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Twenty to 30 percent of patients with ASO- RAD demonstrate atherosclerotic narrowing 1 to 3 cm beyond the takeoff of the renal artery (nonostial lesion) 60 mg cymbalta amex. Nonostial lesions are technically more amenable to percuta- neous transluminal renal angioplasty (PTRA) than ostial ASO-RAD lesions discount 60 mg cymbalta amex, which are technically difficult to dilate and have a high A B restenosis rate after PTRA discount cymbalta 20 mg mastercard. Renal artery stenting has gained wide acceptance for ostial FIGURE 3-2 lesions. Endovascular intervention for nonos- Angiographic exam ples of atherosclerotic renal artery disease (ASO -RAD). A, Aortogram tial lesions includes both PTRA and stents. Surgical renal revascularization is used for B, Intra-arterial digital subtraction aortogram showing severe proximal right renal artery stenosis both ostial and nonostial ASO-RAD lesions. This figure sum m arizes retrospective series on the and 48% at 3 years. Progression to total occlusion occurred only natural history of ASO -RAD. A large series from the Cleveland in arteries with a baseline reduction in lum en diam eter of m ore Clinic in nonoperated patients indicated progression of renal artery than 60%. The cum ulative incidence of progression to total obstruction in 44% ; progression to total occlusion occurred in occlusion in patients with baseline stenosis of 60% or greater 16% of these patients. Reduction in ipsilateral renal size is associ- was 4% at 1 year, 4% at 2 years, and 7% at 3 years. Blood ated with angiographic evidence of progression in contrast to pressure control and serum creatinine were not predictors of patients with nonprogressive (angiographically) ASO -RAD. The risk of renal parenchym al atrophy over tim e in Zierler and coworkers have prospectively studied the progres- kidneys with ASO -RAD has also been described. The from Rim m er and Gennari; with perm ission. This lesion also occurs predominantly in women, is diagnosed between the ages of 15 and 30, is frequently Lesion Frequency, %* Risk of progression Threat to renal function bilateral and highly stenotic, and may progress Intimal fibroplasia and 10 ++++ ++++ to total arterial occlusion. These patients medial hyperplasia should undergo surgical renal revascularization Perimedial fibroplasia 10–25 ++++ ++++ to relieve hypertension and to avoid loss of Medial fibroplasia 70–85 ++ — renal function. Intimal fibroplasia and medial hyperplasia (usually indistinguishable angio- *Frequency relates to frequency of only the fibrousrenal artery diseases. Intimal fibroplasia occurs primarily in FIGURE 3-4 children and adolescents. M edial hyperplasia Frequency and natural history of fibrous renal artery diseases. There are four types of fibrous is found predominantly in adolescents; angio- renal artery disease (fibrous dysplasias): medial fibroplasia, perimedial fibroplasia, intimal graphically it appears as a sm ooth linear fibroplasia, and medial hyperplasia. Although the true incidence of these specific types of stenosis that m ay extend into the prim ary fibrous renal artery disease is not clearly defined, medial fibroplasia is the most common, renal artery branches. M edial hyperplasia, like estimated to account for 70% to 85% of fibrous renal artery disease. The majority of patients intimal fibroplasia, is a progressive lesion and with medial fibroplasia are almost exclusively women who are diagnosed between the ages of is associated with ipsilateral renal atrophy. Although medial fibroplasia progresses to higher degrees of stenosis in about Surgical renal revascularization is recommended one third of cases, complete arterial occlusion or ischemic atrophy of the involved kidney is for patients with either intimal fibroplasia or rare. Intervention on this type of fibrosis dysplasia is for relief of hypertension because the medial hyperplasia to avoid lifelong antihyper- threat of progressive medial fibroplasia to renal function is negligible. Perimedial fibroplasia is tensive therapy and to avert renal atrophy. A, Right renal arteri- ogram dem onstrating weblike