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We understand our own role and we embrace our situation buy 10mg uroxatral with mastercard prostate cancer ultrasound. Using self-care support to reduce unnecessary health service use is important buy uroxatral 10 mg on-line man health at 40. We acknowledge that not all adults who are parenting children are biological parents order 10mg uroxatral visa prostate yourself before god. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed buy discount uroxatral 10mg mens health 8 hour diet, the full report) may be included in professional journals provided that xxv 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. Self-care support interventions constitute a central aspect of this agenda and are intended to empower individuals and enhance their self-care capacities and capabilities, while 13 14, simultaneously reducing the fiscal burden on health-care systems. Growing dissatisfaction with impersonal services, greater desire for personal control in health interactions and enhanced awareness of the potential impact of lifestyle on longevity and well-being have all complemented the drive to optimise 8 15, health outcomes, without exacerbating rising health-care costs. The English strategy for the NHS, the Five Year Forward View,3 emphasises the importance of health promotion, ill-health prevention and early intervention for sustainable health-care services, and mandates new models of care, including self-care, to facilitate efficiency savings alongside improved patient outcomes. A global economic crisis means that substantial effort continues to be invested in improving the efficiency of health-care systems. Yet, despite self-care being advocated as a key way in which to increase efficiency, 16 17, there remains uncertainty regarding the scale of the contribution that can be made. Evidence for the success of self-care support has predominantly focused on individually centred outcomes of behavioural change and, until recently, ambiguity has surrounded the impact of these models on health service utilisation and costs. Initial reports of the effects of self-care support on health-care utilisation have not 17–23 been consistently replicated across studies and the focus of interventions on enhancing intermediate outcomes such as self-efficacy has generated debate regarding the relevance of existing evidence to 24 25, service commissioners. A previous National Institute for Health Research-funded systematic review, REducing Care Utilisation thRough Self-management InterVEntions (RECURSIVE),26 successfully responded to this challenge by attempting to determine which models of self-care support were associated with significant reductions in health service utilisation without compromising the health outcomes of adults with LTCs. This review concluded that self-care support in adults is associated with small but significant improvements in quality of life (QoL) and, importantly, that only a minority of self-care support studies report reductions in health-care utilisation in conjunction with reductions in health status. However, patterns of health- and social-care utilisation in children and young people may be qualitatively and quantitatively very different from adults, and potential differences in the factors and systems influencing engagement in self-care 27–30 support across the lifespan make it difficult to extrapolate these findings to younger populations. This review applies the approach employed by RECURSIVE26 to this different population. It builds on two 31 32, previous National Institute for Health Research-funded reviews that investigated the effectiveness and acceptability of self-care support interventions for children and young people with long-term physical and mental health conditions, both updating and integrating them into a single data set. 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 provided that 1 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. A commonly accepted definition of self-care8 is: The actions people take for themselves. Contains public sector information licensed under the Open Government Licence v1. This shift in control has implications for HCPs in that, within a philosophy of self-care, professionals work with patients, services users and their families as partners. This may occur via a variety of methods and techniques (e. In this study we have chosen to use the term self-care support rather than self-management support because this broader term incorporates self-management, self-help, recovery and resilience support. Furthermore, the term self-care support is more appropriate in describing the interventions examined. Compared with other nations, evidence points to a disproportionate number of UK children dying from non-communicable Self-care Resilience Strengthening the ability to self-care Self-care in health Self-management Self-help in mental Recovery promotion Managing long-term health Living well with a Disease/condition physical health Managing (common) long-term prevention conditions mental health mental health conditions condition FIGURE 1 Relationship of self-care concepts. Fifteen per cent of children aged between 11 and 15 years experience long-term illness or disability and 10% have a 40–42 mental health problem. Over the last decade, child health policy has highlighted the vulnerability of these children and emphasised the need for health services to engage with them and support them 38 39 43, , –45 effectively in self-care behaviours. The case for early intervention in LTCs is compelling. Children diagnosed with LTCs face a lifetime of symptom management, and the extent to which they and their families negotiate this in childhood is likely to influence their longer-term health outcomes, life chances and subsequent patterns of health service 31 39, utilisation. Providing optimal, evidence-based support for self-care thus has the potential to make a significant and sustained contribution to NHS efficiency, as well as improving care quality and delivering direct benefits to patient health. The role and effectiveness of different forms of self-care support in adults has been explored. An already extensive evidence base includes rigorous evaluations of the Expert Patients Programme and assistive technologies through the Whole System Demonstrator programme. Comprehensive models of self-care argue that self-care cannot be divorced from the broader context in which it occurs. In children and young people, self-care knowledge, attitude and behaviour change50 are open to influence from health