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Whitford et al (2014) wished to substantiate that the cingulate bundle is cheap 100mg lasix with mastercard heart attack high bride in a brothel, in fact buy discount lasix 40mg online arteria palatina ascendens, a series of sub-connections, and to identify which, if any are faulty in schizophrenia. They identified 5 (at least) sub-connections and one of these, which connects the rostral (front) and caudal (back) regions of the anterior cingulate gyrus was abnormally constructed (Fractional Anisotropy (FA)) in people experiencing psychosis (delusions and hallucinations). They also identified a separate sub-connection which was abnormally constructed in people experiencing negative symptoms of schizophrenia (this will be further discussed in Chapter 7). The primary auditory cortex is a bilateral region located on the upper sides of the temporal lobes (within the lateral sulcus) and extending into the lateral fissure of the temporal lobe – in old terminology, in Brodmann areas 41, 42 and 22. A recent study (Wigand et al, 2015) of this interhemispheric pathway in schizophrenia patients with verbal hallucinations concluded that this symptom was the result of microstructural changes in the interhemispheric auditory pathway. Case histories Case history: 1 Cynthia Campbell was 17 years of age and attended a local Catholic school. She lived with her parents and 15 year old sister, Melissa, in a middle class suburb of a large city. Her only other sibling, Libby, was older, in the Army, and stationed overseas. She had found schoolwork difficult, and although she had daydreamed about becoming a teacher and helping children like herself, who had struggled, she was adamant that she would not go to university. That would mean a part-time Technical College course, but she thought she could probably manage. She knew some sort of qualification was essential for a comfortable working life. If all else failed, she could join the Army, like Libby. She had just broken up with Sam, an 18 year old who was attending a different school. She had loved him, he was her first intimate lover, but he had found someone else. When she was going out with Sam she started smoking some marihuana at parties on Saturday nights. On one occasion she took one “speed” (amphetamine/stimulant) tablet. Since the break-up she had sought a supplier of marihuana and had smoked after school two or three times a week. She turned as if to run out of the room, but froze, standing, listening. Melissa was frightened and cowered down into her chair. Her parents stood up, not quickly, as when faced by an attacker, but questioningly. Her parents took her from the table to the sofa and sat on either side. She could not say if it was a male or a female voice, but she heard her name clearly called. There were some other words and short sentences, most of which were muffled. That is, she lacked insight while she was hallucinating, but she gained insight into her situation when the hallucination stopped and she was able to check with her companions. That morning she saw a palomino horse walk through the kitchen wall, turn left and walk down the hall before disappearing. She was calm and interested in the sight while this was happening, but terrified when it was over. She sensed that she had lost control over her mind and her environment. They immediately arranged for her to see a general practitioner. They thought the roots of the problem may have been the break-up of her relationship with Sam and the pressure she was under to make decisions about what she wanted to do in life. The general practitioner thought schizophrenia was the most likely diagnosis. A possibility which avoided them all was drug induced hallucinations. A series of investigations were performed, including an electroencephalogram (EEG; attaching electrodes to the head to measure the electrical activity of the brain). She was treated with medication for epilepsy and advised to avoid illegal drug. Epilepsy is associated with a physical brain abnormality, but can be worsened by emotional stress and the use of certain drugs, particularly mind-altering substances. Case history: 2 Michael Wells was a twice married chef of 29 years of age. He lived with Holly, his second wife and her child from another relationship, in an inner Sydney tenement house. He had a son, Ned, from his first marriage; he rarely saw the boy as his ex-wife had moved interstate. Michael had a good job at a chef in a restaurant near his home. He had the delusion that Ned was going to be sold by his ex-wife, and hallucinations of voices and sirens. The most disabling symptom, however, had been his inability to think clearly. He could not orchestrate his cooking, he could not get everything coming together and ready to serve at the same time. He would start thinking about one dish and then be distracted by another, and then another, and in the end, they would all be spoiled. But now there was a note of apprehension and irritation in his voice, which suggested he would be reluctant to do the same again. Michael shook his head as if to clear it of sleep, and the look of concentration on his face increased. He pushed on, “Fuck off, fuck off, fuck off, fuck off…” he muttered, like a muted machine gun, to himself, from time to time. He got an earlier appointment with his psychiatrist. One month earlier, Michael had wanted to stop his medication. He made the point that he had been well for five years and that his medication had side effects: it reduced his sexual drive and made him tired. His doctor said that he was still at risk of a recurrence of acute schizophrenia, that things were going well for him, and that his relationship and his job could be at risk if he got sick again. In the end they decided it would be reasonable, in the first instance, to reduce his medication by half, and to reassess the situation in a month or so. He had more energy and he felt as if he was making progress.