stenosis with interposed segm ents of dilatation (large beads) typical of m edial fibroplasia (“string of beads” lesion). The lesion of medial fibroplasia characteris- tically affects the distal half of the main renal artery, frequently extending into the branches, is often bilateral, and angiographically gives the appearance of multiple aneurysms (“string B of beads”). Histologically, this beaded lesion is characterized by areas of proliferation of fibroblasts of the media surrounded by fibrous connective tissue (stenosis) alternating with areas of medial thinning (aneurysms). Inspection of the renal angiogram in panel A indicates that the width of areas of aneurys- mal dilatation is wider than the nonaffected proximal renal artery, an angiographic clue to medial fibroplasia. A, Selective right renal arteriogram shows a tight stenosis in the m id portion of the renal artery with a sm all string of beads appearance, typical of peri- m edial fibroplasia. Perimedial fibroplasia, accounting for 10% to 25% of the fibrous renal artery dis- eases, is also observed almost exclusively in women. The stenotic lesion occurs in the mid and distal main renal artery or branches B and may be bilateral. Angiographically, serial A stenoses are observed with small beads, which are smaller in diameter than the unaffected portion of the renal artery. This highly stenotic lesion may progress to total occlu- sion; collateral blood vessels and renal atro- phy on the involved side are frequently observed. Pathologically, the outer layer of the media varies in thickness and is densely fibrotic, producing a severe reduction in lumen diameter (panel B). Renal artery dis- section and/or thrombosis are common. A, Selective right renal arteriogram dem onstrating a localized, highly stenotic, sm ooth lesion involving the distal renal artery, from intim al fibroplasia. Intim al fibroplasia occurs prim arily in children and adolescents and angiographi- cally gives the appearance of a localized, highly stenotic, sm ooth lesion, with post- stenotic dilatation. It m ay occur in the prox- im al portion of the renal artery as well as B in the m id and distal portions of the renal A artery, is progressive, and is occasionally associated with dissection or renal infarc- tion. Pathologically, idiopathic intim al fibro- plasia is due to a proliferation of the intim al lining of the arterial wall. Intim al fibroplasia of the renal artery m ay also occur as an event secondary to atherosclerosis or as a reactive intim al fibroplasia consequent to an inciting event such as prior endarterectom y or balloon angioplasty. Surgical intervention or pecutaneous transluminal renal angioplasty Atherosclerotic Medial fibroplasia (PTRA) typically produce good cure rates for Men and women Women the hypertension in medial fibroplasia and Age >50–55 y Age 20–40 y these lesions are technically quite amenable to Total occlusion common Total occlusion rare PTRA. In contrast, ASO-RAD is, technically, much less amenable to PTRA (particularly Ischemic atrophy common Ischemic atrophy rare ostial lesions), and surgical intervention or Surgical intervention or angioplasty: Surgical intervention or angioplasty: PTRA produce mediocre-to-poor cure rates Mediocre cure rates of the hypertension Good cure rates of the hypertension of the hypertension. ASO-RAD and medial Less amenable to PTRA More amenable to PTRA fibroplasia m ay cause hypertension and when the hypertension is cured or markedly improved following intervention, the patient m ay be viewed as having “renovascular FIGURE 3-8 hypertension. The m ost far m ore likely to occur in patients with com m on types of renal artery disease (atherosclerotic renal artery disease [ASO -RAD] and m edial fibroplasia than in patients with m edial fibroplasia) are com pared here. In general, ASO -RAD is observed in m en and ASO-RAD. ASO-RAD and medial fibroplasia wom en older than 50 to 55 years of age, whereas m edial fibroplasia is observed prim arily involve both main renal arteries in approxi- in younger white wom en. Total occlusion of the renal artery and, hence, atrophy of the mately 30% to 40% of patients.