services, 51–53 parents and peers. Adolescence, in particular, is often characterised by increased risk-taking, lack of 27 29 54, , –56 adherence to treatment regimens and a greater than normal deterioration in health status. The importance of developing child- and young person-centred models that are developmentally appropriate and reflect the roles of parents and peers is increasingly being recognised. For some interventions, acceptability has also been demonstrated. Qualitative studies reveal that children, young people and parents all value the opportunities that group-based self-care support provide to interact with others in similar situations to themselves. Interventions that use e-health methods 31 32, to deliver self-care support have been judged to be feasible and applicable. Yet, despite a developing body of evidence on the clinical effectiveness of self-care support interventions for children and young people, key knowledge gaps remain. There has been insufficient synthesis of quantitative data on health-care utilisation and the comparative effectiveness of different self-care support strategies. Previous reviews and meta-analyses have focused almost exclusively on intermediate or clinical outcomes, and rigorous evaluations of the cost-effectiveness of self-care interventions and their impact on health-care utilisation are lacking. Moreover, existing reviews do not explore associations between content and outcomes; they typically treat outcomes and costs as separate concepts and rarely have an explicit focus on the joint effects of outcomes and costs. Assessing the efficiency of self-care support Commensurate with trends in the adult population, long-term physical and mental health conditions in 59–61 children and young people are increasing. Self-care support offers these young people and their families the opportunity to work collaboratively with professionals, actively participate in health-care decision-making and ensure that care is personalised to their needs. This has the potential to improving patient outcomes while simultaneously reducing resource utilisation and costs. 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 provided that 3 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. Rigorous and comprehensive evaluation of the effects of self-care support for children and young people thus demands concurrent evaluation of patient outcomes and health-care costs. As shown in Figure 2, plotting these effects against each other can identify models of self-care that are able to reduce costs without comprising outcomes for children and young people (quadrant A) and distinguish these from models that reduce both outcomes and costs (quadrant B), or improve outcomes at increased cost (quadrant C). Systematic reviews and meta-analyses bear witness to the number of trials of self-care support for children and young people that have been conducted. Although not always designed to enable a full economic analysis, many present sufficient data to enable the intervention to be placed on the cost-effectiveness plane. Systematic synthesis of these data is required to inform evidence-based decision-making and the commissioning of high-quality, technically efficient services. Review aim The review reported here aimed to take account of health-care utilisation and costs in conjunction with health outcomes to provide evidence-based guidance on the provision of cost-effective self-care support for children and young people with long-term physical and mental health conditions. C: More effective D: Less effective More costly More costly Study data A: More effective B: Less effective Less costly Less costly Better outcomes FIGURE 2 Example matrix showing effects on utilisation and outcomes. What models of self-care support are associated with significant reductions in health-care utilisation without compromising health outcomes for children and young people with LTCs?

Given the activating qual- cortical paralimbic structures uroxatral 10 mg for sale androgen hormone use in cattle. Ho and Gillin and colleagues and paralimbic function related to the pathophysiology of (53) demonstrated that whole brain and regional cerebral depression buy uroxatral 10mg free shipping prostate cancer prognosis. In contrast to meostatic mechanisms in mood disorders patients discount uroxatral 10 mg overnight delivery prostate ejaculaton, perhaps healthy controls order 10mg uroxatral overnight delivery duke prostate oncology, depressed subjects show large activations secondary to cortical hyperarousal. These areas include anteriorly located paralimbic structures such as the ventral striatum, anterior cingulate cortex, and medial prefrontal cortex. The lower two images show the same comparisons,butindepressed patients. Clark and colleagues (56) found that alcoholism played to clarify this notion. Further, the in order to generate hypotheses about specific brain struc- presence of sleep disruption at 5 months was shown to pre- tures that show a relationship between increased beta power dict relapse by 14 months. Regions that demon- pothesis that schizophrenia is a spillover of the dream state strated significant correlations between beta power and rela- into wakefulness. Finally, in the depressed conflicting with increases, decreases, as well as no change being found (58,59). This study demonstrated a similar treated subjects may reflect effects of medication withdrawal relationship between electrophysiologic arousal and glucose and/or changes related to the acute psychotic state (61). They found that depressed patients who remitted states; and in never-medicated, neuroleptic- demonstrated high pretreatment relative glucose metabolic treated, as well as unmedicated patients (58); however, not rates in the medial prefrontal cortex were more likely to all studies show these deficits. Studies that fail to find differ- respond to sleep deprivation. Other groups have described similar reduc- stable when polysomnographic studies were repeated at 1 tions in delta counts. Consistent with this view, delta sleep abnormalities have been found to correlate with negative symptoms (60) and with impaired outcome at 1 Sleep Deprivation Studies and at 2 years (71). The help clarify the primary nature of sleep abnormalities. A defect in this structure could explain in remitted schizophrenic patients (58). There is evidence (65) that following total sleep dep- context of a neurodevelopmental framework for schizophre- rivation, recovery of Stage 4 sleep is diminished in schizo- nia. Converging evidence suggests a substantial