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Outcomes & impact portfolio summary & review april 2012, for ukern

Impact & Outcomes CSG
PORTFOLIO SUMMARY & REVIEW
June 2012, FOR UKERN
Written and Prepared by: Professor Gus A Baker
CSG Core working group: Gus A Baker, Ann Jacoby, Mike Kerr, Helen Cross, Henry
Smithson, Jill Clayton Smith, Graham Boyd and Sarah Monkman 1. Summary:
• A comprehensive review of impact and outcomes related studies on the UKERN research portfolio between Feb 2010 and 2012 was undertaken, and compared against published national and international epilepsy research priorities. • The UK is active in epilepsy research, with a broad range of basic science and clinical studies, both industry and investigator lead, taking place across several centres with diverse funding sources. There is a history in the UK of conducting research that draws attention to understanding the impact of epilepsy and its treatment, particularly in respect of quality of life issues. More recently attention ahs been drawn to a better understanding to the neuropsychological consequences of epilepsy and an appreciation of the effects of AEDs on teratogenicity. • Impact and outcome studies cover a range of a broad scientific endeavours
Aim of this document:
This Report brings together published research recommendations for research of direct relevance with respect to impacts and outcomes of epilepsy: • Determine the most important areas for future research relevant to the impacts and • Compare all the recommendations of future research to the current portfolio of research in the UK, and known studies in development elsewhere and identify significant gaps in the research portfolio Consensus on the most important areas for future research for Impact and
Outcomes
There are a number of recent documents highlighting the need to address gaps in research and these include the European Brain Council 2006, ILAE Taskforce, 2009, NINDS Epilepsy Research Benchmarks, 2007 and DUETS report, Patient’s priorities for research into epilepsy 2008. The most relevant recommendations in relation to the Impact
and Outcomes group can be grouped into the following sections:
Section 1 Identification of the cause and extent of Cognitive Impairment and
Co-morbidities
• Identify the cause and extent of cognitive impairment and psychiatric comorbidity associated risk factors using prospective and case‐control studies in people with • Research into memory problems • Develop and assess interventions to ameliorate cognitive impairment and • Identify the cause and extent of cognitive impairment and psychiatric comorbidity and analyse associated risk factors using prospective and case‐control studies in • Delineate the natural history of comorbidities in epilepsy, including the nature of the relationship between specific comorbidities and the underlying causes of epilepsy, specific features of epilepsy (e.g., age of onset, frequency of seizures, interictal epileptiform abnormalities), and treatment [e.g., antiepileptic drugs (AEDs), surgery]. • Determine if the affective, attentional, and cognitive disorders in people with epilepsy are the same as those in people without epilepsy with respect to natural history, presentation, treatment, and underlying mechanisms. • Develop at least one efficacious care model for the diagnosis and treatment of epilepsy and validate that it improves the outcomes for patients with comorbidities. • Develop and implement a standardized protocol for screening pharmacologic and non-pharmacological treatments of epilepsy for their amelioration or exacerbation of neuropsychiatric and cognitive comorbidities. Section 2 Treatment of Neuropsychological conditions and Co-morbidities
• Treatment of Epilepsy Comorbidities (cognitive, neuropsychiatric, other adverse Short term: determine whether the treatments used for cognitive or neuropsychiatric conditions in isolation are effective when utilised in people with epilepsy (or whether different strategies are required) Short term: develop at least one efficacious care model for the diagnosis and treatment of epilepsy and validate that it improves the outcomes for patients with comorbidities. • Develop and assess interventions to ameliorate cognitive impairment and • Develop and validate novel treatments and management strategies for cognitive and neuropsychiatric disorders of people with epilepsy that are not adequately treated with currently available therapies. • Research into treatments with fewer side effects a. Noted that for many patients side effects are more worrying/harder to b. Including specifically physical, intellectual /cognitive, emotional side • Determine the optimal treatments for the neuropsychiatric and cognitive Section 3 Patient Education and Support
• Determine the impact of genetic testing on medical care and patient counselling. • Research into the level of expertise among the medical profession, and other relevant professionals (schools, employers) • Research into the effectiveness of psychological support/support with psycho‐social • Research on patient information provision/access to the right specialists/information. Section 4 Others
• Research into stigma associated with epilepsy
• Develop/validate effective methods for the treatment of Non‐Epileptic Seizures
• Research into the level of expertise among the medical profession, and other
relevant professionals (schools, employers). • Research on patient information provision/access to the right specialists/information. 8. Summary
Porfolio.
