The research questions here are: l What is the estimated resource use and cost associated with delivery of the HeLP intervention? This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed discount 100 mg lady era otc breast cancer 49ers jersey, the full report) may be included in professional journals 41 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising purchase 100mg lady era with visa women's health foxboro. 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. Informed through prior development research, and through conduct of the earlier exploratory RCT of 27 28, HeLP, the delivery of the HeLP intervention involves resource use and cost primarily for the staff inputs required during delivery (contact and non-contact activities), for HeLP co-ordinators, the drama co-ordinator, actors and activity/workshop co-ordinators. Teaching staff are present for some activities and take an active role in others, but based on findings from prior pilot research their time input is not considered additional/ incremental input over and above their expected teaching role. Therefore, costs associated with teaching input are not included in the base-case cost analysis; time inputs are described, and these are included in a sensitivity analysis. Additional resource use and costs are incurred in the training of the delivery staff and for materials/ consumables used to support the delivery of the intervention. Data on resource use for delivery of the HeLP intervention were collected within the trial through completion of contact sheets by HeLP co-ordinators at every contact, by component of HeLP, describing who was involved (staff type) in the contact (component of HeLP) and the time inputs for each person involved, including time associated with planning/preparation and related travel time. Given the importance of the drama components in the HeLP intervention, alongside the data collected by HeLP co-ordinator contact sheets, the drama co-ordinator provided details of the estimated resource use associated with the delivery of drama across the HeLP intervention. Estimates for resource use associated with the training required for those staff engaged in delivery of the HeLP intervention were provided by the HeLP study co-ordinator based on their experiences in the running of the trial. Estimates of materials/consumables needed to support delivery of the HeLP intervention are based on within-trial requirements and projected estimates for future delivery. Unit costs for staff inputs are predominantly taken from those published Unit Costs for Health and Social Care staff grades reported by Curtis and Burns. TABLE 18 Unit costs (GBP) used to estimate cost of delivery of HeLP intervention Resource Unit cost (£) Source HeLP co-ordinator 41. Calculation of unit cost per hour based on cost structure reported in Curtis and Burns57 (excludes overheads) [e. This band was chosen given rough equivalence to the Equity rate for actors of £440 per week. Calculation of unit cost per hour based on cost structure reported in Curtis and Burns57 (excludes qualifications, non-staff costs and capital costs) [e. Calculation of unit cost per hour based on cost structure reported in Curtis and Burns57 (excludes qualifications and capital costs) Training – See Appendix 7 Other costs – Consumables (see below) FTE, full-time equivalent; GBP, Great British pounds. This unit cost includes costs associated with management and travel/transport. A higher rate, as above, is applied in sensitivity analyses. 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 43 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. These other additional costs (totalling £940 across the cohort of 27 classes) were assumed to be for a 12-month period and were distributed across the cohort in base-case analyses. Development of modelling framework (Exeter Obesity Model) to estimate the cost-effectiveness of the HeLP intervention versus usual practice As set out in the prespecified economic analysis plan,43 the framework for estimating the cost-effectiveness of the HeLP intervention is based on development of and subsequent use of a decision-analytic model to predict the future costs and benefits associated with an expected between-group difference in the HeLP RCT primary outcome measure of BMI SDS. A two-stage economic model has been developed, described in more detail below, to predict future adult weight status, from weight status profiles at 24-month follow-up in the HeLP RCT (BMI SDS) at age 11–12 years, and thereafter, in stage 2, to predict a profile of future weight-related health events (e. T2DM or CHD) as a function of the predicted adult weight status profiles (i. The aim of the modelling framework – the Exeter Obesity Model – was to capture the difference in costs and outcomes, over time in adult years, associated with weight status profiles at 24-month follow-up for treatment and control participants in the HeLP RCT at age 11–12 years. A decision-analytic model was developed based on a review of published models in this area (i. The model was informed and populated based on literature review for 5960, parameter inputs, and against good practice modelling guidance. The aim of the model-based framework was to estimate the cost-effectiveness of the HeLP intervention, assumed at this stage to be a relatively low-cost public health intervention, versus usual practice. The setting is a UK public health setting, involving a school-based intervention as a means of having an impact on future adult weight status and health status through reduced incidence of adverse health events. The decision-analytic context is the question on the cost-effectiveness of the HeLP intervention versus usual practice, and the