I2 Access to other services It was also pointed out that generic 30 mg cymbalta free shipping, through signposting or referral to other services or resources generic 40mg cymbalta with visa, therapists may support wider outcomes being achieved purchase cymbalta 30 mg free shipping, or have an impact on outcomes directly. In addition, it sought to identify the other outcomes that evaluations of therapy interventions may need to consider. We report findings relevant to these study objectives in this chapter. We begin by briefly reminding the reader of the core constructs of the ICF outcomes framework. After this, we report on other outcomes that participants believed should be considered when evaluating therapy interventions. The final sections of this chapter explore issues of outcome measurement, including views about the adequacy of existing measures, goal attainment scaling and issues related to deciding follow-up time-points. The International Classification of Functioning, Disability and Health outcomes framework As reported in Chapter 4, in 2002 the WHO proposed a conceptual model of disability that identified three outcome domains: body structure and function, activity, and participation. Setting this issue aside for a moment, within this framework study participants identified three possible objectives of therapy interventions: l progress or improvement l maintenance or prevention of deterioration l recovery to previous levels of function, activities and participation. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 53 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. In the majority of interviews, participation was spontaneously identified as an ultimate objective of therapy interventions. The move from an exclusive focus on functional, or clinical, outcomes was welcomed across all of the practitioner groups represented in this study: One of the best things in the last ten to fifteen years has been the push towards the focus on what are the needs of the child in terms of outcomes, rather than specific clinical outcomes. O2 However, the way this concept of participation was defined, or interpreted, within the context of delivering physiotherapy, occupational therapy or speech and language therapy, varied between participants and across all three professions. Furthermore, some participants reported that it was also the case that other terms were being used to refer to what was, ostensibly, the same concept: I think that participation would be a fairly strong shared outcome in occupational therapy. From a social science perspective, it is much more around choice and having the opportunity to make a choice about what is meaningful to you. F2 The notion of participation as a unidimensional concept, or something that can be captured using a single measure, was challenged by some interviewees, who argued that more work was needed to define, or specify, participation and participation outcomes. The absence of a conceptual framework was seen as contributing to confusion among practitioners about what constitutes participation. In addition, this was regarded as a key impediment to the use of participation as an outcome indicator: Participation is a really complex issue. O2 When we asked study participants to define participation, the concepts spontaneously elicited included: l engagement with their community l engagement with broader society l social experiences, relationships and social networks l employment 54 NIHR Journals Library www. Within these concepts, some interviewees emphasised that the core feature of participation was having the opportunity to take part in activities, experiences and relationships, as opposed to taking part. The ease by which participation was achieved was also highlighted as an important, but perhaps under-recognised, facet:. O2 Among some, the concept of participation appeared to be defined, to a greater or lesser extent, in terms of engagement with the mainstream world, and typical development. But actually a lot of families like it when there are other children with similar difficulties. Families find it very supportive for themselves, and often their children [appear to] really enjoy it as well. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 55 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. THERAPY OUTCOMES The need for individualistic, child-centred approaches to defining participation The argument was made that it is critical not to make assumptions or be prescriptive about what participation is, or represents, for an individual child. It was, however, acknowledged as highly challenging among some populations. Does the concept work for all groups of children with neurodisability and for all therapy interventions? Leading on from the previous point, some interviewees expressed the view that further work was required on what participation means, and what participation outcomes are, for certain populations. This included neonates and very young children, children with disordered states of consciousness, children with profound and multiple disabilities, and typically developing children with a recently sustained severe brain injury. Participation as an outcome indicator for therapy interventions? Although, broadly, there was a consensus that any therapy intervention should be grounded in the objective of participation, concerns were voiced about whether, or how, it could be operationalised as a measure of intervention effectiveness. It also suggests a view that participation is the end point of a collective effort, rather than something achieved by a single intervention. Among some study participants, this raised questions or concerns about the (universal) appropriateness of participation as an outcome indicator for therapy interventions. The following arguments were made to support this position. The shift to multitherapy and integrated teams (see Chapter 3) working to the same goals is testament to the multifaceted approach required to support participation. A physio will address posture and stability (and can measure that), but for the OT the focus is on the outcome of whether the child can take part in sport. I1 Participation keeps the focus on the outcomes important for the child and family, regardless of who precisely did what to achieve them: the therapist, the doctor, the therapy assistant. While a therapist may not be able to say that they have enabled a child to achieve these things, they could pinpoint specific contributions – for example, the child bathing unaided, or able to get up and down stairs unaided. J1 l At the other end of the spectrum, questions were raised about the appropriateness of participation as an indicator of intervention effectiveness for a child referred to a therapist with a mild and specific physical impairment/functional difficulty. It would also be counterproductive, leading to the exclusion from future research of therapy interventions perceived as having a direct, or more significant, effect on other outcome domains: We need to be more modest about the studies we are doing and actually, paradoxically, through that we will have more impact. When the concept was perceived as higher-level/global or longer-term outcome, its appropriateness as an outcome indicator was questioned. If, however, interviewees argued that it could (also) be conceptualised as relevant to particular times, setting or activities, then the notion of participation as an appropriate outcome measure was more meaningful and acceptable. Operationalising participation as an outcome indicator Concerns A number of key concerns were raised about operationalising participation as an outcome measure in evaluations of therapy interventions. I2 Second, the individualised nature of participation – replicated in goals-focused approaches to therapy interventions – was regarded as sitting uncomfortably with standardised measures. But, to do that, you have to look several years down the line. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 57 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. THERAPY OUTCOMES It was noted that longer-term follow-up points may run counter to some models of research funding.