Methods: Research projects underway in the UK were identified by a search of clinical
research network and funders websites, and supplemented by information obtained via electronic calls to epilepsy related mailing lists and personal contacts. A questionnaire was sent to all project PI's and they were asked to return information about the project. All available information on projects identified as primarily focused on Impact and Outcomes (I&O) of epilepsy (and related conditions) were reviewed by members of the I&O clinical study group (CSG) using a pro forma to extract information about study design, patient group and outcomes. Reviewers were asked to comment on relevance of the research. 9. Results:
A total of 40 studies (appendix 1) were allocated to the I&O CSG. Available material for each study varied considerably, with abstracts obtained for only 20 Nature of the studies
Of these studies the majority of studies were related to research specifically investigating the neuropsychological consequences of epilepsy. There were two studies relating to pre- conceptual counselling and the neurodevelopmental effects of exposure to antiepileptic drug treatment. One study relating to studying patient perceived side effects of anti- epileptic drug treatment and three studies relating to quality of life/resilience and decision Which Organisations were funding
The majority of the studies were funded by Epilepsy Action or ERUK with the MRC and Welcome Trust supporting between them only three of the identified studies. Location of Research Work conducted
The majority of studies were conducted at either Kings College London or University College London. However other institutions such as the Universities of Sheffield, Liverpool, Cambridge and Oxford were also involved in conducting research in the area of Review of the abstracts
There was a predominance of studies [11] relating to neuropsychological functioning. These included research into long-term forgetting [see abstracts 5 & 6], reorganisation of language and memory systems [see abstract 4], the consequences of temporal lobe surgery [see abstract 8], the neuropsychological profile of JME [see abstract 9], the neuroatonomical basis of frontal lobe cognitive dysfunction [see abstract 13], transient epileptic amnesia and facial recognition [see abstract 22] and improved spatial learning as a result of restoration of neurogenesis. These studies were rated as being “very relevant” There were two studies relating to the outcome of pregnancy and pre-conceptual counselling conducted by the Liverpool and Manchester Neurodevelopment group [LMNDG]. These studies were rated as highly relevant. This is a fairly contentious area of research and both these papers are part of a concerted effort to address this area. Patient perceived Quality of life There were two studies from the University of Liverpool Outcomes research group; they were related as highly relevant. One study focussed on the role of resilience in determining quality of life and one study looking at a better understanding of Quality of life The single study by Wieshmann and colleagues has been investigating patient perceived side effects of AED treatment. It was also ranked as very relevant by the reviewers. Impact of Epilepsy and its treatment Two studies were involved in understanding the impact of epilepsy. One of the studies focussed on how families adjust to having a child with epilepsy, while the other considers the impact of memory problems. The latter study attempts to understand the relationship between objective and subjective complaints of memory functioning for people with epilepsy. A third study in this section explores the reporting of depression as a co- morbidity of epilepsy by the Cardiff Research Group. The latter study has implications for the management of co-morbidities in general practice, while the former studies are much more empirical in their nature but important raise awareness about the wider impact of 14 Summary
There is a body of research in the UK that has a strong record of publishing high quality research into the impact and outcomes of epilepsy and its treatment. The abstracts reviewed clearly identify that there remains a desire to conduct high quality research that directly relates to helping improve the quality of life of those with the condition. The breadth and depth of research highlights the interest that this condition engenders and the scope available to conduct meaningful research. It is important to understand that while the authors have attempted to be inclusive in the coverage of research under the banner of the I & O, there is very likely research that has not been captured and therefore not reviewed. It was not possible, within the remit of the group, to identify every piece of research currently being conducted in this arena. However the abstracts reviewed probably reflect areas of research that are currently being conducted. Conclusions