modelling framework was not intended to be an accurate prediction of the life experiences of children by weight status through adult years. The development of a model-based framework was set out conceptually in a prespecified economic analysis plan. Results Estimating the resource use and cost of the HeLP intervention The HeLP intervention was delivered to children in 16 schools, reflecting the delivery of the intervention to 27 classes (Table 19). Within-trial data on resource use for delivery were from 719 HeLP co-ordinator contact sheets, representing data on 94% of expected contacts with schools and accounting for school- and class-level activities. Summary data on aggregate resource use across all 27 classes, by staff type and with time (hours) by type of time input (preparation, task and travel), are presented in Table 20. Data by staff type and by school-class configuration are presented in Table 21, showing economies of scale as school size increases. Table 22 reports the estimated total costs for delivery of HeLP across all 16 schools (and 27 classes). Overall, it is estimated to cost approximately £144,749 for delivery of HeLP to the 16 schools, with 27 classes, giving a mean estimated cost per child at £214 (n = 676). Drama staff costs make up 41% of the estimated delivery costs, with HeLP co-ordinator costs accounting for 37% of the overall estimated costs for delivery (when combined, these primary cost components are 78% of the costs for delivery of HeLP). Estimates of the cost for training required for staff involved in delivery of HeLP, and other costs, are based on expected requirements for delivery across a cohort of 16 schools (27 classes), with training for four HeLP co-ordinators (one trainer), two drama facilitators and eight (two teams) actors. The details of the cost estimates of training are provided in Appendix 7. Estimated delivery costs for HeLP by school-class configuration are presented in Table 23, providing an estimate by school size (i. The estimated mean costs by class, and by child per class, show a mean cost per class (per child) that reduces as the school size increases, from £5724 (£229) for a school with one class to £15,390 (£205) for a school with three classes. 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 45 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. ECONOMIC EVALUATION TABLE 20 Resource use by staff type by type of contact (preparation, task and travel): total across 16 schools, 27 classes Type of staff hours (mean) HeLP Teaching Activity Drama Delivery requirement co-ordinator staff co-ordinator facilitator Actor Preparation time Class-level activities 228. Notes (1) No distinction has been made between contact and non-contact time in costing the intervention. However, it is expected that the provision and delivery of HeLP would be at the level of geographical region, involving a mix of school sizes. Sensitivity analysis 1: actors unit costs uprated to £25. This hourly rate is based on guidance from the drama provider for the potential salary level for professional actors, but is aligned here with salary structure for a similarly paid health-care worker using the Agenda for Change band 5 for health staff57 (see Table 20) and unit costs from Curtis and Burns.

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Notably order discount lady era on-line women's health clinic kalgoorlie, orbital frontal lesions predict social disin- Some studies suggest that the impairments found in chil- hibition and impulsivity generic lady era 100 mg mastercard pregnancy bleeding, and dorsolateral lesions affect dren with ADHD cannot be accounted for by psychiatric organizational abilities, planning, working memory, and at- comorbidity (50). Studies of children with ADHD find impairment ADHD may predict a greater degree of neuropsychological in all these neuropsychological domains. This latter finding suggests that familial psychological test data—along with the clinical features of ADHD and neuropsychological impairment identify a the disorder—implicate both orbitofrontal and dorsolateral more biologically based type of ADHD. In contrast, the mesial milial cases of ADHD with lesser neuropsychological im- prefrontal region, where lesions predict dysfluency and the pairments may have other etiologic factors. Children with slowing of spontaneous behavior, is not implicated in ADHD do not appear to be impaired on simple motor ADHD. The 'pre- are caused by specific, not generalized, deficits (51). Given the known role of subcortical networks as These studies have also shown adults with ADHD to be modulators of prefrontal functioning, the term frontosubcor- impaired in other functions known to affect children with tical seems appropriate for ADHD. These include the following: perceptual-motor behavioral or cognitive dysfunction that looks 'frontal' but speed as assessed by the digit symbol/coding tests (54,55); may be influenced by subcortical projections. For example, the cingulate cortex influences mo- Test (57,58). Because neuropsychological tests are free of tivational aspects of attention and in response selection and the potential biases of self-reported symptoms, the finding inhibition. The brainstem reticular activating system regu- that the neurocognitive profiles of adults with ADHD are lates attentional tone and reticular thalamic nuclei filter in- similar to those of children with ADHD suggests that the terference. Working memory deficits implicate a distributed diagnosis of ADHD is valid as applied in adulthood. Moreover, the atten- literature, not findings that have been consistently repli- tional problems of children with ADHD may implicate a cated. Although there are inconsistencies among studies, it