Amygdala andanterior cingulateactivations dur- imaging techniques that provide good temporal resolution cheap lasix 40 mg mastercard heart attack demi lovato lyrics. They both used PET with F-fluorodeoxyglucose; because of its low temporal resolution discount lasix amex blood pressure medication best time to take, this technique may be insensitive to a relatively brief or nonhomogeneous acti- vation of the anterior cingulate. Functional magnetic resonance imag- ing of cocaine versus nature video. Individual differ- encemapsshowamygdala andanteriorcingulateacti- vationinthreepilotcocaine patients. One interpretation that inte- ventral part of the striatum. It is a prominent terminal re- grates the earlier observations with those in the explicit cue gion for DA cells projecting from the ventral tegmental area, paradigms is that orbitofrontal cortex hyperactivity is associ- and much animal research points to this mesolim- ated with enhanced responsivity to cues, whether naturally bic–nucleus accumbens pathway as a critical substrate for occurring or presented by a laboratory experiment. Orbito- the reinforcing effects of natural rewards (88), cocaine, and frontal cortex hypoactivity, on the other hand, clearly does other drugs of abuse (89). In humans, the size of the nucleus not prevent cue-induced craving and may represent a differ- accumbens is about 5 mm. Thus, the nucleus accumbens ent vulnerability (see summary below). The The insular cortex is located interior to the lateral sulcus. Subjects given a (double-blinded) infusion of saline orbitofrontal cortex; it also reflects input from the viscera solution in the fMRI magnet showed clear activation of (autonomic nervous system) and sensory systems. Three lab- the nucleus accumbens if they had previously received an oratories have reported activation of the insula in response infusion of cocaine in this novel environment. The nucleus to cocaine-related cues, but the effects vary. This striking finding suggests that a (64) reported activation of the right insula in response to druglike response to cocaine cues can be established with a the cocaine infusion environment; no correlation with crav- single trial. Given the disparate findings, additional was an unpredicted decrease in rCBF, but the larger dorsal studies will be needed to sort out the nature and direction striatum (which receives primary projections from the sub- of cue effects in the insula. It was not differentially activated but did not report on nucleus accumbens. Orbitofrontal Cortex This is in contrast to the common finding of amygdala The orbitofrontal cortex is located in the ventromedial re- activation across several cue studies. The orbitofrontal cortex is richly the hippocampus and interconnected to it, the amygdala is interconnected with DA-related regions involved in reward not activated by explicit memory demands; rather, it sup- and stimulus–reward learning (90). Three studies (64,83, ports functions of implicit, emotional memory (92). The remaining two studies, in Other Structures which fMRI was used, did not report on the orbitofrontal cortex response (84,86) (ventral orbital regions are often Dorsolateral Prefrontal Cortex difficult to image with fMRI because of artifact introduced The dorsolateral prefrontal cortex, best known for its role by air in the sinus cavities). In the three studies finding an in working memory, was not differentially activated by the orbitofrontal cortex response to cues, the subjects were in uninterrupted, narrative cocaine videos in our PET study early cessation (ranging from 18 hours to 7 days); in the (47), although craving was robust. Similarly, it was not acti- two studies finding no orbitofrontal cortex activation to vated by the paradigm of Kilts et al. These alternating conditions may preliminary conclusions about the substrates of the state have engaged working memory in the cocaine subjects be- and, importantly, for generating new hypotheses that will cause the same cocaine users reappeared in an ongoing drug help to refine the emerging picture. Despite the variability scenario that was interrupted by the nondrug video seg- in imaging techniques, analysis techniques, the abstinence/ ments. Controls are generally less engaged by cocaine stim- treatment status of the subjects, and the varied methods uli and therefore would also be expected to show less engage- used to induce cocaine desire, several convergent findings ment of working memory. A similar explanation