A number of observations can be made in respect of the studies reviewed today and these • Recently published documents [see section 3] have highlighted a number of gaps in the research agenda that have relevance for the I & O group and these include: the identification and cause of cognitive impairment; identification and cause of co- morbidity; development of care models and interventions; providing treatment for both cognitive impairment and co-morbidities; determine the impact of psycho- educational programmes and the development of intervention programmes for • The pattern of research in the UK, as gleamed from the abstracts, goes someway in meeting the recommendations of the various reports. • The most obviously glaring deficit is the development of intervention programmes for neuropsychology and the co-morbidities. The authors are aware of recent funding from the UK NIHR to conduct trials to investigated psychoeducational programmes in adults and children with epilepsy. However there is no known research investigating programmes that address intervention for ameliorating the impact of neuropsychological deficits or co-morbidities such as anxiety and • It is the opinion of members of the I & O group that programmes of research aimed at intervention are probably the most difficult to devise, implement and fund. However the UK has an enviable record of multi-centre studies which inevitably will be necessary to conduct this type of research. The challenge will be to persuade funding bodies to recognise the importance of these areas and provide sufficient funding to support well designed studies. • In light of the impending retirement of key leaders into research focussing on impact and outcome there is a need to develop individuals or groups who are likely to be taking a major role in the next decade. As part of succession planning it will be necessary for the funding agencies to consider proving support e.g. grants and fellowships to help develop the future “stars” in this area of research. APPENDIX I: ABSTRACTS AVAILABLE FOR REVIEW
1. RESILIENCE
A considerable body of research highlights that epilepsy has the potential to produce marked decrements in quality of life (QOL); but QOL outcomes in epilepsy are heterogeneous, with some people maintaining good QOL in face of poorly controlled epilepsy and others reporting poor QOL despite their condition being well controlled. Most studies to date have emphasised risk factors for impaired QOL. Much less addressed is the We will examine the role of resilience, ie. the process of achieving positive outcomes in adverse conditions, for life quality in people with epilepsy (PWE) and explore factors promoting it. We will focus on the processes by which individuals manage to maintain high QOL despite developing epilepsy, referring not only to individual psychological traits, but also to a range of external factors. Our findings will be important for informing future intervention studies to maximise QOL and full potential of PWE. TRAJECTORIES
Seizures and epilepsy can have a profound impact on a person’s quality of life. To date, research on quality of life in epilepsy has largely been concerned with the quality of life of people with already established epilepsy. As a result, we do not have a clear understanding of what factors contribute to changes in quality of life, both good and bad, that occur from the point of diagnosis of epilepsy onwards. We propose to continue following up a large group of people with newly diagnosed epilepsy, who agreed to take part in a study comparing different antiepileptic drug treatments. We will follow everyone for four years, collecting information about their health, everyday functioning and quality of life, using postal questionnaires. This will allow us to detect any changes that occur in quality of life and what is responsible for these changes. Our study will allow us to investigate how and why quality of life is affected by having epilepsy. The findings will be valuable for both patients and healthcare professionals treating them, since they will help us to understand how those affected can best be supported medically and socially to maintain a good quality of Taylor J & Baker GA (2010). Newly diagnosed epilepsy: Cognitive outcome at five years. Epilepsy & Taylor J, Jacoby A, Baker GA, Marson AG, Ring A, Whitehead M. Factors predictive of resilience and vulnerability in new-onset epilepsy. Epilepsia, online. Doi: 10.1111/j.1528-1167.2010.02775.x Baker GA & Taylor J, on behalf of the SANAD group (in submission). Newly diagnosed epilepsy: Cognitive outcome at 12 months. Re-submitted to Epilepsia Taylor J, Jacoby A, Baker GA, Marson AG. Self-reported and parent-reported quality of life of children and adolescents with new-onset epilepsy. Re-submitted to Epilepsia. COGNITIVE CONSEQUENCES OF IN UTERO EXPOSURE TO SECOND GENERATION
