Consequences of how third sector organisations are commissioned in the NHS and local authorities in England: a mixed-methods study.

Background: As a matter of policy, voluntary, community and social enterprises contribute substantially to the English health and care system. Few studies explain how the National Health Service and local authorities commission them, what outputs result, what contexts influence these outcomes and what differentiates this kind of commissioning. Objectives: To explain how voluntary, community and social enterprises are commissioned, the consequences, what barriers both parties face and what absorptive capacities they need. Design: Observational mixed-methods realist analysis: exploratory scoping, cross-sectional analysis of National Health Service Clinical Commissioning Group spending on voluntary, community and social enterprises, systematic comparison of case studies, action learning. Social prescribing, learning disability support and end-of-life care were tracers. Setting: Maximum-variety sample of six English local health and care economies, 2019-23. Participants: Commissioning staff; voluntary, community and social enterprise members. Interventions: None; observational study. Main outcome measures: How the consequences of commissioning compared with the original aims of the commissioners and the voluntary, community and social enterprises: predominantly qualitative (non-measurable) outcomes. Data sources: Data sources were: 189 interviews, 58 policy and position papers, 37 items of rapportage, 692,659 Clinical Commissioning Group invoices, 102 Freedom of Information enquiries, 131 survey responses, 18 local project group meetings, 4 national action learning set meetings. Data collected in England during 2019-23. Results: Two modes of commissioning operated in parallel. Commodified commissioning relied on creating a principal-agent relationship between commissioner and the voluntary, community and social enterprises, on formal competitive selection ('procurement') of providers. Collaborative commissioning relied on 'embedded' interorganisational relationships, mutual recognition of resource dependencies, a negotiated division of labour between organisations, and control through persuasion. Commissioners and voluntary, community and social enterprises often worked around the procurement regulations. Both modes were present everywhere but the balance depended inter alia on the number and size of voluntary, community and social enterprises in each locality, their past commissioning experience, the character of the tracer activity, and the level of deprivation and the geographic dispersal of the populations served. The COVID-19 pandemic produced a shift towards collaborative commissioning. Voluntary, community and social enterprises were not always funded at the full cost of their activity. Integrated Care System formation temporarily disrupted local co-commissioning networks but offered a longer-term prospect of greater voluntary, community and social enterprise influence on co-commissioning. To develop absorptive capacity, commissioners needed stronger managerial and communication capabilities, and voluntary, community and social enterprises needed greater capability to evidence what outcomes their proposals would deliver. Limitations: Published data quality limited the spending profile accuracy, which did not include local authority commissioning. Case studies did not cover London, and focused on three tracer activities. Absorptive capacity survey was not a random sample. Conclusions: The two modes of commissioning sometimes conflicted. Workarounds arose from organisations' embeddedness and collaboration, which the procurement regulations often disrupted. Commissioning activity at below its full cost appears unsustainable. Future work: Spending profiles of local authority commissioning; analysis of commissioning in London and of activities besides the present tracers. Analysis of absorptive capacity and its consequences, adjusting the concept for application to voluntary, community and social enterprises. Comparison with other health systems' commissioning of voluntary, community and social enterprises. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128107) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 39. See the NIHR Funding and Awards website for further award information.

National Health Service commissioners and local councils often buy health and care services from voluntary, community and social enterprises. This study aimed to explore how commissioners and voluntary, community and social enterprises worked together and where improvements could be made. We talked to commissioners and voluntary, community and social enterprises in six areas across England and focused on services for learning disabilities, social prescribing and end-of-life care. We analysed National Health Service financial accounts to see how much the National Health Service was spending on services provided by voluntary, community and social enterprises. We surveyed how commissioners and voluntary, community and social enterprises were using information and knowledge to make decisions. We organised events bringing together commissioners and voluntary, community and social enterprises to share knowledge and experience. We found there were two ways commissioners bought services from voluntary, community and social enterprises. One was commodified (a buying-and-selling model), the other collaborative (based on working together). Both were happening at the same time in all the areas of the study, but usually one of them was more present than the other. We saw a general move towards collaboration, but some areas were further along with this than others. Various things helped commissioners and voluntary, community and social enterprises collaborate, such as: paying voluntary, community and social enterprises enough for their services; having people and networks that encouraged others to work with voluntary, community and social enterprises; and including voluntary, community and social enterprises in making decisions about health and care. Commissioners and voluntary, community and social enterprises might therefore lean further towards working together to see how collaborative commissioning can be further developed; how to make contract prices cover voluntary, community and social enterprises' costs; how to enable longer-term contracts; and how to enable less hurried, more considered ways of renewing contracts (e.g. by putting draft contract specifications out to pre-tender consultation). The new Integrated Care Systems in local areas could encourage all this to happen, but pressures elsewhere in the health and care sector might make it more difficult.

Cytokine profiles and their roles in development of provoked vulvodynia.

Provoked, localized, vulvodynia (PVD) is the main subtype of vulvodynia. Although the etiology of PVD is still a topic of debate, inflammation caused by cytokines responding to a dysregulated microbiome is one of the leading proposed theories. Therefore, the purpose of our study is to further explore the cytokine profiles in the study group with PVD using multiplex immunoassays based on electrochemiluminescence. We compared a panel of 26 distinct cytokines levels in the study group with PVD (n = 23) to the control group (n = 18) and cytokine concentrations were measured using MESO QuickPlex SQ 120 instrument with 5 different multiplex assays. Statistical analysis used the Mann-Whitney U test, two-sided p-values, and a significance level of α = 0.05. Differences in cytokine concentrations are described as negligible, small, medium, or large based on Cliff's δ. Concentrations of three cytokines were significantly lower in the PVD group: a large difference in IP-10 (p = 0.029*) and medium differences in IL-1RA4 (p = 0.030*) and IL-12 (p = 0.034*). One cytokine level was significantly higher in the PVD group: a medium difference for IL-6 (p = 0.037*). Due to the lack of consistency in elevation of inflammatory profiles, it is not enough to support persistent inflammation as the etiology behind PVD. However, these findings may indicate there is a possible immune response deficiency in some patients who have PVD. The resemblance of cytokine profile in our study to cytokine profile of people with chronic yeast infection further support this proposed mechanism behind PVD. Future studies involving history and testing for yeast infection are necessary to explore this possibility further.