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However order cymbalta 30mg on-line, in The motor predominance of their clinical signs is in keeping this model -synuclein is not expressed in apoptotic pro- with the pathologic findings cymbalta 60mg low price, which indicate neuronal loss files; it is exclusively upregulated in normal-appearing neu- restricted to neurons of the SNpc and the locus coeruleus rons purchase cymbalta 40mg line, suggesting that it plays a role either in maintaining (146). Vila and co-workers (155) reached a simi- region, and a marker for this region, D6S305, was found lar conclusion in a model of chronic MPTP toxicity. Screening support of the possibility that -synuclein may play a role of complementary DNA (cDNA) libraries with a probe for in a plasticity response in these injury models is the observa- a putative exon, which was also deleted in this patient, led tion that -synuclein mRNA in SN is up-regulated during to the identification of a sequence encoding an open reading the first 4 postnatal weeks, a period of maximal differentia- frame for a 465amino acid protein (89). The deduced tion and synaptogenesis among DA neurons (85). What amino acid sequence of this protein contains a ubiquitin precise role -synuclein plays in the development of DA homology domain at the N-terminal, and a ring-finger neurons remains to be established. The gene encoding the protein is gous -synuclein null mice have thus far shown no obvious large [ 500 kilobase (kb)], and contains 12 exons. Deletion abnormalities in numbers or morphology of DA neurons; mutations were identified in four other affected patients density of striatal dopaminergic terminals; the number, in three independent families, confirming the pathogenetic morphology, or patch/matrix distribution of striatal neu- significance. These animals, however, do exhibit an in- pressed in various regions, including the SN (89). In addition, they show diminished behavioral activa- dividuals from 18 unrelated Japanese families revealed four tion following administration of amphetamine (4). The deletions affected exon has been a tendency to assume that the mutations cause a 3, exon 4, and exons 3 to 4, and a 1–base pair (bp) deletion toxic gain of function related to aggregation. It is important in exon 5resulted in a frameshift and an early stop. Further to keep in mind, however, that its function is unknown, and molecular analysis of non-Japanese families in Europe, re- that a loss of function may relate to disease pathogenesis. In vealed that in addition to deletion mutations, a variety of that regard, we have found that -synuclein mRNA levels point mutations resulting in either truncation or missense are diminished in the SNpc of patients with sporadic PD could also cause the phenotype (3). Markopoulou and colleagues (103) have shown in a identified patients with a late age of onset, up to 58 years 1786 Neuropsychopharmacology: The Fifth Generation of Progress in one case, and indicated that in some instances the clinical auto-oxidation of DA. This auto-oxidation generates toxic phenotype was indistinguishable from idiopathic PD (3). In addition, the pres- There is now growing recognition that mutations in par- ence of neuromelanin in the cell may alter the ability of kin may cause what clinically resembles idiopathic PD. In metal ions to participate in the production of reactive oxy- an investigation of the scope of the molecular and clinical gen species (145). Among early-onset patients without affected selectively destroy DA neurons—6-hydroxydopamine (6- family members, 18% had mutations. Many of the duce superoxide anion radical, H2O2, and hydroxyl radical. In all, 19 different rearrangements of exons mutations tions can be directed toward catecholamine neurons. More- were identified, including multiplications as well as dele- over, it can be limited to acting on DA neurons by pre- tions, and there were 16 different point mutations (101). By immunohistochemistry, the protein has been lo- Interestingly, like 6-OHDA, DA itself is a selective neu- calized at the regional level to SN and locus coeruleus, and rotoxin for DA neurons (38,54,61,62,114,135). This seems at the cellular level to the cytoplasm (139). Nuclear staining to be in large part due to its ability to oxidize to form was not observed. Parkin has been shown to play a role in reactive oxygen species, including DA quinone, which has protein degradation as a ubiquitin-protein ligase (140). Thus, it seems possible that DA itself can be a source teins or abnormal regulation of the half-life of normal cellu- of oxidative stress, particularly under conditions of increased