It has been shown that mothers who take antiepileptic drugs (AEDs) during pregnancy have an increased risk of having a baby with a physical malformation, such as a cleft lip and palate. There is also evidence to suggest that exposure to AEDs in the womb can have a long-term impact on the intellectual and cognitive abilities of children, including language skills, memory and intelligence. Studies to explore the long-term consequences of exposure to older AEDs (such as carbamazepine and sodium valproate) during pregnancy are currently underway. However additional projects are required to determine whether the newer AEDs (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagibine, topiramate, and virgabatrin) have similar The researcher team will identify a total of 160 children (aged 6 years and over), born to mothers with epilepsy who were treated with the AEDs gabapentin, topiramate or levetiracetam during pregnancy, using the UK Epilepsy & Pregnancy Register. They will then assess the cognitive ability of these children, at home or in school, using a variety of specially designed tasks. This project will offer new information about the long-term consequences of exposure to modern AEDs in the womb, and will be immediately applicable to patients. Prospective mothers with epilepsy will therefore have the chance to make more informed decisions about their drug treatment during pregnancy. 4. INVESTIGATING
REORGANISATION OF LANGUAGE AND MEMORY SYSTEMS IN TEMPORAL
LOBE EPILEPSY
The absence of major aphasia following anterior temporal lobectomy to treat TLE has been interpreted as evidence that anterior temporal cortex has little role to play in speech comprehension and production. This contrasts with studies in patients with semantic dementia, and some functional imaging studies on normal subjects. My study will investigate the functional anatomy of speech comprehension and production, with emphasis on anterior and mesial temporal lobe structures, in patients with chronic TLE who have not undergone neurosurgery. In particular, it will assess whether reorganisation accompanies chronic focal temporal lobe epileptic activity, invalidating inferences about normal organisation drawn from the behavioural effects of anterior temporal lobectomy. In parallel, the study will investigate episodic verbal memory encoding and retrieval that accompanies speech comprehension and production. 5. ACCELERATED
LONG-TERM
FORGETTING IN EPILEPSY: THE ROLE OF INTERFERENCE
The majority of people with epilepsy have problems with their memory. These problems may be partly due to a recently discovered form of memory impairment called Accelerated Long- term Forgetting (ALF). People with ALF can learn information well but find that it fades rapidly from memory over a period of days to weeks. This project is investigating why some people with epilepsy forget things more quickly than they should. Normally, new memories are gradually strengthened or ‘consolidated’ over time. Based on our previous work, we suspect that, in epilepsy, memory consolidation is disrupted by ongoing mental activity. Furthermore, we expect that a period of mental inactivity (peace and quiet) after learning will help to reduce forgetting. We are studying forgetting rates in a group of people particularly prone to ALF – those with a form of epilepsy called transient epileptic amnesia. In particular, we are examining how memory performance varies according to the amount and type of mental activity that follows learning. By understanding the mechanisms that lead to rapid forgetting in epilepsy, we are working towards the development of strategies and memory aids specifically targeted to helping people with epilepsy. THE NEURAL BASIS OF ACCELERATED LONG-TERM FORGETTING IN EPILEPSY