may for regions of activation have been obtained. The most com- account for activation of the dorsolateral prefrontal cortex monly activated regions during cocaine cues, across the lab- in the paradigm of Grant et al. Two repetitions of the same brief cocaine video clip during the 18 studies that parsed the ventral (nucleus accumbens) from period of F-fluorodeoxyglucose uptake. In an ongoing the dorsal striatum showed activation by cocaine cues in fMRI study (Listerud et al. This study will bens for a 'cocaine-associated environment' (the fMRI directly test the hypothesis that dorsolateral prefrontal cor- magnet! The orbitofrontal cortex was also activated by cues in the (three) studies of cocaine subjects in recent cessation. The hippocampus was not regularly activated by cocaine Cerebellum cues, which suggests that the cue-induced state does not The cerebellum, important in motor coordination and re- depend on declarative memory/factual recall. The dorsolat- tention of simple motor schemas, was not activated in our eral prefrontal cortex was not activated in most of the cue PET study with 15O bolus in which videos were used to studies but was activated by cocaine cues that were intermit- induce craving for cocaine (47). Similarly, it was not acti- tent or repeated; this activation may be relatively indepen- vated by the cues of Maas et al. The cerebellum was differentially acti- cerebellum was not activated in most cue studies, although vated in the study of Wang et al. The The brain regions activated by cocaine cue paradigms (highly ritualized and overlearned) handling of cocaine para- (amygdala, anterior cingulate, nucleus accumbens, insula) phernalia may have triggered motor memories and schemas, do substantially overlap those activated by cocaine itself in a cerebellar function. In support of this notion, the study the fMRI study of Breiter et al. Most cue paradigms, even tween craving and cerebellar activation. This correlation those in which fMRI is used, have not yet described the would occur if handling of paraphernalia acted both as a temporal pattern of the signals from these regions during potent conditioned cue for drug craving and as a trigger for cues; such information would permit a more detailed com- motor memories/highly practiced motor schemas related to parison of cue effects with the multiple effects of cocaine cocaine preparation. No studies have yet examined the ventral tegmental area or basal forebrain in Sensory/Association Cortex response to cues. In addition to the regions discussed, one imaging study The orbitofrontal cortex deserves special mention in the has shown differential activation of visual association areas discussion of craving and drug motivation. Orbitofrontal (peristriate) by cocaine cues (83), and two studies have dysfunction in other disorders has been associated with diffi- shown differential activation of the inferior parietal lobe culties in modulating rewarded or punished behavior (e. As additional neuroimaging studies accrue, it will be contingencies) (93), impaired somatic/emotional response easier to determine whether less common activations such in anticipation of the consequences of a decision ('future as these reflect a feature of the paradigms used or a feature insensitivity') (94), and perseverative, compulsive behaviors of the target state. Clinically, some of these same difficulties have been 1586 Neuropsychopharmacology: The Fifth Generation of Progress noted in substance abusers, which raises the possibility of little support for the notion of a 'sensitized' substrate, a core deficit in some patients (95). Long-term users of sometimes proposed as a potential mechanism for stimulant amphetamine are impaired on a decision-making task that drug craving/incentive motivation. Beyond the first week places demands on ventromedial prefrontal (orbital) func- of cessation, cocaine patients often exhibit resting hypoac- tion (96), and long-term administration of stimulants tivity in limbic and frontal regions in comparison with con- clearly erodes orbitostriatal inhibitory function in primates trols. Exposure to cocaine cues or to a stimulant can produce (93). Whether such orbitofrontal cortex deficits predate a significant activation in these affected brain regions, but drug use in humans, predispose to it, or are a consequence the absolute level of brain response is often no greater than of it, the news for long-term cocaine users is not good; in controls, and may even be less.