reorganiza- phrenia. Pronounced reductions dysfunction and schizophrenia (66). Thus, the maturational pro- physiology of psychiatric disorders. Tandon and associates tional parameters discussed in the preceding. No association has been seen be- tion of cortical and subcortical brain regions have been ob- tween sleep abnormalities and depressive symptoms (61), served in schizophrenia. Activation of the cholinergic sys- pointing to a thalamocortical dysfunction (64). Studies that have system alterations, are reversed following sleep in schizo- phrenia (80). Disturbances in catecholaminergic mecha- zapine following acute administration (87). Neylan and associates delta sleep has also received some attention. Adenosine, an relapse has larger impairments in sleep. The effects of neuro- amino acid neuromodulator has drawn increasing interest leptic discontinuation continued to worsen from 2 to 4 in recent years as a possible endogenous sleep-promoting weeks of a neuroleptic-free condition, and did not correlate agent, as it tends to accumulate during waking hours (83). These findings highlight the im- Adenosine agonists have been proposed as possible thera- portance of controlling for medication state in investigation peutic agents in schizophrenia (84). Chapter 134: Sleep Disturbances and Neuropsychiatric Disease 1955 Future Directions significant losses or in acute depressive episodes. First, functional brain imaging studies sug- velop an episode of major depression. Second, sleep architecture changes dramati- pressed bereaved volunteers. These findings are similar to cally during development; sleep studies during development those of elderly patients with recurrent unipolar depression. These findings are similar to those of Cartwright for schizophrenia are likely to be fruitful (92). Elderly people creased internal 'arousal' (shifting toward a more show greater rigidity in sleep patterns, with less intersubject continuous on-line state of readiness to process salient and intrasubject variability in habitual sleep times compared stimuli). The changes in sleep often parallel tion processing related to both homeostatic and adaptive the changes in cognitive function in demented patients (98). A large-scale community based study of bridged successfully. Nighttime is significantly stressed in late-life, that is, in response to awakenings, however, were more disturbing to caregivers. Increased muscular activity, contractions of subjects were identified in association with nocturnal and periodic limb movements may prevent slow wave sleep awakenings: (a) patients with only daytime inactivity; (b) and foster light fragmented sleep. Disorganized respiration patients with fearfulness, fidgeting, and occasional sadness; also is found (109). Sleep archi- sleep recordings have been used extensively to characterize tecture abnormalities include decreases in stages 3 and 4 alterations in brain function across diverse mental disorders. Loss of sleep spindling and K complexes have also that can uncover the brain mechanisms that underlie these been noted in dementia. Sleep apnea has been observed in descriptive changes. Nocturnal behavioral disruptions, or ize changes in information processing during sleep in rela- 'sundowning' are reported commonly in the clinical man- tion to mental disorders. Despite extensive clinical research in this area, the brain function as it transitions throughout the sleep/wake pathophysiology of sundowning, including its relationship cycle. In this manner, the functional neuroanatomic basis with brain mechanisms that control sleep/wake and circa- of the electrophysiologic abnormalities can be determined dian regulation remain unclear. The discovery of the genetic basis of narcolepsy ease and that the sleep changes are secondary manifestations brings the dream of uncovering the genetic basis of sleep of the disorder. If sleep is viewed as generated by core sleep disruption into closer view. The authors thank craps, pains, nightmares, vivid dreams, visual hallucinations, Robert Y. These changes may result from the disease itself, or to complication from treatment with dopaminergic agents (103–105,107). Regularly occurring periods of eye be related to this comorbid disorder (103). Science Sleep architecture abnormalities include increased awak- 1953;118:273–274. Recherches sur les structures nerveuses et les meca- Chapter 134: Sleep Disturbances and Neuropsychiatric Disease 1957 nismes responsables des differentes phases du sommeil physio- 23. Is there a relationship between roimag 1999;91:59–78.

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Pinto dos Santos J uroxatral 10mg visa prostate cancer 51, Loureiro A buy uroxatral 10 mg mastercard man health hq, Cendoroglo M eto M buy 10mg uroxatral prostate cancer 12, et al discount uroxatral 10mg visa mens health 10k glasgow. O kuda K, H ayashi H , Yokozeki KEA: M ode of nosocom ial H CV and in the staff caring for them. N atov SN , Pereira BJG: H epatitis C infection in patients on dialysis. PCR analysis of hem odialysis tis C infection by polymerase chain reaction among hemodialysis ultrafiltrate and whole blood. M orales JM , Fernandez-Zatarain G, M unoz M A, et al. ASAIO Trans 1991, ture and outcom e allograft m em branous glom erulonephritis in renal 37:97–109. N atov SN , Pereira BJG: H epatitis C infection in patients on dialysis. LaQ uaglia M P, Tolkoff-Rubin N E, Dienstag JL, et al. Am J Kidney D is 1988, feron therapy on H CV infection of hem odialyzed patients. Kidney Int 1994, tions in renal transplant patients. M ahony JF: Long term results and com plications of transplantation: 110. C virus RN A in organ donors positive for hepatitis C antibody and in the recipients of their organs. Seney FD Jr, Burns DK, Silva FG: Acquired immunodeficiency syndrome Transplantation 1994, 54:832. Vitting KE, Gardenswartz M H , Zabetakis PM , et al. Cockfield SM , Prieksaitis JK: Infection with hepatitis C virus increas- 124. Renal Disease in Patients Infected with Hepatitis and Human Immunodeficiency Virus 7. Clinicopathologic Conference: Fever and acute renal failure in a infections. In Renal and Urologic Aspects of H IV failure due to acyclovir: case report and review of the literature. Valeri A, N eusy AJ: Acute and chronic renal disease in hospitalized 154. Rao TK, Friedman EA: Outcome of severe acute renal failure in patients 131. Rao TK, Friedm an EA: Renal syndrom es in the acquired im m unode- with acquired immunodeficiency syndrome. Am J Kidney Dis 1995, ficiency syndrom e (AIDS): lessons learned from analysis over 5 years. Bourgoignie