wider distribution of neural networks. A system mainly in- is notable that the pattern of deficits that has emerged is volving right prefrontal and parietal cortex is activated dur- similar to what has been found among adults with frontal ing sustained and directed attention across sensory modali- lobe damage. The inferior parietal lobule and superior temporal support the hypothesis that the frontal cortex or regions sulcus are polymodal sensory convergence areas that provide projecting to the frontal cortex are dysfunctional in at least a representation of extrapersonal space and play an impor- some children with ADHD. Because neuropsychological tests provide indirect mea- sures of brain function, we must be cautious in using them Neuroimaging Studies to make inferences about the locus of brain impairment in ADHD. Yet because many of these tests have been standard- Fortunately, hypotheses based on neuropsychological infer- ized on normative populations and administered extensively ence can be tested with neuroimaging paradigms. Because to brain-damaged populations, observed deficits tests can neuroimaging studies provide direct assessments of brain Chapter 43: Pathophysiology of ADHD 581 TABLE 43. STRUCTURAL NEUROIMAGING STUDIES OF ADHD Study Diagnosis Method Findings Shaywitz et al. First, and adults with ADHD that used computed tomography the adolescent samples studied may have been more hetero- or magnetic resonance imaging. Among these studies, the geneous than the adult samples. Although all the adults had most consistent findings implicated frontal cortex, usually persistent ADHD, some of the adolescent cases may have limited to the right side, cerebellum, globus pallidus, cau- remitted by adulthood. Thus, frontal dopaminergic hypoac- date, and corpus callosum. Several other regions were less tivity may be associated with persistent ADHD only. Consistent with these findings, the natively, Ernst et al. These mice shift from the midbrain in childhood to the prefrontal cor- show learning impairments, impulsiveness, and hyperactiv- tex in adults. Metabolic mapping studies suggest that their behavioral Anterior cingulate cortex, lying on the medial surface deficits are associated with lower 2-deoxyglucose uptake in of the frontal lobe, has strong connections to dorsolateral the left striatum and the frontal and parietal cortex (61). In contrast to sion tomography, single photon emission tomography, controls, the adults with ADHD failed to activate the ante- functional magnetic resonance imaging, or electroencephal- rior cingulate cortex. The most consistent findings were hypoactivity of kin et al. The neurochemical basis of brain dysfunction in ADHD found gender differences in lateralization (63), future stud- was studied by Dougherty et al. They measured DAT ies will need to assess gender differences and to determine density by single photon emission computed tomography how they may be related to the male predominance of the with the radiopharmaceutical iodine 123–labeled altropane. Their findings were consistent with the catecholamine hy- 582 Neuropsychopharmacology: The Fifth Generation of Progress TABLE 43. FUNCTIONAL NEUROIMAGING STUDIES OF ADHD Study Diagnosis Method Findings Lou et al. Taken together, the brain imaging anomalies and malformations of the posterior fossa were studies fit well with the idea that dysfunction in frontosub- more common among patients with ADHD compared with cortical pathways occurs in ADHD. How- with the report of a father and son, both having methyl- ever, given that several other studies showed partial agenesis phenidate-responsive ADHD secondary to frontal lobe epi- of the corpus callosum or anomalies of the cerebellar vermis lepsy (68). Notably, the frontosubcortical systems that con- (also formed before birth), it seems reasonable to conclude trol attention and motor behavior are rich in that at least some children with ADHD have a very early catecholamines, which have been implicated in ADHD by onset of brain abnormalities. In a novel approach to assessing brain regions implicated in ADHD, Herskovits et al. Compared with head-injured children who did not develop Figure 43. To address this issue, Nopoulos et diagnosis is valid. These studies leave no doubt that ADHD Chapter 43: Pathophysiology of ADHD 583 Faraone et al. These investigators reasoned that cases that remit before adolescence could have a smaller genetic component to their disorder than persistent cases. Evidence supporting this hy- pothesis derives from several studies. In a prospective follow- A up study, Biederman et al. Thus, these data suggest that children with persistent ADHD have a more familial form of ADHD than those whose ADHD remits by adoles- cence. The 57% rate of ADHD among children of adults with ADHD was much higher than the more modest 15% risk for ADHD in sib- lings of referred children with this disorder. These findings were consistent with a prior study by Manshadi et al. C They studied the siblings of 22 alcoholic adult psychiatric patients who met DSM-III criteria for ADD, residual type. The authors compared these patients with 20 patients A: ADHD in siblings. Forty- one percent of the siblings of the adult ADD probands were diagnosed with ADHD compared with 0% of the non- ADHD comparison siblings. Moreover, studies of more distant relatives are In another retrospective study, Biederman et al. These investigators found that the relatives of adoles- The Harvard/Massachusetts General Hospital (Boston) cent probands had higher rates of ADHD compared with ADHD family project studied two independent samples of the relatives of child probands.

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I. Kent. Drury University.