Exploring the use of strategic frameworks in dental practice

This paper explores the use of strategic frameworks in NHS and private dental practice. It reviews the policy context of dentistry and suggests the challenges in this context will require dental practices to prioritise understanding and engagement with a strategic approach. A strategic approach will be required in order to enhance and improve performance. Two specific strategic frameworks will be explored in terms of their relevance to NHS and private dental practic

Excavations and the afterlife of a professional football stadium, Peel Park, Accrington, Lancashire: towards an archaeology of football

Association football is now a multi-billion dollar global industry whose emergence spans the post-medieval to the modern world. With its professional roots in late 19th-century industrial Lancashire, stadiums built for the professionalization of football first appear in frequency in the North of England. While many historians of sport focus on consumerism and ‘topophilia’ (attachment to place) regarding these local football grounds, archaeological research that has been conducted on the spectator experience suggests status differentiation within them. Our excavations at Peel Park confirm this impression while also showing a significant afterlife to this stadium, particularly through children’s play

MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

Background: Propionic acidaemia (PA) results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS) to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes.Methods: Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging.Results: MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group.Conclusions: The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to replenish a compromised Krebs cycle and that this is a marker of compromised aerobic respiration within brain tissue. Thus there is a need for improved brain protective strategies during acute metabolic decompensations. MRS provides a non-invasive tool for which could be employed to evaluate novel treatments aimed at restoring basal ganglia homeostasis. The results from the liver transplantation sub-group supports the hypothesis that liver transplantation provides systemic metabolic stability by providing a hepatic pool of functional propionyl CoA carboxylase, thus preventing further acute decompensations which are associated with the risk of brain infarction

Incidence of Primary Mitochondrial Disease in Children Younger Than 2 Years Presenting With Acute Liver Failure

Background: Mitochondrial liver disease (MLD), and in particular mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an important cause of acute liver failure (ALF) in infancy. Early and accurate diagnosis is important because liver transplantation (LT) is often contraindicated. It is unclear which methods are the best to diagnose MLD in the setting of ALF. Objective: The aim of the study was to determine the incidence of MLD in children younger than 2 years with ALF and the utility of routine investigations to detect MLD. Methods: Thirty-nine consecutive infants with ALF were admitted to a single unit from 2009 to 2011. All were extensively investigated using an established protocol. Genes implicated in mitochondrial DNA depletion syndrome were sequenced in all cases and tissue mtDNA copy number measured where available. Results: Five infants (17%) had genetically proven MLD: DGUOK (n ¼ 2), POLG (n ¼ 2), and MPV17 (1). Four of these died, whereas 1 recovered. Two had normal muscle mtDNA copy number and 3 had normal muscle respiratory chain enzymes. An additional 8 children had low hepatic mtDNA copy number but pathogenic mutations were not detected. One of these developed fatal multisystemic disease after LT, whereas 5 who survived remain well without evidence of multisystemic disease up to 6 years later. Magnetic resonance spectroscopy did not distinguish between those with and without MLD. Conclusions: Low liver mtDNA copy number may be a secondary phenomenon in ALF. Screening for mtDNA maintenance gene mutations may be the most efficient way to confirm MLD in ALF in the first 2 years of life

Using mobile phone technology to support young liver transplant recipients moving to adult services: a systematic rapid review

Background: The process and preparation of moving from child to adult services (transition) is a challenging period of time for young people and represents significant changes in care and support systems. The proliferation of mobile phone applications for health purposes suggests that it is an area for further investigation. Objective: The review explores the potential to use mobile phone technology to help support young liver transplant recipients moving to adult services. It represents the first review conducted in this specialism and considers a new model of support for young liver patients. Methods: A systematic rapid review of the published peer-reviewed literature. Results: Two searches were conducted: Search 1: the use of technology to support transition to adult services (6 studies) and Search 2: how best to support liver transplant recipients during transition (6 studies). Discussion: Research shows that to achieve positive transition young people need information about their condition and transition. The process needs to be guided by transition readiness, rather than the young persons’ age. Although parents and support networks should be in place and are valued, transition should build upon self-management and independence. Results suggest that there appears to be scope to use mobile phone technology to support transition. This is the first time a review has explored the types of issues or concerns facing liver transplant patients and how these can be addressed through mobile phone technology