Accelerated long-term forgetting (ALF) is an unusual type of memory disorder recently recognised to affect some people with epilepsy. People with ALF seem able to learn new information perfectly well, but find that it “leaks away” over following days. This is distinct from memory problems seen in brain diseases like Alzheimer’s dementia, where the difficulty is with learning itself. ALF is clinically important. Its cause is unknown and it may be treatable. It is also scientifically important, having the potential to reveal the mechanisms by which new memory traces become stabilised (or consolidated) in the brain over time. This project is investigating the brain mechanisms that underlie ALF. Our hypothesis is that ALF is caused by abnormal electrical activity in the brain, especially occurring during sleep, which disrupts normal processes of memory consolidation. This is being investigated in a group of patients with transient epileptic amnesia, a form of epilepsy in which ALF is particularly common, as well as in healthy people. Participants learn some information in the evening, have their brain waves (electroencephalogram, EEG) recorded whilst they sleep and then have their memory tested the following morning. We are examining whether abnormalities in patients’ brain waves can explain their forgetting. We also examine participants’ brain waves whilst they learn and whilst they try to remember to see whether these processes are also abnormal in ALF. This is being done using magnetoencephalography, a technique that is much better than EEG at localising where in the brain signals arise. EPILEPSY IN INFANCY: SPECTRUM OF AETIOLOGIES, NATURAL HISTORY AND OUTCOME
PREDICTORS
Epilepsy is a brain disorder characterised by recurrent, unprovoked seizures. It affects around 75, 000 children in the United Kingdom, many of whom develop learning and behavioural problems. The incidence of childhood epilepsy is greatest in the first year of life, and it is this group who remain most at risk for developmental compromise. Evidence suggests that early control of seizures is associated with better developmental outcome. However, many children are referred late in the natural history of the epilepsy. This is in part because there is a lack of knowledge about the specific natural history of the early onset epilepsies that would allow early identification of children who are at particular risk. The purpose of this investigation is to address this gap in knowledge by carrying out a population-based study enrolling children at the time of their diagnosis with epilepsy at under 2 years of age and continuing to follow them up through childhood. We have carried out testing at baseline (diagnosis) and 1 year follow up. Currently, children are undergoing further follow up at 2.5-5.5 years, a suitable age for detecting social or cognitive impairments as such skills normally develop quickly over this period. By relating this new information to what we already know about the early characteristics of the epilepsy in these children, we will address an important gap in knowledge to allow earlier identification and treatment of infants at particular risk. THE CONSEQUENCES OF TEMPORAL LOBE EPILEPSY SURGERY
Uncontrolled epilepsy commonly arises from the brain’s temporal lobe and surgical resection stops seizures in 70% of patients. This operation, however, may affect language, memory, decision-making vision and mood. We will use MRI brain scans to investigate these brain functions, which are normally carried out in the temporal and frontal lobes. We will find out how epilepsy in the temporal lobe, and surgical removal of the front part of the temporal lobe, affects these functions and the connections of these parts to the rest of the brain. We will ascertain which MRI scans, taken before surgery, may predict problems afterwards. This will enable us to minimise the risks of surgery. By repeating the testing of brain function and vision and MRI scans 3 and 12 months after surgery, we will be able to see how the brain compensates for the surgical removal of the anterior part of one temporal lobe. We will also develop new ways of visualising the white matter connections and of integrating this information with scans that show the brain’s anatomy and function, and we will make these methods freely available to other NEUROPSYCHOLOGICAL PROFILES OF PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY
AND THEIR SIBLINGS