lar proteins may play a role in cell death. DA turnover and decreased antioxidant defenses (see below). MPTP acts via its active product MPP , which is selec- PATHOGENETIC MECHANISMS tively taken up into DA neurons via the DA transporter, and inhibits complex I activity in mitochondria. Inhibition Free Radicals and Deficits in Energy of complex I not only interferes with adenosine triphosphate Metabolism (ATP) synthesis, but also results in augmented production The concept that free radical–mediated injury may underlie of superoxide anion radical. The possible role of superoxide the neuronal degeneration that occurs in PD has been, and radical in MPTP toxicity has received direct support by the continues to be, the leading hypothesis for its pathogenesis. This theory is also referred to as the oxidant stress hypothesis The free radical hypothesis of PD has also received sup- or the endogenous toxin hypothesis. In their review, Fahn port from studies of human postmortem brain. Free radicals and Cohen (34) point out that the free radical hypothesis can cause injury to cells by damaging DNA, proteins, and is appealing because four aspects of the neurochemistry of lipids of the cell membrane. There is evidence from post- DA neurons and their local environment within the SN mortem studies for free radical–induced modification of make the concept plausible. First, a major degradative path- each of these classes of molecules. Dexter and co-workers way for DA is its oxidative deamination by monoamine (24) have shown that in PD brain there is a reduction in oxidases A and B. This process results in the enzymatic levels of polyunsaturated fatty acids, which provide an index production of H2O2, which, while itself not a free radical, of the amount of substrate available for lipid peroxidation, can nevertheless react nonenzymatically with ferrous or cu- and an increase in levels of malondialdehyde, an intermedi- pric ions via Fenton-type reactions to form highly reactive ate in the lipid peroxidation process. Second, DA can react nonenzymatically dialdehyde was regionally specific for the SN. These workers with oxygen to form quinones and semiquinones, with the subsequently confirmed evidence for abnormal lipid peroxi- production of superoxide, hydrogen peroxide, and hydroxyl dation in PD by identifying a tenfold increase in cholesterol radicals. Third, the SN, particularly the SN pars reticulata, lipid hydroperoxide, an early marker in the lipid peroxida- is rich in iron, which as mentioned above, may in its ferrous tion process (25). Free radicals are also capable of directly state catalyze the formation of hydroxyl radicals from H2O2. The possibility that such stated above, it remains the foremost and most widely tested protein changes may also occur in PD brain is supported hypothesis of neural degeneration in PD. Nevertheless, it by the demonstration that protein adducts of 4-hydroxy-2- remains only a hypothesis, and it has its shortcomings (17). In addition, it must be remembered that nonaminergic neu- Postmortem studies have also revealed neurochemical ronal groups, such as the nucleus basalis, which is choliner- features that may predispose the PD brain to oxidative dam- gic, also degenerate in PD, and aspects of the free radical age. Reduced glutathione is an important endogenous anti- hypothesis that are dependent on catecholamine metabo- oxidant, and it has been reported to be reduced in the SN lism are not relevant to the degeneration of these structures. Jenner and colleagues (80) have confirmed low levels of reduced glutathione in the SN of PD patients, Programmed Cell Death and have shown that the alteration is disease-specific. Inter- estingly, they have also shown that reductions are observed The concept that a genetically regulated cell death process in patients with incidental Lewy body disease, which may may underlie the neuron-specific degenerations of later life be a preclinical form of PD (49). This finding suggests that has gathered great attention in recent years. The pro- the reduced levels of glutathione may be a fundamental and grammed cell death hypothesis in fact may be related to primary abnormality in PD, rather than a secondary change. Although A number of postmortem studies have also suggested traditional concepts of free radical injury have centered on that abnormalities of iron metabolism may underlie the neu- the ability of toxic molecules to directly injure cellular con- rodegeneration of PD. It is also apparent that in some settings Dexter and colleagues (26) reported increased levels of iron programmed cell death may be carried out by the controlled in the SNpc of PD patients.