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Naturally occurring reduced cholesterol may also be associated with non–illness-related mortality (116 generic lasix 40mg online pulse pressure stroke volume relationship, 120–123) cheap lasix 100 mg without a prescription pulse pressure 31, largely attributable to suicide (116,122). Low Vasopressin serum cholesterol has been reported in psychiatric inpatients Whereas Virkkunen et al. Reduced serum vasopressin concentrations among impulsive and nonim- cholesterol has also been related to the severity of borderline pulsive violent offenders (8), Coccaro et al. It is also found in male forensic patients (130), aggres- sons, particularly men (108). Despite a significant inverse sive conduct-disordered children and adolescents with at- correlation between CSF vasopressin and PRL[d-FEN] re- tention deficit disorder (131), and suicidal adolescents sponse, the positive relationship between aggression and (132). CSF vasopressin remained even after the influence of PRL[d-FEN] response on the aggression score was taken into account. These data are consistent with those from MOLECULAR GENETICS animal studies in which vasopressin antagonists reduced ag- gression in golden hamsters, whereas 5-HT uptake inhibi- An understanding of the molecular genetics of impulsive tors increased central 5-HT activity and reduced central aggression is currently emerging with the rise of association vasopressin concentration and levels of aggressive behavior studies involving various DNApolymorphisms of candidate in the same species (109). One of the first notable studies in this area was that human studies may be accounted for by significant differ- of Brunner et al. The presence of this mutation function also contributed to failures to inhibit responses to was associated with evidence of altered catecholamine me- stimuli associated with punishment on a 'go/no-go' learn- tabolism (i. Al- cerebral dysfunction has also been related to increased hos- though no other families with this specific MAO A point tility. Verbal signal decoding and P300 amplitudes in an mutation have been reported, this report highlighted the evoked potential paradigm predicted impulsiveness and potential of the candidate gene approach to the molecular anger in prison inmates (147). In terms of regional localiza- genetics of aggression. At about the same time, Nielson et tion, neuropsychological tasks sensitive to frontal and tem- al. Thus, neuropsychological and associated with a reduction of CSF 5-HIAA concentration cognitive studies do suggest that abnormalities of higher in impulsive violent offenders (nearly all with DSM-III integrative functions, consistent with reduced cortical in- IED) (134). In the same study, the presence of the L allele hibitory influences on aggression, result in more disinhibi- was also associated with history of suicide attempts in all tion of aggressive behaviors. Although this finding was not replicated laboratory paradigms may discriminate aggressive individu- by Abbar et al. The PSAP has been externally validated in violent offenders and more specifically for severe suicide attempts. However, sional measures of impulsive aggression (137). In this brief the heritability of these laboratory measures has not been report of only 21 personality-disordered subjects, those with systematically assessed in studies of families or sibs of impul- the LL genotype had significantly higher aggression scores sive or aggressive probands, a logical prerequisite to an endo- than subjects with the UU genotype. However, an associa- phenotypic approach to borderline personality disorder. It Neuroanatomy of Aggression may be that the TPH polymorphism is in linkage disequilib- rium with different genes in different populations. Lappa- Prefrontal cortex, particularly prefrontal orbital cortex and lainen et al. Astudy of a 5- roles in the generation of aggression as well. The critical HT6 receptor allelic variant in patients with schizophrenia role of prefrontal orbital cortex is exemplified by the case and in controls was negative for an association with aggres- of Phineas Gage, a solid, upstanding railroad worker, who, sive behavior (141). NEUROPSYCHOLOGY OF AGGRESSION Other clinical cases support the central role of orbital pre- frontal cortex in regulation of aggression (153–157). Irrita- The relationship between aggression and neuropsychology bility and angry outbursts have also been associated with is in part dependent on the syndrome in which aggression damaged orbital frontal cortex in neurologic patients (158), is observed. For example, the cognitive impairment of de- and frontal and temporal hypoperfusion has been noted mentia may be associated with aggressive behavior. Lesions of prefrontal lescents with conduct disorder, verbal processing deficits are cortex, particularly orbital frontal cortex, early in childhood associated with greater aggressiveness and antisocial behav- can result in antisocial disinhibited, aggressive behavior later ior (144). Low executive cognitive function is also related in life (160). Chapter 119: Pathophysiology and Treatment of Aggression 1715 Temporal lobe lesions have also been associated with a in orbital frontal cortex (176). These deficits were more susceptibility to violent behavior, as suggested by multiple pronounced in persons without psychosocial deprivation case reports of patients with temporal lobe tumors. In a study of patients with personality disorders, an study of violent patients, many anterior inferior temporal inverse relationship was found between life history of aggres- lobe tumors were reported (161,162), and aggressive behav- sive impulsive behavior and regional glucose metabolism ior has been associated with temporal lesions (163). Al- in orbital frontal cortex and right temporal lobe. Patients though temporal disease may express itself in a variety of meeting criteria for borderline personality disorder had de- ways, there does appear to be a clear association between creased metabolism in frontal regions corresponding to temporal pathology and aggressive behavior. Single photon emission computed tomography with rage