J: Glom erulosclerosis associated with H IV infection. Bourgoignie JJ: Renal com plications of hum an im m unodeficiency Contem p Issues N ephrol 1996, 29:59–75. Cantor ES, Kim m el PL, Bosch JP: Effect of race on expression of tal glomerulosclerosis in the acquired immunodeficiency syndrome. N acquired im m unodeficiency syndrom e–associated nephropathy. Ann Intern M ed 1984, nephropathy: a detailed m orphologic and com parative study. Clin N ephrol 1984, and safety of cidofovir in patients with hum an im m unodeficiency 21:197–204. M azbar SA, Schoenfeld PY, H um phreys M H : Renal involvem ent in Chem other 1995, 39:882–886. Seidel EA, Koenig S, Polis M A: A dose escalation study to determ ine H ospital. H um phreys M H : H um an im m unodeficiency virus–associated 7:941–945. Rao TKS, Berns JS: Acute renal failure in patients with H IV infections. In m egalovirus retinitis in patients with AIDS: the H PM C peripheral N ephrology, vol 1. Tokyo: Springer-Verlag; cytom egalovirus retinitis trial. Rashed A, Azadeh B, Abu Rom eh SH : Acyclovir-induced acute tubu- occurrence in specific risk groups. N Engl J M ed 1989, sulfadiazine in patients with AIDS. Carbone LG, Bendixen B, Appel GB: Sulfadiazine-associated obstruc- 165. J Am Soc induced crystalluria in AIDS patients with toxoplasm a encephalitis. Cohen AH , N ast CC: H IV-associated nephropathy: a unique com - 143. Becker K, Jablonowski H , H aussinger D: Sulfadiazine-associated bined glom erular, tubular and interstitial lesion. M odern Pathol nephrotoxicity in patients with the acquired im m unodeficiency 1988, 1:87–97. Bourgoignie JJ, Pardo V: The nephropathology in hum an im m uno- 145. Tashim a KT, H orowitz JD, Rosen S: Indinavir nephropathy [letter]. Cohen AH : Renal pathology of H IV-associated nephropathy. Pardo V, Strauss J, Abitbol C: Renal disease in children with H IV 127:119–125. Com iter S, Glasser J, Al-Askari S: Ureteral obstruction in a patient 150:287–292. H um phreys M H : H um an im m unodeficiency virus–associated 149. Shuka RR, Kim m el PL, Jum ar A: M olecular biology of H IV-1 and of the genitourinary tract. J Am Soc Nephrol 1997, peritoneal dialysis and survival of H IV infected patients with end- 8:492A. Casanova S, M azzucco G, Barbiano di Belgiojoso G, et al. Kim m el PL, M ishkin GJ, Um ana W O : Captopril and renal survival in patients with hum an im m unodeficiency virus nephropathy. Korbet SM , Schwartz M M : H um an im m unodeficiency virus infection Kidney D is: 1996, 28:202–208. Kim m el PL, Phillips TM : Im m une-com plex glom erulonephritis associ- 182. W atterson M K, Detwiler RD, Bolin P Jr: Clinical response to pro- ated with H IV infection. Schectman JM , Kimmel PL: Remission of hepatitis B–associated mem- branous glomerulonephritis in human immunodeficiency virus infection.

The clinical leadership is often sessional – lack of continuality generic uroxatral 10 mg on line anti androgen hormone pills, e uroxatral 10mg with mastercard prostate one a day. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed discount 10mg uroxatral overnight delivery mens health towie, 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 purchase uroxatral 10 mg without a prescription prostate cancer urine test. 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. This is a surprising finding given the roles of these respondents. This was not a survey of GPs in general or of nurses and others of the > 1. If only to help resolve tensions arising from cognitive dissonance, one might reasonably have expected a more optimistic and positive assessment of the future of the CCGs from this population group. Questions were also raised about the continuing rationale. These responses, and others shown in Table 13, suggest that the future for CCGs was felt to be uncertain among many of the senior players who are needed to make them work. 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 123 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. Our morale is very low Clinical leadership will become clinical responsibility/accountability not leadership Too small, too much duplication, too much money spent on paying clinicians to do pure management roles Clinical engagement will reduce further Availability of GPs to provide clinical leadership uncertain Unlikely to survive due to lack of clinical engagement I think rationalisation is positive but also a shame as clinician–managerial relationship teams have matured to a point where I expect our CCGs to be considerably more effective going forward 124 NIHR Journals Library www. Only relevant up to next election in May 2020 Unsure Who knows? 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 125 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. EME HS&DR H TA PGfAR PHR Part of the NIHR Journals Library www. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health Published by the NIHR Journals Library . Self-care support for children and adolescents with long-term conditions: the REfOCUS evidence synthesis. Health Services and Delivery Research ISSN 2050-4349 (Print) ISSN 2050-4357 (Online) This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www. HS&DR programme The Health Services and Delivery Research (HS&DR) programme, part of the National Institute for Health Research (NIHR), was established to fund a broad range of research. It combines the strengths and contributions of two previous NIHR research programmes: the Health Services Research (HSR) programme and the Service Delivery and Organisation (SDO) programme, which were merged in January 2012. The HS&DR programme aims to produce rigorous and relevant evidence on the quality, access and organisation of health services including costs and outcomes, as well as research on implementation. The programme will enhance the strategic focus on research that matters to the NHS and is keen to support ambitious evaluative research to improve health services. For more information about the HS&DR programme please visit the website: http://www. The final report began editorial review in October 2016 and was accepted for publication in May 2017. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. However, they do not accept liability for damages or losses arising from material published in this report. This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HS&DR programme or the Department of Health. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HS&DR programme or the Department of Health. 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 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising.