JME constitutes 12 percent of all epilepsies. In some cases, there are subtle abnormalities in the frontal lobes on MRI scanning, and there has been speculation that JME is associated with frontal lobe or executive dysfunction. The frontal lobes are important for planning, problem solving, memory and social interactions. They provide the motivation and cognitive capacity that get us through our daily tasks, and generate language. All these roles are called executive functions. 1. Are people with JME more likely to exhibit signs of executive dysfunction using routine psychometric tests compared with a sibling and control? Siblings are included because there is a genetic aspect to JME. Close relatives can have abnormal EEGs. We want to know if they have subtle executive dysfunction. 2. Are people with JME more likely to display behaviours in keeping with executive dysfunction compared to 3. Does mental effort trigger brief epileptic discharges in JME patients, potentially disrupting how new memories are formed? This will have implications for how people with JME learn. The study will provide insights enabling the development of patient centred services for people with epilepsy FAMILES WITH CHILDREN WITH EPILEPSY: DECISION MAKING AT DIAGNOSIS
This study will investigate the consequences within families of caring for a child with epilepsy. In particular it considers how diagnosis of epilepsy influences family relationships, especially caring, parenting, grandparenting and sibling relations. It also focuses on how families respond to uncertainty and changes in the management of the condition over time and the role of lay beliefs with particular reference to diet in caring for an epileptic child. The study employs a qualitative research design, involving interviews with 20 children aged 7-14, their main carer and a sibling. Roughly a third of these children will be from families who have recently been diagnosed and a third from those who have been diagnosed for at least five years. Both of these groups will be recruited from amongst children attending neurology clinics. A third group will be recruited from amongst those children being treated using the ketogenic diet. This will enable the project to further investigate the experiences of families who have lived with epilepsy for some time and sought an THE ROLE OF ILLNESS REPRESENTATION IN THE EXPERIENCE OF POOR MEMORY IN
PEOPLE WITH EPILEPSY: NEW IMPLICATION AND QUALITY OF LIFE.
Although there is little doubt that people with epilepsy suffer from memory impairment, studies do not consistently demonstrate significant relationships between subjective and objective memory. This study uses a rigorous methodological design, with subjective and objective measures that assess corresponding domains (i.e., verbal and visual memory), to investigate the nature of memory complaints by considering roles for anxiety and depression, possible decline from pre-morbid abilities, and non-memory cognitive difficulties. The idea that subjective memory complaints may be related to people’s beliefs about their epilepsy is investigated using the Common Sense Model of illness representations Hall, K., Isaac, C. & Harris, P. (2009). Memory Complaints in Epilepsy: an Accurate Reflection of Memory Impairment or an Indicator of Poor Adjustment? A Review of the Literature. Clinical Psychology Review, 29, Hall, K.E., Isaac, C.L., Harris, P. & Rowe, R. (2008). Using illness representations to understand the nature of memory complaints in epilepsy. Journal of the International Neuropsychological Society, 14, Suppl.2, 71. 12. IDENTIFYING
DEPRESSION IN PEOPLE WITH EPILEPSY ATTENDING THEIR GENERAL
PRACTITIONERS’
We explored whether some simple questionnaires could be used in general practice to identify depression in people with epilepsy. Our study showed that two short scales were very accurate in identifying depression in people with epilepsy. In fact depression was present in over a third of people. We also asked people with epilepsy how they would like to get help if they were depressed. People showed quite a range of possible ways including seeing the GP or talking to friends and family. This work will help us to understand better how depression in people with epilepsy can be addressed in Margrove KL, Mensah SA, Thapar AK & Kerr MP (2011) Help-Seeking and Treatment Preferences for Depression in Epilepsy. Epilepsy & Behavior (in press) Margrove K, Mensah SA, Thapar AK & Kerr MP(2011) Depression screening for patients with epilepsy in a primary care setting using the PHQ-2 and the NDDI-E. Epilepsy & Behavior (in press) THE NEUROANATOMICAL BASIS OF FRONTAL LOBE COGNITIVE DYSFUNCTION IN
FRONTAL LOBE AND IDIOPATHIC GENERALISED EPILEPSIES
