GP 'consortia', the new commissioning bodies in the NHS. This paper questions whether this is an appropriate development for a health system in which the major objective of resource allocation is to promote equal opportunity of access for equal needs. The chief reservation raised is that of circularity and the perpetuation of resource bias, the concern being that an existing social, demographic and geographical bias in the use of health care resources will be reinforced through the use of historic utilisation data. Demonstrating that there are legitimate reasons to suspect that this will be the case, the paper poses the question whether health systems internationally should more openly address the key limitations of empirical methods that select risk adjusters on the basis of existing patterns of health service utilisation.
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http://dx.doi.org/10.1016/j.healthpol.2010.10.014DOI Listing
July 2011

Synthesis of the positron-emitting radiotracer [(18)F]-2-fluoro-2-deoxy-D-glucose from resin-bound perfluoroalkylsulfonates.

Org Biomol Chem 2009 Feb 8;7(3):564-75. Epub 2008 Dec 8.

School of Chemistry, University of Southampton, Highfield, Southampton, UKSO17 1BJ.

A new approach to the synthesis of 2-fluoro-2-deoxy-d-glucose (FDG, [(19/18)F]-) is described, which employs supported perfluoroalkylsulfonate precursors , where the support consists of insoluble polystyrene resin beads. Treatment of these resins with [(19)F]fluoride ion afforded protected FDG [(19)F]- as the major product, and the identities of the main byproducts were determined. Acidic removal of the acetal protecting groups from [(19)F]- was shown to produce [(19)F]FDG. The method has been applied to the efficient radiosynthesis of the imaging agent [(18)F]FDG, and was shown to produce the radiochemical tracer in good radiochemical yield (average 73%, decay corrected).
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http://dx.doi.org/10.1039/b816032eDOI Listing
February 2009

Deprivation, demography, and the distribution of general practice: challenging the conventional wisdom of inverse care.

Br J Gen Pract 2008 Oct;58(555):720-6, 728; discussion 727-8

School of Law & Social Science, University of Plymouth, Plymouth.

It is generally believed that the most deprived populations have the worst access to primary care. Lord Darzi's review of the NHS responds to this conventional wisdom and makes a number of proposals for improving the supply of GP services in deprived communities. This paper argues that these proposals are based on an incomplete understanding of inverse care which underestimates the degree to which, relative to their healthcare needs, older populations experience low availability of primary care. Many deprived practices appear to have a better match between need and supply than practices serving affluent but ageing populations. However, practices serving the oldest and most deprived populations have the worst availability of all.
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http://dx.doi.org/10.3399/bjgp08X342372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553532PMC
October 2008

A formula for unfairness.

Health Serv J 2006 Nov;116(6032):18-9

School of Law and Social Studies, Plymouth University.

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November 2006

The pursuit of equity in NHS resource allocation: should morbidity replace utilisation as the basis for setting health care capitations?

Soc Sci Med 2004 Feb;58(3):539-51

Department of Social Policy and Social Work, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK.

Although the English NHS has been described as a world leader in pioneering methods of distributing expenditure in relation to population needs, concerns about the legitimacy of using the current utilisation-based model to allocate health service resources are mounting. In this paper, we present a critical review of NHS resource allocation in England and demonstrate the feasibility and impact of using direct health estimates as a basis for setting health care capitations. Comparing target allocations for the inpatient treatment of coronary heart disease in a sample of 34 primary care trusts in contrasting locations in England, we find that a morbidity-based model would result in a significant shift in hospital resources away from deprived areas, towards areas with older demographic profiles and towards rural areas. Discussing the findings in relation to a wider policy context that is generally concerned to direct more health care resources towards the poor, the paper concludes by calling for greater clarity between the goals of health care equity and health equity. Whilst the former demands that the legitimate needs of demographically older populations for more health care resources are acknowledged, the goal of health equity requires real political commitment to resource broader social policy initiatives.
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http://dx.doi.org/10.1016/s0277-9536(03)00217-xDOI Listing
February 2004

The neurotoxicity induced by ethanol withdrawal in mature organotypic hippocampal slices might involve cross-talk between metabotropic glutamate type 5 receptors and N-methyl-D-aspartate receptors.

Alcohol Clin Exp Res 2003 Nov;27(11):1724-35

Department of Molecular and Biomedical Pharmacology, University of Kentucky Chandler Medical Center, Lexington 40546, USA.