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When possible generic 10mg uroxatral fast delivery prostate cancer 02, If the mother has untreated early syphilis at delivery uroxatral 10 mg lowest price prostate cancer 40 year old male, 10 a full 10-day course of penicillin is preferred cheap uroxatral 10 mg on-line man health 8th, even if ampicil- days of parenteral therapy can be considered order uroxatral 10mg amex man health personal trainer. Te use of agents Scenario 3 other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history Infants who have a normal physical examination and a of infection with T. For instance, a lumbar puncture might document serum quantitative nontreponemal serologic titer the same or CSF abnormalities that would prompt close follow-up. Other less than fourfold the maternal titer and the tests (e. Passively transferred maternal Older infants and children aged ≥1 month who are identi- treponemal antibodies can be present in an infant until age fed as having reactive serologic tests for syphilis should have 15 months; therefore, a reactive treponemal test after age 18 maternal serology and records reviewed to assess whether months is diagnostic of congenital syphilis. If the nontrepone- they have congenital or acquired syphilis (see Primary and mal test is nonreactive at this time, no further evaluation or Secondary Syphilis and Latent Syphilis, Sexual Assault or Abuse treatment is necessary. If the nontreponemal test is reactive at of Children). Any child at risk for congenital syphilis should age 18 months, the infant should be fully (re)evaluated and receive a full evaluation and testing for HIV infection. Recommended Evaluation Infants whose initial CSF evaluations are abnormal should • CSF analysis for VDRL, cell count, and protein undergo a repeat lumbar puncture approximately every 6 • CBC, diferential, and platelet count months until the results are normal. A reactive CSF VDRL • Other tests as clinically indicated (e. Aqueous crystalline penicillin G 200,000–300,000 units/kg/day IV, administered as 50,000 units/kg every 4–6 hours for 10 days Special Considerations Penicillin Allergy If the child has no clinical manifestations of disease, the Infants and children who require treatment for syphilis CSF examination is normal, and the CSF VDRL test result is but who have a history of penicillin allergy or develop an negative, treatment with up to 3 weekly doses of benzathine allergic reaction presumed secondary to penicillin should be penicillin G, 50,000 U/kg IM can be considered. Tis treatment also would Penicillin Shortage be adequate for children who might have other treponemal infections. During periods when the availability of penicillin is com- promised, the following is recommended (see http://www. All seroreactive infants (or infants whose mothers were 1. For infants with clinical evidence of congenital syphilis seroreactive at delivery) should receive careful follow-up (Scenario 1), check local sources for aqueous crystalline examinations and serologic testing (i. If IV penicillin G is every 2–3 months until the test becomes nonreactive or the limited, substitute some or all daily doses with procaine titer has decreased fourfold. Nontreponemal antibody titers penicillin G (50,000 U/kg/dose IM a day in a single daily should decline by age 3 months and should be nonreactive dose for 10 days). Te serologic with careful clinical and serologic follow-up. Ceftriaxone must response after therapy might be slower for infants treated after be used with caution in infants with jaundice. If these titers are stable or increase after ≥30 days, use 75 mg/kg IV/IM a day in a single daily dose age 6–12 months, the child should be evaluated (e. For older infants, the dose should be enteral penicillin G. Terefore, ceftriaxone should be used in consultation who have had a severe reaction to penicillin stop expressing pen- with a specialist in the treatment of infants with congenital icillin-specifc IgE (238,239). Management may include a repeat CSF examination safely with penicillin. Penicillin skin testing with the major and at age 6 months if the initial examination was abnormal. For infants without any clinical evidence of infection at high risk for penicillin reactions (238,239). Although these (Scenario 2 and Scenario 3), use reagents are easily generated and have been available for more a. Manufacturers are working to ensure ceftriaxone is inadequate therapy. For premature infants who have no other clinical evidence accompanying minor determinant mixture. Skin-test–positive patients should be desensitized Evidence is insufcient to determine whether infants who before initiating treatment. Patients who have positive test results should be desensitized. One approach suggests that persons Management of Persons Who with a history of allergy who have negative test results should be regarded as possibly allergic and desensitized. Another Have a History of Penicillin Allergy approach in those with negative skin-test results involves test- No proven alternatives to penicillin are available for treating dosing gradually with oral penicillin in a monitored setting in neurosyphilis, congenital syphilis, or syphilis in pregnant women. Penicillin also is recommended for use, whenever possible, in If the major determinant (Pre-Pen) is not available for skin HIV-infected patients. In patients with reactions not likely to be IgE-mediated, or hypotension). Readministration of penicillin to these patients outpatient-monitored test doses can be considered. Because anaphylactic reactions to penicillin can be fatal, every efort should be made Penicillin Allergy Skin Testing to avoid administering penicillin to penicillin-allergic patients, unless they undergo acute desensitization to eliminate anaphy- Patients at high risk for anaphylaxis, including those who lactic sensitivity. Skin-test reagents for identifying persons at risk for adverse reactions to penicillin* skin-test reagents before being tested with full-strength reagents. In these situations, patients should be tested in a Major Determinant monitored setting in which treatment for an anaphylactic • Benzylpenicilloyl poly-L-lysine (PrePen) (AllerQuest, reaction is available. If possible, the patient should not have Plainville Connecticut) (6 x 10-5M). Te underlying epidermis is pierced with * Adapted from Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med a 26-gauge needle without drawing blood. Beall and test is positive if the average wheal diameter after 15 minutes Annals of Internal Medicine. Te histamine controls should be positive to frozen source. Intradermal Test Diseases Characterized by If epicutaneous tests are negative, duplicate 0. Te margins of the Urethritis, as characterized by urethral infammation, can wheals induced by the injections should be marked with a ball result from infectious and noninfectious conditions. An intradermal test is positive if the average wheal if present, include discharge of mucopurulent or purulent diameter 15 minutes after injection is >2 mm larger than the material, dysuria, or urethral pruritis. Asymptomatic infections initial wheal size and also is >2 mm larger than the negative are common. Tis is a straight- Gram-stain microscopy, frst void urine with microscopy, and forward, relatively safe procedure that can be performed orally leukocyte esterase) are not available, patients should be treated or IV. Although the two approaches have not been compared, with drug regimens efective against both gonorrhea and oral desensitization is regarded as safer and easier to perform. Further testing to determine the specifc etiology Patients should be desensitized in a hospital setting because seri- is recommended because both chlamydia and gonorrhea are ous IgE-mediated allergic reactions can occur. Desensitization reportable to health departments and a specifc diagnosis might usually can be completed in approximately 4–12 hours, after improve partner notifcation and treatment. Culture, nucleic which time the frst dose of penicillin is administered. After acid hybridization tests, and NAATs are available for the detec- desensitization, patients must be maintained on penicillin tion of both N.