Frontal lobe epilepsy and juvenile myoclonic epilepsy are two common types of epilepsy. Affected individuals are at risk of cognitive problems including difficulty making decisions, planning and concentrating. Such difficulties have a bad effect on a person’s ability to function at work and in everyday situations. We can use brain scans to measure what areas of the brain are working when people are making decisions and doing other cognitive tasks. We plan to scan people with these two types of epilepsy and find out whether they have faulty brain function and connections, that are associated with any cognitive problems. We will also follow people with frontal lobe epilepsy who have surgery to see what cognitive changes take place. The findings from this study will increase our understanding of these two disorders and provide information that will help us to better advise people and identify those who would be at risk of further cognitive problems if they were to have surgery to treat their epilepsy 1. Vollmar C, O’Muircheartaigh J, Barker GJ, Symms MR, Thompson P, Kumari V, Duncan JS, Janz D, Richardson MP, Koepp MJ. Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study. Brain 2011;134(Pt 6):1710-9 2. O'Muircheartaigh J, Vollmar C, Barker GJ, Kumari V, Symms MR, Thompson P, Duncan JS, Koepp 3. Vulliemoz S, Vollmar C, Koepp MJ, Yogarajah M, O'Muircheartaigh J, Carmichael DW, Stretton J, 4. O'Muircheartaigh J, Vollmar C, Traynor C, Barker GJ, Kumari V, Symms MR, Thompson P, Duncan 5. Centeno M, Thompson PJ, Koepp MJ, Helmstaedter C, Duncan JS 6. Vollmar C, O'Muircheartaigh J, Barker GJ, Symms MP, Thompson PJ, Kumari V, Duncan JS, Richardson MP, Koepp MJ. (2010) Identical, but not the same: Intra-site and Inter-site Reproducibility of Fractional Anisotropy Measures on two 3.0 Tesla scanners. Neuroimage. 2010 15;51(4):1384-9 14. SOCIAL
UNDERSTANDING
IN CHILDREN WITH EPILEPSY
Children with epilepsy are at increased risk of communication and behavioural problems and deficits in social cognition may be a contributory factor to poor outcomes. This research involved three studies that assessed different aspects of social cognition and social attention in a group of children with uncomplicated epilepsy. The first study involved 55 children with epilepsy and 69 typically developing children. It employed socio- cognitive and socio-perceptual tasks that asked children to interpret and reason upon mental and emotional states, assessments of IQ, expressive language and parental report measures of communication and behaviour. The main findings indicate children with epilepsy had greater difficulty with the socio-cognitive reasoning task compared to typically developing children beyond IQ and language. The degree of socio- cognitive impairment was associated with increased parental reports of communication and behavioural problems in children with generalized seizures. Children with focal seizures showed the poorest performance across most of the assessed domains and no clear link emerged between socio-cognitive reasoning and reported problems in this group. The second study involved 57 children (34 with epilepsy) and addressed mental states attribution processes and executive function. Atypical mental states attribution was associated with poor executive function in children with epilepsy with increased behavioural problems and this was not associated with epilepsy related factors. The third study used an eye-tracker to measure social attention and response inhibition to dynamic displays of gaze and emotion. It involved 59 children (25 with epilepsy). Children with epilepsy were slower to produce a correct response in conditions that demanded increased inhibitory control. Analysis of the error latencies also provided evidence of atypical gaze and emotion processing that was linked to parental reports of social problems in children on and off medications. This may be a preliminary indicator of social attention deficits that persist beyond active seizures. Lunn, J. F., Lew, A.R., Tomlin, P., Basu, H., Lewis, C., Roach J., Rakshi, K. and Martland, T. (2010) Social Understanding in Children with Epilepsy. Paper presented at the British Pyschological Society Developmental Psychology Section Conference, 12-15 September 2010, London, UK. Lunn, J. F., Lew, A.R., Tomlin, P., Basu, H., Lewis, C., Roach J., and Martland, T. (2009) Social Understanding in Children with Epilepsy. Poster presented at the Biennial Meeting of the Society for Research in Child Development, 2-5 April 2009, Denver, USA. INVESTIGATING THE RELATIONSHIP BETWEEN SLEEP DISTURBANCE AND LEARNING IN
CHILDREN WITH BENIGN EPILEPSY OF CHILDHOOD WITH CENTROTEMPORAL SPIKES
(BECCTS)