Background: We recently reported that the sodium salt of acamprosate (Na-acamprosate) demonstrates the characteristics of an antagonist at metabotropic glutamate type 5 receptors (mGluR5s) rather than at N-methyl-d-aspartate receptors (NMDARs). Because mGluR5s are able to enhance the function of NMDARs, this interplay may be involved in the dysregulation of glutamatergic transmission during ethanol withdrawal. The following studies use organotypic hippocampal slice cultures at a mature age to investigate the potential for this interplay in the neurotoxicity associated with withdrawal from long-term ethanol exposure.

Methods: At 25 days in vitro, organotypic hippocampal slice cultures prepared from male and female 8-day-old rats were exposed to an initial concentration of 100 mM ethanol for 10 days before undergoing a 24-hr period of withdrawal. The effects of Na-acamprosate; 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893), a noncompetitive antagonist at mGluR5s; 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester, a noncompetitive antagonist at mGluR1s; dizocilpine (MK-801), a noncompetitive NMDAR antagonist; and staurosporine on the neurotoxicity induced by ethanol withdrawal were assessed by determining differences in propidium iodide uptake. Polypeptide levels of mGluR5s and the NR1 and NR2B subunits of NMDARs were also determined via Western blot analyses after 10 days of ethanol exposure.

Results: Significant neurotoxicity was always evident in the CA1 hippocampal region after a 24-hr withdrawal period. This spontaneous neurotoxicity resulted from intrinsic changes induced by the long-term presence of ethanol. Na-acamprosate (200-1000 microM), SIB-1893 (200-500 microM), MK-801 (20 microM), and staurosporine (200 nM) were all neuroprotective. The polypeptide levels of mGluR5s and NR1 and NR2B subunits of NMDARs were all increased after ethanol exposure; however, the increase in mGluR5s did not achieve statistical significance.

Conclusions: From this model of long-term ethanol exposure and withdrawal, the functional interplay between mGluR5s and NMDARs might represent a novel target for the prevention of neurotoxicity associated with ethanol withdrawal.
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http://dx.doi.org/10.1097/01.ALC.0000093601.33119.E3DOI Listing
November 2003

Allocating resources for health and social care: the significance of rurality.

Health Soc Care Community 2003 Nov;11(6):486-93

Department of Social Policy and Social Work, University of Plymouth, Plymouth, UK.

Whilst an allowance is made for sparsity in the allocation of resources for social care services in England, rurality is not a significant factor in health resource allocation. This lack of consistency in resource allocation criteria has become increasingly visible as health and social services departments are required to work in partnership across a range of areas. Differences in funding mechanisms also raise the question of why it is legitimate to make adjustments for rurality in the distribution of some public services, but not for others. Against this background, the present paper considers the case for a rural premium in health resource allocation which, it proposes, can be made on four grounds. First, there is evidence that the current National Health Service (NHS) formula introduces systematic biases in favour of urban areas in the way in which it expresses 'need' for healthcare. Secondly, the way in which the current system compensates for unavoidable variations in the costs of providing services takes insufficient account of the additional costs associated with rural service provision. Thirdly, with a growing emphasis on the need to attain national quality standards, rural primary care trusts and social services departments can no longer tolerate lower levels of services. Finally, a case for a rural premium can be made on the basis of precedent. England is the only country in the UK that does not make a major adjustment for rurality in its NHS formula. The paper concludes that the English NHS resource allocation system has done little to counter marked service deprivation in rural areas. Given evidence that rural local authorities also spend less on social care services and direct provision, this raises serious questions about the extent to which the needs of vulnerable people in English rural areas are being adequately served.
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http://dx.doi.org/10.1046/j.1365-2524.2003.00454.xDOI Listing
November 2003

Polyamines contribute to ethanol withdrawal-induced neurotoxicity in rat hippocampal slice cultures through interactions with the NMDA receptor.

Alcohol Clin Exp Res 2003 Jul;27(7):1099-106

Department of Pharmacology, University of Kentucky, Tobacco and Health Research Institute, Lexington 40546-0236, USA.

Background: Several reports demonstrate that withdrawal from long-term ethanol exposure is associated with significant central nervous system neurotoxicity, produced at least in part by increased activity of N-methyl-d-aspartate receptors (NMDARs). Recent evidence suggests that elevations in the synthesis and release of the polyamines spermidine and spermine, which are known modulators of NMDARs, contribute to the increased activity of the receptor during ethanol withdrawal. Therefore, the goal of this investigation was to examine what role, if any, spermidine and spermine have in the generation of ethanol withdrawal-induced neurotoxicity.