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Who has provided what kinds of leadership to make these initiatives work? Who else might it be worth talking to in order to gain further perspectives on this? What issues from your perspective would it be useful to focus on and understand better? With respect to service change discount cymbalta 40 mg line, how did this come to be a priority? Build detailed chronology – when did it start and what milestone? What obstacles were faced and how were/are these (being) overcome? What role did clinical leaders play in these service changes? What role was played by managers in the service changes? Charts were produced using Microsoft Excel® (2010; Microsoft Corporation 60 mg cymbalta with amex, Redmond quality 60mg cymbalta, WA, USA). For the Kruskal–Wallis test, a randomisation procedure was used to calculate p-values because of the preponderance of ties. The analysis of variance results were taken into account only when residual plots indicated that the analysis of variance model was adequate. Questions where the p-value for the association was < 0. However, because of the multiple testing of many specific questions, attention concentrated on associations with smaller p-values. Not all such associations were reported on in Chapter 3, with a subjective choice being made depending on the statistical strength of the association and on its salience in the context of the study. Statistical calculations were performed using the R statistical programming language (version 3. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 113 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Patient centred, patient focused Outcome focused Clarity and structure, practical patient focus Clear evidence-based thinking. Clear understanding of what is needed to maximise the potential for front-line staff to work effectively together in the interest of their patients They have an understanding of resources Clear insight into the operational implications of challenges to services and service redesign Rapid option appraisal Relationships and Strategic clinical leadership influence and followed by all clinicians and officers collaboration Experience and judgment Patient engagement and member engagement;. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 115 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Agenda driven by managers Over managers Over secondary care Tiers and tiers of bureaucracy NHSE! Consultants are much more used to this environment Management blocking clinical change become of worry of loss of trust income. The clinical leadership is often sessional – lack of continuality, e. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 117 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 119 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Prime contractor arrangement and outcome-based commissioning Table 12 shows a brief overview of the answers with percentages rounded to the nearest 5%. The answers to this question suggested some fundamental differences in the beliefs and perspectives held by those who hold positions on CCGs. As Table 12 shows, the majority leaned towards a view that commissioning through the use of contracts with clearer specification of outcomes was the surest way to proceed. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 121 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 6 committed to the general principle and logic. A surprisingly high number of CCG board members (10%) admitted that they did not know what the terms meant. Another significant group (around 15%) comprised persons opposed to these contracting approaches in principle and/or viewed them as too complicated, impractical and overhyped. A significant number of these sceptics were more attracted to what they saw as emerging models such as MCPs and the STPs, which gave hints that they leaned more towards planning and collaboration rather than completion and contracts. Other responses were: I think this will take longer than 2–3 years to have an impact. It is difficult to get good reliable outcome measures in a number of areas. I think the major issue will be that acute providers will have a disproportionate influence, and too much effort will be spent on managing this. Prime contractor arrangements could be hugely important due to the risk around sustainability of individual providers and the blurring of responsibilities for sector based activity (i. They will only work, however, if there is a strong and sustainable provider in the economy who can lead on them. Wait to see, the power still seems to be with providers, and will continue to be so while the reorganisations are targeted at commissioners for political expediency. Other respondents suggested the potential value of outcome-based commissioning: It is very important. Creative solutions will require a focus on the patient and their desired outcomes. The current PbR [payment by results] framework and mechanism is a significant limiting factor on real transformation of service delivery. Need to be realistic and flexible about commissioning for outcomes. The future of Clinical Commissioning Groups Finally, the survey asked an open-ended question inviting these CCG board members to share their expectations about the future of their CCGs and CCGs in general. The notable feature arising from answers to this telling question is that the vast majority of respondents (65%) judged that CCGs – the organisations on which they were serving and devoting considerable amounts of their time – will not survive. Others (30%) expressed huge uncertainty about the future. Only a small minority of respondents said that they expected CCGs to continue.