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Cost–consequence analysis Table 35 summarises the results of the cost–consequence analysis trusted uroxatral 10 mg prostate cancer 5k harrisburg pa. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed purchase 10 mg uroxatral mens health magazine recipes, the full report) may be included in professional journals 67 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising purchase uroxatral 10mg visa prostate cancer zigns. Applications for commercial reproduction should be addressed to: NIHR Journals Library discount 10mg uroxatral mastercard mens health 6 pack challenge diet, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. HEALTH ECONOMICS RESULTS TABLE 35 Clinical effectiveness and cost-effectiveness outcomes (adjusted where appropriate): cost–consequence analysis Phase Cost/health impact Intervention Control Difference p-value Annual costs (£) impact Implementation cost: total 25,349. Notes Values in brackets represent 95% CI unless indicated otherwise. Budget impact of the Predictive RIsk Stratification Model in the study area The annualised budget impact of PRISM per 100,000 population in the trial area during the intervention phase is detailed in Table 36. During the 1-year duration of the intervention phase, the total cost of primary and secondary care was £1. Taking into consideration the implementation costs of PRISM of £11,487 per 100,000 population, this results in an increased cost of £1. Furthermore, after adjustment for covariate effects, the rise in health-care costs that coincided with the PRISM scoring tool in the trial area and 1-year intervention phase gave an estimated increase in budgetary impact to a mean £7. Limitations of the health economic analysis There are several limitations associated with the economic analysis. The implementation cost for the PRISM scoring tool was costed according to the procedure and use as recorded in the trial. Any changes in routine use will result in costs to differ from the ones reported here. Hospital admissions in the SAIL database are coded as elective, emergency and other. No length of stay data were available for this study for elective inpatient stays. They were therefore costed according to the national average as reported in the NHS Reference Costs 2014/15,68 which will introduce bias. However, this was addressed in the sensitivity analysis. However, hospitalisation length of stay was censored at the end of the study. Hence, the analysis will underestimate the true hospitalisation costs during the intervention phase. Although this will introduce bias, considering that the intervention phase was already found to be more costly, this will not change the direction of the results. Secure anonymised information linkage records GP event-days. We have therefore costed GP event-days according to consultation trends in general practice, which might not be entirely accurate as the trend data only includes the period between 1998 and 2008. Effects of this were addressed in the sensitivity analysis. Ideally, the economic evaluation would have been undertaken from a societal perspective. We planned to use questionnaire data (Client Service Receipt Inventory) to estimate the cost of social care but because of the complexity of the data linkage with the SAIL database, social care costs could not be included in the analysis, which will cause an underestimation of the true costs in both the control and intervention phases. 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 69 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. HEALTH ECONOMICS RESULTS Although the cost difference between the intervention and control phase is statistically significant, this result has to be interpreted with caution because of the large sample size included in the analysis and the skewness of the data. Although generalised linear models and log-transformation are not ideal to address the common problems with cost data (i. The budget impact analysis only considered the trial population rather than an all-Wales or other per country-based population. However, the trial-based analysis provides an illustration of the likely budgetary demands (based on a 100,000 population) of the PRISM scoring tool on the NHS. In particular, it aimed to identify the processes of change associated with introducing and implementing the PRISM tool within primary care services. We start by presenting the views of policy-makers involved with development and roll-out of PRISM, and staff from Welsh health boards who were invited to pilot PRISM within their chronic conditions management programmes. We then explore local aspects of the context for the PRISMATIC study, by reporting on the expectations of and views on PRISM from community health staff and health board staff in the ABM UHB areas at baseline of the study. We then examine the process of adoption of PRISM in general practice within the PRISMATIC trial, through reporting the views and experiences of staff from the 32 general practices at three time points: baseline, mid-trial and end of trial. This analysis is informed by the NPT described in Chapter 3. The four components or tasks associated with implementing innovation in normal health-care practice are summarised in Box 2. We conclude the presentation of qualitative data with reflections from an AMB UHB manager at the end point of the PRISMATIC trial intervention on the potential and use of the PRISM tool in their area. This chapter also contains information on the implementation and use of PRISM from the surveys administered to participating practices, to complement the interviews and focus groups. Normalisation process theory suggests that each of these tasks is shaped by factors that promote or inhibit the extent to which participants look on a new practice as meaningful. Respondents Table 37 summarises the stages in which each of the three main staff groups participated in the qualitative data collection, as well as the number of staff involved. Health services policy-makers, managers and community health staff During 2013 we conducted face-to-face interviews with policy and health board managers (n = 12) to explore the story of developing the PRISM tool. Six respondents had responsibility for supporting and implementing chronic conditions management policy (including developing the PRISM tool) at an all-Wales level and worked for the Welsh Government or an agency which advised the Welsh Government on this BOX 2 Normalisation process theory: components of implementing innovation in health care l How people understand the innovation and its purpose (coherence). 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 71 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. STAKEHOLDER VIEWS: THE PREDICTIVE RISK STRATIFICATION MODEL IMPLEMENTATION AND USE TABLE 37 Summary of qualitative data collection stages Time point Baseline: pre PRISM Mid-trial: 3–6 months End of trial: 18 months Staff group activation post PRISM activation post PRISM activation All-Wales policy-makers and health 12 interviews Not interviewed Not interviewed board staff Local health board and community 1 focus group (n = 7) Not interviewed 1 interview staff General practice staff 4 focus groups (GPs, 22 interviews (GPs, 19 interviews (GPs, n = 21; PMs, n = 10; n = 18; PMs, n = 4) n = 17; PMs, n = 2) nurses, n = 2) 9 questionnaires (GPs, 15 questionnaires (GPs, 11 interviews (GPs, n = 7; PMs, n = 2) n = 14; PMs, n = 1) n = 10; PMs, n = 1) matter. The other six respondents had regional responsibility for planning and delivering chronic conditions management services in Welsh health boards. At baseline (before PRISM was introduced to GP practices), we conducted a focus group with seven ABM UHB staff with a responsibility for the management, redesign and/or delivery of primary and/or community care services. Two of them were practising nurses involved in delivering community care, and one was a GP working in a management role at the time of the focus group. One respondent had a role which spanned the whole of ABM UHB, whereas the remaining six respondents worked in a particular locality or network. Part-way through the focus group, we presented a handout explaining PRISM and giving examples of screenshots. At the end of the trial, we interviewed one ABM UHB manager. Two other ABM UHB locality managers declined to participate, saying they had changed roles and had no knowledge of the PRISM implementation. We also circulated a short questionnaire about the PRISM implementation to members of the baseline ABM UHB focus group, but none was returned completed. Staff from general practitioner practices trialling the Predictive RIsk Stratification Model tool At baseline, we invited each GP who had been nominated as lead for PRISM in a participating practice to attend one of four focus groups, along with other staff members (such as PM or nurse), if desired. Thirty-three respondents attended focus groups: group A (GPs, n = 5; PMs, n = 4; nurses, n = 1), group B (GPs, n = 4; PMs, n = 3; nurses, n = 1), group C (GPs, n = 7; PMs, n = 1), group D (GPs, n = 5; PMs, n = 2). We also interviewed 10 GPs who were unable to attend a focus group, by telephone (n = 7) or in person (n = 3); in one of the face-to-face interviews, the GP was joined by their PM.