A post-operative reaction to povidone­iodine in a postpartum woman: A case report.

Introduction: High infection rates after cesarean section are a major concern in the United States. A majority of antiseptics have irritant properties if they are not used as specified in companies' guidelines. Allergic contact dermatitis caused by povidone­iodine is infrequent and is misdiagnosed by clinicians who fail to differentiate allergy from irritation. This case report describes an allergic reaction to povidone­iodine after cesarean section. Case Presentation: A 28-year-old underwent a repeat low transverse cesarean-section at 39 weeks of gestation. The patient informed the medical team that she had no known allergies and no significant past medical history. The new hospital protocol included cleaning the skin over the planned incision site multiple times with povidone­iodine 7.5% scrub followed by povidone­iodine 10% paint. The surrounding skin was prepped with chlorhexidine. The patient complained of an allergic reaction on her skin the night after the procedure, with severe itching, and stated that it got progressively worse. The patient was started on an oral regimen of steroids and hydroxyzine. The itching slowly improved and at discharge the patient was continued on hydroxyzine and steroids were discontinued. By the patient's six-week postpartum visit, skin hypopigmentation had completely resolved. Conclusion: This case illustrates a reaction to povidone­iodine after cesarean section. This allergic reaction could not be attributed to any other portions of the procedure.

Hypoxia-induced carbonic anhydrase mediated dorsal horn neuron activation and induction of neuropathic pain.

ABSTRACT: Neuropathic pain, such as that seen in diabetes mellitus, results in part from central sensitisation in the dorsal horn. However, the mechanisms responsible for such sensitisation remain unclear. There is evidence that disturbances in the integrity of the spinal vascular network can be causative factors in the development of neuropathic pain. Here we show that reduced blood flow and vascularity of the dorsal horn leads to the onset of neuropathic pain. Using rodent models (type 1 diabetes and an inducible endothelial-specific vascular endothelial growth factor receptor 2 knockout mouse) that result in degeneration of the endothelium in the dorsal horn, we show that spinal cord vasculopathy results in nociceptive behavioural hypersensitivity. This also results in increased hypoxia in dorsal horn neurons, depicted by increased expression of hypoxia markers such as hypoxia inducible factor 1α, glucose transporter 3, and carbonic anhydrase 7. Furthermore, inducing hypoxia through intrathecal delivery of dimethyloxalylglycine leads to the activation of dorsal horn neurons as well as mechanical and thermal hypersensitivity. This shows that hypoxic signalling induced by reduced vascularity results in increased hypersensitivity and pain. Inhibition of carbonic anhydrase activity, through intraperitoneal injection of acetazolamide, inhibited hypoxia-induced pain behaviours. This investigation demonstrates that induction of a hypoxic microenvironment in the dorsal horn, as occurs in diabetes, is an integral process by which neurons are activated to initiate neuropathic pain states. This leads to the conjecture that reversing hypoxia by improving spinal cord microvascular blood flow could reverse or prevent neuropathic pain.

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

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.

Clinical experience with polygenic risk score in subjects with early cognitive concerns.

BACKGROUND: There is mounting evidence that lifestyle interventions and behavioural changes play a significant role in maintaining cognition and function, as well as preventing dementia. Consequently, it is important that clinicians confronted with subjects with early cognitive concerns, have appropriate tools available to assist in diagnosis and to facilitate risks management appropriately. The application of polygenic risk score (PRS) tests has the potential to contribute towards management planning and to reduce the burden of testing in subjects with low overall risk. METHODS: This retrospective analysis considered the application of genoSCORETM in a small cohort of patients seen over a six month period in a London Memory Clinic. The test was offered to selected patients in the clinic with MCI not clinically attributable to dementia, or cognitively normal individuals concerned about their risks of dementia. The impact upon clinical management and lifestyle modification was reviewed. genoSCORE, a polygenic risk score algorithm, was developed by Cytox to assess genetic risk for the future development of Late-Onset Alzheimer's disease (LOAD). RESULTS: Patients receiving the genoSCORE test included those with early MCI, subjective memory complaints and a small number concerned about their risk of dementia. In each case, a medical history was taken and individuals assessed using the Addenbrooke's Cognitive Examination, conducted either in clinic or remotely. genoSCORE polygenic risk score was easy to conduct and well received. The results stimulated individuals at risk of developing LOAD to make lifestyle adjustments and thereby potentially modifying their dementia risk. CONCLUSIONS: In this study, the genoSCORE PRS test provided a valuable assessment of genetic risk of individuals most likely to decline cognitively decline towards AD and as such, contributed significantly to clinical management decisions. The ease and effectiveness of home sampling of saliva as source DNA for the PRS test was a major factor and well aligned with the continuing need for remote consultations in the light of COVID-19 concerns. Further larger-scale studies to determine the full clinical and associated economic impact of the genoSCORE PRS test are required.

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

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.

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

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 (P < 0.01). RAGE expression level and ROS accumulation in A-PDLSCs were clearly higher than those in N-PDLSCs (P < 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.

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

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.

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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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

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.