The recognition of a role for sleep in the consolidation of learning and memory raises the possibility that chronic sleep disturbance in some epilepsy syndromes restricts children's learning and development. Benign Epilepsy of childhood with centrotemporal Spikes (BECCTS) is a relatively common form of childhood epilepsy featuring brief seizures that mostly occur during sleep. Treatment of this syndrome is guided by an assumption that the syndrome is relatively benign, given that seizures usually occur at night and children grow out of their epilepsy. However, a number of distinct learning problems have recently been associated with BECCTS. The aim of our research is to investigate the link between sleep disturbance and learning in children with BECCTS and the further possibility that learning problems may be helped with effective treatment. We will investigate children with BECCTS with a combination of electroencephalography (EEG), sleep analysis and assessments of learning consolidation. We will analyse EEG, sleep quality and learning ability to see if there are any links between these factors. We will then repeat the EEG recording, analysis of sleep and learning tasks after treatment with anti-convulsant medication or placebo. Further data analysis will determine whether EEG, sleep quality or learning is improved by treatment. NATURALISTIC STUDY OF THE SHORT-TERM COURSE OF NON-EPILEPTIC SEIZURES
Non-epileptic seizures (NES) look like epileptic seizures but are not accompanied by abnormal electrical activity in the brain. NES are thought to have psychological causes, such as trauma or stress. Psychological therapy is considered the treatment of choice for NES, although there is little evidence that it is effective, and it is not widely available in the NHS. We are planning to do a RCT of a psychological intervention in the future. This study will tell us how many patients become free of seizures over a five months period after the diagnosis has been explained to them. This will allow us to calculate the group sizes for our future RCT in which active psychological treatment after the diagnosis will be compared to no specific treatment. NATIONAL GENERAL PRACTICE STUDY OF EPILEPSY- LONG TERM
Most long term studies of people with a first epileptic seizure have been hospital-based, and this is likely to depict epilepsy as a chronic, progressive, incurable disorder. The National General Practice Study of Epilepsy was set up in the 1980s to follow a group of people in whom the General Practitioner (GP) The group of people notified to the study has been follow-up since the 1980s, and many articles have been published. The most recent paper showed that the risk of premature mortality was still increased 20 years We sent a follow-up form to GPs of survivors in 2009-10 and plan to analyse the outcome in terms of seizure control. We will use statistical techniques to analyse the time to the first seizure. We will also describe patterns of seizure outcome (for example, people in whom no further seizures ever occurred, individuals who had early seizures but later stopped having seizures, or people in whom the first subsequent seizure occurred many years later). We aim to be able to give people diagnosed with a first seizure a more realistic idea of what the outcome may be in terms of seizure control. UK ANTI- EPILEPTIC DRUG REGISTER
The UK Anti Epileptic Drug Register is a surveillance tool for AED with aim to identify the most effective AED with the least adverse effects for both partial and generalized epilepsies. Patients are invited to provide information on AED efficacy and adverse effects anonymously. The register is web based but patients can use a paper version. As of the 4th of September 2011 we have 600 data sets. At the Walton Centre the register is supported by the IT department and the Clinical Trials Unit. We are grateful for the support from Epilepsy Action, both financially and by advertising the register. In a small pilot study using the LAEP we found that in monotherapy Lamotrigine (LTG) was overall the drug with the least adverse effects. In a separate study just under 50% of patients on Levetiracetam reported aggression towards others as being a sometimes or always a problem. Large numbers are necessary for the surveillance of the ever increasing number of AED. We are planning to advertise the register nationwide and have expanded the team. 1. Wieshmann U, Tan GM, Baker G. Self reported symptoms in patients on antiepileptic drugs in monotherapy. Acta Scan Neurol. accepted for publication. 2. Wieshmann U, Baker G. Self reported Anger and Depression in Patients on Levetiracetam in Mono and Polypharmacotherapy. Abstract ILAE York 2011.

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