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From the first to the second tively correlated with fear intensity and was negatively corre- presentation of the videotapes buy generic uroxatral 10 mg on line prostate natural supplements, rCBF decreased in bilateral lated with euphoria intensity effective uroxatral 10mg androgen hormone. Similar results were reported secondary visual cortex and right medial temporal cortex generic uroxatral 10mg prostate cancer doctor, by Servan-Schreiber et al uroxatral 10 mg without a prescription prostate with grief definition. Similar results induced sadness in healthy subjects have implicated both anterior paralimbic and nonparalimbic frontal cortical areas have also been reported by Wright et al. Some studies of behaviorally induced sad- ness have also found rCBF changes within the amygdala (71, Conditioning and Extinction 120,121). Of note, studies of other behaviorally induced negative emotions, including anger (39,67) and guilt (127), Fear conditioning involves the presentation of a neutral stim- have likewise found activation of anterior paralimbic corti- ulus (i. After Processing Unpleasant, Arousing, or repeated presentations of the CS and US, the CS alone Threat-Related Stimuli begins to elicit fear-related autonomic changes, such as skin conductance responses. Subsequently, over repeated presen- In functional imaging studies of responses to unpleasant tations of the CS without the US, fear responses decline, pictures (73), several studies have found amygdala activation and this process is referred to as extinction. Existing research when contrasted with a neutral (63,72) or pleasant picture suggests that the amygdala plays a critical role in fear condi- (92) comparison condition. In a separate study, Lane et tioning (27,35,74,75,141), and the medial prefrontal cortex al. Functional imaging to study healthy subjects who viewed a videotape of snakes studies have also demonstrated a correlation between amyg- (CS) both before and after the video was paired with shock dala activity during encoding of emotionally arousing pic- (US) (49,52). Although left occipital and superior frontal cortex. A Habituation comparison of the CS versus CS conditions yielded The term habituation refers to a decrement in responses activation in right thalamus, orbitofrontal cortex, and supe- over repeated presentations of a stimulus. There was a positive correlation between 956 Neuropsychopharmacology: The Fifth Generation of Progress activation in thalamus and in right amygdala, orbitofrontal including limbic, paralimbic, and sensory areas. Morris and colleagues subse- with animal data, human imaging results point to a role for quently used PET and backward masking techniques to the amygdala in fear conditioning and for the frontal cortex study rCBF responses to conditioned face stimuli with and in extinction. The accessory role of the hippocampus in without awareness in healthy male subjects (87). CS conditions were compared with all CS conditions, bilateral activation in amygdala was observed. Right amyg- dala activation was found in the condition in which subjects POSTTRAUMATIC STRESS DISORDER were aware; left amygdala activation was found in the condi- Amygdalocentric Neurocircuitry Model tion in which subjects were unaware of the emotionally expressive face stimuli. We previously presented a neurocircuitry model of PTSD In a single-trial fMRI study, LaBar et al. In the acquisition condition, a tex, and other heteromodal cortical areas purported to me- colored shape (CS ) was paired with a shock (US), whereas diate higher cognitive functions (103). Briefly, this model a different colored shape (CS ) was never paired with hypothesizes hyperresponsivity within the amygdala to shock. No shocks were delivered during the extinction con- threat-related stimuli, with inadequate top-down gover- dition. Comparing CS with CS trials revealed activa- nance over the amygdala by medial prefrontal cortex, specif- tion in periamygdaloid cortex and amygdala during early ically, the affective division of anterior cingulate cortex acquisition and early extinction trials, respectively. Amygdala hyperresponsivity tion in both these regions declined over time. Buchel¨ and mediates symptoms of hyperarousal and explains the indeli- colleagues also used a single-trial fMRI to study the neural ble quality of the emotional memory for the traumatic correlates of fear conditioning in healthy subjects (26). To disambiguate the effects of the CS and US, Further, we propose that in threatening situations, patients the US was not presented on half of the CS trials (i. The critical comparison, CS unpaired versus to regions that mediate fight-or-flight responses and away CS , revealed activation in anterior cingulate, bilateral in- from widespread heteromodal cortical areas, as a neural sub- sular, parietal, supplementary motor, and premotor cortex. A time by event type interaction revealed that fMRI signal in amygdala decreased over time in the CS unpaired condition Structural Imaging Findings relative to the CS condition. These researchers also found conditioning- Bremner and colleagues (21) found that right hippocampal related hippocampal activation that declined over time. In addition, the PTSD group exhibited poorer performance on a standard measure of ver- Summary bal memory, and their percent retention scores on this test Taken together, functional imaging studies in healthy were directly correlated with right hippocampal volume human subjects extend findings from animal research. Gurvits and colleagues (58) used mMRI activity in limbic and paralimbic regions, whereas