attacks, and studies of patients who have under- studies have also suggested reduced perfusion in prefrontal gone amygdalectomy (164), although destructive behaviors cortex, as well as focal abnormalities in left temporal lobe have also been observed in the context of coagulation of the and increased activity in anteromedial frontal cortex in lim- amygdala (165). Patients with bilateral amygdala damage bic system in aggressive persons with reduced prefrontal judged unfamiliar persons to be more trustworthy than con- perfusion in antisocial personality-disordered alcoholism trols, a finding consonant with the role of the amygdala in (179), and hypoperfusion in the left frontoparietal region social judgments of potential threat (166). The association of violent behavior with aggressive be- Cingulate cortex has also been implicated especially in pos- havior with localized seizure activity provides a further guide terior regions in aggressive borderline patients (178), a find- to brain regions implicated in the modulation of aggression. However, only a few patients with temporal Extensive connections between amygdala and prefrontal lobe epilepsy engage in aggressive behaviors in the interictal cortex have been described, suggesting an inhibitory influ- or periictal periods (170–172). These clinical correlations, ence of frontal cortex on the amygdala (181). Amygdalo- although pointing to regions of interest for imaging studies, tomy has been associated with reduced aggressive outbursts cannot directly address the circuitry involved in impulsive in patients with intractable aggression (182), but there have aggression in the absence of specific neurologic disease. Imaging Neurotransmitter Systems in Structural Imaging and Aggression Aggression Reduced prefrontal gray matter has been associated with Serotonin autonomic deficits in patients with antisocial personality disorders characterized by aggressive behaviors (173). Al- Ascending serotonergic neurons from the raphe nuclei though these deficits are not visually perceptible, they reach project widely throughout the brain, including projections statistical significance and are consistent with the neurologic to dorsolateral prefrontal cortex and medial temporal lobe. Diffuse tracts extend from dorsal and medial raphe project Functional Imaging and Aggression to frontal lobe. Both 5-HT2A and 5-HT1A receptors are One technique used to identify brain activity in individuals found in high concentrations in human prefrontal cortex, as displaying aggressive behavior is the assessment of in vivo are 5-HT transporter sites (183), and patients with localized cerebral glucose metabolism through positron emission to- frontotemporal contusions show significantly lower 5-HT mography. Studies of this type tend to implicate brain hypo- metabolites in CSF than patients with diffuse cerebral con- metabolism in a variety of regions but particularly frontal tusions (184). Greater -CIT binding to 5-HT transporters and temporal cortex. In psychiatric patients with a history has also been reported in nonhuman primates with a higher of repetitive violent behavior, decreased blood flow consis- -CIT binding associated with greater aggressiveness (185). In a study of homicide gressive behavior in posterior orbital frontal cortex and me- offenders, bilateral diminution of glucose metabolism was dial frontal cortex in the amygdala, whereas increased 5- observed in both medial frontal cortex and at a trend level HT2A number in orbital frontal cortex, posterior temporal 1716 Neuropsychopharmacology: The Fifth Generation of Progress cortex, and amygdala have been correlated with prosocial may have a disinhibiting effect on the generation of aggres- behavior in primates (186).

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Any analysis focused on a single aspect of health-care utilisation is vulnerable to error buy discount lasix on-line heart attack white sea acapella remix. Arguably order 100mg lasix mastercard peak pulse pressure qrs complex, cost shifting may have been a greater risk had substantial reductions in health service utilisation been revealed. In this instance, it would have become crucial to ascertain whether the observed effects reflected genuine reductions in health service use or whether costs had simply been transferred to other health-care sectors or on to patients. With the exception of ED visits and hospital admissions, health service utilisation data were inconsistently reported by the primary studies in our review. Total cost outcome data are necessary to provide policy-makers and service providers with clear evidence of the efficiency (or otherwise) of self-care support. By definition, these data sum costs across all service sectors and include the costs of delivering the intervention that is intended to generate these cost changes. Few primary studies reported total cost data in the current review, prohibiting this more robust analysis. Some of the studies in our review distinguished between scheduled and non-scheduled health service use, but did not report care appropriateness per se. We did not distinguish between elective and unplanned admissions in our analysis, nor did we distinguish between legitimate and inappropriate ED use. The effects of self-care support interventions on these different forms of health service utilisation may conceivably be very different. The optimal assessment of the hypothesis underlying this review would have been to restrict our analysis to the most comprehensive assessment of costs, including those related to NHS service use, social care and other services (e. From an operational perspective, it is difficult to foresee how self-care support interventions justified from a societal perspective will be implemented. Although any necessary reallocation of resources can be identified, transfers between sectors are not always considered desirable or feasible. Our review included 97 studies, of which only 35 reported formal economic analyses. The broader evidence base included in our review is reflective of a larger number of studies that report useful data on health service utilisation. Systematic assessment of this wider literature makes an important and much-needed contribution to policy and service development. 