The experiences of young liver patients transferring from children's to adult services and their support needs for a successful transition

Background: The period of transition from pediatric to adult services represents a time when young people need support, information, and appropriate care in order to successfully move. It is a period that is associated with nonadherence and disengagement with care. Objective: To explore the experiences of young liver transplant recipients transitioning to adult services and determine what they require in order to achieve a successful move. The research also explored the possibility of using a mobile phone application (app) as a tool to support transition. Design: Qualitative approach using novel arts-based focus groups and one-to-one interviews. Participants: Twenty-one young people aged 16 to 25 years, 16 health-care professionals involved in their care, and 7 young people as follow-up. Participants used services provided by the 3 liver centers in England (Leeds, Birmingham, and London). Results: Data highlighted the variability of transition pathways in England for young people moving from child to adult health services. The results showed that they required clear information regarding transition processes including specific medical information and that there was a shortfall in such information. Support was required in the form of a designated transition coordinator or similar specialist who could act as a point of reference and guidance throughout the process. Transitions needed to be individualized and based upon transition readiness rather than age, although the research showed that age cut-offs were still used. Conclusion: Young people welcomed apps to provide information, reminders, contacts, and connections. Future research should explore the efficacy of such apps

The experiences of young liver patients transferring from children's to adult services and their support needs for a successful transition

Background: The period of transition from pediatric to adult services represents a time when young people need support, information, and appropriate care in order to successfully move. It is a period that is associated with nonadherence and disengagement with care. Objective: To explore the experiences of young liver transplant recipients transitioning to adult services and determine what they require in order to achieve a successful move. The research also explored the possibility of using a mobile phone application (app) as a tool to support transition. Design: Qualitative approach using novel arts-based focus groups and one-to-one interviews. Participants: Twenty-one young people aged 16 to 25 years, 16 health-care professionals involved in their care, and 7 young people as follow-up. Participants used services provided by the 3 liver centers in England (Leeds, Birmingham, and London). Results: Data highlighted the variability of transition pathways in England for young people moving from child to adult health services. The results showed that they required clear information regarding transition processes including specific medical information and that there was a shortfall in such information. Support was required in the form of a designated transition coordinator or similar specialist who could act as a point of reference and guidance throughout the process. Transitions needed to be individualized and based upon transition readiness rather than age, although the research showed that age cut-offs were still used. Conclusion: Young people welcomed apps to provide information, reminders, contacts, and connections. Future research should explore the efficacy of such apps

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

Background. Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses

Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome

Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher’s exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4+ T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4+ T cell epitopes

Management of hepatic epithelioid haemangio-endothelioma in children: what option?

Hepatic epithelioid haemangio-endothelioma (HEHE) is an endothelium-derived tumour of low-to-medium grade malignancy. It is predominantly seen in adults and is unresponsive to chemotherapy. Liver transplantation is an accepted indication when the tumour is unresectable. Hepatic epithelioid haemangio-endothelioma is very rare in children and results after transplantation are not reported. The aim of this study is to review the experience of three European centres in the management of HEHE in children. A retrospective review of all paediatric patients with HEHE managed in three European centres is presented. Five children were identified. Four had unresectable tumours. The first had successful resection followed by chemotherapy and is alive, without disease 3 years after diagnosis. One child died of sepsis and one of tumour recurrence in the graft and lungs 2 and 5 months, respectively, after transplant. Two children who had progressive disease with ifosfamide-based chemotherapy have had a reduction in clinical symptoms and stabilisation of disease up to 18 and 24 months after the use of platinum-based chemotherapy. HEHE seems more aggressive in children than reported in adults and the curative role of transplantation must be questioned. Ifosfamide-based chemotherapy was not effective. Further studies are necessary to confirm if HEHE progression in children may be influenced by platinum-based chemotherapy