other ter- to study seven Vietnam combat veterans with PTSD, seven ritories of heteromodal association cortex exhibit decreased Vietnam combat veterans without PTSD, and eight nonvet- activity. However, similar patterns of limbic and paralimbic erans without PTSD. These investigators found signifi- activation may be observed in association with other emo- cantly smaller hippocampal volumes bilaterally for the tional states, and hence this general profile should not be PTSD group in comparison with both control groups. Exposures to unpleasant, Across the 14 veterans, hippocampal volume was inversely arousing, or threat-related stimuli often produce detectable correlated with extent of combat exposure and PTSD symp- amygdala responses, which can be associated with enhanced tom severity. Habi- been reported in mMRI studies of PTSD resulting from tuation can be observed in widely distributed brain regions, childhood abuse. Bremner and colleagues (22) found 12% Chapter 65: Structural and Functional Imaging of Anxiety and Stress Disorders 957 smaller left hippocampal volumes in 17 adult survivors of age and dendritic atrophy in the CA3 region (117). More- childhood abuse with PTSD than in 21nonabused compar- over, chronic stress during development is capable of inhib- ison subjects. Stein and colleagues (134) found 5% smaller iting normal cellular proliferation within the hippocampus, left hippocampal volumes in 21adult survivors of childhood a process mediated by glucocorticoids and glutamatergic sexual abuse (most of whom had PTSD) than in 21non- transmission by an N-methyl-D-aspartate receptor–depen- abused comparison subjects. Furthermore, total hippocam- dent excitatory pathway (57). However, the PTSD cortisol levels and decreased hippocampal volumes have also group had smaller intracranial and cerebral volumes than been found in patients with major depressive disorder (25). The hippocampus is also involved in the modulation of the Taken together, the results of structural neuroimaging hypothalamic-pituitary-adrenal (HPA) axis, and lesions to studies of adult samples suggest that PTSD is associated hippocampus appear to increase the release of glucocorti- with reduced hippocampal volume, which, in turn, may coids during stress (43,60); this, in turn, may further dam- be associated with cognitive deficits and PTSD symptom age the hippocampus (116). Although the extent of traumatic exposure may be Although these findings may have great relevance to anxi- correlated with hippocampal volume, it appears that differ- ety and stress disorders, the picture is complicated by the ences between PTSD and control groups cannot be ex- finding that cortisol levels are characteristically reduced, plained by traumatic exposure alone (58). Stress, Glucocorticoids, and the Functional Imaging Findings Hippocampus Semple and colleagues used PET to study six patients with In this review about neuroimaging of anxiety and stress combat-related PTSD and comorbid substance abuse versus disorders, it is worth elaborating on the potential relation- seven normal control subjects (125). For example, with the control group, the PTSD group exhibited greater sustained, fatal social stress in vervet monkeys was associated rCBF during both task conditions within orbitofrontal with degeneration of neurons in the CA3 region of the cortex. In the pro- mersion stress in rats was related to structural damage to voked versus control condition, patients exhibited increased hippocampus (CA3 and CA2 fields) and deceased local CBF rCBF within anterior cingulate cortex, right orbitofrontal, in hippocampus (42). Interpreta- coids is associated with hippocampal damage in both rats tions of this initial study, with regard to the pathophysiology and primates. Using a similar paradigm and a comparison group, Shin Woolley and colleagues found that daily corticosterone in- and colleagues studied eight women with childhood sexual jections decreased dendritic branching and length in the abuse–related PTSD and eight matched trauma-exposed CA3 region of the rat hippocampus (145). However, a group-by-condition inter- implanted in hippocampus) was related to neuronal shrink- action revealed that the control group manifested a 958 Neuropsychopharmacology: The Fifth Generation of Progress significantly greater rCBF increase within anterior cingulate These results suggest that PTSD may be characterized by cortex than did the PTSD group, whereas the PTSD group amygdala hyperresponsivity to general threat-related stim- showed significantly greater rCBF increases within anterior uli, consistent with our neurocircuitry model of PTSD. Bremner and colleagues (20) also used script-driven imagery and PET to study rCBF in ten female survivors of childhood sexual abuse with Imaging Studies of Neurochemistry PTSD and 12 without PTSD. Consistent with the findings Schuff and colleagues used mMRI and MRS to study seven of Shin et al. Although these investigators found a nonsignificantly in the PTSD group. Liberzon and col- PTSD and 11 healthy comparison subjects without histories leagues (76) used SPECT to study rCBF in 14 Vietnam of maltreatment (37). The PTSD group had lower NAA/ veterans with PTSD, 11 veteran control subjects, and 14 creatine ratios in pregenual anterior cingulate gyrus. In separate scanning sessions, subjects result is consistent with those of symptom provocation PET listened to combat sounds and white noise. In the combat studies (20,23,129), which have reported failure to activate sounds versus white noise comparison, all three groups anterior cingulate in PTSD.

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