Methods: Neurotoxicity (measured as fluorescence of the cell death indicator propidium iodide, PI), glutamate release (measured by high-performance liquid chromatography analysis), and polyamine concentrations (by high-performance liquid chromatography) were measured in rat hippocampal slice cultures undergoing withdrawal from chronic (10 day) ethanol exposure (100 mM). In addition, the effects of the polyamine synthesis inhibitor di-fluoro-methyl-ornithine (DFMO, 0.1-100 nM) and NMDAR polyamine-site antagonists ifenprodil, arcaine, and agmatine (1 nM-100 microM) on ethanol withdrawal- and NMDA-induced neurotoxicity were measured.

Results: Ethanol withdrawal significantly increased glutamate release (peaking at 18 hr with a 53% increase), increased concentrations of putrescine and spermidine (136% and 139% increases, respectively, at 18 hr), and produced significant cytotoxicity in the CA1 hippocampal region (56% increase in PI staining relative to controls) of the cultures. The cell death produced by ethanol withdrawal was significantly inhibited by ifenprodil (IC(50) = 14.9 nM), arcaine (IC(50) = 37.9 nM), agmatine (IC(50) = 41.5 nM), and DFMO (IC(50) = 0.6 nM). NMDA (5 microM) significantly increased PI staining in the CA1 region of the hippocampal cultures (365% relative to controls), but ifenprodil, arcaine, agmatine, and DFMO all failed to significantly affect this type of toxicity.

Conclusions: These data implicate a role for polyamines in ethanol withdrawal-induced neurotoxicity and suggest that inhibiting the actions of polyamines on NMDARs may be neuroprotective under these conditions.
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http://dx.doi.org/10.1097/01.ALC.0000075824.10502.DDDOI Listing
July 2003

Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors.

Alcohol Clin Exp Res 2002 Dec;26(12):1779-93

Department of Molecular and Biomedical Pharmacology, University of Kentucky Chandler Medical Center, Lexington 40546-0236, USA.

Background: Several reported effects of acamprosate within the glutamatergic system could result from interactions with metabotropic glutamate receptors (mGluRs). The following experiments were performed to determine whether acamprosate could compete with trnas-ACPD (+/--1-aminocyclopentane-trans-1,3-dicarboxylic acid, an equimolecular mixture of 1S, 3R and 1R, 3S-ACPD and an agonist at both group I and group II mGluRs) sensitive binding sites and protect against trans-ACPD-induced neurotoxicity in organotypic hippocampal slice cultures.

Methods: A P2 membrane preparation of cortices, cerebellums, and hippocampi of adult, male Sprague Dawley rats was used to determine the abilities of N-methyl-D-aspartic acid (NMDA) and trans-ACPD to displace [3H]glutamate in both the absence and the presence of the sodium salt of acamprosate (sodium mono N-acetyl homotaurine or Na-acamprosate). A comparison of the effects of 100 microM guanosine 5'-triphosphate on unlabeled glutamate, trans-ACPD, and Na-acamprosate was performed in the same paradigm. For the neurotoxicity studies, organotypic hippocampal slice cultures from male and female 8-day-old neonatal rats were exposed to either 500 microM -ACPD or 50 microM NMDA for 24 hr in normal culture medium containing serum on day 20 in vitro. The effects of Na-acamprosate and 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893), a noncompetitive antagonist at metabotropic type 5 receptors (mGluR5s), were assessed by determining differences in propidium iodide uptake as compared with neurotoxic challenges alone.

Results: Na-acamprosate displaced 31% of [3H]glutamate but did not compete with NMDA for [3H]glutamate binding sites. Na-acamprosate displayed total competition with trans-ACPD. The presence of 100 microM guanosine 5'-triphosphate differentially altered the displacing capabilities of the two mGluR agonists, unlabeled glutamate and trans-ACPD, as compared with Na-acamprosate. Na-acamprosate (200-1000 microM) and SIB-1893 (20-500 microM) both were neuroprotective against trans-ACPD induced neurotoxicity that likely results from mGluR potentiation of NMDARs. In turn, Na-acamprosate and SIB-1893 had no direct effects on NMDA-induced neurotoxicity.