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 method of increasing service efficiency, there remains uncertainty regarding the scale of the contribution that can be made. Although a previous review has suggested that self-care support interventions may reduce hospital use and total costs in adults, our study has demonstrated potentially smaller effects in children and young people. Understanding the reason for these differences may be an important focus for future research efforts. Self-care support resonates with multiple policy strategies, including philosophical shifts towards partnership working and the delivery of personalised care. Consideration must thus be given to both its processes and outcomes, and the potential breadth of benefits that it will confer. Specific attention should be given to different stakeholder perspectives and whose views – population, policy, professional or patient – are the most important when minimal effects on QoL and health service utilisation are observed. 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 43 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. DISCUSSION AND CONCLUSIONS The impact of self-care support interventions may depend less on intervention intensity and more on its delivery mechanisms Rigorous evaluation of the efficiency of self-care support interventions for children and young people with LTCs demands concurrent evaluation of patient well-being and health utilisation effects. The suggestion that self-care support may minimally benefit QoL, but not translate into marked benefits for health service use held, across different age groups, intervention intensities and settings. Constraints on the number of data underpinning these results demand some caution in their interpretation. In line with our protocol and previous review,26 we categorised intervention intensity according to a broad typology and compared pure or facilitated self-care support with more intensively facilitated or case-managed care. The threshold for intensive facilitation took account of both amount of self-care support (> 2hoursor four sessions), as well as the nature of the support provided. This threshold was an arbitrary empirical threshold that provided a reasonable distribution of studies among the different categories. Reductions in ED use were not consistent across LTCs or intervention type. Preliminary analyses suggest a significant reduction in emergency use for children aged < 13 years, children and young people with asthma and children and young people receiving more intensively facilitated self-care support interventions. However, the existing evidence base is of only moderate size and these different findings will, in part, reflect differences in the number of studies available and the precision of the pooled effects. Pooled effects suggest a significant benefit for self-care support interventions for asthma that is not confirmed in mental health. Self-care support interventions for children and young people can vary considerably in the extent to which they target different service utilisation behaviours and this potential influence may be meaningful. It is plausible, for example, that, although written action plans to control asthma exacerbations may play a direct role in avoiding ED visits, self-care support for mental health may be more focused on longer-term recovery and patient empowerment. Notably, however, the potential burden of these different intervention models may also differ. Preliminary data in our permutation plots suggest that, although self-care support interventions can reduce utilisation for children and young people with asthma, compromises in their QoL cannot definitively be ruled out. Compromises in QoL were less evident for mental health conditions, although meaningful interpretation is currently limited by a lack of available data. Our review did not explore differences in the effects of interventions with different content; this information was inconsistently reported by the primary studies in our review. Service developers might usefully explore the process and content of those interventions that did and did not compromise outcomes in the current review to assess the implications of this for future service design. Direct consideration of the aim and purpose of different self-care support interventions, including the rationale for delivering higher-intensity self-care support, may benefit service delivery. Optimal assessment of the effects of more and less intensive self-care support demands a head-to-head 79 98 99 111 178 191, , , , , comparison. Meta-regression is possible, but has limited utility in moderate-to-small data sets as a result of a lack of available power. The variability that we observed in intervention descriptions also challenges its use. Lack of standardisation in the terminology and level of detail used to describe self-care support interventions meant that meta-regression had limited function in the context of the current evidence base. Preliminary analyses suggest that face-to-face delivery may be necessary to secure minimal benefits for ED use but, at present, the evidence base does not discriminate between outpatient clinic or community settings. Further research is needed to confirm which approach works best, in what context and for what condition. Without evidence to suggest that health service utilisation is differentially impacted by different delivery models, decisions regarding where or how to deliver self-care may usefully be determined by patient and practitioner preferences and available service resources. Self-care in relation to children and young people is known to be complex and conceptually different from that of adult populations. Those developing and designing self-care support interventions might usefully consider the extent to which reductions in utilisation are an explicit goal of the intervention, the extent to which health professionals are prepared and willing to transfer 211 51 53– responsibility to families and the extent to which parents and young people are willing to receive it.