Conclusions: Na-acamprosate demonstrates the binding and functional characteristics that are consistent with a group I mGluR antagonist. The functional similarities between Na-acamprosate and SIB-1893 support an interaction of Na-acamprosate at mGluR5s. The neuroprotective properties of acamprosate and possibly its ability to reduce craving in alcohol-dependent patients may result from its alterations in glutamatergic transmission through mGluRs.
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http://dx.doi.org/10.1097/01.ALC.0000042011.99580.98DOI Listing
December 2002

Acamprosate, MK-801, and ifenprodil inhibit neurotoxicity and calcium entry induced by ethanol withdrawal in organotypic slice cultures from neonatal rat hippocampus.

Alcohol Clin Exp Res 2002 Oct;26(10):1468-78

Department of Molecular and Biomedial Pharmacology, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40546-0236, USA.

Background: The antirelapse drug acamprosate has previously been reported to inhibit activating effects of polyamines on -methyl-D-aspartic acid receptor (NMDAR) function. Because increased synthesis of polyamines has been suggested as a mechanism for potentiation of NMDAR function during ethanol withdrawal, we evaluated the effects of acamprosate, MK-801, and ifenprodil in a cell culture model of ethanol withdrawal-induced neurotoxicity.

Methods: Organotypic hippocampal cultures from 8-day-old neonatal rats were maintained in vitro for 23 days before experimental use. The ethanol withdrawal model consisted of exposing cultures to ethanol (70-100 mM) for 4 days before being "withdrawn" into Calcium-Locke's buffer for 1 hr and then into minimal medium for 23 hr. Uptake of (45)CaCl(2) and propidium iodide by damaged cells was assessed 1 hr and 24 hr after the start of ethanol withdrawal, respectively. Additional studies examined effects of exposure to NMDA (50 microM) or spermidine (100 microM) on withdrawal-induced hippocampal damage. Last, these studies examined the ability of the sodium salt of acamprosate (Na-acamprosate, 200 microM), ifenprodil (50 microM), or MK-801 (30 microM) to inhibit neurotoxicity and (45)Ca(2+) entry produced by these insults.

Results: Ethanol withdrawal was associated with significantly greater toxicity and (45)Ca(2+) entry, relative to controls. Exposure to spermidine and NMDA during ethanol withdrawal further increased neurotoxicity and (45)Ca(2+) entry. Acamprosate, ifenprodil, and MK-801 almost completely prevented ethanol withdrawal-induced toxicity and (45)Ca(2+) entry. Acamprosate also reduced spermidine-induced neurotoxicity during ethanol withdrawal but was ineffective against NMDA-induced toxicity or (45)Ca(2+) entry at this time.

Conclusions: The results support the contention that acamprosate, like ifenprodil, interacts with polyamines and that these compounds may be effective in reducing consequences of ethanol withdrawal. NMDAR activation is also strongly implicated in ethanol withdrawal neurotoxicity, but whether acamprosate causes any of these effects in this preparation directly via the NMDAR remains uncertain.
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http://dx.doi.org/10.1097/01.ALC.0000033261.14548.D2DOI Listing
October 2002

Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil.

Brain Res 2002 Oct;952(1):71-7

Department of Molecular and Biomedical Pharmacology, University of Kentucky, Cooper and University Drives, Lexington, KY 40546-0236, USA.

Ifenprodil, arcaine and agmatine have all been reported to inhibit the NMDA receptor by actions at polyamine-sites, however the specific sites with which these compounds interact is unknown. Here we used radioligand binding of [3H]MK-801 to a membrane preparation from rat cerebral cortex to investigate the interactions of these compounds with the NMDA receptor complex. In the absence of exogenous polyamines, agmatine reduced [3H]MK-801 binding only at concentrations over 500 micro M, as opposed to the putative polyamine-site antagonists arcaine and ifenprodil which directly reduce ligand binding at much lower concentrations (5 micro M) in the absence of polyamines. In our studies, all three compounds significantly reduced spermidine-potentiated [3H]MK-801 binding, however agmatine was the only compound effective at concentrations below those that produced direct inhibition of [3H]MK-801 binding. Under these conditions, agmatine had a K(i)=14.8 micro M for spermidine-potentiated [3H]MK-801 binding and displayed characteristics of a competitive antagonist. Agmatine, as well as ifenprodil and arcaine, also displaced [3H]spermidine from rat cortical membranes at concentrations similar to those that were effective at reducing spermidine-potentiated [3H]MK-801 binding. In conclusion, these data suggest that agmatine reduces the potentiating effects of polyamines by competitive antagonism at a specific site on the NMDA receptor complex, and that these actions of agmatine differ from those of ifenprodil and arcaine.
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http://dx.doi.org/10.1016/s0006-8993(02)03198-0DOI Listing
October 2002